Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
they give rise to all the other major brain cell types , which include oligodendrocytes , astrocytes , and neurons .
however , molecular pathways , which are complicated and control the proliferation and differentiation of nscs , have been characterized incompletely to date . there is multiple indirect evidence suggesting a critical role of mirnas in nscs [ 47 ] .
post - transcriptional control mediated by mirnas was identified as a further important regulation level , especially in neural proliferation where the action of these negative modulators of gene expression is pervasive .
mirnas are small single - stranded non - coding rnas molecules which participate in the transcriptional regulation of eukaryotic genes and produce biological effects through inhibiting translation or destabilizing target mrnas [ 1012 ] .
mirnas act as vital adjusters in multiple biological processes , including cell metabolism , differentiation , proliferation , and apoptosis .
mir-126 is highly enriched in endothelial cells and previous studies found that mir-126 plays critical roles in vascular integrity and can promote angiogenesis during embryonic development [ 1518 ] .
reported that the expression level of mir-126 was downregulated after spinal cord injury and that it can promote angiogenesis and attenuate inflammation in rats .
however , the effects of mir-126 in nscs is still unclear ; therefore , we intended to study its role in nscs proliferation and survival .
the immortalized human nsc lines hb1.f3 and hb1.a4 were maintained with dulbecco s modified eagle s medium ( dmem , sigma ) containing 10% fetal bovine serum ( fbs ) .
total rna was extracted from cell lines with a mirvanamirna isolation kit ( applied biosystems , foster city , ca , usa ) according to the manufacturer s instructions .
the expression level of mir-126 was detected by qrt - pcr according to the taqman mirna assays protocol ( applied biosystems ) and normalized by u6 small nuclear rna ( rnu6b ; applied biosystems ) with the 2 method .
lv3-pglv - h1-gfp+puro plasmids with mir-126 mimics and negative control ( lv - mir-126 and lv - mir - nc ) were purchased from genepharma ( shanghai , china ) . hb1.f3 and
hb1.a4 stably expressing mir-126 were established by transfecting lentivirus according to the manufacturer s instructions .
cells were plated in 96-well plates in triplicate at approximately 1000 cells per well and cultured in the growth medium .
cells were then treated with the indicated reagent and the numbers of cells per well were measured by the absorbance ( 450 nm ) of reduced water - soluble tetrazolium salt ( wst ) at the indicated time points .
cells were plated into 6-well plates at a density of 1000 cells / well in 2 ml medium .
the colonies were observed using a phase - contrast microscope at a magnification of 4 ( we counted the colonies containing at least 50 cells ) .
cells were transfected with mir-126 mimics or their respective controls and were harvested after transfection at 48 hours and then marked with the annexinv / pi double staining kit ( bd biosciences , usa ) according to the manufacturer s instructions .
flow cytometry was used to assess the apoptotic cells in triplicates and all assays were repeated at least 3 times .
student s t test or one - way anova were used for analysis when appropriate .
the immortalized human nsc lines hb1.f3 and hb1.a4 were maintained with dulbecco s modified eagle s medium ( dmem , sigma ) containing 10% fetal bovine serum ( fbs ) .
total rna was extracted from cell lines with a mirvanamirna isolation kit ( applied biosystems , foster city , ca , usa ) according to the manufacturer s instructions .
the expression level of mir-126 was detected by qrt - pcr according to the taqman mirna assays protocol ( applied biosystems ) and normalized by u6 small nuclear rna ( rnu6b ; applied biosystems ) with the 2 method .
lv3-pglv - h1-gfp+puro plasmids with mir-126 mimics and negative control ( lv - mir-126 and lv - mir - nc ) were purchased from genepharma ( shanghai , china ) . hb1.f3 and
hb1.a4 stably expressing mir-126 were established by transfecting lentivirus according to the manufacturer s instructions .
cells were plated in 96-well plates in triplicate at approximately 1000 cells per well and cultured in the growth medium .
cells were then treated with the indicated reagent and the numbers of cells per well were measured by the absorbance ( 450 nm ) of reduced water - soluble tetrazolium salt ( wst ) at the indicated time points .
cells were plated into 6-well plates at a density of 1000 cells / well in 2 ml medium .
the colonies were observed using a phase - contrast microscope at a magnification of 4 ( we counted the colonies containing at least 50 cells ) .
cells were transfected with mir-126 mimics or their respective controls and were harvested after transfection at 48 hours and then marked with the annexinv / pi double staining kit ( bd biosciences , usa ) according to the manufacturer s instructions .
flow cytometry was used to assess the apoptotic cells in triplicates and all assays were repeated at least 3 times .
ibm spss 19.0 statistical software was used to analyze the data . student s t test or one - way anova were used for analysis when appropriate .
to further study the potential function of mir-126 in nscs , hb1.f3 and hb1.a4 were stably transfected with mimics or negative control ( nc ) .
as indicated in figure 1a , mir-126 mimics showed good overexpression effects both in hb1.f3 and hb1.a4 and both cell lines overexpressing mir-126 showed marked cell growth increase ( figure 1b , 1c ) . to further confirm the function of mir-126 on cell proliferation and growth , soft agar colony formation assay was performed .
as shown in figure 2a , 2b , the colony formation was significantly increased by mir-126 compared with the negative control group .
we next investigated the function of mir-126 in the regulation of cell apoptosis by flow cytometry .
cells overexpressing mir-126 displayed a significant decrease in the apoptotic rate when compared with the control group ( figure 3a , 3b ) .
these results suggest that mir-126 may inhibit apoptosis in nscs , which may contribute to the growth induction features of mir-126 .
to further study the potential function of mir-126 in nscs , hb1.f3 and hb1.a4 were stably transfected with mimics or negative control ( nc ) .
as indicated in figure 1a , mir-126 mimics showed good overexpression effects both in hb1.f3 and hb1.a4 and both cell lines overexpressing mir-126 showed marked cell growth increase ( figure 1b , 1c ) . to further confirm the function of mir-126 on cell proliferation and growth , soft agar colony formation assay was performed .
as shown in figure 2a , 2b , the colony formation was significantly increased by mir-126 compared with the negative control group .
we next investigated the function of mir-126 in the regulation of cell apoptosis by flow cytometry .
cells overexpressing mir-126 displayed a significant decrease in the apoptotic rate when compared with the control group ( figure 3a , 3b ) .
these results suggest that mir-126 may inhibit apoptosis in nscs , which may contribute to the growth induction features of mir-126 .
they can profoundly regulate the expression of massive target genes that encode proteins , which may finally lead to the change of biological function .
mir-126 , which is located in intron 7 of the egf - like domain 7 ( egfl7 ) gene , is a microrna that is highly enriched in endothelial cells   and regulated by the transcription factors ets-1 and ets-2 in endothelial cells .
previous studies found that mir-126 promoted angiogenesis during embryonic development and after injury by targeting spred1 and pik3r2 .
also , knockdown of mir-126 resulted in delayed angiogenic sprouting , collapsed blood vessels , widespread hemorrhages , and partial embryonic lethality during zebrafish and mouse embryogenesis .
it is also involved in cell growth regulation in several organs , such as colorectal cancer , gastric cancer , and liver carcinoma , by regulating multiple target genes , including insulin receptor substrate , p85 , pi3k , akt , and crk [ 2629 ] .
reported that mir-126 plays an important role in angiogenesis and inflammation after contusion spinal cord injury in rats .
in the current study , we verified that when the expression level of mir-126 was overexpressed by mimics transfection , the proliferation and survival of nscs were both significantly promoted .
cck8 assay and colony formation assay both demonstrated that mir-126 can induce the proliferation of nscs .
although the mechanism is not yet completely understood , our study provides further evidence in this area .

Answer:
backgroundthe aim of this study was to investigate the potential function of mir-126 in neural stem cells ( nscs).material / methodsexpression level of mir-126 was detected by quantitative real - time pcr ( qrt - pcr ) .
 mir-126 overexpression was established by transfecting mir-126 mimics into human nsc lines ( hb1.f3 and hb1.a4 cells ) .
 its effects on cell proliferation were studied using cell - counting kit-8 ( cck8 ) assay , colony formation assays .
 flow cytometry was performed to evaluate the effect of mir-126 on cell survival.resultscck8 assay and colony formation assay showed that overexpression of mir-126 promoted cell proliferation and increased colony numbers in hb1.f3 and hb1.a4 cells .
 the flow cytometry confirmed the results that mir-126 inhibited cell apoptosis.conclusionsmir-126 promoted the proliferation and survival of nscs .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the dietary magnesium intake tends to be lower than that recommended worldwide even in western countries .
several factors have been identified to be trigger for lowering magnesium intake including the waterborne magnesium factor , the loss of magnesium during food refining , and the magnesium content of vegetarian diets , as well as various metabolic situations such as hypertension , pregnancy , osteoporosis , drug therapy , alcoholism , stress , and even cardiac trauma .
magnesium is the most abundant intracellular divalent cation that is important for physiological processes including neuromuscular function and maintenance of cardiovascular tone .
the importance of magnesium intake in relation to cardiovascular diseases has been increasingly described , so that its intake can be inversely related to the risk of hypertension and type 2 diabetes mellitus   and may improve serum lipid profiles .
recent surveys in sweden [ 3 , 4 ] have indicated that vegetarian diets provide a more adequate intake of magnesium , as illustrated in table 4 . note that the magnesium intake of men and women on vegetarian diets was considerably greater than the rda requirement ; this was attributed to the high intake of vegetables and whole - grain cereals by these individuals .
recent studies have shown that some components of the mediterranean diet such as vegetables , legumes , and nuts are rich sources of magnesium ; therefore , it seems that the high adherence to the mediterranean diet is associated with high consumption of magnesium .
