Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy.

BACKGROUND Plasminogen activator inhibitor-1 (PAI-1) is increased in kidneys of humans and animals with diabetic nephropathy and is associated with extracellular matrix (ECM) accumulation. PAI-1 may promote ECM buildup by preventing plasmin and matrix metalloproteinase (MMP) activation. However, the importance and mechanism of PAI-1 action in the pathogenesis of diabetic nephropathy is unknown. METHODS We investigated the effect of streptozotocin (STZ)-induced diabetes in wild-type (PAI-1(+/+)) mice and mice null for PAI-1 (PAI-1(-/-)). After 1 month of diabetes, animals were placed in metabolic cages for 24-hour urine collection. Total RNA was isolated from kidney cortex for reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis, and Western blots were quantitated from cortical protein. Primary mesangial cells were grown from Sprague-Dawley rats and used in signal transduction studies. RESULTS Urinary albumin excretion (UAE) in diabetic PAI-1(+/+) mice increased >threefold, but remained unchanged in PAI-1(-/-) mice. Transforming growth factor-beta (TGF-beta) and fibronectin message and protein levels were lower in diabetic PAI-1(-/-) vs. PAI-1(+/+) mice, suggesting that PAI-1 deficiency impaired TGF-beta expression despite diabetes. Indeed, recombinant PAI-1 directly stimulated TGF-beta message and protein via mitogen-activated protein kinase (MAPK) signal transduction in cultured mesangial cells. Urokinase plasminogen activator (uPA) inhibited this PAI-1 action in a dose-dependent manner. The inhibitory effect of antibody to uPA receptor (uPAR) on PAI-1-induced TGF-beta function suggested that uPAR mediated the cellular effect of PAI-1. CONCLUSION PAI-1 can regulate TGF-beta expression by binding to uPAR and activating the extracellular-regulated signal kinase (ERK)/MAPK pathway. Therefore, PAI-1 contributes to diabetic nephropathy by regulating TGF-beta and renal ECM production and may be a therapeutic target in diabetic nephropathy.
Phospholipid-binding Sites of Phosphatase and Tensin Homolog (PTEN)

Background: PTEN activity is enhanced by PI(4,5)P2 via either an allosteric or interfacial effect. Results: 31P field cycling NMR with spin-labeled PTEN detects a PI(4,5)P2-binding site near but not in the active site. Conclusion: A model for PTEN identifies Lys-13 and Arg-47 as part of the PI(4,5)P2 site. Significance: Occupation of the PI(4,5)P2-binding site on PTEN stabilizes productive interfacial binding. The lipid phosphatase activity of the tumor suppressor phosphatase and tensin homolog (PTEN) is enhanced by the presence of its biological product, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This enhancement is suggested to occur via the product binding to the N-terminal region of the protein. PTEN effects on short-chain phosphoinositide 31P linewidths and on the full field dependence of the spin-lattice relaxation rate (measured by high resolution field cycling 31P NMR using spin-labeled protein) are combined with enzyme kinetics with the same short-chain phospholipids to characterize where PI(4,5)P2 binds on the protein. The results are used to model a discrete site for a PI(4,5)P2 molecule close to, but distinct from, the active site of PTEN. This PI(4,5)P2 site uses Arg-47 and Lys-13 as phosphate ligands, explaining why PTEN R47G and K13E can no longer be activated by that phosphoinositide. Placing a PI(4,5)P2 near the substrate site allows for proper orientation of the enzyme on interfaces and should facilitate processive catalysis.
Regional Cerebral Blood Flow Abnormalities in Nondemented Patients With Memory Impairment

Background. Patients with objective evidence of memory impairment have been considered to be at risk for developing Alzheimer's disease (AD). However, little is known about patterns of regional cerebral blood flow abnormalities and their prognostic significance in these patients. Methods. The authors retrospectively studied 28 nondemented subjects with memory loss and investigated patterns of blood flow abnormalities on single photon emission computed tomography (SPECT). Results. The patients were followed up for more than 2 years; during follow‐up, 14 patients (50%) developed AD. The onset of memory impairment in patients who progressed to AD was significantly earlier than in those who remained in a nondemented condition. SPECT data from the initial evaluation were analyzed by region of interest analysis and statistical parametric mapping. Interestingly, both groups of patients shared hypoperfusion in the medial temporal regions and the posterior cingulate. In addition to these regions, significant blood flow reduction in the parietal and anterior cingulate cortices was detected in patients who progressed to AD. Conclusions. These results demonstrate that (1) subjects with an earlier onset of memory loss have an increased risk for developing AD, (2) SPECT can be useful for distinguishing subjects with memory loss who will rapidly progress to AD from those who will not, and (3) perfusion impairment typical of AD was evident even in subjects with memory impairment who remained nondemented.
Mirror movements in healthy humans across the lifespan: effects of development and ageing

