Miracle-dz/UniFAR-FTUs huggingface dataset:
Astrocyte heterogeneity across the brain and spinal cord occurs developmentally, in adulthood and in response to demyelination

Astrocytes have emerged as essential regulators of function and response to injury in the brain and spinal cord, yet very little is known about regional differences that exist. Here we compare the expression of key astroglial markers (glial fibrillary acidic protein (GFAP) and Aldehyde Dehydrogenase-1 Family Member L1 (ALDH1L1)) across these disparate poles of the neuraxis, tracking their expression developmentally and in the context of demyelination. In addition, we document changes in the astrocyte regulatory cytokine interleukin 6 (IL-6), and its signaling partner signal transducer and activator of transcription 3 (STAT3), in vivo and in vitro. Results demonstrate that GFAP expression is higher in the developing and adult spinal cord relative to brain. Comparisons between GFAP and ALDH1L1 expression suggest elevations in spinal cord GFAP during the early postnatal period reflect an accelerated appearance of astrocytes, while elevations in adulthood reflect higher expression by individual astrocytes. Notably, increases in spinal cord compared to whole brain GFAP were paralleled by higher levels of IL-6 and STAT3. Equivalent elevations in GFAP, GFAP/ALDH1L1 ratios, and in IL-6, were observed in primary astrocyte cultures derived from spinal cord compared to cortex. Also, higher levels of GFAP were observed in the spinal cord compared to the brain after focal demyelinating injury. Altogether, these studies point to key differences in astrocyte abundance and the expression of GFAP and IL-6 across the brain and spinal cord that are positioned to influence regional specialization developmentally and responses occurring in the context of injury and disease.
Endothelial nitric oxide synthase deficiency in mice results in reduced chondrocyte proliferation and endochondral bone growth.

OBJECTIVE Nitric oxide (NO) and aberrant chondrocyte differentiation have both been implicated in the pathogenesis of osteoarthritis, but whether these processes are connected is unknown, and the role of specific NO synthase (NOS) enzymes in chondrocyte physiology is unclear. This study was undertaken to examine the effects of inactivation of endothelial cell NOS (eNOS) on cartilage development in mice. METHODS Skeletal growth and development of mice carrying a null mutation in the eNOS gene was compared with that of their control littermates. In situ analyses were complemented by experiments with primary chondrocytes and tibial explants from these mice. RESULTS Mice that were deficient in eNOS showed increased fatality and reduced bone growth, with hypocellular growth plates and a marked reduction in the number of proliferating chondrocytes. In vitro studies demonstrated lower chondrocyte numbers and reduced endochondral bone growth in mutant mice, suggesting that the role of eNOS signaling in chondrocyte proliferation is cell autonomous. Reduced chondrocyte numbers appear to be caused by decreased cyclin D1 and increased p57 expression in mutant mice, resulting in slower cell cycle progression and earlier cell cycle exit. In addition, expression of early chondrocyte markers such as SOX9 was reduced, and prehypertrophic markers were expressed prematurely in mutant mice. CONCLUSION Our findings identify a novel and important role of eNOS in chondrocyte proliferation and endochondral bone growth and demonstrate that loss of eNOS results in premature cell cycle exit and prehypertrophic chondrocyte differentiation during cartilage development.
Intracellular responses and morphology of rat ventral complex of the lateral lemniscus neurons in vivo

