Miracle-dz/UniFAR-FTUs huggingface dataset:
Multimodal MRI Imaging of Apoptosis-Triggered Microstructural Alterations in the Postnatal Cerebral Cortex

Prematurely born children often develop neurodevelopmental delay that has been correlated with reduced growth and microstructural alterations in the cerebral cortex. Much research has focused on apoptotic neuronal cell death as a key neuropathological features following preterm brain injuries. How scattered apoptotic death of neurons may contribute to microstructural alterations remains unknown. The present study investigated in a rat model the effects of targeted neuronal apoptosis on cortical microstructure using in vivo MRI imaging combined with neuronal reconstruction and histological analysis. We describe that mild, targeted death of layer IV neurons in the developing rat cortex induces MRI-defined metabolic and microstructural alterations including increased cortical fractional anisotropy. Delayed architectural modifications in cortical gray matter and myelin abnormalities in the subcortical white matter such as hypomyelination and microglia activation follow the acute phase of neuronal death and axonal degeneration. These results establish the link between mild cortical apoptosis and MRI-defined microstructure changes that are reminiscent to those previously observed in preterm babies.
1,25-Dihydroxyvitamin D3 Ameliorates Th17 Autoimmunity via Transcriptional Modulation of Interleukin-17A

ABSTRACT A new class of inflammatory CD4+ T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4+ T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH)2D3 repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH)2D3 on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH)2D3/VDR, and a direct effect of 1,25(OH)2D3 on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases.
Enhanced neutrophil response in chronic obstructive pulmonary disease

BACKGROUND Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. METHODS Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 andl-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFα). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference –3.4 (95% CI of the difference –5.1 to –1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference –77 (95% CI of the difference –102 to –52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5)v 45 (3); mean difference –46 (95% CI of the difference –61 to –31), p<0.001) and after stimulation with TNFα (MFI 340 (15) v 263 (11); mean difference –77 (95% CI of the difference –119 to –34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. CONCLUSIONS These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.
Entrepreneurial innovativeness and growth ambitions in thick vs. thin regional innovation systems

Abstract Research in economic geography has paid increasing attention to regional innovation systems (RISs) as a potential vehicle for growth and development. Yet despite an increasing amount of research studying RISs in particular and economic regions in general, we have limited knowledge about their influence on entrepreneurs and entrepreneurship. We respond to this knowledge gap and study if entrepreneurs’ localization in thick vs. thin RISs affects their innovativeness and growth ambitions. Thick RISs are predominately urbanized spaces that include organizations of higher-level education, R&D intensive milieus, and an ample industry sector, while thin RISs to a lesser degree encompass these features. Empirically, we analyse 870–917 entrepreneurial firms in Agder of Southern Norway. Based on trade and labour markets, as defined by the EU’s classification of local administrative units (LAU1), we identify two thick and six thin RISs in Agder. Econometric analyses show that entrepreneurs located in thick RISs are more innovative than entrepreneurs located in thin RISs, but there are no significant differences concerning entrepreneurs’ growth ambitions. In light of our findings, we discuss the potential agency role played by entrepreneurial firms at a micro level on path dependent features of RISs at a macro level.
The 5'-end of hTERT mRNA is a good target for hammerhead ribozyme to suppress telomerase activity.

Because the expression level of hTERT, a catalytic subunit of human telomerase, is a rate-limiting determinant of telomerase activity, hTERT mRNA would be an excellent target of hammerhead ribozymes for the regulation of telomerase activity. We studied the efficiency of several hammerhead ribozymes targeting hTERT mRNA by transient and stable transfection procedures. To screen the potency of the ribozymes, transient ribozyme transfection and telomerase determination were performed. The ribozyme targeting 13 nucleotides downstream from the 5'-end of hTERT mRNA (13-ribozyme) exhibited the strongest telomerase-inhibitory activity, and the ribozyme to target 59 nucleotides upstream from the poly(A) tail showed clear activity. A stable transfection study confirmed that the 13-ribozyme suppressed telomerase. These observations suggest that the 13-ribozyme can regulate telomerase activity and may possess potential for cancer therapy.
Structure of the X (ADRP) domain of nsp3 from feline coronavirus

