Miracle-dz/UniFAR-FTUs huggingface dataset:
Transforming Growth Factor-β Supports the Rapid Morphogenesis of Heterotopic Endochondral Bone Initiated by Human Osteogenic Protein-1 via the Synergistic Upregulation of Molecular Markers

Members of the transforming growth factor-β (TGF-β) superfamily of proteins, the bone morphogenetic proteins (BMPs) and the TGF-β isoforms, are involved in the coordination of cartilage and bone differentiation both in embryonic development and in postnatal life. Both osteogenic protein-1 (OP-1) and TGF-β1 have been shown to be potent regulators and inducers of heterotopic endochondral bone induction in non-human primates. In marked contrast, TGF-β1 does not induce heterotopic endochondral bone in rodents. In the primate, the osteogenic properties of OP-1 are synergistically enhanced by the combined administration of TGF-β1. The binary application of OP-1 (0.1, 0.3, 1.0 and 3.0μg) and TGF-β1 (0.01, 0.03 and 0.1 μg) to 25 mg of guanidinium-inactivated insoluble collagenous bone matrix as carrier in the rodent heterotopic bioassay for 7, 12 and 21 days resulted in a classical synergistic, dose-dependent and temporal up-regulation of OP-1-induced endochondral bone formation. There were significant increases in alkaline phosphatase activity (day 12) and calcium content (days 12 and 21). mRNA expression of OP-1, TGF-β1, BMP-3 and collagens type II and IV, markers of bone formation, showed an up-regulation of the genes (days 12 and 21) by the binary applications of the morphogens. Histologically, single applications of OP-1 elicited a dose dependent induction of endochondral bone formation while the binary applications resulted in a temporal acceleration of the morphogenetic cascade. The optimal ratio of OP-1/TGF-β1 was 30:1 by weight for endochondral bone formation and expression of molecular markers. The present data provides insights to the mechanisms of synergistic molecular therapeutics for endochondral bone formation in clinical contexts.
Iron- and molybdenum-repressible outer membrane proteins in competent Azotobacter vinelandii

Azotobacter vinelandii produced three major proteins of 93,000, 85,000, and 81,000 daltons and a minor 77,000-dalton protein in the outer membrane of Fe-limited cells, and these cells were competent for transformation by DNA. The synthesis of these proteins was repressed in Fe-sufficient medium. Mo limitation of nitrogen-fixing cells resulted in the hyperproduction of a 44,000-dalton protein and the production of a minor 77,000-dalton protein in the outer membrane. Mo limitation enhanced competence in Fe-limited medium and induced competence in Fe-sufficient medium. The 44,000-dalton protein was replaced by a 45,000-dalton protein when Fe-sufficient medium also contained NH4+, but the cells were noncompetent. The synthesis of these proteins was repressed in Mo-sufficient medium and by NH4+ in Fe-limited medium. All of the culture supernatants contained a blue-white fluorescent material (absorbance maximum, 214 nm) which appeared to coordinate Fe3+, Fe2+, MoO4(2-), WO3(2-), and VO3(-).
Transferring Whose Knowledge? Exchanging Whose Best Practices? On Knowing about Indigenous Knowledge and Aboriginal Suicide

Over the better part of a decade we have been hard at work re-fashioning a still earlier decade’s worth of work on identity development and youth suicide in order to better fit these efforts to the special circumstances of Canadian Aboriginal youth—an ongoing effort aimed at explaining two deeply puzzling matters. One of these concerns the heartbreakingly high rate of suicide widely known to mark and often stigmatize aboriginal youth; an overall suicide rate that is reported to be higher than that of any culturally identifiable group in the world (Kirmayer, 1994). The second of these known facts of the matter (owed largely to our own research) is that the rate of aboriginal youth suicide varies dramatically from one community to another. As our research in British Columbia clearly demonstrates, more than 90% of aboriginal youth suicides occur in only 10% of the bands, with some communities suffering rates as much as 800 times the national average, while more than half of the province’s 200 First Nations bands have not experienced a single youth suicide in the almost 15 years for which such figures are available. What obviously needs explaining in the face of such disparities—what inquiring minds most want to know—is what is different about those communities without such suicides, and those in which youth suicide occurs in epidemic proportion?
Epidermal tight junctions in health and disease

