Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of nerve growth factor by murine smooth muscle cells: Role of the p75 neurotrophin receptor on sympathetic and sensory sprouting

Elevating levels of nerve growth factor (NGF) can have pronounced effects on the survival and maintenance of distinct populations of neurons. We have generated a line of transgenic mice in which NGF is expressed under the control of the smooth muscle α‐actin promoter. These transgenic mice have augmented levels of NGF protein in the descending colon and urinary bladder, so these tissues display increased densities of NGF‐sensitive sympathetic efferents and sensory afferents. Here we provide a thorough examination of sympathetic and sensory axonal densities in the descending colon and urinary bladder of NGF transgenic mice with and without the expression of the p75 neurotrophin receptor (p75NTR). In response to elevated NGF levels, sympathetic axons (immunostained for tyrosine hydroxylase) undergo robust collateral sprouting in the descending colon and urinary bladder of adult transgenic mice (i.e., those tissues having smooth muscle cells); this sprouting is not augmented in the absence of p75NTR expression. As for sensory axons (immunostained for calcitonin gene‐related peptide) in the urinary bladders of transgenic mice, fibers undergo sprouting that is further increased in the absence of p75NTR expression. Sympathetic axons are also seen invading the sensory ganglia of transgenic mice; these fibers form perineuronal plexi around a subpopulation of sensory somata. Our results reveal that elevated levels of NGF in target tissues stimulate sympathetic and sensory axonal sprouting and that an absence of p75NTR by sensory afferents (but not by sympathetic efferents) leads to a further increase of terminal arborization in certain NGF‐rich peripheral tissues. J. Comp. Neurol. 521:2621–2643, 2013. © 2013 Wiley Periodicals, Inc.
Pathophysiology and Physiologic Assessment of the Asthmatic Patient

In asthma there is marked variability in pul­ monary function and a propensity to develop bronchoconstriction in response to a variety of external factors, or "triggers. " In such patients, the simple assessment of spirometric function may be diagnostic, particularly if carried out before and after inhaled (or oral) bronchodilators. Assessment of the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) also allows evaluation of the severity of the condition and the degree of reversibility. Serial spirometric assess­ ment is the minimum necessary to determine the progress of the condition and to evaluate the effect of therapeutic intervention. In some patients, it may be necessary to carry out a more detailed assessment of respiratory function, with measure­ ment of the mechanical properties of the lungs, gas exchange, and, if indicated, responsiveness of the airways to nonspecific and specific triggers. Before detailing the alterations in pulmonary physiology that are present in the asthmatic pa­ tient, it is important to review the basis of those tests of lung function that are particularly useful. These include lung volume and the factors that influence it, airflow resistance, airway reactivity, and gas exchange.
Drinking water in an urban area in South India - A community based cross sectional study.

Background Globally, 1.1 billion people lack access to improved drinking water supply and drink water that is grossly contaminated. Hence, study of water treatment assumes utmost importance in order to ensure the safety of the water consumed especially in fast developing cities. This study would provide information of drinking water management practices in the study area. We studied the sources, the treatment and storage facilities of drinking water in households and assessed the free chlorine levels in the drinking water. Method This community based cross sectional study was conducted in Mangalore - a city of Karnataka State in South India. Using convenience sampling, 100 households were visited in the area of Boloor. Information was collected regarding demographic profile, household drinking water sources, treatment and storage practices followed by testing for free chlorine in the drinking water using O-Toluidine. Results Study population had high literacy rate and 83% had their main source of drinking water from municipality, 17% had private water source. Among these 6% households had bore wells, 10% had protected dug well. Overall 99% had improved source of drinking water. Sumps were present in 32% of the households. Of these 34.4 % cleaned it once a month. Boiling was found to be the preferred choice of water treatment; but 5% of the population (lower socio economic status) did not use any method to treat water in their households. Overall, 43% households drank water by pouring to glass from storage vessel, 34% dipped glass into vessel using hands, 23% had tap system and 84.2% of the households cleaned their storage vessel daily. O-Toluidine test showed no free chlorine in drinking water in any of the homes. Conclusion Study population had access to improved water. However households lacked appropriate storage and handling practices of drinking water which needs to be evaluated further.
Intraspinal stretch receptor neurons mediate different motor responses along the body in lamprey

