Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of distinct type IV collagen networks in glomerular development and function.

BACKGROUND In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen result in progressive renal failure. This nephropathy appears to relate to the arrest of a switch from an alpha 1/alpha 2 to an alpha 3/alpha 4/alpha 5 network of type IV collagen in the developing glomerular basement membrane (GBM; Kalluri et al, J Clin Invest 99:2470, 1997). METHODS We examined the role of this switch in glomerular development and function using a canine model of X-linked nephritis with a COL4A5 mutation. The electron microscopic appearance and the expression of the alpha 1-alpha 6 chains of type IV collagen in the GBM was correlated with glomerular function. RESULTS In normal neonatal glomeruli, once capillary loops were present, there was staining of GBM for the alpha 1-alpha 5 chains. Prior to this stage, only alpha 1 and alpha 2 chains were present, with rare glomeruli positive for the alpha 5 chain. As glomeruli matured, the alpha 1 and alpha 2 chains tended to disappear from the GBM, with the alpha 3-alpha 5 chains remaining. In affected male dogs, only the alpha 1 and alpha 2 chains were detected at any stage. GBM ultrastructure in these dogs remained normal until one month and proteinuria did not appear until two months. CONCLUSION Our results show that normal glomerular development involves a switch in type IV collagen networks. In affected male dogs, a failure of this switch results in an absence of the alpha 3/alpha 4/alpha 5 network and a persistence of the alpha 1/alpha 2 network in GBM. GBM ultrastructure and glomerular function remain normal for one month, indicating that GBM deterioration in Alport syndrome begins as a postnatal process. Hence, only the alpha 1/alpha 2 network is essential for normal glomerular development, whereas the alpha 3/alpha 4/alpha 5 network is essential for long-term maintenance of glomerular structure and function.
Ecological Succession of Bacterial Communities during Conventionalization of Germ-Free Mice

ABSTRACT Little is known about the dynamics of early ecological succession during experimental conventionalization of the gastrointestinal (GI) tract; thus, we measured changes in bacterial communities over time, at two different mucosal sites (cecum and jejunum), with germfree C57BL/6 mice as the recipients of cecal contents (input community) from a C57BL/6 donor mouse. Bacterial communities were monitored using pyrosequencing of 16S rRNA gene amplicon libraries from the cecum and jejunum and analyzed by a variety of ecological metrics. Bacterial communities, at day 1 postconventionalization, in the cecum and jejunum had lower diversity and were distinct from the input community (dominated by either Escherichia or Bacteroides). However, by days 7 and 21, the recipient communities had become significantly diverse and the cecal communities resembled those of the donor and donor littermates, confirming that transfer of cecal contents results in reassembly of the community in the cecum 7 to 21 days later. However, bacterial communities in the recipient jejunum displayed significant structural heterogeneity compared to each other or the donor inoculum or the donor littermates, suggesting that the bacterial community of the jejunum is more dynamic during the first 21 days of conventionalization. This report demonstrates that (i) mature input communities do not simply reassemble at mucosal sites during conventionalization (they first transform into a “pioneering” community and over time take on the appearance, in membership and structure, of the original input community) and (ii) the specific mucosal environment plays a role in shaping the community.
Inhibition of ChoK is an efficient antitumor strategy for Harvey-, Kirsten-, and N-ras-transformed cells.

An increasing amount of evidence suggests that elevated PCho levels are related to the transforming properties of the H-Ras oncoprotein. Based on these observations, we have designed an antitumor strategy using choline kinase, the enzyme responsible of PCho production, as a novel target for drug discovery. However, little relationship between this lipid-related pathway and the other two Ras members, N- and K-ras, has been established. Since N- and K-ras are the most frequently mutated ras genes in human tumors, we have analyzed the PC-PLD/ChoK pathway and the sensitivity to ChoK inhibition of all three ras-transformed cells. Here we demonstrate that transformation by the three Ras oncoproteins results in increased levels of PCho to a similar extent, resulting from a similar constitutive increase of ChoK activity. As well, sensitivity to choline kinase inhibitors as antiproliferative drugs is similar in cell lines transformed by each of the three ras oncogenes, being in all cases higher than parental, nontransformed cells. In addition, H, K and N-ras-induced alterations in PC metabolism is discussed. These results indicate that ChoK can be used as a general target for anticancer drug design against Ras-dependent tumorigenesis.
Immunodeficiency associated with anorexia nervosa is secondary and improves after refeeding

