gebhart/patrepeval huggingface dataset:
Inositol and IP3 Levels Regulate Autophagy—Biology and Therapeutic Speculations (2005)

We recently showed that lithium induces autophagy via inositol monophosphatase (IMPase) inhibition, leading to free inositol depletion and reduced myo-inositol-1,4, 5-triphosphate (IP3) levels. This represents a novel way of regulating mammalian autophagy, independent of the mammalian target of rapamycin (mTOR). Induction of autophagy by lithium led to enhanced clearance of autophagy substrates, like mutant huntingtin fragments and mutant alpha-synucleins, associated with Huntington's disease (HD) and some autosomal dominant forms of Parkinson's disease (PD), respectively. Similar effects were observed with a specific IMPase inhibitor and mood-stabilizing drugs that decrease inositol levels. This may represent a new therapeutic strategy for upregulating autophagy in the treatment of neurodegenerative disorders, where the mutant protein is an autophagy substrate. In this Addendum, we review these findings, and some of the speculative possibilities they raise.
Nephrocystin interacts with Pyk2, p130 Cas , and tensin and triggers phosphorylation of Pyk2 (2001)

Juvenile nephronophthisis type 1 is caused by mutations of NPHP1, the gene encoding for nephrocystin. The function of nephrocystin is presently unknown, but the presence of a Src homology 3 domain and its recently described interaction with p130(Cas) suggest that nephrocystin is part of the focal adhesion signaling complex. We generated a nephrocystin-specific antiserum and analyzed the interaction of native nephrocystin with endogenous proteins. Immunoprecipitation of nephrocystin revealed that nephrocystin forms protein complexes with p130(Cas), proline-rich tyrosine kinase 2 (Pyk2), and tensin, indicating that these proteins participate in a common signaling pathway. Expression of nephrocystin resulted in phosphorylation of Pyk2 on tyrosine 402 as well as activation of downstream mitogen-activated protein kinases, such as ERK1 and ERK2. Our findings suggest that nephrocystin helps to recruit Pyk2 to cell matrix adhesions, thereby initiating phosphorylation of Pyk2 and Pyk2-dependent signaling. A lack of functional nephrocystin may compromise Pyk2 signaling in a subset of renal epithelial cells.
Upregulation of Connexin43 Gap Junctions During Early Stages of Human Coronary Atherosclerosis (1995)

Interactions between cells form the framework for understanding the pathogenesis of atherosclerosis, but little information is available on the role of direct intercellular communication via gap junctions in this process. To investigate gap junction expression in the pathogenesis of human atherosclerosis, lesions representing different stages of the disease were obtained from coronary arteries of hearts removed from patients undergoing cardiac transplantation. Twelve hearts, each providing 1 to 3 segments of artery, were used in the study. Sections were examined by confocal laser scanning microscopy after immunofluorescent labeling with a specific antibody against connexin43, the major gap-junctional protein of smooth muscle cells, to permit high-definition visualization of immunolabeled gap junctions through the depth of the specimen. Double labeling using anti-connexin43 and cell type-specific antibodies demonstrated colocalization of gap junctions with smooth muscle cells but not with macrophages, a relationship confirmed by electron microscopy. Regions of intimal thickening and early atheromatous lesions showed markedly increased expression of connexin43 gap junctions between intimal smooth muscle cells compared with the undiseased vessels. This increase in gap junctions was most marked in regions of intimal thickening, semiquantitative analysis of the confocal digital images revealing a > 10-fold increase compared with the undiseased vessel. The quantity of labeled gap junctions in early atheromatous lesions, although higher than that of the undiseased vessel, was lower than that of intimal thickenings, and this trend toward reduced levels of gap junction immunolabeling with lesion progression continued, the value observed in the most advanced atheromatous lesions being lower than that of the undiseased vessel. As the quantity of gap junctions declined, their distribution became more patchy and the sizes of individual junctions larger. The results suggest that enhanced expression of gap junctions between smooth muscle cells may play a role in maintaining the synthetic phenotype during early growth of the atherosclerotic plaque.
A protocol for embryonic stem cell derivation by somatic cell nuclear transfer into human oocytes (2014)