In lampreys, stretch receptor neurons (SRNs) are located at the margins of the spinal cord and activated by longitudinal stretch in that area caused by body bending. The aim of this study was a comprehensive analysis of motor responses to bending of the lamprey body in different planes and at different rostrocaudal levels. For this purpose, in vitro preparation of the spinal cord isolated together with notochord was used, and responses to bending were recorded from SRNs, as well as from motoneurons innervating the dorsal (dMNs) and ventral (vMNs) parts of a myotome. It was found that SRNs were activated on the convex (stretched) side of the preparation during bending both in the yaw and in the pitch plane. By contrast, responses of motoneurons depended on the site and plane of bending. In the yaw plane, concave responses to bending of rostral segments and convex responses to bending of mid‐body segments prevailed. In the pitch plane, convex responses in dMNs and concave responses in vMNs to bending in mid‐body segments prevailed. These spinal reflexes could contribute to feedback regulation of locomotor body undulations and to the control of body configuration during locomotion. After a longitudinal split of the spinal cord, only convex responses in motoneurons were present, suggesting an important role of contralateral networks in determining the type of motor response. Stimulation of the brainstem changed the type of motor response to bending, suggesting that these spinal reflexes can be modified by supraspinal signals in accordance with different motor behaviors. J. Comp. Neurol. 521:3847–3862, 2013. © 2013 Wiley Periodicals, Inc.
Puerarin Attenuates N-Methyl-D-aspartic Acid–induced Apoptosis and Retinal Ganglion Cell Damage Through the JNK/p38 MAPK Pathway

Purpose:To explore the protective effect of puerarin on N-methyl-D-aspartic acid (NMDA)-induced retinal ganglion cells (RGCs) injury and its underlying mechanism. Materials and Methods:Primary RGCs were isolated from P3-P7 Sprague-Dawley rats and purified by sequential immunopanning using Thy1.1 antibodies. NMDA was used to mimic the glutamate activation, cell apoptosis, reactive oxygen species (ROS), malondialdehyde levels, SOD and NO production, nNOS and iNOS expression, as well as caspase-3 activity, Bcl-2, and Bax expression in the RGCs were analyzed by ELISA, RT-PCR, and Western blotting. A rat model of retinal injury was used to detect the protective effect of puerarin. Results:Puerarin protected against NMDA-induced RGCs injury in a dose-dependent manner. Compared with the NMDA-treated group, puerarin pretreatment significantly reduced ROS and malondialdehyde levels, promoted SOD and NO production, and downregulated nNOS and iNOS expression in the RGCs. Mechanism analysis showed that pretreatment with puerarin could effectively offset the increase of Bax expression and caspase-3 activity brought by NMDA, and promote Bcl-2 expression in the RGCs. Puerarin pretreatment also effectively inhibited NMDA-induced JNK and p38 phosphorylation in the RGCs, whereas pretreatment with either JNK agonist anisomycin or p38 agonist P79350 could significantly compensate the effects caused by puerarin. Furthermore, puerarin prevented RGCs loss in the retinal injury induced by intravitreal NMDA in a rat model. Conclusions:The present results of this study demonstrated that puerarin protected against NMDA-induced apoptosis and RGCs damage through the JNK/p38 MAPK pathway.
Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment

Background: Ecto-5′-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to the formation of immunosuppressive tumor microenvironment and is related to exacerbated prognosis, increased risk of metastasis and resistance to immunotherapy of various tumors. However, the prognostic significance of NT5E in pan-cancer is obscure so far. Methods: We explored the expression level of NT5E in cancers and adjacent tissues and revealed the relationship between the NT5E expression level and clinical outcomes in pan-cancer by utilizing the UCSC Xena database. Then, correlation analyses were performed to evaluate the relationship between NT5E expression and immune infiltration level via EPIC, MCP-counter and CIBERSORT methods, and the enrichment analysis were employed to identify NT5E-interacting molecules and functional pathways. Furthermore, we conducted single-cell analysis to explore the potential role of NT5E on single-cell level based on the CancerSEA database. Meanwhile, gene set enrichment analysis (GSEA) in single-cell level was also conducted in TISCH database and single-cell signature explorer was utilized to evaluate the epithelial-mesenchymal transition (EMT) level in each cell type. Results: The expression level of NT5E was aberrant in almost all cancer types, and was correlated with worse prognosis in several cancers. Notably, NT5E overexpression was related to worse overall survival (OS) in pancreatic adenocarcinoma (PAAD), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), stomach adenocarcinoma (STAD), uveal melanoma (UVM) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (p < 0.01). NT5E-related immune microenvironment analysis revealed that NT5E is associated positively with the degree of infiltration of cancer-associated fibroblasts (CAFs) and endothelial cells in most cancers. Enrichment analysis of cellular component (CC) demonstrated the critical part of NT5E played in cell-substrate junction, cell-substrate adherens junction, focal adhesion and external side of plasma membrane. Finally, single-cell analysis of NT5E illuminated that EMT function of CAFs was elevated in basal cell carcinoma (BCC), skin cutaneous melanoma (SKCM), HNSC and PAAD. Conclusion: NT5E could serve as a potential prognostic biomarker for cancers. The potential mechanism may be related to the upregulated EMT function of CAFs, which provides novel inspiration for immunotherapy by targeting CAFs with high NT5E expression.
Tauopathies: A Distinct Class of Neurodegenerative Diseases

Tauopathies: A Distinct Class of Neurodegenerative Diseases Neurodegenerative diseases are characterized by neuronal loss and intraneuronal accumulation of fibrillary materials, of which, neurofibrillary tangles (NFT) are the most common. Neurofibrillary tangles also occur in normal aging and contain the hyperphosphorylated microtubule-associated protein tau. A detailed presentation is made of the molecular bases of Alzheimer's disease (AD), postencephalitic parkinsonism, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease, frontotemporal dementia (FTD), Down's syndrome, myotonic dystrophy (DM) and Niemann-Pick Type C (NPC) disease, which are considered to be common tauopathies. The unique human tau gene extends over 100 kb of the long arm of chromosome 17 and contains 16 exons. The human brain contains six tau isoforms that contain from 352 to 441 amino acids. To date, 34 pathogenic tau mutations have been described among 101 families affected by FTD with parkinsonism linked to chromosome 17 (FTDP-17). These mutations may involve alternative splicing of exon 10 that lead to changes in the proportion of 4-repeat- and 3-repeat-tau isoforms, or may modify tau interactions with microtubules. Tau aggregates differ in degree of phosphorylation and in content of tau isoforms. Five classes of tauopathies have been defined depending on the type of tau aggregates. The key event in tauopathies is the disorganization of the cytoskeleton, which is based on mutations/polymorphisms in the tau gene and lead to nerve cell degeneration. In this review, tauopathies as a distinct class of neurodegenerative diseases are discussed with emphasis on their molecular pathology and genetics.
The orexinergic neurons receive synaptic input from C1 cells in rats

The C1 cells, located in the rostral ventrolateral medulla (RVLM), are activated by pain, hypoxia, hypoglycemia, infection, and hypotension and elicit cardiorespiratory stimulation, adrenaline and adrenocorticotropic hormone (ACTH) release, and arousal. The orexin neurons contribute to the autonomic responses to acute psychological stress. Here, using an anatomical approach, we consider whether the orexin neurons could also be contributing to the autonomic effects elicited by C1 neuron activation. Phenylethanolamine N‐methyl transferase‐immunoreactive (PNMT‐ir) axons were detected among orexin‐ir somata, and close appositions between PNMT‐ir axonal varicosities and orexin‐ir profiles were observed. The existence of synapses between PNMT‐ir boutons labeled with diaminobenzidine and orexinergic neurons labeled with immunogold was confirmed by electron microscopy. We labeled RVLM neurons with a lentiviral vector that expresses the fusion protein ChR2‐mCherry under the control of the catecholaminergic neuron‐selective promoter PRSx8 and obtained light and ultrastructural evidence that these neurons innervate the orexin cells. By using a Cre‐dependent adeno‐associated vector and TH‐Cre rats, we confirmed that the projection from RVLM catecholaminergic neurons to the orexinergic neurons originates predominantly from PNMT‐ir catecholaminergic (i.e., C1 cells). The C1 neurons were found to establish predominantly asymmetric synapses with orexin‐ir cell bodies or dendrites. These synapses were packed with small clear vesicles and also contained dense‐core vesicles. In summary, the orexin neurons are among the hypothalamic neurons contacted and presumably excited by the C1 cells. The C1–orexin neuronal connection is probably one of several suprabulbar pathways through which the C1 neurons activate breathing and the circulation, raise blood glucose, and facilitate arousal from sleep. J. Comp. Neurol. 522:3834–3846, 2014. © 2014 Wiley Periodicals, Inc.
Distributions of vesicular glutamate transporters 1 and 2 in the visual system of tree shrews (Tupaia belangeri)