Several studies have addressed the question of starvation effects on immune function by means of changes in lymphocyte subsets, cytokine induction or lymphocyte activation. Anorexia nervosa (AN) patients are severely malnourished and contradictory results have been obtained regarding the accompanying immunodeficiency, including its assignation as a part of the primary nervous disorder. In the present work, an extensive immunological function examination was carried out on 40 AN patients who were compared with a control group of 14 healthy girls. The AN patients were also classified according to their nutritional status (by the Body Mass Index: BMI), this being critical for a better understanding of these secondary immunodeficiency bases. Moreover, another immune system study was performed on five patients after refeeding. Lymphocyte subsets and function, cytokine induction and peripheral blood concentrations, and innate as well as humoral immunity were evaluated. Deregulation in the cytokine network, owing to the interaction of the central nervous (CNS) and immune systems, seems to be the initial immune alteration in AN immunodeficiency but it has not been disproved that the immunodeficiency is a direct consequence of the original psychiatric perturbation. Spontaneous high levels of circulating interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α) have been observed; this is probably one of the causes of the anomalies found in the T‐cell subpopulations (mainly the naive CD4+CD45RA+ reduction and the cytotoxic CD8+ increase) and T‐cell activation status (mainly the down‐regulation of the CD2 and CD69 activation pathways). This finally leads to an impairment, not only in T‐cell function but also in T‐cell to B‐cell co‐operation. The AN specificity of these results is confirmed by the fact that these immune alterations improve after refeeding and when nutritional status becomes less critical, which also suggests that AN immunodeficiency is indeed secondary to malnutrition.
Relationships between family histories of stroke and of hypertension and stroke mortality: Nippon Data80, 1980–1999

A family history of stroke seems to be related with increased risk of stroke although the relationship is not always significant. Increased risk of stroke is strongly associated with hypertension, which might be also associated with family history. However, investigations into the relationship between family history of hypertension and stroke mortality are scarce. We investigated whether a family history of stroke and that of hypertension evaluated using a simple questionnaire could predict stroke mortality in Japanese. We obtained parental histories of stroke and of hypertension from 8,037 randomly selected general Japanese without history of cardiovascular disease and followed them for 19 years. The multivariate adjusted hazard ratios (HRs) for total stroke mortality, intra-cerebral hemorrhage mortality and for cerebral infarction mortality according to family history were estimated using the Cox proportional hazards model. The prevalences of family histories of stroke and of hypertension were 20.6% and 31.1%, respectively. A family history of stroke was not related to total stroke mortality, intra-cerebral hemorrhage mortality or to cerebral infarction mortality. Meanwhile, a family history of hypertension was positively related to total stroke mortality among women aged less than 60 years and men aged 60 or more years (women: HR=3.41, 95% confidence interval [CI]: 1.49–7.81; men: HR=1.50, 95% CI: 1.00–2.24) even after adjustment for systolic blood pressure. In conclusion, a family history of stroke could not predict total stroke mortality. However, a family history of hypertension might predict an increased risk for total stroke.
The Belt and Road Initiative’s effect on supply-chain trade: evidence from structural gravity equations

This article considers the effect of China’s Belt and Road Initiative on supply-chain trade for 64 economies in the period 2002–2011. We employ a structural gravity equation to estimate the impact of trade-cost reducing measures—notably infrastructural improvements and the creation of free trade agreements—on supply-chain trade and welfare in general equilibrium. We find that infrastructural investments will yield asymmetric benefits to China, Russia and Southeast Asian countries stemming from greater European market access. Our results also suggest that China’s alternatives to foster (inter)regional economic growth through the Regional Comprehensive Economic Partnership and the Trans-Pacific Partnership offer much less attractive economic prospects.
Young chronic hepatitis B patients with nucleos(t)ide analogue-induced hepatitis B e antigen seroconversion have a higher risk of HBV reactivation.