The skin, the largest organ of the body, is an essential barrier that under homeostatic conditions efficiently protects and/or minimizes damage from both environmental (e.g. microorganisms, physical trauma, ultraviolet radiation) and endogenous (e.g., cancers, inflammation) factors. This formidable barrier function resides mainly in the epidermis, a dynamic, highly-stratified epithelium. The epidermis has 2 major barrier structures: stratum corneum, the outmost layer and tight junctions, intercellular junctions that seal adjacent keratinocytes in the stratum granulosum, found below the stratum corneum. In recent years there have been significant advances in our understanding of tight junction function, composition and regulation. Herein we review what is known about tight junctions in healthy skin and keratinocyte culture systems and highlight the dynamic crosstalk observed between tight junctions and the cutaneous immune system. Finally we discuss the preliminary observations suggesting that tight junction function or protein expression may be relevant for the pathogenesis of a number of common cutaneous inflammatory and neoplastic conditions.
Alternative coordination approaches for implementation in Smart Grid

As Smart Grid concept is employed in the electric power system, network load flow and topologyis changingintensively to meet the best generation-demand balancing point. These changes must be accounted for the protection devices in order to enhance their performance. The coordination of directional overcurrent relays is most commonly studied based on fixed network operation and topology within a mesh power system. But the sub-transmission and distribution systems constantly operate differently in order to satisfy the variety of load demand levels throughout the day and year. Hence, if the setting of directional overcurrent relays (DOCRs) change according to the different operations of the system, then relay operation time and sensitivity can both be enhanced. This can potentially improve the protection performance in Smart Grid system. Therefore, the study is carried out based on the comparison among three coordination approaches: conventional (fixed settings), discrete (changing setting groups), and continuous or real time (dynamic settings).
Prevalence of Candida and Trichomonas in Vaginal Discharge of Rural Females not Seeking Medical Help: Microscopy and Its Role in Vaginitis

In rural areas it has been noted that this morbidity is tolerated silently by women due to various social factors as poor awareness, gender inequalities, lack of proper education and lack of focused counselling and financial dependence. Candidiasis and Trichomoniasis are two of the most common causes of vaginal discharge . (1-6). Candida is a yeast like fungus, normally found as the lower genital tract flora in 20-50 % of healthy asymptomatic females (7-8) . Carrier rates are higher in women using broad spectrum antibiotics (9) , pregnant, diabetic women (10-11)
Inhibitory Smads and TGF-β Signaling in Glomerular Cells

ABSTRACT. Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-β, receptor tyrosine kinase (RTK), JAK/STAT, and NF-κB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-β signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in “classical” podocyte-diseases such as FSGS and MCD. TGF-β induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-β signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-β/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-β/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-β response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-β/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.
Simian immunodeficiency virus macaque models of HIV latency

Purpose of reviewThis review will focus on recent developments in several nonhuman primate models of AIDS. These models are being used to address viral latency and persistence during antiretroviral therapy in studies that are not feasible in humans. Recent findingsFurther characterization of the various macaque models of AIDS has demonstrated that several aspects of viral persistence during antiretroviral therapy model HIV-1 infection in humans, including viral decay kinetics. Widespread distribution of viral RNA and viral DNA has been detected in many tissue organs. In addition, the brain has been identified as a site of persistent viral DNA. SummaryThe macaque models of AIDS are well suited for addressing viral persistence during antiretroviral therapy, including viral latency, residual replication, and tissue organ distribution.
Leptin levels in the acute stage of ulcerative colitis

Background and Aims: Leptin, a recently discovered protein, acts as a hormonal feedback signal in regulating adipose tissue mass via hypothalamic mechanisms. Inflammatory bowel disease is often associated with anorexia and weight loss. The aim of the present study was to investigate serum leptin levels during the time course of the acute phase of ulcerative colitis (UC) and to evaluate whether leptin leads to anorexia and bodyweight loss in these patients.
A randomized trial comparing 2.5 mEq/L calcium dialysate and calcitriol to 3.5 mEq/L calcium dialysate in patients on peritoneal dialysis.