Aim Mirror movements are a transient phenomenon during childhood, which decrease in intensity with motor development. An increasing inhibitory competence resulting in the ability of movement lateralization is thought to be the underlying mechanism. We aimed to quantify unintended mirror movements systematically across the lifespan and to investigate the influences of age, sex, handedness, and task frequency.
Leaf Temperature and Vapour Pressure Deficit (VPD) Driving Stomatal Conductance and Biochemical Processes of Leaf Photosynthetic Rate in a Subtropical Evergreen Coniferous Plantation

Photosynthesis is arguably the most important biochemical process on Earth, which is dramatically influenced by environmental conditions. How environmental factors drive stomatal conductance and biochemical processes of leaf photosynthetic rate has not been sufficiently investigated in subtropical China. In this study, we analysed the effects of stomatal and biochemical parameters on the photosynthetic rate of native Masson’s pine (Pinus massoniana Lamb.) and exotic slash pine (Pinus elliottii Engelm.) in response to leaf temperature and vapour pressure deficit (VPD) in subtropical China, based on leaf gas exchange measurements in 2016. Our results showed that there was no significant difference in the light-saturated photosynthetic rate (Asat) between native Masson’s pine and exotic slash pine. The seasonal patterns of maximum rate of the carboxylation (Vcmax25) were basically consistent with seasonal patterns of Asat for both species. The positive effect of leaf temperature on Asat was mainly produced through its positive effect on Vcmax25. Leaf temperature had no significant effect on stomatal conductance. Vcmax25 and gs simultaneously affected Asat in response to VPD. Our results highlighted the importance of biochemical processes in limiting leaf photosynthetic rate in response to environmental conditions in subtropical evergreen coniferous plantations.
Challenges and Opportunities for the Sustainability Transition in Global Trade (Introduction)

In this special issue, we explore the challenges and opportunities arising with respect to normative goals of shifting production and international trade in agriculture towards greater sustainability. Private voluntary sustainability standards have experienced substantial growth in various global markets, reaching 40% of global coffee production, 25% of cocoa, and 15% of palm oil1. Given the rapid expansion of private standards, whether third-party certifications, corporate codes of conduct (Vermeulen 2010), or ‘newer’ regulatory approaches such as multi-stakeholder initiatives, public-private partnerships, and efforts to develop new sustainable business models, it is important to consider what such approaches offer. All of these approaches are seeking to contribute, at differing levels of ambition, towards a sustainability transition.
The effects of resistance exercise training on macro‐ and micro‐circulatory responses to feeding and skeletal muscle protein anabolism in older men

Increases in limb blood flow in response to nutrition are reduced in older age. Muscle microvascular blood flow (MBF) in response to nutrition is also reduced with advancing age and this may contribute to age‐related ‘anabolic resistance’. Resistance exercise training (RET) can rejuvenate limb blood flow responses to nutrition in older individuals. We report here that 20 weeks of RET also restores muscle MBF in older individuals. Restoration of MBF does not, however, enhance muscle anabolic responses to nutrition.
Multivariate analysis of DNA ploidy, p53, c-erbB-2 proteins, EGFR, and steroid hormone receptors for short-term prognosis in breast cancer.

BACKGROUND Several molecular-genetic alterations in breast cancer, including aneuploidy, aberrant expression of p53, c-erbB-2, and EGFR have been associated with poor prognosis in breast cancer particularly in lymph node negative patients. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, a multivariate analysis was performed particularly in lymph node positive breast cancer cases. METHODS One hundred fresh samples of primary breast carcinoma have been studied with flow cytometry for DNA ploidy. On the same specimens steroid hormone receptors (ER and PR) were measured in cytosol fraction using Abbott ELIZA assays, c-erbB-2 and EGFR were determined in the tissue homogenate and mutant p53 protein in the nuclear fraction by Oncogene Science ELISA procedures. In addition, information regarding surgical-pathologic features of the tumor was obtained. Multivariate analysis using Cox's proportional hazards model was done to identify variables predictive of poor prognosis. RESULTS With univariate analysis, tumor size, lymphnode number, p53, c-erbB-2 were predictive of poor short term prognosis. In the multivariate analysis, only c-erbB-2 (P = 0.001) and p53 (P = 0.05) were significant. Subgroup analysis by nodal status yielded significant association of c-erbB-2 (P = 0.001) and p53 (P = 0.04) with lymph node positive breast cancer. CONCLUSIONS Among molecular-genetic prognostic factors, c-erbB-2 was the most strongly predictive of poor short term prognosis followed by p53 in lymph node positive breast cancer.
Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH‐AARP diet and health study

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995–1996, dietary intake data was reported by 494,978 participants of the NIH‐AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy‐adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27–2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84–1.64) p for trend = 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37–2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91–1.78) p for trend = 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5–<25 kg/m2) [HR (95% CI) 0.76 (0.63–0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96–1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90–1.05)]. p for interaction = 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.
Epidemiological and clinicopathological characteristics of lung cancer in a teaching hospital in Iran.