Vesicular glutamate transporter (VGLUT) proteins regulate the storage and release of glutamate from synapses of excitatory neurons. Two isoforms, VGLUT1 and VGLUT2, are found in most glutamatergic projections across the mammalian visual system, and appear to differentially identify subsets of excitatory projections between visual structures. To expand current knowledge on the distribution of VGLUT isoforms in highly visual mammals, we examined the mRNA and protein expression patterns of VGLUT1 and VGLUT2 in the lateral geniculate nucleus (LGN), superior colliculus, pulvinar complex, and primary visual cortex (V1) in tree shrews (Tupaia belangeri), which are closely related to primates but classified as a separate order (Scandentia). We found that VGLUT1 was distributed in intrinsic and corticothalamic connections, whereas VGLUT2 was predominantly distributed in subcortical and thalamocortical connections. VGLUT1 and VGLUT2 were coexpressed in the LGN and in the pulvinar complex, as well as in restricted layers of V1, suggesting a greater heterogeneity in the range of efferent glutamatergic projections from these structures. These findings provide further evidence that VGLUT1 and VGLUT2 identify distinct populations of excitatory neurons in visual brain structures across mammals. Observed variations in individual projections may highlight the evolution of these connections through the mammalian lineage. J. Comp. Neurol. 523:1792–1808, 2015. © 2015 Wiley Periodicals, Inc.
Efferent innervation of turtle semicircular canal cristae: Comparisons with bird and mouse

In the vestibular periphery of nearly every vertebrate, cholinergic vestibular efferent neurons give rise to numerous presynaptic varicosities that target hair cells and afferent processes in the sensory neuroepithelium. Although pharmacological studies have described the postsynaptic actions of vestibular efferent stimulation in several species, characterization of efferent innervation patterns and the relative distribution of efferent varicosities among hair cells and afferents are also integral to understanding how efferent synapses operate. Vestibular efferent markers, however, have not been well characterized in the turtle, one of the animal models used by our laboratory. Here we sought to identify reliable efferent neuronal markers in the vestibular periphery of turtle, to use these markers to understand how efferent synapses are organized, and to compare efferent neuronal labeling patterns in turtle with two other amniotes using some of the same markers. Efferent fibers and varicosities were visualized in the semicircular canal of red‐eared turtles (Trachemys scripta elegans), zebra finches (Taeniopygia guttata), and mice (Mus musculus) utilizing fluorescent immunohistochemistry with antibodies against choline acetyltransferase (ChAT). Vestibular hair cells and afferents were counterstained using antibodies to myosin VIIa and calretinin. In all species, ChAT labeled a population of small diameter fibers giving rise to numerous spherical varicosities abutting type II hair cells and afferent processes. That these ChAT‐positive varicosities represent presynaptic release sites were demonstrated by colabeling with antibodies against the synaptic vesicle proteins synapsin I, SV2, or syntaxin and the neuropeptide calcitonin gene‐related peptide. Comparisons of efferent innervation patterns among the three species are discussed. J. Comp. Neurol. 523:1258–1280, 2015. © 2015 Wiley Periodicals, Inc.
Evaluation of a Trabecular Microbypass Stent With Cataract Extraction in Severe Primary Open-angle Glaucoma