Here we describe detailed methods that allowed us to derive embryonic stem cell lines by nuclear transfer of broblasts from a newborn and from a type 1 diabetic adult. The protocol is based on the insight that 1) agents for cell fusion can act as potent mediators of oocyte activation by compromising maintaining plasma membrane integrity; minimizing the concentration at which they are used, and at least transiently remove calcium from the medium can improve developmental potential. 2) and on the insight that an e cient stimulus for oocyte activation is required; 3) and that histone deacetylase inhibitors facilitate reprogramming after nuclear transfer. A realistic expectation is that this protocol will result in about 10% of the oocytes developing to the blastocyst stage, most of which will be suitable for stem cell derivation.
Hedgehog: an Attribute to Tumor Regrowth after Chemoradiotherapy and a Target to Improve Radiation Response (2006)

These results suggest that activation of the Hh pathway may promote tumor repopulation after chemoradiotherapy and contribute to chemoradiation resistance in esophageal cancers.
Forming Neural Networks Through Efficient and Adaptive Coevolution (1997)

This article demonstrates the advantages of a cooperative, coevolutionary search in difficult control problems. The symbiotic adaptive neuroevolution (SANE) system coevolves a population of neurons that cooperate to form a functioning neural network. In this process, neurons assume different but overlapping roles, resulting in a robust encoding of control behavior. SANE is shown to be more efficient and more adaptive and to maintain higher levels of diversity than the more common network-based population approaches. Further empirical studies illustrate the emergent neuron specializations and the different roles the neurons assume in the population.
Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity (2019)

Mild traumatic brain injury (mTBI) disproportionately affects military service members and is very difficult to diagnose. To-date, there is currently no blood-based, diagnostic biomarker for mTBI cases with persistent post concussive symptoms. To examine the potential of neuronally-derived (NDE) and astrocytic-derived (ADE) exosome cargo proteins as biomarkers of chronic mTBI in younger adults, we examined plasma exosomes from a prospective longitudinal study of combat-related risk and resilience, marine resiliency study II (MRSII). After return from a combat-deployment participants were interviewed to assess TBI exposure while on deployment. Plasma exosomes from military service members with mTBI (mean age, 21.7 years, <i>n</i> = 19, avg. days since injury 151), and age-matched, controls (deployed service members who did not endorse a deployment-related TBI or a pre-deployment history of TBI; mean age, 21.95 years, <i>n</i> = 20) were precipitated and enriched against a neuronal adhesion protein, L1-CAM, and an astrocyte marker, glutamine aspartate transporter (GLAST) using magnetic beads to immunocapture the proteins and subsequently selected by fluorescent activated cell sorting (FACS). Extracted protein cargo from NDE and ADE preparations were quantified for protein levels implicated in TBI neuropathology by standard ELISAs and on the ultra-sensitive single molecule assay (Simoa) platform. Plasma NDE and ADE levels of Aβ42 were significantly higher while plasma NDE and ADE levels of the postsynaptic protein, neurogranin (NRGN) were significantly lower in participants endorsing mTBI exposure compared to controls with no TBI history. Plasma NDE and ADE levels of Aβ40, total tau, and neurofilament light (NFL), P-T181-tau, P-S396-tau were either undetectable or not significantly different between the two groups. In an effort to understand the pathogenetic potential of NDE and ADE cargo proteins, neuron-like cultures were treated with NDE and ADE preparations from TBI and non-TBI groups. Lastly, we determined that plasma NDE but not ADE cargo proteins from mTBI samples were found to be toxic to neuron-like recipient cells <i>in vitro</i>. These data support the presence of markers of neurodegeneration in NDEs of mTBI and suggest that these NDEs can be used as tools to identify pathogenic mechanisms of TBI.
Comparative Surface Studies of Ototoxic Effects of Various Aminoglycoside Antibiotics on the Organ of Corti in the Guinea Pig A Scanning Electron Microscopic Study (1977)