BACKGROUND Lung cancer is one of the most commonly diagnosed cancers and the most frequent cause of cancer-related death worldwide. In Iran, it ranks second and third as the cancer-causing death in men and women, respectively. We carried out this study to find out the demographic, clinical, and histological characteristics and risk factors of lung cancer in a referral tertiary center in Iran. MATERIALS AND METHODS A retrospective study was conducted on cases of primary lung cancer based on the results of registered cancer reports of cytological and pathological specimens between March 2001 and March 2012. Demographic variables, clinical manifestations, histology and location of tumors were determined based on the data found in the medical records of each patient. Definite or probable etiologic factors were identified. Data analysis was performed with SPSS version 16 and a p-value ≤ 0.05 was considered as significant. RESULTS A total of 203 patients, with a mean age of 65.7 years (SD=11.2), with primary lung cancer were identified, 81.3% being men. Of the total, 110 cases (54.2%) were living in urban areas. In 53.2% of cases, the site of tumor was on the right side and in 72.9% of cases the lesion was centrally located. The histological types of lung cancer were squamous cell carcinoma (SCC) in 107 cases (52.7%), adenocarcinoma (AC) in 30 cases (14.8%), and small cell carcinoma (SC) in 27 cases (13.3%). Significant correlations between the gender and residence, smoking, and the histological type and location (central or peripheral) of tumor were found. The percentage of smokers was 75.2% in men and 15.8% in women. CONCLUSIONS Smoking was the most important risk factor and squamous cell carcinoma the most common histological type of lung cancer in our study. Male sex and being a smoker was associated with histological types of SCC while being nonsmoker had relationship with adenocarcinoma.
Clinical utility of C‐terminal telopeptide of type 1 collagen in multiple myeloma

Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C‐terminal telopeptide of type I collagen (CTX‐1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX‐1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX‐1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3–6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX‐1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX‐1 level was highest in the newly diagnosed group (0·771 ± 0·400 μg/l), and lowest in the remission group (0·099 ± 0·070 μg/l) (P < 0·0001). P1NP levels were not statistically different across the patient groups. We conclude that CTX‐1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.
Transformation of lymphocytes by herpesvirus papio

Cotton‐topped (CT) or white‐lipped (WL) marmoset lymphocytes were transformed in vitro with herpesvirus papio (HVP) into permanently growing lymphoblastoid cell lines (LCL). Five of 9 HVP‐transformed CT cell lines contained cells with antigens reacting with antibodies to Epstein‐Barr virus (EBV) capsid antigen (VCA) and/or to EBV‐induced early antigens (EA). None of 12 WL LCL revealed such antigen‐producing cells. Cells from both groups of cultures failed to react with antibodies to the EBV‐specified nuclear antigen (EBNA). Exposure of baboon circulating lymphocytes to X‐irradiated HVP or EBV‐carrying cells, or to suspensions of EBV resulted in establishment of LCL which all contained VCA and/or EA‐positive, but no EBNA‐positive cells. Nuclear antigens were undetectable also with anti‐VCA‐positive sera from baboons, chimpanzees, or other non‐human primates. DNA‐complementary RNA (cRNA) filter hybridization with EBV cRNA showed that with one exception transformed CT or WL marmoset cells contained at least 1‐2 virus genome equivalents per cell, while at least 12‐25 virus genome equivalents per cell were detected in transformed baboon cells. These data need confirmation by DNA‐DNA reassociation kinetics.
Body building and concurrent mass loss: flight adaptations in tree sparrows

Environmental changes are responsible for the evolution of flexible physiology and the extent of phenotypic plasticity in the regulation of birds' organ size has not been appreciated until recently. Rapid reversible physiological changes during different life–history stages are virtually only known from long–distance migrants, and few studies have focused on less extreme aspects of organ flexibility. During moult, birds suffer from increased wing loading due to wing–area reductions, which may impair flight ability. A previous study found that tree sparrows' escape flight (Passer montanus) is unaffected during moult, suggesting compensatory aptness. We used non–invasive techniques to study physiological adaptations to increased wing loading in tree sparrows. As wing area was reduced during natural moult the ratio of pectoral–muscle size to body mass increased. When moult was completed this ratio decreased. We show experimentally a novel, strategic, organ–flexibility pattern. Unlike the general pattern, where body mass is positively coupled to pectoral–muscle size, tree sparrows responded within 7 days to reductions in wing area by reducing body mass concurrently with an increase in pectoral–muscle size. This rapid flexibility in a non–migratory species probably reflects the paramount importance and long history of flight in birds.
Income Redistribution through Taxes and Transfers across OECD Countries