Peritoneal dialysate containing 2.5 mEq/L of calcium has been used to prevent hypercalcemia when calcium-containing phosphate binders are given. However, worsening of hyperparathyroidism may result. Calcitriol used in conjunction with 2.5 mEq/L calcium dialysate is an attractive alternative, but has not been examined in a controlled trial. Eighteen patients were randomly assigned to either a control group (3.5 mEq/L calcium dialysate without calcitriol) or a study group (conversion to 2.5 mEq/L calcium dialysate with oral calcitriol, median dose 0.25 microgram/day). The initial mean serum calcium (9.9 vs 9.6 mg/dL), phosphate (5.4 vs 5.6 mg/dL), median n-terminal parathyroid hormone (PTH) levels (71 vs 55 pg/mL, normal < 25), and median 1,25 (OH)2 vitamin D levels (4 vs 5 pg/mL, normal 15-60 pg/mL) were not different in the two groups. After 8 weeks the serum calcium and phosphate were unchanged from baseline in both groups. The 9 patients who converted to 2.5 mEq/L calcium dialysate had an insignificant fall in the PTH level, not different from the control group. The median 1,25 (OH)2 vitamin D level rose from 4 to 23 pg/mL (p = 0.003) on calcitriol, but remained unchanged in the control group (5 pg/mL). The median doses of oral calcium (0.9 vs 1.1 g/day) and the frequency of serum calcium levels greater than 11 mg/dL (4/9 vs 3/9 patients, 10% vs 8% of all values) were similar in the study and control groups. Aluminum hydroxide was required intermittently for serum phosphate control in 3 patients on 2.5 mEq/L calcium dialysate and 4 on 3.5 mEq/L calcium dialysate. (ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of Reduction Accuracy of Suture-Button and Screw Fixation Techniques for Syndesmotic Injuries

Background: Among the most important predictors of functional results of treatment of syndesmotic injuries is the accurate restoration of the syndesmotic space. The purpose of this study was to investigate the reduction performance of screw fixation and suture-button techniques using images obtained from computed tomography (CT) scans. Methods: Patients at or below 65 years who were treated with screw or suture-button fixation for syndesmotic injuries accompanying ankle fractures between January 2012 and March 2015 were retrospectively reviewed in our regional trauma unit. A total of 52 patients were included in the present study. Fixation was performed with syndesmotic screws in 26 patients and suture-button fixation in 26 patients. The patients were divided into 2 groups according to the fixation methods. Postoperative CT scans were used for radiologic evaluation. Four parameters (anteroposterior reduction, rotational reduction, the cross-sectional syndesmotic area, and the distal tibiofibular volumes) were taken into consideration for the radiologic assessment. Functional evaluation of patients was done using the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale at the final follow-up. The mean follow-up period was 16.7 ± 11.0 months, and the mean age was 44.1 ± 13.2. Results: There was a statistically significant decrease in the degree of fibular rotation (P = .03) and an increase in the upper syndesmotic area (P = .006) compared with the contralateral limb in the screw fixation group. In the suture-button fixation group, there was a statistically significant increase in the lower syndesmotic area (P = .02) and distal tibiofibular volumes (P = .04) compared with the contralateral limbs. The mean AOFAS scores were 88.4 ± 9.2 and 86.1 ± 14.0 in the suture-button fixation and screw fixation group, respectively. There was no statistically significant difference in the functional ankle joint scores between the groups. Conclusion: Although the functional outcomes were similar, the restoration of the fibular rotation in the treatment of syndesmotic injuries by screw fixation was troublesome and the volume of the distal tibiofibular space increased with the suture-button fixation technique. Level of Evidence: Level III, retrospective comparative study.
Expression profile of trophoblast invasion-associated genes in the pre-eclamptic placenta