It was the purpose of this study to establish criteria for use in comparing the toxic effects of aminoglycosid antibiotics on the organ of Corti by means of scanning electron microscopy. Amikacin, Tobramycin and Gentamicin were administered twice a day subcutaneously for 10 days to healthy guinea pigs. One group of animals was sacrificed 1 day after completion of the treatment; the other group was allowed to survive 22 days. Depending upon the dosage of the administered drug, Amikacin (150 mg per kg body weight daily, corresponding to 10 times an average recommended human dose) caused pronounced outer hair cell damage even 1 day after the treatment was stopped. At this time Gentamicin and Tobramycin (150 mg per kg body weight daily, corresponding to 50 times an average human dose) showed less damage. After 22 days' survival, late toxic effects were found mainly in Gentamicin- and Tobramycin-treated animals. After 3 weeks, nearly total outer hair cell loss was found in the basal coil, while the 2nd and 3rd coils were often less severely damaged. At this time Amikacin-treated animals showed severe damage in all coils. 300 mg per kg body weight Amikacin (i.e. 20 times the average human dose) showed about the same toxic effect on sensory cells of the guinea pig as did 150 mg Gentamicin or Tobramycin per kg body weight. We are conscious of the fact that there are problems in correlating the weight of a drug and its probable toxic effect. In comparative animal experiments we consider it useful to standardize the time of exposure, the amount of drug administered (e.g. related to the human dose) and the survival time.
Regulation of obesity and insulin resistance by nitric oxide (2014)

Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a worldwide pandemic with few tangible and safe treatment options. Although it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many "distal" causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity-those that directly regulate energy metabolism or caloric intake-seem to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin-resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease.
Thy-1 Antigen Expression by Cells in the Osteoblast Lineage (1999)

Identification of surface markers involved in osteoblast differentiation provides a method to isolate osteoblasts at various stages of maturation. In this study, we examined expression of the T lymphocyte differentiation antigen, Thy-1, by osteoblastic cells from different species. Murine skeletal progenitor, neonatal calvarial, and adult bone cells (ABCs) were selected to represent osteoblasts at distinct stages of maturation. Flow cytometric analysis showed that Thy-1 expression was undetectable on the progenitor cells (mouse limb bud clones 14 and 17), appeared on calvarial cells (45%+), and was decreased on ABCs (< 10%+). Thy-1 was also detected in situ on osteoblastic cells in mouse calvariae. Thy-1 mRNA expression correlated with cell surface expression. Antigen expression was markedly increased during the cells' proliferative phase in culture. Furthermore, examination of primary rat and human osteoblast-like cells revealed that significant levels of Thy-1 were also expressed on those cells derived from subconfluent culture. This study indicates that osteoblasts express Thy-1 antigen and that its expression is maximal at their earliest stage of maturation, during the proliferative phase, and then declines as the cells mature. In a role similar to the one it plays in the hematopoietic system, Thy-1 antigen may be useful as a differentiation marker in following the development of the osteoblast.
A Comprehensive Study of Physical Parameters, Biomechanical Properties, and Statistical Correlations of Iliac Crest Bone Wedges Used in Spinal Fusion Surgery (1994)

Iliac crest bone wedges are commonly used in spinal fusion procedures and must be capable of withstanding considerable mechanical stress during the healing process. The variability of "quality" of bone materials used in the production of bone wedges suggests that some bone materials may not be suitable for use in vertebral fusion procedures and some quantifiable means of predicting the suitability of bone wedges would be desirable. A total of 250 iliac crest wedges were used in this study. Physical parameters of iliac crest wedges, such as total cross-sectional area, cancellous cross-sectional area, cortical cross-sectional area, percentage of cortical cross-sectional area, "width," and apparent density were determined. The statistical correlations among physical parameters were investigated. These correlations revealed that the relative percentage of cortical and cancellous bone remained fairly constant at 41% and 59%, respectively, regardless of total cross-sectional area of a wedge, that apparent density did not appreciably change with donor age, and that ash (inorganic) and organic content (weight) correlated well with the apparent density.
Upper Gastrointestinal Tract Bleeding in Critically Ill Pediatric Patients (1999)