although the main dietary regimen of iranian population is mediterranean diet components especially the major sources of magnesium , the rate of coronary artery disease ( cad ) risk factors among this population has been considerably high . therefore , in the present study , we tried to determine effect of mediterranean dietary approach on laboratory parameters related to cad risk factors with the focus on serum magnesium concentration among iranian patients with cad .
baseline characteristics and clinical data of 102 consecutive patients with the diagnosis of cad and candidates for isolated coronary artery bypass surgery were entered into the study .
studied data were collected by the review of clinical recorded files in the day of admission . in this study ,
cad was considered significant if there was a 75% or greater stenosis in the cross - sectional diameter and 50% or greater stenosis in the luminal view .
blood samples were drawn from the corresponding peripheral vein into vacutainer tubes after 1214  h of overnight fasting and before operation .
plasma glucose concentrations were assessed by means of a glucose hexokinase method ( pars azmoon kits accredited by bioactiva diagnostica , germany ) . serum total cholesterol , hdl cholesterol , and triglycerides were measured via enzymatic techniques ( pars azmoon kits accredited by bioactivadiagnostica , germany ) .
the friedewald formula was used to calculate low density lipoprotein ( ldl ) cholesterol , except when the triglyceride level was >
blood pressure was calculated as the mean of two measurements , performed in the sitting position after 5 minutes of rest , using a random - zero sphygmomanometer ( hawksley - gelman , lancing , sussex , uk ) .
c - reactive protein ( crp ) level was measured by immunoturbidimetry ( pars azmun , iran ) , and lipoprotein(a ) was measured using tint eliza ( biopool , usa ) .
creatinine was measured with jaffe reaction ( parsazmon kit , tehran , iran ) using an autoanalyzer ( hitachi , tokyo , japan ) .
studied patients were also interviewed on admission to surgical ward and before operation to report the consumption of food items listed as the number of times per day , per month , or per year during the previous year .
we assessed nutritional status by a validated food frequency questionnaire ( ffq ) , previously validated in iran   and a 24-hour dietary recall questionnaire to record the types , amounts , and frequencies of foods consumed .
sum of the consumption of each of several food items was used to determine the overall consumption of the food group to which each item belonged [ 9 , 10 ] .
the diet score was calculated on the basis of mediterranean diet quality index ( med - dqi ) that the construction of the score for this index ( table 1 ) .
the index assigns a score of 0 , 1 , or 2 according to the daily intake of each of the seven components and then final score was reported as a summation of all nutrient scores ranged between 0 and 14 .
we divided studied patients into two groups according to the final score : the groups with final score lower than 5 ( n = 35 ) and those who had final score between 5 and 10 ( n = 67 ) .
we compared categorized variables between the two above groups using chi - square test or fisher 's exact test if required .
multivariate linear regression analysis was used to investigate the potential confounding effects of patients ' characteristics and clinical data on the association between serum magnesium concentration and mediterranean regimen score .
all the statistical analyses were performed using spss version 13.0 ( spss inc . , chicago , il , usa ) .
studied patients had the mean age of 58.8 year ( ranged between 38 and 78 years ) and 40.2% of them were male .
hyperlipidemia and hypertension were observed in 75.5% and 56.9% of patients , respectively , and 51.0% of them were diabetics .
half of the studied patients had moderate functional class , but three coronary arteries were involved in the majority of them ( table 2 ) .
comparison of the concentrations of serum laboratory parameters between the two groups with lower mediterranean dietary score and group with higher dietary score showed no significant differences between the concentration of albumin , last fasting blood sugar , last creatinine , and lipid profiles ( table 3 ) ; however , serum magnesium concentration in the group with dietary score between 5 and 10 was lower than that in group with higher score ( p = 0.026 ) .
linear multivariate regression analysis also showed that the lower mediterranean dietary score was a predictor for serum magnesium concentration after adjusting for confounders ( table 4 ) .
recent studies could confirm the cardioprotective role of intravenous magnesium for prevention of cardiac arrhythmia , pump dysfunction , and death in patients with cad , especially in the immediate postinfarction period [ 12 , 13 ] .
magnesium can inhibit the influx of calcium in vascular smooth muscle cells and therefore inhibit arrhythmic recurrence and the production of il-6 and mmp-1 after reperfusion and prevent the increase of myocardial lesions caused by calcium overload on myocytes .
however , effect of dietary intake of this mineral on control and inhibition of cad risk factors has been questioned .
some researchers have been hypnotized that the low intake of magnesium may be related to the least degree of cardiovascular disease [ 15 , 16 ] .
some others could show that the dietary magnesium intake can be inversely associated with fasting serum insulin , plasma high density lipoprotein - cholesterol , and systolic and diastolic blood pressure . in the present study
, we showed the potential effect of mediterranean dietary regimen on increasing of serum magnesium concentration that can mainly lead to the favorite control and prevention of cad risk factors .
we have shown that not only intravenous magnesium administration can be related to the lower risk of poor outcome in patients with cad , but also these effects can be obtained by dietary intake of this mineral via mediterranean dietary regimen . in a similar study by schrder
, it was found that the high consumption of vegetables , fruits , legumes , nuts , fish , cereals , and olive oil as main components of mediterranean regimen led to high absorption of magnesiumin obesity and type 2 diabetes . also , singh showed that the increased intake of dietary magnesium in association with the general effects of a nutritious diet can offer protection against cardiovascular deaths among high - risk individuals predisposed to cad .
furthermore , in another study , it was observed that the intake of dietary magnesium was associated with a reduced risk of cad ; however , associations between dietary magnesium and coronary events occurring after fifteen years of follow - up were modest .
it seems that the mediterranean dietary regimen and its components as rich pools of magnesiummight optimize micronutrient status in main body organs especially cardiovascular system .   in the present study
, it was also found that the patients ' baseline characteristics and even severity of cad had no relationship with serum magnesium concentration in multivariate analysis .
similarly , in a study by mataix et al . , the risk of hypomagnesemia was not associated with any of the other factors that were investigated such as gender , educational level , obesity , smoking habits , alcohol consumption , and physical exercise .
however , some studies showed that the magnesium intake could decrease in advanced age and in men for each of the different race or ethnic groups .
it seems that the serum magnesium changes are mainly dependant on nutritional habit , metabolicprocesses , inflammatory biomarkers , and other related - potential mechanisms that should be investigated in future studies .   in conclusion , taking mediterranean dietary regimen can be associated with increased level of serum magnesium concentration , and thus this regimen can be cardioprotective because of its effects on serum magnesium .

Answer:
background .
 recent studies confirmed cardioprotective role of intravenous magnesium for the prevention of cardiac events , but effect of dietary intake of this mineral via recommended dietary regimens on control and inhibition of coronary artery disease ( cad ) risk factors has been questioned .
 the aim of the present study was to determine effect of mediterranean dietary approach on serum magnesium concentration among iranian patients with cad .
 method .
 baseline characteristics and clinical data of 102 consecutive patients with the diagnosis of cad and candidates for isolated coronary artery bypass surgery were entered into the study .
 laboratory parameters especially serum magnesium concentration were measured after 1214  h of overnight fasting and before operation .
 nutritional status was assessed by food frequency questionnaire and the diet score was calculated on the basis of mediterranean diet quality index ( med - dqi ) .
 results .
 no significant differences were found in the concentrations of albumin , last fasting blood sugar , last creatinine , and lipid profiles between the groups with mediterranean dietary score < 5 and the group with higher dietary score ; however , serum magnesium concentration in the first group was higher than that in the group with higher dietary score .
 linear multivariate regression analysis showed that the lower mediterranean dietary score was a predictor for serum magnesium concentration after adjusting for confounders .
 conclusion .
 taking mediterranean dietary regimen can be associated with increased level of serum magnesium concentration , and thus this regimen can be cardioprotective because of its effects on serum magnesium .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
auricular defects characterized by absence of the pinna may be congenital ( microtia or anotia ) or acquired as a result of infection , cancer surgery , or traumatic injury .
congenital defects may be associated with auditory canal , middle ear , and inner ear malformations .
the total or partial pinna mutilation may be a consequence of a car accident , war collateral damage , or chemical burn .
recently an increase in the number of patients presenting with pinna lesions due to chemical assault burns , occurring in the domestic or industrial setting , has been reported . whatever the cause , absence of the pinna is an important aesthetic problem , with a permanent effect on the patient 's quality of life , which can often cause severe psychological distress .
the modern era of pinna reconstruction surgery has its foundations in the techniques proposed by tanzer , brent , and nagata [ 46 ] .
the differing techniques for reconstructive plastic surgery of the auricular defect involve usually the insertion of autogenous rib cartilage framework under the skin .
other surgeons have suggested the employment of prostheses made of synthetic material as a good alternative to autogenous costal cartilage [ 7 , 8 ] .
the reconstructive plastic surgery techniques based on the use of autologous cartilage inserts normally require repeated surgery acts at both implant site and donor site .
this creates a significant discomfort both for the pain complained about by the patient and for repeated hospital admissions to the detriment of quality of patient life .
initially , these epitheses were held in place by adhesives that , however , provided poor results in terms of stability and were often associated with skin irritations and deterioration of the prosthesis caused by the adhesive substances . also these defects imply a deterioration of patient quality of life .
currently a superior , innovative surgical technique exists that allows fixation of the ear epitheses by osseointegrated titanium implants ( cochlear bone anchored solutions ab , sweden ) .
basically , this approach reflects an evolution of the implants developed for dental prostheses as proposed by brnemark in 1969 , which have been used for over 40 years in the field of odontostomatology and subsequently were proposed for application with osseointegrated craniofacial implants for use with bone - conduction hearing implant solutions [ 9 , 10 ] . in our study , we describe our experience using these pinna prostheses in 27 patients treated in the last three years .
we discuss the indications for auricular epithesis implant , the surgical technique , and outcomes .
our case series comprised 27 patients ( 24 males and 3 females with a mean age of 33.1 years , range 1687 years ) ( table 1 ) .