Abstract The primary pathology of pre-eclampsia is thought be a defect in placentation due to failure of trophoblast invasion. Here, we aim to identify the expression profile of invasion-associated genes in the pre-eclamptic placenta. Messenger RNA (mRNA) expression levels of extracellular matrix molecule-related genes in five pre-eclamptic placentas and in five strictly matched normal placentas were assayed using complementary DNA (cDNA) microarrays representing over 220 human cytokineassociated or hormone-associated genes. Results demonstrated greater than two-fold higher expression of 18 extracellular matrix molecule genes, including cadherin, collagen, integrin and selectin, in the pre-eclamptic placenta. Extracellular matrix molecule degradationrelated genes, including matrix metalloproteinase (MMP)-10, MMP-13, MMP-15, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-3, plasminogen and plasminogen activator, were also highly expressed in the pre-eclamptic placenta, compared to the normal placenta. Results suggest that the abnormal expression profiles of extracellular matrix molecules and degrading proteinases might be associated with the pathogenesis of pre-eclampsia.
Expression of serotonin receptors and role of serotonin in human prostate cancer tissue and cell lines

Increase in the number of serotonin (5‐HT) releasing neuroendocrine (NE) cells has been shown to be correlated with tumor progression, loss of androgen dependence, and poor prognosis. Serotonin is a well‐known mitogen which mediates a wide variety of physiological effects via multiple receptors, of which receptor subtype 1 (5‐HTR1) has been identified in prostate cancer (PC) cell lines. Recently, 5‐HT has been found to show growth‐promoting activity and to be functionally related to oncogenes.
Executive functions in individuals with Williams syndrome.

BACKGROUND The present study was aimed at investigating working memory (WM) and executive functions capacities in individuals with Williams syndrome (WS) as compared with mental-age matched typically developing (TD) children. METHOD In order to serve the study goal, a sizeable battery of tasks tapping WM as well as attention, memory, planning, categorisation, shifting and inhibition abilities was administered to 15 individuals with WS (mean chronological age of 19.11 and mean mental age of 6.10), and to a group of 15 TD children (mean chronological age of 7.6 and mean mental age of 6.9). RESULTS Participants with WS showed deficits in both verbal and visual-spatial modalities for selective and sustained attention, short-term memory and WM, planning and inhibition. However, considering categorisation and shifting abilities, relatively unimpaired performance emerged on those tasks relying on verbal materials. CONCLUSIONS These findings are both relevant to improve our knowledge about certain qualitative aspects of the anomalous cognitive development in WS as well as for its eventual clinical implications.
Endogenous Zn2+ is required for the induction of long‐term potentiation at rat hippocampal mossy fiber‐CA3 synapses

The functional role of the abundant Zn2+ found in some hippocampal synapses has been an enigma. We show here, using N‐[6‐methoxy‐8‐quinolyl]‐P‐toluenesulfonamide (TSQ) staining, that chelatable‐Zn2+ can be removed from hippocampal synaptic boutons using dietary depletion or with Zn2+ chelators. A chronic dietary deficiency of bouton Zn2+ resulted in the impairment of long‐term potentiation (LTP) at mossy fiber‐CA3 synapses. The averaged normalized fEPSP slope 30 min after tetanus was 209 ± 28% of baseline value in control (mean ± SEM, n = 10), and 118 ± 12% in Zn2+‐deficient rats (mean ± SEM, n = 12, P < 0.01). In the deficient rats with Zn2+ supplements, mossy fiber LTP returned to normal levels. The acute depletion of bouton Zn2+ in the hippocampal slice with membrane‐permeable Zn2+ chelators, dithizone, or diethyldithiocarbamic acid (DEDTC) blocked the induction of mossy fiber LTP. The mean amplitudes of EPSCs after tetanus were 194 ± 22% of baseline value in control (n = 5), compared to 108 ± 14% in dithizone (n = 6) and 101 ± 12% in DEDTC (n = 5). The averaged value of LTP, at the associational commisural fiber‐CA3 synapses, was 193 ± 20% in the control (n = 6), compared to 182 ± 21% (n = 6, P > 0.1) in the presence of dithizone. The blockade of mossy fiber LTP by dithizone was reversible after washout. In addition, normal LTP could be induced by tetanus if exogenous Zn2+ was applied immediately following dithizone. Our results indicate that the endogenous Zn2+ is specifically required for LTP induction at the mossy fiber input into CA3 neurons. Synapse 38:187–197, 2000. © 2000 Wiley‐Liss, Inc.
Seroprevalence, correlates and trends of Helicobacter pylori infection in the Israeli population