Purpose: To evaluate the safety and efficacy of a trabecular microbypass stent combined with cataract surgery in patients with severe open-angle glaucoma. Patients: The series included 59 eyes with severe primary open-angle glaucoma and severe visual field loss as defined by American Academy of Ophthalmology preferred practice pattern criteria. Materials and Methods: Retrospective case series. Patients were implanted with 1 trabecular microbypass stent with concomitant cataract surgery. Primary outcome measures were intraocular pressure (IOP) and number of glaucoma medications. Safety measures included postoperative IOP pressure spikes ≥15 mm Hg or IOP<6 mm Hg at any time point, and the need for additional surgery. Results: The mean preoperative IOP was 19.25±6.97 mm Hg. Postoperatively, the mean IOP was 14.38±3.63 mm Hg (P<0.01) at 12 months and 14.92±3.86 mm Hg (P<0.01) at 24 months. The mean number of glaucoma medications was 2.27±1.06 preoperatively and 1.63±1.17 (P<0.01) at 24 months postoperative, indicating a 28% reduction in medication use. In total, 4 (7%) eyes required additional surgery. In total, 5 eyes (8%) experienced IOP spikes ≥15 mm Hg, 14 (24%) eyes had IOP spikes ≥10 mm Hg. Overall 55% of eyes had a 20% IOP reduction after 24 months of surgery. Eyes with baseline IOP⩽19 had a mean reduction of 2.24 mm Hg 36 months after surgery. Conclusions: Trabecular microbypass stent implantation during cataract surgery safely and effectively lowers IOP and medication use in patients with severe primary open-angle glaucoma.
The interplay between the gut microbiota and metabolism during the third trimester of pregnancy

The gut microbiota undergoes dynamic changes during pregnancy. The gut microbial and metabolic networks observed in pregnant women have not been systematically analyzed. The primary purpose of this study was to explore the alterations in the gut microbiota and metabolism during late pregnancy and investigate the associations between the gut microbiota and metabolism. A total of thirty healthy pregnant women were followed from 30 to 32 weeks of gestation to full term. Fecal samples were collected for microbiome analysis and untargeted metabolomic analysis. The characteristics of the gut microbiota were evaluated by 16S ribosomal RNA gene sequencing of the V3-V4 regions. The plasma samples were used for untargeted metabolomic analysis with liquid chromatography–tandem mass spectrometry. The interplay between the gut microbiota and metabolism was analyzed further by bioinformatics approaches. We found that the relative abundances of Sellimonas and Megamonas were higher at full term, whereas that of Proteobacteria was lower. The correlation network of the gut microbiota tended to exhibit weaker connections from 32 weeks of gestation to the antepartum timepoint. Changes in the gut microbiota during late pregnancy were correlated with the absorbance and metabolism of microbiota-associated metabolites, such as fatty acids and free amino acids, thereby generating a unique metabolic system for the growth of the fetus. Decreasing the concentration of specific metabolites in plasma and increasing the levels of palmitic acid and 20-hydroxyarachidonic acid may enhance the transformation of a proinflammatory immune state as pregnancy progresses.
A Plea for Standardization of Biomarker Assays in the Study of High Risk, Premalignant and Malignant Breast Disease

n the past few years, the field of cancer research has I greatly benefited from recent advances in cellular and molecular biology. Currently, newly recognized biomarkers are being examined as prognostic indicators to identify potentially aggressive tumors and to aid in planning appropriate treatment. A variety of tumor characteristics can provide prognostic information in patients with breast cancer. Although some of these characteristics are firmly established, others require large scale, controlled studies before they can be appropriately utilized. At the present time, no single marker is available that will predict which patient with primary breast cancer is destined to relapse, and controversy remains regarding the prognostic value of new markers (1). However, the availability of biological markers has provided us with an opportunity to understand the initial genetic events leading to the development of breast cancer. To control and ultimately to prevent breast cancer, we must identify the cascade of events that transforms a normal breast cell into a malignant cell. This may only be achieved through the precise knowledge of the complex alterations occurring at the cellular and molecular levels. Knowledge about these genetic events may eventually enable us to design prophylactic intervention, to discover additional biomarkers, to improve our ability to predict risk, and to enhance strategies for early detection. The goal of early detection efforts is to identify patients who will develop breast cancer. This task involves complex issues