The function of the ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL), collectively termed ventral complex of the lateral lemniscus (VCLL), is unclear. Several studies have suggested that it plays a role in coding the temporal aspects of sound. In our study, a sample (n = 161) of intracellular responses to dichotically presented noise or tone bursts was collected from the VCLL of urethane‐anesthetized rats in vivo. Intracellular recordings revealed six distinct response types to tones, distinguished by their synaptic and membrane characteristics as well as firing pattern. Three of these response types were correlated with distinct cellular morphologies revealed by intracellular injection of neurobiotin. 3D reconstructions of recorded neurons within the VCLL showed the spatial distribution of various response properties, including response type, laterality, characteristic frequency (CF), and binaural influences. Cells that responded to monaural (55%) or binaural (45%) stimulation were distributed throughout the VCLL. Almost all VCLL units were responsive to contralateral stimulation (97%). Most neurons were excited by contralateral stimulation (83%), many exclusively (43%), and some in conjunction with ipsilateral inhibition (28%) or excitation (12%). The INLL contained mostly binaural neurons (65%), typically with ipsilateral inhibition and contralateral excitation. These results indicate that the VCLL is not a monaural structure and there is a dorsal‐ventral segregation of binaural and monaural cells. 3D reconstructions of intracellular CFs did not reveal the presence of any tonotopic arrangement within the VCLL. Presumably, the proposed timing role of this structure does not require a systematic representation of tonal frequency. J. Comp. Neurol. 498:295–315, 2006. © 2006 Wiley‐Liss, Inc.
Secure and robust state estimation under sensor attacks, measurement noises, and process disturbances: Observer-based combinatorial approach

This paper presents a secure and robust state estimation scheme for continuous-time linear dynamical systems. The method is secure in that it correctly estimates the states under sensor attacks by exploiting sensing redundancy, and it is robust in that it guarantees a bounded estimation error despite measurement noises and process disturbances. In this method, an individual Luenberger observer (of possibly smaller size) is designed from each sensor. Then, the state estimates from each of the observers are combined through a scheme motivated by error correction techniques, which results in estimation resiliency against sensor attacks under a mild condition on the system observability. Moreover, in the state estimates combining stage, our method reduces the search space of a minimization problem to a finite set, which substantially reduces the required computational effort.
P2Y2 receptor stimulation increases tear fluid secretion in rabbits

Purpose. The purinergic P2Y 2 receptor agonists stimulate active Cl - transport across the excised rabbit conjunctival tissue in vitro. We determined whether UTP or ATP could increase the tear volume and change tear fluid composition in normal rabbits in vivo. Methods. Fifty µL was applied to rabbit eyes of UTP, ATP at concentrations of 0.1, 0.3, 1, 3, 8.5% (1.8–154 mM) or saline. A modified Schirmer test with topical anesthesia was performed 5, 15, 30 and 60 min after the instillation. In studies lasting 30 days, 50 µL of 0.5% UTP was applied 6 times a day for 4 weeks. Tear samples were collected from the conjunctival sac with a glass microcapillary. The protein profile of the tear fluid was analyzed by SDS-polyacrylamide gel electrophoresis and total protein was measured with the Bradford assay. The Easy-Titer rabbit IgG assay kit was used for the determination of immunoglobulin G (IgG). Results. UTP had dose-dependent stimulatory effects on tear secretion. It maximally increased tear secretion about 4-fold 15 min after its application. Similar effects were obtained with ATP. Repeated treatment with UTP reproducibly increased tear volume. Furthermore, UTP did not decrease total protein and IgG concentration in tear fluid and it had no effect on the protein profile. Conclusion. These data indicate that activation of P2Y 2 receptor increases tear fluid secretion accompanied with some proteins in normal rabbits. The purinergic agonists, UTP and ATP, have potential therapeutic value in the treatment of dry eye.
Oral transmission of Candida albicans between partners in HIV‐infected couples could contribute to dissemination of fluconazole‐resistant isolates