The structure of the X (or ADRP) domain of a pathogenic variant of feline coronavirus (FCoV) has been determined in tetragonal and cubic crystal forms to 3.1 and 2.2 Å resolution, respectively. In the tetragonal crystal form, glycerol‐3‐phosphate was observed in the ADP‐ribose‐binding site. Both crystal forms contained large solvent channels and had a solvent content of higher than 70%. Only very weak binding of this domain to ADP‐ribose was detected in vitro. However, the structure with ADP‐ribose bound was determined in the cubic crystal form at 3.9 Å resolution. The structure of the FCoV X domain had the expected macro‐domain fold and is the first structure of this domain from a coronavirus belonging to subgroup 1a.
THE REAL SIZE OF UNDERGROUND ECONOMY: A Case of Pakistan

Informal economy is an observable issue around the globe. Researchers of both the developed and developing countries are continuously investigating its different dimensions (size, determinants, etc). The current study is an attempt to estimate the real size of informality (underground economy) in Pakistan. For its estimation the real factors of economy like employment level, political stability, tax to GDP ratio and cost of working in informal economy are used, over a period (Time series) of 1972 to 2010. HP-Prescott filter method is utilized for obtaining the potential GDP and actual GDP series from the estimated GDP which is estimated through Feasible Generalized Least Square (FGLS)1 and then from these series informal GDP is estimated. About 71 per cent of the informality was found, in the case of Pakistan economy. The finding suggests that combating informality, the factors taken must be targeted properly.
The effect of membrane potential on the mammalian sodium‐potassium pump reconstituted into phospholipid vesicles.

1. We have studied effects of electrical diffusion potentials on active Na+‐K+ exchange in phospholipid vesicles reconstituted with pig kidney Na+, K+‐ATPase. 2. Diffusion potentials, negative inside, were established using outwardly directed K+ gradients plus valinomycin or Li+ gradients plus a Li+ ionophore, AS701. Measurement of fluorescence changes of the carbocyanine dye DiS‐C3‐(5) showed that the ionophores generated potentials of the expected orientation and of sufficient stability for their effects on active transport to be assessed. Measurement of rates of passive 22Na+ fluxes, over a wide range of diffusion potentials, were consistent with the quantitative predictions of the constant‐field flux equation. This result demonstrates that values of diffusion potentials calculated from the Nernst or constant‐field equation are accurate. 3. In some conditions, the inside‐negative potential (‐130 to ‐180 mV) accelerated the rate of ATP‐dependent Na+‐K+ exchange on inside‐out‐oriented pumps, compared to 'control' without the ionophores. Reduction in the size of the diffusion potentials by addition to the medium of Li+ with AS701 or Cs+ with the valinomycin progressively annulled the acceleratory effects, consistent with these being true effects of a change in membrane potentials. 4. At saturating cytoplasmic Na+ and ATP concentrations, the diffusion potential accelerated ATP‐dependent Na+‐K+ exchange by up to about 30% compared to control but this effect disappeared at rate‐limiting ATP concentrations (approximately 1 microM). 5. Using prior knowledge of rate‐limiting steps, we interpret this finding to mean that the conformational transition E2(2K)‐‐‐‐E12K associated with transport of two K+ ions is voltage insensitive while E1P(3Na)‐‐‐‐E2P3Na associated with transport of three Na+ ions is voltage sensitive. The simplest explanation is that the net charge in the transport domain of the protein when no ions, 2K+ or 3Na+ are bound is ‐2, 0 and +1 respectively. 6. The accelerating effect of the negative‐inside diffusion potential on Na+‐K+ exchange is greater at limitingly low cytoplasmic Na+ concentrations than at saturating cytoplasmic Na+ concentrations. Cytoplasmic Na+ activation curves show that the diffusion potential increases the apparent cytoplasmic Na+ affinity and reduces the sigmoidicity of cytoplasmic Na+ activation. 7. A kinetic analysis reveals that this effect on apparent affinity is due to an increase in intrinsic Na+ binding and occurs in addition to the effect on a transport rate constant. (ABSTRACT TRUNCATED AT 400 WORDS)
An Appreciative Inquiry Approach to Evaluating Culture, Structure, and Power in Agricultural Teacher Education Program Reform.