the etiology was congenital in 17 patients ( figure 1 ) who were affected by microtia , while eight had posttraumatic mutilation ( figure 2 ) and two surgical amputation due to neoplasia ( figure 3 ) .
six of the patients with microtia and three of the patients affected by traumatic mutilation had previously undergone plastic reconstructive surgery with rib cartilage grafting and were not satisfied with the results .
these patients requested to have their previously reconstructed ear removed and replaced with an epithesis .
one patient ( patient 12 ) had previously undergone surgery , in a different hospital , using bone - anchored titanium implants but one of the abutments had broken because of a further unlucky trauma .
after six weeks , all the implants were osseointegrated and a retentive bar was fixed to the abutments .
the patients with microtia were offered the option of undergoing treatment with a bone - conduction hearing implant solution ( e.g. , baha ) to concomitantly address their hearing needs in parallel to the auricular rehabilitation with the bone - anchored epitheses .
all patients declined the hearing treatment option , preferring to have the option at a later stage instead . before the surgical field is prepared and with the patient 's face still fully and easily visible , the implant sites should be carefully marked , using methylene blue , down to the bone .
these are ideally placed approximately 20  mm from the center of the external auditory canal opening or anticipated opening .
they are positioned at 8 o'clock and 10:30 on the right side and at 4 o'clock and 1:30 on the left side . in the presence of a complete malformation ,
the supposed location of the external auditory canal is determined by considering a triangle traced on the contralateral hemiface using the following references : the line between the lateral canthus and the auditory canal , the line between the auditory canal and the labial commissure , and the angle formed by these two lines ( figure 1(b ) ) .
we usually perform one - stage surgery , removing tags and remnants in cases of microtia and performing the necessary subcutaneous tissue reduction .
the one - stage surgical procedure can be used in adults to treat auricular defects involving nonirradiated tissue ; the two - stage technique should usually be chosen for paediatric patients and for the treatment of orbital and midface defects and auricular defects in patients with poor bone quality .
drilling begins using the guide drill with the spacer kept on 3  mm . during drilling
the bottom of the hole is repeatedly checked for bone at the base of the site .
if there is adequate bone thickness , drilling continues to a depth of 4  mm .
the next step is to widen the hole to the exact diameter using a 3 or 4  mm drill countersink .
the low - speed setting should be used for implant insertion . in compact cortical bone , a torque setting of 40  ncm is recommended , whereas , in soft bone , a lower torque setting of 20  ncm should be used . the self - tapping fixture with the premounted fixture mount
it is then picked up with the connection to the hand piece , which is placed into the drill hand piece .
the implant is installed without cooling irrigation until the small grooves at the distal end of the implant are well within the canal .
when the flange of the implant has seated , the hand piece will automatically stop .
the titanium standard abutment is picked up with the abutment holder and placed into the implant .
finally a gauze dressing is applied in a figure eight form ( i.e. , foam dressing , soft silicone wound contact layer , or antiseptic dressing ) around the abutments .
all patients were discharged the day after surgery and were revised for the first dressing after seven days .
the implants occurs six weeks after implant to permit sufficient healing and stabilization of the implants . following healing and stabilization of the surgical site
, the patient was sent to the anaplastology technician who prepared the epithesis , modeling it with reference to the contralateral ear and carefully matching the individual 's skin colour ( figures 3(b ) and 3(d ) ) .
the definitive one has two sides : the inner one is an acrylic plate with clips that allow the attachment to a gold - platinum bar fixed to the abutments and the external one is made of soft silicone .
the patients receive two epitheses of different colours : a pale one for winter and a tanned one for summer . when the process of osseointegration is complete , the prosthesis , which has clips , can be easily and securely attached to , or removed from , the gold - platinum cylinder - and - bar system ( figures 3(c ) and 3(d ) ) .
none of the patients we treated experienced problems related to the implants over six months to three years ( osseointegration failure or wound healing problems ) .
only one patient encountered a relatively exuberant scar in the area of surgical remnants removing .
the patients were evaluated for their quality of life , during the week before pinna reconstruction with the short form health survey ( sf-12 ) as a baseline assessment ( t0 ) .
statistical analysis of changes over time was performed via pearson correlations , with a significant change deemed by p  0.05 .
statistical analysis adopting sf-12 score ( short - form health survey , 12 items ) suggests a significant role in quality of life of patients who underwent auricular rehabilitation .
all our patients expressed their satisfaction regarding the short hospitalization and reduced invasiveness compared to other alternative therapies .
they had no adverse psychological reactions ; instead , they were able to resume social relations and usual physical activities .
absence of the ear , congenital or resulting from trauma or surgery , is a defect that can be resolved through reconstructive plastic surgery .
the surgical reconstruction of pinna defects remains a challenging task typically requiring multiple operations with often compromised aesthetic results .
this involves the insertion of either an autogenous rib cartilage framework or a prosthesis made from synthetic material into a subcutaneous pocket behind the ear , created through tissue expansion . in the past , if surgical reconstruction was refused , a patient could undergo an alternative rehabilitative approach using an adhesive - retained prosthesis .
the reconstruction using rib cartilage has some inherent disadvantages : it requires more than one surgical procedure , the risk of complications is relatively higher both at the implant site ( e.g. , infections , bleeding , haematoma , necrosis , and skin graft or cartilage graft exposure ) and at the donor site ( e.g. , infections , haematoma , and scarring ) .
patients are very often dissatisfied with the final outcome because their new ear looks considerably different from the contralateral one and does not meet their expectations [ 13 , 14 ] .
wellisz proposed the use of medpore prostheses made from porous polymer material inserted in subcutaneous pockets .
this procedure is frequently complicated by partial or total rejection and further build - up of scar tissue .
the use of adhesive - retained prostheses is also not without its issues , that is , dermatitis resulting from contact with the adhesives , unpredictable reliability of retention , variability of positioning of the prosthesis , and poorer hygiene directly attributable to the tackiness of the adhesive , as well as a decreased life span of the prosthesis resulting in an increased number of device renewals .
recent studies described the use of osseointegrated auricular prostheses as a good alternative treatment to surgical reconstruction . in this
regard , titanium implant systems for bone - anchored implantable hearing solutions have shown us how such prostheses can be attached safely , securely , reproducibly , and without the need for adhesives [ 11 , 1517 ] .
the procedure discussed in this paper is suitable for patients who are unwilling to undergo plastic reconstructive surgery utilizing rib cartilage , which remains a challenging surgical procedure that involves more than one surgical step and is associated with the risk of complications at the donor site and/or the acceptor site .
similarly , in cases of pinna amputation ensuing following damage to the pinna from chemical burns , the usual techniques of plastic surgery employed hold their inherent difficulties as they involve procedures that require the presence of large areas of intact skin around the lesion ( necessary for the preparation of sliding skin flaps or the use of tissue expanders prior to the placement of subcutaneous implants ) . subsequently ,
the use of these implants is also the only possible solution in cosmetic treatment of oncology patients who have previously undergone several surgical procedures and/or radiotherapy .
radiotherapy does not constitute a contraindication for this procedure , although implant loss is relatively higher in irradiated cases than in nonirradiated cases at the site of treatment .
granstrom reported that the adjunctive use of hyperbaric oxygen could ultimately reduce the risk of implant loss .
it is important to note the reasonably low cost of the implants and epithesis : typically amounting to a total of less than 4000 euros . in all previous reports patients
express their satisfaction regarding the short hospitalization and reduced invasiveness compared to other alternative therapies .
. local skin infection around the fixture could occur , as could the formation of granulation tissue and keloids .
these are complications that can be avoided or resolved using appropriate medication and topical treatments without loss of the fixture .
absolute contraindications for the use of titanium bone implants in prosthetic reconstruction of the auricle are exceptional and may be local or general conditions ( i.e. , resp . ,
contraindications for general anaesthesia need not preclude use of these implants since they can be positioned equally well under local anaesthesia .
this surgical technique is contraindicated in patients younger than 14 years of age , whose skull thickness is not sufficient to support the osseointegrated implant .
preoperative evaluation of bone thickness via ct scans should , nevertheless , be a mandatory part of the surgical planning in all the patients [ 1517 ] . as mentioned earlier , indications for one - stage surgery are auricular defects , adult patients , and nonirradiated tissue , while two - stage technique should be used in young patients ( 1417 years old ) and to treat orbital and midface defects and auricular defects in patients with poor bone quality .
conductive hearing loss due to malformations of the external and middle ear presents in all subjects affected by microtia and can be corrected by combining the placement of titanium implants for auricular rehabilitation with implantation of the fixture and abutment for a baha . in this way , both the sensory and the aesthetic problems can be resolved in a single operation . however , it should be pointed out that all the patients in our series refused to undergo baha implantation after testing the device prior to surgery ; these patients , being well accustomed to hearing on only one side , found the increased auditory perception provided by the baha disorienting and irritating .
the pinna epithesis fixed with bone - anchored titanium implants technique is characterized by excellent aesthetic outcome and lasting results .
for example , they are able to use also helmet required for some sport activities and can swim without the problems related to adhesive epitheses .