SUMMARY We examined the prevalence, correlates and trends of H. pylori infection in Israel using residual sera obtained in 2007–2008 from 1466 Jewish subjects aged 0–77 years and 897 Arabs aged 0–19 years, and in 2000–2001 from 627 Jewish and 575 Arab subjects aged 0–19 years. H. pylori IgG antibodies were measured by ELISA. The age-adjusted H. pylori seroprevalence was 45·2% in Jewish participants. Seropositivity increased with age, reaching 60% at age ⩾50 years and ranged from 24·3% in subjects originating from North America/Western Europe/Australia, to 63·2% in those from Asia/Africa/South America. Among Arabs, H. pylori seroprevalence was 42·1% and reached 65% in adolescents. There was no significant change in seroprevalence between 2000–2001 and 2007–2008. High prevalence of H. pylori was found in Arabs, and in Jews originating from countries of high H. pylori endemicity. These findings are characteristic of countries of diverse ethnic structure and recent immigration.
A highly specific and sensitive fluorescence in situ hybridization assay for the detection of t(4;11)(q21;q23) and concurrent submicroscopic deletions in acute leukaemias

Summary. The translocation t(4;11)(q21;q23) is one of the most frequent 11q23 abnormalities associated with infant leukaemia as well as topoisomerase inhibitor‐induced secondary leukaemias. On the molecular level, the MLL gene on 11q23 is fused to the AF4 gene in the 4q21 region, resulting in a chimaeric MLL/AF4 fusion transcript. These particular chromosome rearrangements are generally considered to be associated with poor prognosis, and therefore accurate detection at diagnosis is of clinical significance. In this study we developed a highly specific dual‐colour fluorescence in situ hybridization (FISH) assay for the detection of the t(4;11) and demonstrate its usefulness for interphase molecular cytogenetics. In our approach, differentially labelled genomic clones that span the breakpoint cluster regions of both genes involved in the specific translocation were used. Thus, t(4;11)‐positive nuclei will display two fusion signals and for t(4;11) cases with concurrent 3′MLL deletions only one fusion signal will be displayed. A very low false‐positive value of less than 0·1% was obtained for interphase cells with two fusion signals. In contrast, in cases with 3′MLL deletions that display only one fusion signal, the rate of false‐positive nuclei was 10·4%. This FISH assay enables the screening of larger series of patients with haematological diseases for t(4;11) translocations and allows the unambiguous detection of associated cryptic deletions.
Red cell immunization in beta thalassaemia major.

OBJECTIVE To find out the frequency, pattern and factors influencing red cell immunization secondary to multiple blood transfusions in patients of beta-thalassaemia major. DESIGN A cross-sectional study. PLACE AND DURATION OF STUDY Armed Forces Institute of Transfusion, Rawalpindi, in November 2002. PATIENTS AND METHODS One hundred and sixty-one patients suffering from beta-thalassaemia major and on regular blood transfusions were included in the study. Their blood samples were tested for blood grouping, direct antiglobulin test and antibody screening/identification using reagents of DiaMed-ID Gel microtyping system. RESULTS The total rate of red cell immunization was found to be 6.84%. Red cell alloantibodies were detected in 4.97% patients, and belonged mainly to Rh system, with one example each of anti-K, anti-Jsb and anti-Jka. Direct antiglobulin test was positive in 3 patients (1.87%) with increased hemolysis. Two had warm panreactive IgG antibodies suggesting red cell autoimmunization. Red cells of the 3rd patient showed sensitization with c-3d, with presence of an autoreactive cold agglutinin in the serum having a titre of 1:4. The red cell alloantibody formation was not influenced by age at first transfusion, number of blood transfusions and ethnicity. CONCLUSION The rate of red cell alloimmunization in beta-thalassaemia major is relatively low in our setup and may be related to red cell homogeneity between the donor and recipient population. Routine pre-transfusion matching of blood, other than ABO and Rh "D" antigens is not recommended because of low rate of red cell alloimmunization, and high costs associated with such testing. Hyperhaemolysis, due to acquired red cell autoantibodies was found to be an important complication. Patients who develop this complication should be tested for presence of underlying alloantibodies and considered for immunosuppressive treatment.