This case study outlines an appreciative inquiry approach to program reform using an agricultural teacher education program at a land-grant university that had begun to suffer from a large decline in student enrollment. Documents were analyzed that provided recommendations toward a master plan for reform made by 23 key agents based on their evaluation of culture, structure, and power within the existing program. The key agents were identified using a conceptual model called the Agricultural Education Networked Learning Circle for Teacher Preparation (AENLC). The documents outlined recommendations in five areas: 1) faculty recruitment and retention; 2) courses and curriculum; 3) certification options; 4) student professional development; and 5) student recruitment. The recommendations were consistent with the literature and the study provided empirical evidence on the practicality of using appreciative inquiry and the conceptual model in creating and leveraging social capital toward teacher education program reform or renewal.
The CD40/CD40 ligand interactions exert pleiotropic effects on bone marrow granulopoiesis

CD40 is a member of the TNFR family and upon interaction with its cognate ligand (CD40L), induces diverse biologic responses related to cell survival/growth. As altered CD40/CD40L interactions have been associated with neutropenia, we investigated the role of CD40/CD40L on human granulopoiesis using immunomagnetically sorted CD34+, CD34–/CD33+, and CD34–/CD33–/CD15+ BM cells, which represent sequential stages of the granulocytic development, the KG‐1 cells that constantly express CD34 and CD33, and LTBMCs that mimic the BM microenvironment. CD40 and CD40L were minimally expressed on CD34+, CD34–/CD33+, and CD34–/CD33–/CD15+ cells, but CD40 was substantially induced in the presence of TNF‐α. Cross‐linking of CD40 in the above cell populations resulted in induction of apoptosis that was enhanced further in the presence of FasL. CD40 activation in primary as wells as in KG‐1 cells resulted in Fas up‐regulation, providing a mechanism for the CD40‐mediated apoptosis. Addition of CD40L in clonogenic assays resulted in a significant decrease in the colony‐forming capacity of BMMCs from patients with chronic neutropenia, presumably expressing high levels of CD40 in the progenitor cells, and this effect was reversed upon CD40 blockade. CD40 was constitutively expressed on LTBMC stromal cells and upon activation, resulted in an increase in G‐CSF and GM‐CSF production. These data show that CD40/CD40L interactions may promote granulopoiesis under steady‐state conditions by inducing the stromal release of granulopoiesis‐supporting cytokines, whereas under inflammatory conditions, they may affect the granulocytic progenitor/precursor cell survival by accelerating the Fas‐mediated apoptosis.
Childhood abuse and initial presentation for HIV care: An opportunity for early intervention

Abstract An alarmingly high prevalence of childhood sexual and physical abuse has been observed in HIV-infected men and women, with rates several times higher than observed in the general population. Childhood abuse history has been associated with worse antiretroviral adherence and negative health behaviours in HIV-infected patients. This study evaluates the relationship between childhood abuse and the timing of presentation for HIV care. Participants in a multi-center prospective cohort study, who established initial HIV care after January 1996 and had a CD4 count available within six months of initial presentation, were included in this analysis. Bivariate contingency tables and multivariate logistic regression were used to evaluate the association of childhood abuse with early presentation for HIV care (initial CD4 count≥200/mm3). Among the 186 subjects included in this analysis, 33% had childhood abuse histories and 58% had an initial CD4 count≥200/mm3. Participants with a history of childhood abuse were more likely to present early for HIV care (AOR=2.12; p=0.03), perhaps because survivors of abuse tend to have higher utilization of health services. Because HIV-infected patients with childhood abuse histories have worse antiretroviral medication adherence and are more likely to engage in high-risk sexual and injection drug use behaviours, early presentation affords clinicians the opportunity for timely institution of interventions that may improve patient outcomes and prevent secondary HIV infections.
Differential response of normal rat mammary epithelial cells to mammogenic hormones and EGF

A simple dissociation procedure and the collagen gel culture system have been utilized to determine the effects of mammogenic hormones and epidermal growth factor (EGF) on the proliferation of normal rat mammary epithelial (RME) cells in serum‐free culture. Epithelial fragments, isolated from normal virgin F344 rat mammary glands by enzyme digestion followed by Percoll density gradient centrifugation, were embedded within a rat tail collagen matrix. A three‐to four‐fold increase in cell number was observed when ovine prolactin (PRL) and progesterone (P) were present in the basal medium during 7 days of culture. Mouse EGF stimulated one cell doubling during the same culture period.
Long‐term hip simulator testing of the artificial hip joint bearing surface grafted with biocompatible phospholipid polymer