Answer:
different surgical solutions have been proposed for reconstruction of the auricle following loss of the pinna through traumatic injury or neoplastic disease or in patients with congenital defects .
 surgical treatment may involve the insertion of an autogenous rib cartilage framework or the use of a porous polymer material inserted into an expanded postauricular flap .
 reconstruction with rib cartilage has yielded good results but requires more than one surgical step , and adverse events can occur both at the donor and at the acceptor site ; cases of prosthesis rejection have also been described following application of the polymeric prosthesis .
 the use of a titanium , dowel - retained silicone prosthetic pinna , fixed to the temporal bone , has recently been proposed .
 this useful surgical approach is indicated particularly after resection of the pinna caused by neoplastic disease or in traumatic auricular injury .
 osseointegrated titanium implants used in 27 patients in this study provided them with a safe , reliable , adhesive - free method of anchoring the auricular prostheses .
 the prostheses allowed recovery of normal physical appearance and all the patients reported that they were completely satisfied with the outcome of the surgical reconstruction .
 no surgical complications , implant failures , or prosthetic failures were encountered over six months to three years .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
rhabdomyolysis is characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation .
the spectrum of the syndrome ranges from asymptomatic serum muscle enzymes elevation to life - threatening extreme enzyme elevations , electrolyte imbalances , and acute renal failure .
we report an elderly lady with a combination of risk factors who developed rhabdomyolytic acute renal failure .
a 65-year - old lady was suffering from type 2 diabetes for the past 30 years , hypertension for the past 20 years , and coronary heart disease for the past 10 years .
the medications included clopidogrel 75 mg / day , amlodipine 10 mg / day , frusemide 40 mg bds , and insulin .
a week before presenting to us , a cardiologist had added atorvastatin 10 mg / day to her prescription .
she presented to us with complaints of severe generalized myalgia , difficulty in assuming upright posture from sitting position , and difficulty in walking of 1 week duration .
she also complained of swelling of feet , face , nausea , loss of appetite and noticed decreased urine output , and reddish discoloration to urine for the last 3 days .
there was no fever , history of trauma , viral exanthem , severe exercise , seizure , uncontrolled blood glucose , and use of herbal medication preceding the illness . on examination
, she was well - built and well - nourished , and had pedal edema and facial puffiness .
she was afebrile with pulse rate of 60 beats per min and blood pressure of 160/90 mm hg .
neurological examination showed 2/5 power in all four limbs , absent deep tendon reflexes , and muscle tenderness with no sensory involvement .
urinalysis showed glucose 2 + , ketone bodies negative , blood positive , red blood cells nil , and white blood cells 1 - 2/hpf .
her hemoglobin was 11.4 g / dl , total leukocyte count 18 , 300 per mm , platelet count 5.0 lakh per mm , esr 20 mm after 1 h , electrocardiogram showed tall peaked and widened t waves with proximal limb steeper than distal limb , and the chest radiograph was normal .
ultrasound abdomen showed right kidney 9.3  3.7 cm and left kidney 9.2  3.2 cm .
the urine and blood cultures were sterile , hiv , hbsag , anti - hcv antibodies , anti - hav igm , and anti - hev igm were negative .
myalagia , reddish discoloration to urine , deterioration of renal function , elevated sgot , creatinine kinase , and increased urine myoglobin led to the diagnosis of rhabdomyolysis .
levothyroxine replacement was initiated at a dose of 50 g / day , increased after 15 days to 100 g / day .
the following three risk factors for the onset of rhabdomyolysis were identified : use of statin , undiagnosed hypothyroidism , and co - administration of amlodipine and clopidogrel .
frusemide was stopped as she had hypokalemia before the onset of illness which was again a risk factor for rhabdomyolysis .
after seven sessions of hemodialysis the urine output improved and serum creatinine stabilized at 3.2 mg / dl .
however , it is difficult to directly compare the incidence of statin myopathy in clinical trials with real world clinical practice given the inconsistent definitions .
the common risk factors for the development of a statin - induced myopathy include high dosages , increasing age , female sex , renal and hepatic insufficiency , diabetes mellitus and concomitant therapy with fibrates , cyclosporine , macrolide antibiotics , warfarin , and digoxin .
individual statins differ in their risk of inducing rhabdomyolysis , with some patients developing this syndrome when switching from one statin to another .
it is probable that genetic factors play a role in the pathogenesis of this syndrome .
the temporal relation between statin therapy and the onset or resolution of myopathy is not fully defined .
a retrospective study of 45 patients with statin myopathy at a tertiary center revealed a mean therapy duration of 6.3 months before symptom onset and a mean duration of 2.3 months for symptom resolution after discontinuation of statin therapy .
patients in primo study developed muscle symptoms after a median of 1 month after initiation of statin therapy , ranging up to 12 months after initiation .
hypothyroidism was reported as a predictor of statin - associated myopathy ( or 1.71 ; ci , 1.10 - 2.65 ) in primo study .
the likely mechanisms of renal impairment in hypothyroidism are the reduction in glomerular filtration rate due to the lower cardiac output and renal blood flow , thyroxine may mediate tubular secretion of creatinine , hypothyroidism may increase creatinine release from muscle , and rhabdomyolysis .
it is possible for two different substrates of the same metabolizing enzyme to compete for catalytic sites on the same enzyme ; through competitive inhibition , one substrate may gain access to these sites whereas the other is excluded .
this process results in metabolism of the drug that successfully accesses the catalytic sites of the enzyme , whereas the excluded drug is metabolized at a significantly slower rate . in the present patient
the present patient provided a caution that hypothyroidism and interaction with other drugs should be considered when patients were going to be initiated on statins .

Answer:
rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation .
 we report a patient with chronic kidney disease who had deterioration of renal function due to combination of risk factors like hypothyroidism and interaction of amlodipine and clopidogrel with statins .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the tree of life ( tol ) is a widely used metaphor to describe the history of life on earth . while darwin argued that the ' coral of life ' may be a more apt description ( since only the surface remains alive , supported by the dead generations beneath it ) , relationships between organisms based on shared characters are best organized using the schematic representation of a tree .
use of molecular markers , in particular small - subunit ribosomal rna , have allowed this metaphor to be extended to microorganisms ; however , this has also presented unique challenges for notions of phylogeny and evolution .
one of the most significant challenges is the impact of horizontal gene transfer , which causes genes that coexist in a genome to have different molecular phylogenies . despite these challenges , the increasing ease with which genomes can be sequenced has reinvigorated attempts to use genomic information to reconstruct the tol .
therefore , a vertical line of descent exists , and could theoretically be reconstructed as a purely bifurcating tree ( that is , an organismal or cytoplasmic tree ) .
however , while evolution presupposes and requires descent via reproduction , the two are not analogous .
evolution is , by definition , the change in the genetic material within a population of organisms across generations ; therefore , any process by which genetic material within a population changes that is unrelated to the reproduction of individuals will show a history that is unrelated to the organismal vertical line of descent .
the sum effect of these other genetic processes may completely obfuscate vertical descent , leaving only some measure of ' relatedness ' based on overall genetic similarity .
two common approaches in constructing a genome - based tol are supermatrix analyses , in which sequence alignments for individual gene families are concatenated into a single dataset that is then used to construct a tree , and supertree analyses , in which a consensus phylogeny is constructed from multiple gene trees . in some cases ,
datasets are generated by finding orthologous genes in all organisms and removing all genes whose conflicting phylogenetic topologies seem to indicate horizontal gene transfer , and then using the remaining genes to reconstruct the presumed vertical lines of descent of the genomes ( see , for example , [ 4 - 6 ] ) .
this approach has an obvious shortcoming in that gene transfer and the resulting phylogenetic conflicts can only be inferred if each individual gene has retained sufficient phylogenetic information to enable its origin to be correctly assigned .
furthermore , the absence of evidence for gene transfer does not constitute evidence for the absence of gene transfer .
thus , combining genes with different histories into a single data set will almost certainly result in a phylogeny that represents neither the history of any individual gene , nor the history of the organism as a whole .
another problem with supermatrix and supertree analyses is that they often give equal weight to genes that have different histories of horizontal gene transfer .
this results in an average or median phylogeny that may not represent organismal history ; if there are ' highways ' of gene sharing  that is , large numbers of genes have , for some reason , been shared between specific groups of otherwise phylogenetically distinct organisms  this can easily be mistaken for a consistent signal supporting an organismal tree . for example , because of such highways of gene sharing these types of analyses group members of the order thermotogales with the firmicutes , and the members of the aquificales with the -proteobacteria .
in contrast , 16s rrna gene phylogenies and concatenated ribosomal protein phylogenies strongly support these two orders as deeply branching bacterial lineages   ( figure 1 ) .
( a ) extensive horizontal gene transfer at all phylogenetic levels combine to produce a ' web of life ' that often obscures the lines of descent between groups ( modified from ) .
copyright ( 2008 ) national academy of sciences , usa . ( b ) major microbial groups as defined by 16s ribosomal rna phylogeny .
bands represent some avenues of extensive gene sharing involving thermotogales , aquificales , and firmicutes .