BACKGROUND It is unclear whether hepatitis B e antigen (HBeAg) seroconversion induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that of spontaneous HBeAg seroconversion. METHODS A total of 148 noncirrhotic NUC-induced HBeAg seroconverters were consecutively enrolled. A historical control of 407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts. RESULTS There were 1652.8 and 465.2 person-years of follow-up for spontaneous and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced seroconverters, spontaneous seroconverters were younger when achieving HBeAg seroconversion. We thus compared these 2 cohorts according to their age at HBeAg seroconversion. In patients achieving HBeAg seroconversion before 30 years of age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5-14.4). Using multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of both endpoints in young HBeAg seroconverters. CONCLUSION NUC-induced HBeAg seroconverters may not have durable response after stopping therapy. For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in NUC-induced seroconverters than spontaneous HBeAg seroconverters.
Structural Analysis of the Mechanism of Inhibition and Allosteric Activation of the Kinase Domain of HER2 Protein

Aberrant signaling of ErbB family members human epidermal growth factor 2 (HER2) and epidermal growth factor receptor (EGFR) is implicated in many human cancers, and HER2 expression is predictive of human disease recurrence and prognosis. Small molecule kinase inhibitors of EGFR and of both HER2 and EGFR have received approval for the treatment of cancer. We present the first high resolution crystal structure of the kinase domain of HER2 in complex with a selective inhibitor to understand protein activation, inhibition, and function at the molecular level. HER2 kinase domain crystallizes as a dimer and suggests evidence for an allosteric mechanism of activation comparable with previously reported activation mechanisms for EGFR and HER4. A unique Gly-rich region in HER2 following the α-helix C is responsible for increased conformational flexibility within the active site and could explain the low intrinsic catalytic activity previously reported for HER2. In addition, we solved the crystal structure of the kinase domain of EGFR in complex with a HER2/EGFR dual inhibitor (TAK-285). Comparison with previously reported inactive and active EGFR kinase domain structures gave insight into the mechanism of HER2 and EGFR inhibition and may help guide the design and development of new cancer drugs with improved potency and selectivity.
MicroRNA-148b is down-regulated in non-small cell lung cancer and associated with poor survival.

BACKGROUND The aim of this study was to clarify the clinicopathological significance of miRNA-148b (miR-148b) expression in NSCLC, and to explore the correlation between miR-148b level and the prognosis of patients with NSCLC. METHODS 151 patients diagnosed with NSCLC between May 2007 and April 2012 were included in the present study. Real-time RT-PCR method was used to assess the expression levels of miR-148b. The differences between two groups were assessed using Student's t -test, and the Kaplan-Meier method was used to estimate overall survival. RESULTS The expression of miR-148b was decreased in tumor tissues compared to corresponding adjacent normal lung tissues (0.37 ± 0.12 vs. 1.00 ± 0.53, P < 0.05). Low miR-148b expression was significantly associated with TNM stage (P = 0.014), lymph node metastasis (P = 0.031), and distant metastasis (P = 0.008). Kaplan-Meier survival analysis showed that patients with low expression of miR-148b had significantly worse overall survival rates compared with those who had cancers with high miR-148b expression (log-rank test P = 0.039). Furthermore, multivariate Cox proportional hazards model analysis showed that miR-148b expression was independently associated with overall survival of patients with NSCLC (HR = 2.357, 95% CI: 1.612-9.212, P = 0.011). CONCLUSION our data indicate that decreased expression of miR-148b in NSCLC tissues has prognostic value.
Human bocavirus in Iranian children with acute respiratory infections

Human bocavirus (HBoV), a virus discovered in Sweden in 2005, has been associated with acute respiratory infections in young children and subsequent reports suggest that HBoV may have a worldwide distribution. This report describes the frequency and clinical presentation of HBoV in 261 Iranian children<5 years old with acute respiratory infections attending two regional hospitals in Rasht, Iran in the winter of 2003–2004. Polymerase chain reaction (PCR) and reverse transcription PCR (RT‐PCR) were used for the detection of HBoV and other respiratory pathogens from nasopharyngeal specimens. HBoV was detected in 21 (8%) children. Fifteen (12%) of these children were identified among 122 children admitted to hospital and 6 (4%) from 139 outpatients (P < 0.05). Most children with HBoV were less than 2 years (17/21, 81%) and 7 (33%) were less than 1 year old. Although HBoV was identified in all ages it affected slightly older children than the respiratory syncytial virus (RSV). The frequency of the virus varied from 1 (3%) in 40 patients in November to 7 (12%) of 61 in February, suggesting a seasonal pattern during the autumn and early winter. Seven children had co‐infections with RSV, adenovirus or influenza A. The relatively high frequency of HBoV suggests that the virus may contribute substantially to acute respiratory infections in children. J. Med. Virol. 79:539–543, 2007. © 2007 Wiley‐Liss, Inc.
Training opportunities in monopsonistic labour markets