Background:Fluconazole resistance has emerged among Candida albicans isolates and has been associated with the prolonged or repeated use of the drug. This study was designed to discover whether transmission of oral isolates could occur between sexual partners and thereby explain fluconazole resistance in patients never treated with the drug. Materials and methods:The oral flora of 10 HIV-infected couples (five heterosexual and five homosexual) were studied. In vitro susceptibility testing and genotyping (restriction fragment length polymorphism with EcoRI and HinfI) were used to delineate strain relatedness for 230 clones (five clones per sample, one to four samples per patient). Results:The genetic diversity of the clones with one DNA subtype was specific to a given patient or a given couple, except in one case in which unrelated patients shared clones of the same genotype. The persistence of clones between partners was stable over time in six out of 10 couples and only transient in one couple. Fluconazole resistance in isolates from patients who had never been treated with azoles was associated in three patients with the first episode of oropharyngeal candidiasis and treatment failure. Conclusion:The observation that couples tended to share genetically indistinguishable clones was highly suggestive of transmission between partners. This phenomenon may, in part, explain the pathogenesis of oropharyngeal candidiasis and the increased frequency of fluconazole resistance both in vitro and in vivo.
The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls

Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine (PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP). Thrombin generation was measured by the calibrated automated thrombogram. The impact of corn trypsin inhibitor (CTI), anti-tissue factor pathway inhibitor (TFPI) antibodies and phospholipids was described. Antibodies against TF were used to assess TF-dependency, and MV-bound PS activity was measured with the Zymuphen MP-activity kit. MVs from the pancreatic cancer patients displayed higher thrombin generation and higher PS-activity than MVs from the healthy control group, while TF-dependency was observed in only 1 out of 13 patient samples. Adequate thrombin generation-curves were only achieved when CTI was omitted and anti-TFPI antibodies were added to PNP prepared in low contact-activating tubes. Addition of phospholipids reduced the significant differences between the two groups, and should be omitted. This modified thrombin generation assay could be useful for measurement of procoagulant circulating MVs, allowing the contribution from MVs affecting both the intrinsic and the extrinsic pathway to be measured.
Fasudil hydrochloride hydrate, a Rho‐kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity in hepatic stellate cells

Abstract: Background/Aims: The Rho–ROCK signaling pathways play an important role in the activation of hepatic stellate cells (HSCs). We investigated the effects of fasudil hydrochloride hydrate (fasudil), a Rho‐kinase (ROCK) inhibitor, on cell growth, collagen production, and collagenase activity in HSCs.
Immunohistochemical profiling based on Bcl‐2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma

Clinical outcome in patients with diffuse large B cell lymphomas (DLBCL) is poorly predictable. Expression of proteins related to germinal centre B (GCB) cell or activated B cells (ABC) and expression of apoptosis‐regulating proteins Bcl‐2 and XIAP have been found previously to be strongly associated with clinical outcome. In this study we aimed to develop an algorithm based on expression of GCB/ABC‐related proteins CD10, Bcl‐6 and MUM1 and apoptosis‐inhibiting proteins Bcl‐2, XIAP and cFLIP for optimal stratification of DLBCL patients into prognostically favourable and unfavourable groups. Expression of CD10 and cFLIP was associated with better overall survival (both p = 0.03), whereas expression of MUM1, Bcl‐2 and XIAP was associated with poor clinical outcome (p = 0.01, p = 0.0007 and p = 0.03, respectively). Multivariate analysis revealed that Bcl‐2 was the strongest prognostic marker followed by CD10 and MUM1. Stratification of patients according to a new algorithm based on expression of these three markers improved patient risk stratification into low and particularly high clinical risk groups (p = 0.04 and p < 0.0001, respectively). We conclude that, in our group of primary nodal DLBCLs, a new algorithm, based on expression of the apoptosis‐inhibiting protein Bcl‐2 and the GCB/ABC‐related proteins CD10 and MUM1, strongly predicts outcome in International Prognostic Index (IPI)‐low and ‐high patients. Its predictive power is stronger than previously published algorithms based on only GCB/ABC‐ or apoptosis‐regulating proteins. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A Clinical Study of the Cutaneous Manifestations of Hypothyroidism in Kashmir Valley