( c ) impact on relationships between thermotogales and aquificales of genome content changes due to extensive horizontal gene transfer .
grey clouds represent groups of shared genes between clades that are non - monophyletic in the 16s tree .
the phylogeny based on these ' gene content ' clouds is quite distinct from that of 16s or other ribosome - based trees .
if stringent criteria are applied to remove or down - weigh transferred genes from supertree or supermatrix analyses , the resulting trees at best represent the history of only a minor fraction of the genome , largely consisting of ribosomal proteins , effectively a ' tree of one percent ' . even if this remaining ' genome core ' retains a strong signal of vertical descent , this does not capture the true evolutionary history of genomes ; that is , a web where different strands depict the history of different genes .
a ribosomal tree of life has other shortcomings , in that within taxonomic orders many recombination and lineage sorting events may occur , and ribosomal genes are so highly conserved that such events at the tips of the tree may not be detectable .
however , it can still provide a useful backbone for a reticulated genomic or organismal phylogeny , especially with respect to sets of genes that clearly have undergone horizontal transfer between more distantly related groups . while ribosomal protein and rna encoding genes have been transferred in the past ( see discussion in ) , these genes are resistant to transfer , with most transfers occurring between close relatives .
these properties make a phylogenetic reconstruction using ribosomal rna and proteins an ideal scaffold upon which to map horizontal gene transfers , clearly depicting their distinct contribution to genomic ( and organismal ) evolution .
several attempts have been made to capture this web - like genome history ( see , for example ,   using ribosomal rrna as a backbone ( figure 1 ) .
conceptually , this method is distinct from any ' tree of one percent '   or genome averaging approach in that rather than being discarded , genes undergoing horizontal transfer are included in the final reconstruction without obscuring the vertical signal , even if that vertical signal is preserved only in a minority of genes .
in this issue , puigbo , wolf and koonin   present an approach for salvaging the tol that is a variant on other supertree methods , in which nearly 7,000 phylogenetic trees of prokaryotic genes ( a ' forest of life ' ) are compared in order to determine a central tendency in their topologies .
the trees are built from clusters of orthologous groups of proteins ( cogs ) , and the central tendency is deduced from a set of nearly universal trees ( nuts ) , defined by puigbo et al . as those trees generated from a set of cogs that are represented in > 90% of the analyzed prokaryote taxa .
what distinguishes their approach from earlier supertree analyses  apart from the very large number of genes included in the comparison  is that it does not depend on a concatenation of highly conserved proteins or rrnas , or on a supertree generated by ' pruning ' down to those genes giving a consistent topology , to determine a central tendency . instead ,
calculate an ' inconsistency score ' that is a measure of how representative a particular topology of each tree is to the rest of the trees in the forest of life . in reconstructing the central tendency in such a broad distribution of gene phylogenies , the work by puigbo et al . also shows the difficulty in resolving deep branches , which often simply collapse into radiations without any topological structure . in confronting this problem ,
they show that the relationship between phylogenetic depth and resolution supports a tree - like structure for these deep branches .
this result is significant in that it suggests that there is no need to postulate exotic ' big bang ' radiations early in evolution ; rather , deep phylogenies can still be represented as bifurcating evolutionary events , albeit with extremely short branches that can prove difficult ( or sometimes impossible ) to resolve . integrating the vertical descent of organisms and their genomes with the myriad phylogenetic patterns produced by horizontal gene transfer is essential for a truly comprehensive understanding of evolution .
a new method that acknowledges and promotes this integration , even if falling short of fully encompassing the intricate details of a complex genome - based biological reality , represents progress towards this goal , and it now appears that a vertical signal can be discerned , if not clearly resolved .
work in the authors ' lab is supported through the nsf assembling the tree of life ( deb 0830024 ) and nasa exobiology ( nag5 - 12367 and nnx07ak15 g ) programs .

Answer:
reconstructing the ' tree of life ' is complicated by extensive horizontal gene transfer between diverse groups of organisms .
 while numerous conceptual and technical obstacles remain , a report in this issue of journal of biology from koonin and colleagues on the largest - scale prokaryotic genomic reconstruction yet attempted shows that such a tree is discernible , although its branches can not be traced .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a coracoid fracture is a rare orthopaedic condition as it accounts for only 2  10 % of all scapular fractures and < 0.1% of all fractures . in even rarer cases coracoid fractures
we present an unusually rare case of a simultaneous fracture of the coracoid process and the lateral end of clavicle .
the patient was treated with shoulder arm sling for 6 weeks followed by physiotherapy . at 6 months
follow up the patient was pain free with full range of motion at right shoulder .
concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs .
ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle .
coracoid fractures alone are themselves a rare occurrence amounting to approximately < 0.1% of all fractures and even only 5% of all fractures of the shoulder [ 1 - 3 ] .
no reliable figures currently exist to determine the prevalence of a simultaneous distal clavicle and coracoid fracture .
a 60 year old gardener presented with a history of injury to her shoulder as her arm was pulled by a lawn mower .
the patient did not have any previous injury or degenerative condition to this shoulder prior to this accident .
physical examination showed swelling and bruising around shoulder , tenderness and restricted movements of the right shoulder .
ct and plain radiographs of the shoulder displayed a displaced coracoid fracture and non - displaced fracture of the distal end of clavicle at the time of injury ( fig .
the patient was placed in a shoulder arm sling for six weeks and was then referred to physiotherapy .
some doubtful angulation of the coracoid process is visible but fracture is not appreciated clearly .
1b- ct scan conforms the fracture of lateral end of clavicle and also displace coracoid fracture . at three months
the patient was pain free and back to working as a gardener with a free range of movement in the right shoulder .
3 months follow up radiographs showing no further displacement of the fracture with early consolidation at the fracture site .
when fractures of coracoid and distal clavicle co - exist , misdiagnosis is common because both the fractures may not be seen on standard projections .
the stryker notch view is recommended for detection of these fractures . furthermore ct imaging is advised if radiographs initially fail to show any bony injuries of the shoulder , but clinical examination suggests otherwise .
the mechanism of injury is probably the result of a resisted flexion of the arm and elbow which led to a forceful pull of the muscles , pectoralis minor and the coracobrachialis , that insert into the coracoid .
this has previously been described in two other case studies concomitant coracoid fractures and acromioclavicular dislocation .
the patient suffered an ipsilateral avulsion of the coracoid which would be considered as a type ii according to ogawa et al and a distal clavicle fracture which would be considered as a type i according to the neer s classification .
it is to this day still controversial how to treat coracoid or distal clavicle fractures individually , let alone if they are present concomitantly .
details and consequent treatment methods of coracoid fractures have also yet to be established in literature .
ogawa et al have recommended surgical treatment of coracoid fractures combined with other shoulder injuries , but have otherwise shown similar outcomes between operative and non - operative treatment of coracoid fractures alone .
they did however recommend non - operative management of type ii fractures as these do not disturb the scapuloclavicular connection .
there does not seem to be a general consensus on the treatment of distal clavicle fractures too .
robinson et al have recommended non - operative management of distal clavicle fractures in the middle aged or elderly patients . out of the 101 patients treated non - operatively with distal clavicle fractures , only in 14% of cases
rokito et al compared nonoperative and operative treatment of a total of 30 type ii distal clavicle fractures retrospectively and did not reveal any significant difference in terms of ucla , constant and asesscore . on
the other hand haidar et al and meda etal advocate the use of clavicular hook plates .
these studies however did not compare the operative treatment to non- operatively treated control groups [ 10 , 11 ] .
the option of treating a symptomatic nonunion of the distal clavicle was described by kang et al who achieved 100% bone union in 10 patients following orif with an oblique locking t - plate and autogenous bonegraft .
lasda et al described successful treatment of a concomitant acromioclavicular dislocation and coracoid fracture conservatively .
eleven years later carr et al further described two cases of concomitant coracoid fracture and acromioclavicular dislocation which were treated conservatively with good results .
recently duan et al published a case report of operative treatment of an acromioclavicular dislocation in combination with a coracoid fracture which was treated with a hook plate .
they described the problem of only partial bone union after 5 months and the additional plate removal that needed to be done 12 months after the initial operation .
only one case report by ruchelsman however has described the operative treatment of a concomitant lateral clavicle and coracoid fracture . in his case
he then proceeded with a open distal clavicle excision and reduction of the coracoclavicular interval with screw fixation achieving an excellent clinical outcome .
they commented that high index of suspicion is needed to avoid missing such combination injuries at shoulder girdle and additional radiological investigations should be done if pain at shoulder girdle is persistent .
in view of the sparse and controversial literature available , we believe that the patient should be appropriately informed of both operative and nonoperative options treatment options . in our case the patient preferred nonoperative management which resulted in an excellent clinical result .
concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs .
ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle . even in cases with displacement
a conservative management will result in a good clinical outcome as seen in our case .

Answer:
introduction : a coracoid fracture is a rare orthopaedic condition as it accounts for only 2  10 % of all scapular fractures and < 0.1% of all fractures . in even rarer cases coracoid fractures are also associated with other bony injuries of the shoulder .
 there is currently no consensus on the treatment of such injuries.case report : we present an unusually rare case of a simultaneous fracture of the coracoid process and the lateral end of clavicle .
 the patient was treated with shoulder arm sling for 6 weeks followed by physiotherapy . at 6 months
 follow up the patient was pain free with full range of motion at right shoulder.conclusion:concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs .
 ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle .
 we have treated this injury non operatively with a good clinical outcome .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a 23-year - old female presented with an asymptomatic , erythematous , atrophic macule on the upper right side of her back that increased gradually in size within the last four years without any symptoms ( figure 1a ) . on physical examination the surface of the lesion was smooth and no induration was examined on palpation .
dermatoscopic evaluation of the lesion using 3gen dermlite - ii pro hr and documented with dermlite - foto 3gen ( llc , dana point , ca , usa ) showed a homogenous pigment network on a purplish erythematous background ( figure 1b ) .
histopathological examination of h&e ( hematoxylin and eosin ) stained sections revealed epidermal atrophy , increase in melanin in basal keratinocytes and heavy dermal cellular infiltrate composed of spindle - shaped cells arranged in a storiform pattern that extended into the subcutaneous tissue ( figure 2 ) .
immunhistochemical staining for cd34 was positive , while factor xiiia was negative ( figure 3a , b ) .
dfsp is a rare , slow growing , locally invasive cutaneous neoplasm of fibrohistiocytic origin with intermediate grade malignancy with an incidence between 0.85.0 cases per 1 million persons per year .
the atrophic presentation of dfsp is the rarest variant of this infrequent neoplasm , which was first described in 1985 .
the non - protuberant dfsp can be considered the early clinical stage of dfsp before developing the typical protuberant feature unless it remains as a non - protuberant tumor that is called atrophic dfsp .
it occurs as an atrophic , asymptomatic plaque that can be difficult to distinguish from morphea , morphea like basal cell carcinoma , scar , lipoatrophy and atrophic dermatofibroma .
although the clinical appearance of atrophic dfsp is different from common protuberant type , histopathological features are similar .
atrophic presentation of the lesions may be due to the marked cellularity of the tumor cells in the dermis and infiltration to the subcutaneous fat .