ABSTRACT This paper studies the empirical relationship between the extent of monopsonistic power observed in occupational labour markets and the training opportunities available to workers in those markets; using data from the American National Longitudinal Survey of Youth of 1979. The results reveal a positive and significant association between monopsony power and training availability. The estimated association is found to be stronger for individuals with a college degree, with longer tenure in their jobs, and higher wages. These results are consistent across several econometric specifications that control for time, occupation, and individual fixed effects.
Measuring The Efficiency of Indonesian Sharia Rural Banks: Two Stage Approach

This paper aims to measure the efficiency level of Sharia Credit Banks in Indonesia over the period of 2012 to 2015. In the first stage, this study uses a Two Stage Approach to measure the level of efficiency with Data Envelopment Analysis (DEA) using the Banxia Frontier Analysis (BFA) software. Then, the second stage involves the analysis of factors that influence the efficiency level of a bank by panel data regression method. On the basis of the test, it is revealed that the Sharia Rural Banks in Indonesia during the study period are not been fully efficient. Some internal factors of the bank, namely BOPO ratios, have a significant adverse impact on the efficiency, while KPPM has a positive and significant influence on the efficiency of BPRS in Indonesia. Meanwhile the total asset, NPF and ROA variables have no significant effect on the efficiency, while the interest rate or BI Rate and inflation have a positive and significant influence on the efficiency of the BPRS.
Evidence That Heparin Saccharides Promote FGF2 Mitogenesis through Two Distinct Mechanisms*

Heparin-like saccharides play an essential role in binding to both fibroblast growth factors (FGF) and their receptors at the cell surface. In this study we prepared a series of heparin oligosaccharides according to their size and sulfation level. We then investigated their affinity for FGF2 and their ability to support FGF2 mitogenesis of heparan sulfate-deficient cells expressing FGFR1c. Tetra- and hexasaccharides bound FGF2, but failed to dimerize the growth factor. Nevertheless, these saccharides promoted FGF2-mediated cell growth. Furthermore, whereas enzymatic removal of the non-reducing end 2-O-sulfate group had little effect on the 1:1 interaction with FGF2, it eliminated the mitogenic activity of these saccharides. This evidence supports the symmetric two-end model of ternary complex formation. In contrast, even at very low concentrations, octasaccharide and larger heparin fragments conferred a potent mitogenic activity that was independent of terminal 2-O-sulfation. This correlated with the ability to dimerize FGF2 in an apparently cooperative manner. This data suggests that potent mitogenic signaling results from heparin-mediated trans-dimerization of FGF2, consistent with the asymmetric model of ternary complex formation. We propose that, depending on saccharide structure, there are different architectures and modes of ternary complex assembly that differ in stability and/or efficiency of transmembrane signaling.
Pemberdayaan Masyarakat Oleh PT Nestle Indonesia Melalui Kelompok Sapi Perah Budi Luhur