Background: Thyroid disorders are known to involve all the organ systems of the body, the skin being no exception. The association of thyroid disorders with cutaneous manifestations is complex. Both hypothyroidism and hyperthyroidism are known to cause these changes. Aims: The present study was designed to ascertain the varied cutaneous manifestations of hypothyroidism. Materials and Methods: This study was a hospital based clinical study conducted in collaboration with the Endocrinology Division (Department of Medicine) of SMHS Hospital (associated teaching hospital of Government Medical College Srinagar), over a period of one year, from May 2010 to May 2011. Four hundred and sixty consecutive diagnosed cases of hypothyroidism constituted the subject material for the study and were evaluated for the presence of any cutaneous manifestation. Results: In our study group of 460 patients, there were 416 females and 44 male patients. The predominant cutaneous symptom in our hypothyroid patients was dry coarse skin (65.22%), followed by hair loss (42.6%) and puffy edema (38.48%). The most common cutaneous sign observed in hypothyroid patients was xerosis (57.17%), followed by diffuse hair loss (46.09%), altered skin texture (31.74%), coarse scalp hair (29.35%) and puffy face (28.69%). Conclusions: The interaction between thyroid gland and skin is of profound clinical importance in dermatological practice. So, dermatologists need to be cognizant of the ways in which these two organs interact.
Selection of Windows for W-Operator Combination from Entropy Based Ranking

When training morphological operators that are locally defined with respect to a neighborhood window, one must deal with the trade off between window size and statistical precision of the learned operator. More precisely, too small windows result in large restriction errors due to the constrained operator space and, on the other hand, too large windows result in large variance error due to often insufficient number of samples. A two-level training method that combines a number of operators designed on distinct windows of moderate size is an effective way to mitigate this issue. However, in order to train combined operators, one must specify not only how many operators will be combined, but also the windows for each of them. To date, a genetic algorithm that searches for window combinations has produced the best results for this problem. In this work we propose an alternative approach that is computationally much more efficient. The proposed method consists in efficiently reducing the search space by ranking windows of a collection according to an entropy based measure estimated from input-output joint probabilities. Computational efficiency comes from the fact that only few operators need to be trained. Experimental results show that this method produces results that outperform the best results obtained with manually selected combinations and are competitive with results obtained with the genetic algorithm based solution. The proposed approach is, thus, a promising step towards fully automating the process of binary morphological operator design.
A weight‐of‐evidence approach for deriving a level of concern for atrazine that is protective of aquatic plant communities

Atrazine is a selective triazine herbicide widely used in the United States primarily for control of broadleaf weeds in corn and sorghum. In 2003, the US Environmental Protection Agency (USEPA) concluded that atrazine poses potential risks to sensitive aquatic species. Consequently, a surface water monitoring program was developed to assess whether measured levels of atrazine could impact aquatic plants in vulnerable watersheds. To facilitate evaluation of the monitoring data, the Agency needed to establish a level of concern (LOC) below which atrazine would not cause unacceptable adverse effects to aquatic plant communities. Several attempts at developing a community‐level LOC have followed from USEPA but none have been formally accepted or endorsed by independent Scientific Advisory Panels. As part of registration review, the USEPA needs to revisit development of a community‐level LOC for atrazine that will be protective of aquatic plant communities. This article reviews 4 methods that can or have been used for this purpose. Collectively, the methods take advantage of the large number of single species and mesocosm studies that have been conducted for aquatic plants exposed to atrazine. The Plant Assemblage Toxicity Index (PATI) and the Comprehensive Aquatic Systems Model for atrazine (CASMATZ2) incorporate single‐species toxicity data but are calibrated with micro‐ and mesocosm study results to calculate community‐level LOCs. The Brock et al. scoring system relies exclusively on mesocosm studies. Single‐species toxicity data were used in a modified version of the USEPA's Water Quality Criteria (WQC) method. The 60‐day LOCs calculated using the 4 methods ranged from 19.6 to 26 µg/L. A weight‐of‐evidence assessment indicated that the CASMATZ2 method was the most environmentally relevant and statistically reliable method. Using all 4 methods with weights based on method reliability, the weighted 60‐day LOC was 23.6 µg/L. Integr Environ Assess Manag 2017;13:686–701. © 2016 SETAC
PLATELET-ACTIVATING FACTOR AND HYPERACUTE REJECTION