immunhistochemical staining is important to distinguish dfsp from atrophic dermatofibroma and medallion - like dermal dendrocyte hamartoma .
while dfsp cells are positive for cd34 and negative for factor xiiia , atrophic dermatofibroma cells are usually negative for cd34 and both of cd34 and factor xiiia are positive in the medallion - like dermal dendrocyte hamartoma [ 3 , 4 ] .
dermatoscopic studies of dfsp are very rare in the literature . in 2013 , bernard et al reported the first study of dermatoscopic analysis of dfsp in 15 cases .
delicate pigment network , vessels , structureless light brown areas , shiny white streaks , pink background coloration and structureless hypopigmented or depigmented areas were defined as six main dermatoscopic features of dfsp . in 2014 , dermatoscopic features such as peripheral dilated vessels forming a mesh - like pattern , milky - red areas , whitish linear structures and fine pigment network were reported in a series of four cases of dfsp . to our knowledge , only one case of atrophic dfsp was presented with dermatoscopic features in the literature .
the reported dermatoscopic findings of that case were branching vessels on a yellowish background without pigment network .
the authors suggested that the dermatoscopic features might be the result of dermal atrophy and close approximation the subcutis to the epidermis .
in contrast , our case showed dermatoscopically regular brown lines reticular on a purplish erythematous background .
homogenous brown lines reticular seen in our case correspond to the accumulation of melanin in basal keratinocytes , while the erythematous background is the result of dilated vessels in the dermal plexus . here , the smooth surface reflects the stratum corneum being normal .
the most frequent dermatoscopic pattern associated with dermatofibromas , a well - known and benign cousin of dfsp , is the central white scar - like patch and peripheral delicate pigment network .
the histopathologic correlation of white scar - like patch in dermatofibroma is pronounced fibrosis within the papillary dermis .
contrary to dermatofibromas , fibroplasia in the upper half of the dermis is uncommonly observed in dfsp which may explain the absence of white scar - like areas in our case . in conclusion , we have presented the dermatoscopic findings in an unusual case of atrophic dfsp .
atrophic dfsp should be kept in the differential diagnosis for atrophic and depressed skin lesions , particularly those seen on the trunks of women .
dermatoscopy , a noninvasive method , may not only help to differentiate atrophic dfsp from other skin diseases but may also indicate the need for histopathological examination since the disease has prognostic significance .

Answer:
dermatofibrosarcoma protuberans ( dfsp ) is an uncommon locally aggressive mesenchymal tumor with a high local recurrence rate .
 atrophic dfsp is a rare variant of dfsp characterized by a non - protuberant lesion .
 we report on a 23-year - old female , who presented with an atrophic , asymptomatic macule on the right side of her back 2 cm in diameter .
 dermatoscopic examination revealed homogenous pigment network on a purplish erythematous background .
 the histopathological finding of the incisional biopsy material was consistent with dfsp .
 to our knowledge , this is the second case of atrophic dfsp discussing the dermatoscopic features of this relatively rare condition .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
microsatellites are simple sequence repeats ( ssrs ) that exhibit complex patterns in their frequency of occurrence , genomic distribution , mutability , function and evolution . apart from being the source of informative genetic markers , microsatellites per se
have attracted a lot of attention with respect to their origin , distribution , expansion , mutation and disintegration ( 17 ) .
questions are also asked about the functional role of microsatellites in particular and biological significance of the microsatellites in general ( 4,812 ) .
genetic studies and whole genome sequence analysis have established non - random distribution , variability and high mutability as characteristics of microsatellites .
evidences are accruing , which support the role of microsatellites in gene regulation , transcription and protein function ( 13 ) .
existence of qualitative and quantitative differences between microsatellites of different genomes and their role in adaptive evolution have also been theorized ( 2,8 ) .
however , such studies require information on type ( mono to hexa ) , motif ( gc% ) , abundance ( motif preferences ) , frequency , distribution ( linkage group - wise and chromosomal position ) , location ( exon , intron , regulatory element and transposon ) , nature ( perfect , imperfect and compound ) and copy number ( existence of paralogs ) of microsatellites not only on a whole genome basis but also as a comparative analysis of multiple genomes that are related by phylogeny ( for instance , fully sequenced primate genomes or fungal genomes or insect genomes ) to draw functional conclusions .
whole genome sequences of insects have lived up to the reputation of diversity and have thrown immense variability in size and organization of their genomes . among others , there are five fully sequenced insect genomes : drosophila melanogaster ( as a model organism it provides maximum annotated data ) , anopheles gambiae ( another dipteran but economically highly important as malarial vector ) , tribolium castaneum ( relatively early insect order of coleoptera ) , apis mellifera ( hymenoptera , relatively a recent insect order ) and bombyx mori ( economically important as silk - producing member of lepidoptera , members of which are crop pests ; also significant as a model for insect development ) .
researchers attempting to understand the biology and evolution of microsatellites are often faced with the following questions : ( i ) do microsatellites occur everywhere in the genome ? ( ii )
( v ) does the gc content of the motif affect the length , repeat units or mutation rate of microsatellites ?
( viii ) do microsatellites occur as families of common flanking sequences in the genomes ( paralogs ) ?
insatdb , unlike many other microsatellite databases that cater to only the needs of microsatellites as markers , allows users to address the above - mentioned questions by accessing qualitative and quantitative genome level microsatellites profile of a single insect or to carry out comparative genomic analysis using all the five genomes .
t.castaneum sequences were downloaded from genbank ( ) and bombyx mori sequences were downloaded from .
repeats were extracted employing tandem repeat finder version 4 ( 14 ) . to ensure that the extracted repeat sequences were real microsatellites , those with less than five repeat units and shorter than 15 bp in length were excluded .
tandem repeat finder does not employ minimal alignment score for detecting microsatellites ; rather a probabilistic model of random repeat sequences specified by per cent identity and frequency of insertions and deletions .
this includes calculation of average per cent identity between the copies ( pm ) and average percentage of insertions and deletions ( pi ) .
the algorithm has a pair of matching probability and indel probability values ( pm = 0.80 , pi = 0.10 ) as default to cover most divergent copies at every locus .
we used two sets of alignment parameters ( match , mismatch , gap ) , ( + 2 , 3 , 5 ) and ( + 2 , 5 , 7 ) to score the matches . all the microsatellites with a minimum alignment score of 30 are reported in the database , which means that both perfect and imperfect microsatellites are listed .
smit , r. hubley and p. green , unpublished data ; ) to obtain indices marking the occurrence of simple repeats , tandem repeats , segmental duplications , interspersed repeats including sines , dna transposons , retrotransposons , lines , etc .
further , sequences were analysed for the delineation of exons and introns using genscan ( 15 ) . flanking sequences of microsatellites
were aligned to catalogue paralogous microsatellites that exhibit identical origin and hence considered belonging to the same microsatellite family .
occurrence of two or more microsatellites contiguously with intervening non - repeat sequence of 70 bp were separately categorized as compound repeats .
it stores microsatellites from all the five insect genomes separately as well as carries complete annotations of these microsatellites .
the database also provides basic information on each of the five insects and important links to obtain further knowledge , and contains a tutorial page and a glossary page .
end users with adequate computational capabilities can batch download full complement of microsatellites ( insect - wise ) , microsatellite sequences , compound microsatellites and full list of microsatellite loci existing as families .
these data are made available as csv files , which are compatible with spreadsheet programmes such as ms excel .
alternatively , details of the microsatellites with highly specific characteristics may be queried using a multi - option query sheet ( figure 2 ) .
the options include insect ( one at a time ) ; location ( intron , exon , i.e. boundary , upstream , intergenic , repeat elements  single or in combination ) ; repeat type ( motif size , mono- to hexa - nucleotide ) or actual repeat motif ( by essentially entering up to five repeat motifs ) ; gc% ( fixed value or range ) ; repeat size in either base pairs or number of units ( fixed value or range ) ; repeat kind ( perfect or imperfect ) . once insect and location options
the output is primarily a list of microsatellites annotated for all options of the query sheet and the output table is generated as a hierarchical pre - sorted list .
each microsatellite is given a unique i d that also carries genomic sequence i d and corresponding indices .
if the number of microsatellites selected based on the options of the query sheet exceeds 500 , the output is split into sets of 500 microsatellites . in addition , a csv file containing total output is also made available for downloading . if the query options do not select any microsatellite , a message indicating zero output is displayed and a back button is provided to refine the options .
ssr motif and 100 bp each of the left and right flanking sequences are given for each microsatellite entry , which allows users to carry out sequence analysis of microsatellite vis -  - vis locus .
in addition , users can select individual microsatellites to convert them into locus - specific markers .
this is facilitated by automatic uploading of repeat and flanking sequences of the selected microsatellite into primer3 query form ( 16 ) .
screen shots of ( a ) insatdb homepage , ( b ) multi - option query sheet , ( c ) output table and ( d ) analysis page .
our analysis showed that microsatellite content of five fully sequenced insect genomes is independent of both genome size and gc content ( table 1 ) .
the database consists of a dedicated section ( analysis ) that describes the types of analysis that can be carried out using the data obtained from insatdb .
some of the quick observations and inferences from a comparative genomic analysis are given in this section .
microsatellite content of insect genomes preponderance of di- and tri - nucleotide repeats is observed in drosophila and anopheles , whereas tri- and tetra - nucleotide repeats are abundant in bombyx and tribolium . on the whole ,
shorter microsatellites are abundant in the five insect genomes ; as the length of the microsatellite increases their number decreases logarithmically typified by bombyx and drosophila microsatellites ( > 90% of the microsatellites < 50 bp ) ; on the other hand , anopheles and tribolium have longer microsatellites in a relatively high frequency . shorter microsatellites
not only predominate microsatellite population in the five insect genomes , but also seem to possess higher number of imperfect repeat units . on the other hand , microsatellites spanning > 100 bp consisted of perfect , rather than imperfect repeats .
interruptions , if at all , occur mainly in the middle region of the repeat sequence and the ends seem to be selected against decomposition . on the whole ,
there is no linear correlation between gc content and the average number of repeat units .
average length of the microsatellite across gc range is 37  9 bp and between 0 and 5% gc content , microsatellites tend to be longer than 60 bp .
compound microsatellites account for nearly 3.2% in the insect genomes analysed ; owing to high density of microsatellites , apis has higher number of compound loci ( 6.12% ) .
anopheles and apis genomes have as many as 50 and 60% of the total microsatellites in coding region , respectively .
bombyx genome has only 10% of the microsatellites in regions spanning exons , introns and their boundary .
more than 70% of the microsatellites present in exons are trinucleotide repeats except in apis , where 50% tri- and 25% dinucleotide repeats are present in exonic regions .
microsatellites in insects are at rich ( on an average 23.4% gc ) ; however , they exist within regions that are not always at rich .
incorporation of microsatellite data from additional insects , query facility for better comparative genomic analysis such as gene - based microsatellite extraction and conservation analysis are planned .
additionally , based on users ' feedback , supplementary features will be added to make insatdb a single window system for insect genome analyses using microsatellite tools .