Kemiskinan sebagai salah satu masalah kesejahteraan sosial yang sejak dulu hingga kini masih menjadi agenda utama pembangunan dunia. Bentuk kemiskinan yang mendasar adalah perampasan kesejahteraan. Kemiskinan sering dialami oleh negara berkembang (developing countries) dan hingga kini masih berpusat di wilayah pedesaan seperti yang dialami Indonesia. Oleh karena itu PT Nestle selaku bagian dari sektor privat yang memiliki kewajiban untuk mendukung dan membantu memecahkan permasalahan terkait kemiskinan yang dialami oleh negara. Wujud dari upaya tersebut adalah dengan mendukung dan melakukan pemberdayaan masyarakat melalui Kelompok Sapi Perah Budi Luhur yang dianggap satu-satunya strategi untuk mengurangi kemiskinan. Mengapa harus sapi perah? karena semakin meningkatnya kebutuhan susu yang dibutuhkan manusia dalam rangka human investment. Kelompok Budi Luhur adalah salah satu kelompok peternak sapi perah yang berhasil di wilayah Jawa Timur. Keberhasilan yang dicapai tentu tidak lain juga berkat bantuan dan peran dari PT Nestle yang berpartisipasi aktif mendukung kegiatan pemberdayaan yang mereka lakukan. Oleh karena itu menarik dilihat lebih dalam mengenai bagaimana pelaksanaan pemberdayaan masyarakat yang dilakukan PT Nestle melalui Kelompok Sapi Perah Budi Luhur. Metode yang digunakan adalah metode kualitatif agar hasil yang didapat lebih dalam dan tajam. Berdasarkan penelitian yang dilakukan menghasilkan kesimpulan bahwa pemberdayaan yang dilakukan PT Nestle selama ini menghasilkan dampak yang positif khususnya bagi para peternak sapi perah dan dalam rangka mengurangi kemiskinan dan pengangguran diwilayah pedesaan. Namun, bentuk program pemberdayaan yang diberikannya selama ini masih sebatas pemberian bantuan berupa subsidi peralatan untuk mendukung kegiatan bisnis persusuan
Attachment insecurity predicts child active resistance to parental requests in a compliance task.

AIM We studied the effects of early mother-child relationship quality and child temperament on the development of child compliance and active resistance in a large population-based cohort study (n = 534). BACKGROUND Parenting and the quality of the parent-child relationship can either hamper or support the development of child compliance directly or in interplay with child temperament. METHODS Mother-infant dyads were observed at 14 and 36 months and maternal and child behaviours were independently coded. The quality of compliance was assessed at 36 months in a clean-up task. Child behaviour was coded using a system differentiating between two dimensions: Compliance and Active Resistance. RESULTS Controlling for concurrent maternal sensitivity, child temperament, and gender children with a more insecure attachment relationship showed higher levels of active resistance during Clean-Up than more securely attached children. The effect was stronger for boys than for girls and mainly driven by attachment avoidance. CONCLUSIONS Early attachment is an important contributor to child socialization of moral behaviour.
Increased Stroke Risk and Lipoprotein(a) in a Multiethnic Community: The Northern Manhattan Stroke Study

Context: Elevated lipoprotein(a) [Lp(a)] is associated with ischemic stroke (IS) among Whites, but data is sparse for non-White populations. Objective: Using a population-based case-control study design with subjects from the Northern Manhattan Stroke Study, we assessed whether Lp(a) levels were independently associated with IS risk among Whites, Blacks and Hispanics. Design and Setting: Lp(a) levels were measured in 317 IS cases (mean age 69 ± 13 years; 56% women; 16% Whites, 31% Blacks and 52% Hispanics) and 413 community-based controls, matched by age, race/ethnicity and gender. In-person assessments included demographics, socioeconomic status, presence of vascular risk factors and fasting lipid levels. Logistic regression was used to determine the independent association of Lp(a) and IS. Stratified analyses investigated gender and race/ethnic differences. Results: Mean Lp(a) levels were greater among cases than controls (46.3 ± 41.0 vs. 38.9 ± 38.2 mg/dl; p < 0.01). After adjusting for stroke risk factors (hypertension, diabetes mellitus, coronary artery disease, cigarette smoking), lipid levels, and socioeconomic status, Lp(a) levels ≧30 mg/dl were independently associated with an increased stroke risk in the overall cohort (adjusted odds ratio, OR, 1.8, 95% confidence interval, CI, 1.20–2.6; p = 0.004). There was a significant linear dose-response relationship between Lp(a) levels and IS risk. The association between IS risk and Lp(a) ≧30 mg/dl was more pronounced among men (adjusted OR 2.0, 95% CI 1.1–3.5; p = 0.02) and among Blacks (adjusted OR 2.7, 95% CI 1.2–6.2; p = 0.02). Conclusion: Elevated Lp(a) levels were significantly and independently associated with increased stroke risk, suggesting that Lp(a) is a risk factor for IS across White, Black and Hispanic race/ethnic groups.