This paper produces a comprehensive assessment of income redistribution to the working-age population, covering OECD countries over the last two decades. Redistribution is quantified as the relative reduction in market income inequality achieved by personal income taxes, employees’ social security contributions and cash transfers, based on household-level micro data. A detailed decomposition analysis uncovers the respective roles of size, tax progressivity and transfer targeting for overall redistribution, the respective role of various categories of transfers for transfer redistribution; as well as redistribution for various income groups. The paper shows a widespread decline in redistribution across the OECD, both on average and in the majority of countries for which data going back to the mid-1990s are available. This was primarily associated with a decline in cash transfer redistribution while personal income taxes played a less important and more heterogeneous role across countries. In turn, the decline in the redistributive effect of cash transfers reflected a decline in their size and in particular by less redistributive insurance transfers. In some countries, this was mitigated by more redistributive assistance transfers but the resulting increase in the targeting of total transfers was not sufficient to prevent transfer redistribution from declining.
Electrophoretic Karyotypes and Genome Sizing of the Pathogenic Fungus Paracoccidioides brasiliensis

ABSTRACT Here we present the karyotype analysis and genome sizing ofParacoccidioides brasiliensis, a pathogen refractory to conventional genetic analysis. We have established pulsed-field gel electrophoresis (PFGE) conditions to resolve the high-molecular-weight chromosomal bands of two clinical isolates ofP. brasiliensis. Both isolates showed four megabase-sized bands, ranging from 2.0 to 10.0 Mbp. Significant differences in chromosome sizes and in the chromosomal location of genes for the gp43 antigen and chitin synthase were found. Different technical approaches were employed to estimate the DNA content and to define the ploidy ofP. brasiliensis. An estimated genome size in the range of 45.7 to 60.9 Mbp was provided by the analysis of data generated by measuring the amplitude of fluorescence intensity of DAPI (4′,6-diamidino-2-phenylindole)-stained nuclei (by confocal microscopy). The nuclear genome size estimated by confocal microscopy is twice that estimated by the average sum of the molecular weight of chromosome-sized DNA molecules by PFGE, suggesting that each separatedP. brasiliensis chromosomal band is diploid.
Flame Goes Out: Determinants of Individual Support at the 2024 Hamburg Games Referendum

This study used the opportunity to conduct a survey with a contingent valuation method scenario in the weeks prior to an actual referendum on bidding for the 2024 Olympic Summer Games in Hamburg. Only 41.2% of respondents planned to vote favorably and 30.1% reported a positive willingnessâ€ toâ€ pay. We allowed respondents to state the institution they would give the money to ensure it is wisely spent. The preferred institutions were a foundation and an account in trust. The findings indicate that individual voters have their own complex utility function of costs and benefits which should be considered by public officials. (JEL H41, L83, Z23, Z28)
Psychophysiological protective factors for male subjects at high risk for criminal behavior.

OBJECTIVE This study examines the role of elevated autonomic nervous system reactivity in protecting individuals at high risk for criminal behavior from antisocial outcomes. The authors hypothesized that subjects with criminal fathers who did not become criminals themselves were biologically protected from such an outcome because of, in part, heightened responsiveness of the autonomic nervous system. METHOD Ninety-four male subjects were placed into one of four study groups: criminal with criminal father (N = 26), noncriminal with criminal father (N = 24), criminal with noncriminal father (N = 20), and noncriminal with noncriminal father (N = 24). Skin conductance and heart rate data were gathered in an orienting paradigm. RESULTS Skin conductance and heart rate orienting reactivity were found to be significantly higher in the group of noncriminal subjects with criminal fathers than in the other three groups. CONCLUSIONS For subjects at high risk for criminal behavior, heightened autonomic nervous system responsiveness appears to be associated with lower likelihood of criminal outcome.
Optically induced magnetization in a diluted magnetic semiconductor: Hg1-xMnxTe.

This paper reports the observation of light-induced magnetization in ${\mathrm{Hg}}_{1\ensuremath{-}x}{\mathrm{Mn}}_{x}\mathrm{Te}$ by a novel technique combining optical pumping and superconducting quantum interference detection. We show that the magnetization is due to orientation of Mn ions caused by spin transfer from polarized electrons and holes to Mn centers in the process of spin-flip exchange scattering. This interpretation goes beyond a mean-field approach. The effect furnishes direct information on the spin-lattice relaxation in dilute magnetic semiconductors.