Answer:
insatdb presents an interactive interface to query information regarding microsatellite characteristics per se of five fully sequenced insect genomes ( fruit - fly , honeybee , malarial mosquito , red - flour beetle and silkworm ) .
 insatdb allows users to obtain microsatellites annotated with size ( in base pairs and repeat units ) ; genomic location ( exon , intron , up - stream or transposon ) ; nature ( perfect or imperfect ) ; and sequence composition ( repeat motif and gc% ) .
 one can access microsatellite cluster ( compound repeats ) information and a list of microsatellites with conserved flanking sequences ( microsatellite family or paralogs ) .
 insatdb is complete with the insects information , web links to find details , methodology and a tutorial .
 a separate  analysis section illustrates the comparative genomic analysis that can be carried out using the output .
 insatdb is available at .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
radial extracorporeal shock wave therapy ( rswt ) generates pressure waves through the
 collision of solid bodies1 .
there are a few recent
 reports regarding the effectiveness of extracorporeal shock wave therapy ( eswt ) on
 neurogenic heterotopic ossification ( ho ) in the lower extremity , but to our knowledge , the
 use of eswt or rswt to treat neurogenic ho in the upper extremity has not been reported in
 the literature4 .
we report 2 cases of rswt used to treat neurogenic ho in the upper extremities . in both
 cases , improvements in pain ,
range of motion ( rom ) , muscle strength , and hand function were
 observed .
each patient gave their written informed consent and agreed to participate in the
 treatment .
this case report was approved by the ethics committee of the sahmyook medical
 center .
a 49-year - old man was admitted to our physical medicine and rehabilitation ( pmr )
 department .
a subarachnoid hemorrhage ( sa ) occurred 10 months prior to admission and
 neurogenic ho of the left shoulder and elbow was diagnosed 2 months before his admission .
he
 had been taking disodium etidronate 800  mg per day ( fig .

1.(a ) in case a , bone scan , x - ray , and musculoskeletal ultrasound demonstrate ho in the
 left shoulder and elbow .
arrows indicate the ho
 sites.ho : heterotropic ossification ; subs : subscapularis ; cp : coracoid process ; un : ulnar
 nerve ; me : medial epicondyle ; olec : olecranon ) . in spite of the medication , he continued to complain of constant pain , limited rom ,
 muscle weakness , and impaired hand function .
rswt was administered to the inferior portion
 of the coracoid process of the left shoulder and the medial epicondyle ( me ) of the left
 elbow using ultrasonographic ( usg ) guidance .
the target points of rswt were the ho area that
 could be seen with usg .
( a ) in case a , bone scan , x - ray , and musculoskeletal ultrasound demonstrate ho in the
 left shoulder and elbow .
: heterotropic ossification ; subs : subscapularis ; cp : coracoid process ; un : ulnar
 nerve ; me : medial epicondyle ; olec : olecranon
a 52-year - old man with a 6-month history of hypoxic brain injury was admitted to our pmr
 and diagnosed with neurogenic ho of the right elbow ( fig .
 1 ) .
rswt was administered to the ho area including the me and olecranon of the
 right elbow using usg guidance .
medications were not subsequently required due to a good
 response to rswt . in both cases , rswt was administered using the master plus mp 2000 ( storz ,
 tgerwilen , switzerland ) , and the rswt protocol consisted of 3,000 pulses at a frequency of
 12  hz during each treatment .
the intensity level ranged from 25 bars , and it was
 administered 5 times a week for 4 weeks , a total of 20 treatments . during rswt , all other
 treatments , including physical and occupational therapy , were continued as usual .
both
 patients were allowed to take previously prescribed oral medications but additional
 analgesics or antispastic medications were not permitted .
pain assessed with the numerical rating scale ( nrs ) , rom , muscle strength assessed with the
 manual muscle test ( mmt ) , a hand evaluation test , and the jebsen - taylor hand function test
 were evaluated prior to each treatment , after treatment , and following 1 month of treatment .

pain was reduced from 8 to 0 on the nrs , and the patients remained pain - free
 for 1 month after treatment . in case a , rom of flexion , abduction , adduction , internal rotation , and external rotation
 of the left shoulder and additionally , flexion of the left elbow was improved and
 maintained .
the mmt result also showed improvement and the improvement was maintained for 1
 month ( table 1table 1.range of motion , manual muscle test , hand evaluation test and , jebsen - taylor hand
 function test resultstestcase acase bbeforeafterfollow up upbeforeafterfollow uprange of motion()shoulderflexion 90140 * 145*extension 202020abduction90130 * 130*adduction1020 * 20*internal rotation6070 * 70*external rotation2060 * 60 * elbowflexion 90100 * 100 * 4080 * 85*extensionfullfullfullfullfullfullsupination7070706065 * 80*pronation7060606062 * 80*manual muscle testshoulderflexionfairfair+*fair+*extensionfairgood*good*abductionfairfair+*fair+*horizontal abductionfairfair+*fair+*horizontal adductionfairgood*good*elbow flexionfairgood*good*fairfairfairextensionfairgood*good*fairfairfairhand evaluation test grasp power ( kg)1420 * 18 * 121212lateral pinch ( kg)3.54.5 * 5.5 * 1.52.5 * 2*tripod pinch ( kg)23.0 * 2.5 * 211.5nine - hole pegboard ( sec)30.625.7 * 25.0 * 13865.1 * 58.7*purdue pegboard test ( number ) 1112 * 12 * 03 * 1*jebson - taylor hand function test
 ( sec)writing55.3445.00 * 43.71*ntntntcard turning9.317.87 * 8.76 * 11.0411.076.9*small common object12.1610.59 * 10.15*nt47.3 * 19.5*feeding13.8112.25 * 10.94*ntnt25*stacking checkers7.134.50 * 4.12*ntntntlarge light object ( sec)5.845.914.81 * 8.125.71 * 6.34*large heavy object ( sec)6.945.78 * 4.63 * 8.697.12 * 5.06*follow up period was 4 weeks .
functional testing of hand strength and speed of hand movement showed
 improvements that were maintained at least for 1 month after the end of treatment ( table 1 ) .
follow up period was 4 weeks . improved score ; nt : not testable ;
 affected side in case b , right elbow flexion , supination , and pronation were improved , the improvements
 were maintained for 1 month . in contrast to case a , improvement in the mmt result was not
 seen ( table 1 ) . in the hand function test ,
the
 strength of the hand and speed of hand movement improved , and these improvements were
 maintained at least for 1 month after the end of treatment ( table 1 ) .
ho is a complicated and significant medical problem characterized by abnormal growth of
 bone in soft tissues , commonly around large joints . in its severe form
, the condition causes
 pain , limited rom , and loss of function in the affected joint .
neurogenic ho is associated with injuries to the central nervous
 system , occurs 24 months after a neurological insult , and mainly affects the major synovial
 joints between spastic muscles6 .
primary treatment is a combination of gentle passive rom exercises and bisphosphonate
 medication , such as disodium etidronate or nonsteroidal anti - inflammatory drugs .
surgical
 excision may be considered for complicated cases , but surgical complications and
 postoperative recurrence are common4 .
eswt has been described in several case reports as a new treatment strategy for neurogenic
 ho , but it has been restricted to the lower extremities7 .
eswt has been shown to promote bone healing in stress fractures ,
 avascular necrosis , and delayed and/or bony nonunion , and it has been widely used for
 managing the pain of various musculoskeletal conditions8 .
eswt consists of a sequence of single sonic pulses characterized by
 high peak pressure ( 1001,000 bars ) of short duration ( 0.2 s ) and has a focused pressure
 field with deep penetration depth .
compared with eswt , rswt is characterized by 110 bars of pressure of 0.20.5  ms duration
 and has a radial pressure field with shallow penetration depth . despite the physical
 differences , the stimulation effects and therapeutic mechanisms of eswt and rswt are almost
 the same1 . in our cases , pain , rom , muscle strength , and hand function improved although imaging
 studies with radiographs and bone scans showed no changes .
this result is consistent with
 previous studies that reported improvement in pain and function without changes in imaging
 studies7 , 8 .
based on the results of these studies , it is our opinion that
 imaging findings do not accurately reflect the pain and function caused by neurogenic
 ho .
the mechanism of pain reduction with eswt or rswt is not well known and there are several
 hypotheses9 .
eswt or rswt generates
 oscillations in tissue that lead to improvement of microcirculation and metabolic
 activity1 .
immediate pain reduction
 after eswt could be the result of a hyperstimulation analgesic effect10 .
the improvements observed in rom , mmt , and hand function of the present two cases could be
 associated with pain reduction , since proper management of pain caused by neurogenic ho with
 rswt could have been the cause of the improvements in rom and hand function .
as reported by previous studies , in our cases , the improvements in pain , rom , mmt , and hand
 function were maintained for 1 month after the rswt treatment7 .
the mechanism of the long - term maintenance of the improvements is
 not known but rswt in the early phase of neurogenic ho is effective at preventing
 progression .
they were the inferior
 part of the coracoid process of the left shoulder and the me of the left elbow in case a ,
 and the me and olecranon of the right elbow in case b. imaging guidance when administering
 rswt for treating neurogenic ho could help to correctly focus on the ho site and avoid the
 other vulnerable structures such as vessels and nerves2 , 10 . in conclusion , rswt improved the pain , rom , and hand function of two patients with upper
 extremity neurogenic ho .
further studies are needed to support these results and to
 understand the mechanism behind the effectiveness of rswt , as well as to devise a protocol
 for rswt for neurogenic ho .