The pathogenesis of hyperacute transplantation reactions includes the activation of a cascade of nonspecific inflammatory reactions that precipitates the destruction of the target organ. Platelet-activating factor (P AF) represents an important component of these inflammatory cascades. and we have examined the influence of a specific PAF receptor antagonist (SRI 63-441) on the inhibition of hyperacute rejection in two experimental models. the rejection of rat cardiac allografts by presensitized recipients and guinea pig-to-rat and mouse-torat cardiac xenografts. Our results demonstrate that inhibition of PAF function by SRI 63-441 has a variable effect on the survival of cardiac allografts in presensitized rat recipients. In the ACI to sensitized BN cardiac allograft model. the use of SRI 63-441 alone. or in combination with CsA. FK506, or prostaglandin Ez (PGEz). does not prolong graft survival. As we have previously reported, SRI 63-441 does act as a single agent to prolong the survival of ACI to sensitized LEW grafts, and this survival effect is synergistic when combined with CsA. Here we extend these results to demonstrate that this survival is also extended when FK506 is used in the ACI-to-LEW model. Concordant mouse-torat cardiac xenografts are also relatively resistant to prolongation of graft survival following treatment with SRI 63-441 alone or in combination with CsA or FK506. Discordant xenografts appear to be more susceptible to inhibition of the rejection reaction with SRI 63-441. When either donor or recipient animals were treated with SRI 63-441 alone, or in combination with CsA or FK506, there was significant prolongation of guinea pig-to-rat cardiac xenograft survival. These results are consistent with our earlier description of the effectiveDe&8 of SRI 83-441 iD preventing the rejection of catto-rabbit kidney xenografts. We believe that these re-
Differential Effect of Intracoronary Infusion of Mobilized Peripheral Blood Stem Cells by Granulocyte Colony–Stimulating Factor on Left Ventricular Function and Remodeling in Patients With Acute Myocardial Infarction Versus Old Myocardial Infarction: The MAGIC Cell-3-DES Randomized, Controlled Trial

Background— The efficacy of intracoronary infusion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) has not been compared between patients with acute (AMI) versus old myocardial infarction (OMI). In addition, the potential risk of restenosis associated with G-CSF–based stem cell therapy has not been evaluated in the setting of drug eluting stent (DES) implantation. Methods and Results— We randomly allocated 96 patients with myocardial infarction who underwent coronary revascularization with DES for the culprit lesion into 4 groups. Eighty-two patients completed 6-month follow-up; AMI cell infusion (n=25), AMI control (n=25), OMI cell infusion (n=16), and OMI control group (n=16). In cell infusion groups, PBSCs were mobilized by G-CSF for 3 days and delivered to infarcted myocardium via intracoronary infusion. The AMI cell infusion group showed a significant additive improvement in left ventricular ejection fraction (LVEF) and remodeling compared with controls (change of LVEF: +5.1±9.1% versus −0.2±8.6%, P<0.05; change of end-systolic volume: −5.4±17.0 mL versus 6.5±21.9 mL, P<0.05). In OMI patients, however, there was no significant change of LVEF and ventricular remodeling in spite of significant improvement of coronary flow reserve after cell infusion. G-CSF–based cell therapy did not aggravate neointimal growth with DES implantation. Conclusions— Intracoronary infusion of mobilized PBSCs with G-CSF improves LVEF and remodeling in patients with AMI but is less definite in patients with OMI. G-CSF–based stem cell therapy with DES implantation is both feasible and safe, eliminating any potential for restenosis.