To prevent periprosthetic osteolysis and subsequent aseptic loosening of artificial hip joints, we recently developed a novel acetabular highly cross‐linked polyethylene (CLPE) liner with graft polymerization of 2‐methacryloyloxyethyl phosphorylcholine (MPC) on its surface. We investigated the wear resistance of the poly(MPC) (PMPC)‐grafted CLPE liner during 20 million cycles in a hip joint simulator. We extended the simulator test of one liner to 70 million cycles to investigate the long‐term durability of the grafting. Gravimetric, surface, and wear particle analyses revealed that PMPC grafting onto the CLPE liner surface markedly decreased the production of wear particles and showed that the effect of PMPC grafting was maintained through 70 million cycles. We believe that PMPC grafting can significantly improve the wear resistance of artificial hip joints. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:369–376, 2014.
Ubiquitination of Neuronal Nitric-oxide Synthase in Vitro and in Vivo *

It is established that suicide inactivation of neuronal nitric-oxide synthase (nNOS) with guanidine compounds, or inhibition of the hsp90-based chaperone system with geldanamycin, leads to the enhanced proteolytic degradation of nNOS. This regulated proteolysis is mediated, in part, by the proteasome. We show here with the use of human embryonic kidney 293 cells transfected with nNOS that inhibition of the proteasome with lactacystin leads to the accumulation of immunodetectable higher molecular mass forms of nNOS. Some of these higher molecular mass forms were immunoprecipitated by an anti-ubiquitin antibody, indicating that they are nNOS-polyubiquitin conjugates. Moreover, the predominant nNOS-ubiquitin conjugate detected in human embryonic kidney 293 cells, as well as in rat brain cytosol, migrates on SDS-polyacrylamide gels with a mobility near that for the native monomer of nNOS and likely represents a conjugate containing a few or perhaps one ubiquitin. Studies in vitro with the use of 125I-ubiquitin and reticulocyte extracts could mimic this ubiquitination reaction, which was dependent on ATP. The heme-deficient monomeric form of nNOS is preferentially ubiquitinated over that of the heme-sufficient functionally active homodimer. Thus, we have shown for the first time that ubiquitination of nNOS occurs and is likely involved in the regulated proteolytic removal of non-functional enzyme.
Chronic periaortitis: a spectrum of diseases

Purpose of reviewChronic periaortitis includes idiopathic retroperitoneal fibrosis, perianeurysmal retroperitoneal fibrosis, and inflammatory abdominal aortic aneurysms. This review analyses the different aspects of the disease and highlights evolving concepts concerning its pathogenesis, diagnosis, and management. Recent findingsIt has recently been reported that asbestos exposure is a major risk factor for idiopathic retroperitoneal fibrosis. An increasing number of studies showing an association with autoimmune diseases clearly support the hypothesis of a close link between autoimmunity and chronic periaortitis. Furthermore, various findings (eg, constitutional symptoms, the involvement of other organs, high acute-phase reactant levels) support the hypothesis that chronic periaortitis may be a manifestation of a systemic disease and challenge the well-known theory of a local immune response to antigens in atherosclerotic plaque. In addition to CT and MRI, which are the diagnostic modalities of choice, positron emission tomography may be useful in monitoring disease activity and response to therapy. Although there is a lack of prospective randomized trials, recent studies have highlighted the role of steroids, immunosuppressive agents, and tamoxifen in the medical treatment of chronic periaortitis. SummaryChronic periaortitis is a rare disease with protean manifestations but, if correctly diagnosed, can be successfully managed. It should be approached in the setting of a systemic process, and clinicians must be aware that other organs may be affected. Its clinical course is chronic-relapsing, so a careful follow-up is essential. Further studies are needed to investigate the pathogenetic mechanisms and the most appropriate therapeutic options.
An analytical commutation law for parasitic forces and torques compensation in coreless linear motors

For ideal coreless linear motors, simple classical commutation using three-phase sinusoidal currents is sufficient to achieve low propulsion force ripple and zero parasitic force and torque in non-driving directions. However, in nonideal coreless linear motors, there are various parasitic forces and torques for which the classical commutation cannot compensate. This paper proposes an analytical commutation law which can eliminate the parasitic forces and torques. Simulation results with a finite element method model are presented to demonstrate the effectiveness of the proposed commutation law.