Answer:
[ purpose ] to report the effects of radial extracorporeal shock wave therapy ( rswt ) on
 heterotopic ossification ( ho ) .
 [ subjects and methods ] two cases of neurogenic ho in the
 upper extremity were administered rswt using the master plus mp 2000 ( storz ,
 tgerwilen , switzerland ) and ultrasonographic guidance . the rswt protocol consisted of
 3,000 pulses at a frequency of 12  hz during each treatment .
 the intensity level ranged
 from 25 bars , and it was administered 5 times a week for 4 weeks , a total of 20
 treatments .
 [ results ] rswt improved pain , range of motion , and hand function in 2 patients
 with neurogenic ho in the upper extremity .
 [ conclusion ] further studies are needed to
 support these results and to understand the mechanism and to devise the protocol of rswt
 for neurogenic ho .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
after their biosynthesis at the endoplasmic reticulum , secreted proteins are transported to the golgi complex , where they are post - translationally modified and sorted for secretion , plasma membrane delivery , or delivery to prelysosomes .
the golgi contains multiple subcompartments , termed cis ( early ) , medial ( middle ) , and trans ( late ) cisternae ; each of these subcompartments houses different sets of glycosyltransferases and other enzymes .
proteins enter the golgi at the cis compartment and exit at the trans compartment , but how they move from one cisterna to the next is still being determined .
two possible models are widely discussed [ 1 - 3 ] . according to the cisternal maturation ( or progression ) model ,
cargo remains in a given compartment and different enzymes arrive there to convert a cis cisterna into a medial one or a medial cisterna into a trans cisterna .
alternatively , cargo moves from one golgi compartment to the next , encountering different enzymes in each subsequent compartment until it reaches the trans cisterna , where it is then sorted into carriers bound for post - golgi destinations .
this second class of model could use vesicles to transport cargo from one compartment to the next or compartment - connecting tubules through which cargo could pass .
conversion of one golgi compartment into another by high - resolution , live cell video microscopy .
a limitation of those studies is that one of the compartment markers that was monitored is a peripheral membrane protein that is likely to reversibly bind to and release from the golgi surface .
the situation may be more complex in mammalian cells , where golgi cisternae are stacked tightly together , unlike yeast ; it is hard to imagine a single cisterna moving from one side of the well - stacked structure to the other .
nevertheless , large procollagen cargo traverses the golgi without ever leaving a cisterna , in support of a maturation model . to complicate matters ,
membrane tubules have been detected between golgi cisternae under conditions of active secretion ; this scenario would permit cargo movement from one side of the stack to the next without maturation or vesicle transfer .
important new clues to how golgi compartments might  mature come from a study of golgi - localized , ras - related , rab family gtpases in yeast .
rab gtpases are localized to different membrane compartments and catalyze the formation of functionally distinct , membrane microdomains that are important for transport vesicle formation , vesicle motility , and vesicle ( or compartment ) docking and fusion .
rab gtpases help early endosomes mature into later endosomes by a process called rab conversion .
the early endosomal rab5 protein recruits a specific guanine nucleotide exchange factor ( gef ) that activates rab7 .
rab7 then recruits rab7-specific effectors to that compartment , thereby converting an early endosome into a late endosome .
this type of rab cascade ( figure 1b ) was first described for a yeast golgi rab , ypt32p , recruiting the gef for the subsequent acting sec4p rab .
( a ) endoplasmic reticulum , golgi , and endosome membranes are capable of homotypic fusion and fission .
( b ) rab cascades occur when sequentially acting rabs recruit guanine nucleotide exchange factors ( gefs ) and gtpase - activating proteins ( gaps ) to membranes .
raba recruits a gef that will convert the subsequent acting rab to its active form .
rabb can then recruit a gap that will inactive the previous acting rab , thereby removing it from the newly formed , second compartment .
rivera - molina and novick   have now used live cell video microscopy to detect rab conversion at the yeast golgi : they see compartments containing the early golgi rab , ypt1p , convert into a compartment containing the late golgi rab , ypt32p .
( although the light microscopy method employed could not resolve structures smaller than about 200 nm , the images were nevertheless highly compelling . )
the process involves the recruitment of ypt32p by the gtpase - activating protein ( gap ) that inactivates ypt1p : gyp1p . upon inactivation
, ypt1p becomes a substrate for removal from membranes by another protein , gdi ( gdp - dissociation inhibitor ) .
the removal of rabs from the membranes makes this work subject to one of the same limitations of the previous studies ; nevertheless , these markers permitted the authors to detect an important molecular transformation .
the data provide a direct molecular mechanism for compartment inter - conversion at the golgi , reminiscent of maturation in the endocytic pathway .
golgi compartments were seen to be dynamic , undergoing a certain amount of fission and fusion . in some cases ( 30% )
, a ypt32p compartment appeared to fuse to a ypt1p compartment to yield a mixed compartment or a mixed compartment appeared to undergo segregation and fission to yield separate ypt1p and ypt32p compartments  .
what this means is that , yes , yeast golgi compartments undergo apparent maturation by rab conversion , and at the same time , cargo may get the
fast track from one compartment to the next by intermittent cisternal fusion and fission events ( figure 2a , b ) . importantly , although a compartment will seem to mature , it is actually forming from a stable predecessor .
early golgi has the capacity to fuse with other early golgi cisternae and so on .
fission is favored in the absence of microtubules or when golgin proteins are depleted from cells .
glycosyltransferases are localized to cis ( red ) , medial ( yellow ) , and trans ( orange ) golgi compartments but rarely have a perfectly sharp distribution .
thus , for example , cis - golgi homotypic fusion events can occur with another cis compartment ( step 1 ) or perhaps a medial ( yellow ) compartment ( or both ) .
similarly , a medial cisterna may be able to fuse with a trans cisterna ( orange ) . in this manner
, a large cargo may be able to encounter all golgi - processing enzymes without entering a transport vesicle , indicated by fusion steps ( arrows ) 1 , 2 , and then 3 .
the ability of golgi cisternae to undergo fission and fusion has been known since the 1970s : simple , nocodazole - triggered depolymerization of microtubules causes the mammalian golgi to fragment into mini - stacks that disperse throughout the cytoplasm , and drug washout leads to rapid stack reassembly ( figure 2a ) .
this indicates that the golgi is capable of fission as soon as microtubules are lost and of fusion with itself as soon as microtubules repolymerize .
compartment collisions likely enhance fusion , and cytoskeletal motor proteins that decorate the golgi and connect it to both microtubules and actin cables are sure to contribute to both fusion and fission events , as is true in the endocytic pathway ( figure 1a , c ) . are intercisternal fusion / fission connections required for membrane traffic ?
transport is only partially blocked in nocodazole - treated cells and this condition favors stack fission .
but homotypic fission and fusion are likely much more prevalent than previously anticipated because cellular depletion of any one of many different golgi proteins (  golgins ) generates mini - stacks that are clustered near the microtubule - organizing center .
such transient fusion and fission could yield the tubules that have been detected in electron micrographs of mammalian cell golgi complexes .
fission and fusion would make it possible to accommodate extra - large cargoes , such as collagen , that are too big to fit into conventional transport vesicles .
as is well established for the endocytic pathway , rab gtpases would define specific subdomains and retain specific golgi enzyme subsets there .
compartments would be defined by their distinct rab gtpases , and adjacent cisternae might fuse at some frequency that allows cargoes to encounter sequentially acting , processing enzymes . in a mixed compartment , rab gefs and gaps would segregate individual rabs into separate regions that would be segregated upon the simple action of a membrane - associated , cytoskeletal motor protein to drive fission .
order within the stack would be maintained by the relationship between specific rabs and their cognate activators ( gefs ) and inactivators ( gaps ) , which are designed to permit rabs to function in a sequential cascade .
indeed , the proteins that stack the cisternae may use a rab cascade to achieve their position in the stack . at the trans golgi
, rabs would also initiate the process by which specific cargoes are collected into distinct transport carriers and delivered to their final destinations .
validation and clarification of this model will require defining which rabs build which specific golgi enzyme microdomains and determining the specific molecular interactions that permit fission , fusion , and enzyme organization .
vesicles are likely to be involved in golgi transport : we know that cop - i - coated vesicles collect kdel receptors for delivery back to the endoplasmic reticulum ; in this case , we can postulate that such vesicles bud from a rab gtpase - organized , functional membrane microdomain .
the same proteins that drive vesicle targeting and fusion may also participate in cisternal docking and fusion to permit protein transport across this central cellular compartment .
the mechanism by which depletion of any one of at least 10 different golgin proteins leads to mini - stack formation will likely tell us much about how proteins move through the mammalian golgi stack .

Answer:
the golgi complex is a central processing station for proteins traversing the secretory pathway , yet we are still learning how this compartment is constructed and how cargo moves through it .
 recent experiments suggest a key role for ras - like rab gtpases and provide important new ideas for how the golgi may function .