Similar to adults, children under physiologic stress can develop an imbalance in defensive (mucosal layer, motility) and aggressive (gastric acid, bile salts, enzymes) factors responsible for maintaining a healthy gastrointestinal tract. Hypoxia in the gastrointestinal tract likely disrupts the defensive factors, thereby permitting damage by aggressive factors to upper gastrointestinal epithelium that may progress to stress ulceration and acute upper gastrointestinal tract bleeding (UGIB). The basic pathophysiology may be similar in children and adults; however, differences in the time to developing ulceration, ulcer location, and number of ulcers have been reported. Functional development of the gastrointestinal tract is influenced by disease, gestational and postnatal age, and exposure to and type of enteral feedings, thereby confounding the development and prophylaxis of UGIB in neonates and infants. In addition, pharmacotherapy decisions are often complicated by drug administration issues and adverse effects.
The unique properties of dipeptidyl-peptidase IV (DPP IV / CD26) and the therapeutic potential of DPP IV inhibitors. (1999)

This review deals with the properties and functions of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5). This membrane anchored ecto-protease has been identified as the leukocyte antigen CD26. The following aspects of DPP IV/CD26 will be discussed : the structure of DPP IV and the new family of serine proteases to which it belongs, the substrate specificity, the distribution in the human body, specific DPP IV inhibitors and the role of CD26 in the intestinal and renal handling of proline containing peptides, in cell adhesion, in peptide metabolism, in the immune system and in HIV infection. Especially the latest developments in the search for new inhibitors will be reported as well as the discovery of new natural substrates for DPP IV such as the glucagon-like peptides and the chemokines. Finally the therapeutical perspectives for DPP IV inhibitors will be discussed.
Spray Adjuvant, Formulation, and Environmental Effects on Synergism from Post-Applied Tank Mixtures of SAN 582H with Fluazifop-P, Imazethapyr, and Sethoxydim (1998)

The effect of adding a spray adjuvant to SAN 582H tank mixtures with fluazifop-P, imazethapyr, and sethoxydim was evaluated. SAN 582H synergistically increased broadleaf signalgrass control with reduced rates of all three postemergence (POST) herbicides when no spray adjuvant was used and when crop oil concentrate was added. For example, broadleaf signalgrass control increased from 50% to 83% when SAN 582H was tank-mixed with 52 g ai/ha sethoxydim and crop oil concentrate. In another experiment, several formulations of SAN 582H, including blank solvent-only formulations (no SAN 582H), were evaluated in combination with a reduced rate of sethoxydim to determine the source of synergism from tank mixtures. The SAN 582H molecule, not the carrier solvents in formulated product, was determined to be the source of synergism. The synergistic properties of SAN 582H were compared to other chloroacetamides. Synergism from acetochlor was similar to SAN 582H when applied POST with a reduced rate of either fluazifop-P, imazethapyr, or sethoxydim for grass control. Metolachlor also synergistically increased the control of grasses with the POST herbicides; however, metolachlor caused considerable phytotoxicity when applied alone and synergistic interactions were detected less frequently. The efficacy of sethoxydim mixed with SAN 582H was evaluated under different soil moisture conditions. Broadleaf signalgrass control increased from 81% to 93% under dry, moisture-stressed conditions when 210 g/ha sethoxydim was tank- mixed with SAN 582H.
Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice (2012)

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected.
FADD/MORT1 Is a Common Mediator of CD95 (Fas/APO-1) and Tumor Necrosis Factor Receptor-induced Apoptosis (1996)

CD95 (Fas/APO-1) and tumor necrosis factor receptor-1 (TNFR-1) are related molecules that signal apoptosis. Recently, a number of novel binding proteins have been proposed to mediate the signaling of these death receptors. Here we report that an N-terminal truncation of one of these candidate signal transducers, FADD/MORT1, abrogates CD95-induced apoptosis, ceramide generation, and activation of the cell death protease Yama/CPP32. In addition, this dominant-negative derivative of FADD (FADD-DN) blocked TNF-induced apoptosis while not affecting NF- kappaB activation. FADD-DN bound both receptors, and in the case of CD95, it disrupted the assembly of a signaling complex. Taken together, our results functionally establish FADD as the apoptotic trigger of CD95 and TNFR-1.
Immune regulatory mechanisms in allergic conjunctivitis: insights from mouse models (2008)

Allergic conjunctivitis involves early phase and late phase reactions. The early phase reaction is IgE antibody-dependent, whereas the late phase reaction is IgE-independent and is mediated by inflammatory cells, especially eosinophils. Recent studies on mouse models of allergic conjunctivitis have provided important insights into the immune regulation of both the early phase reaction and late phase reaction of allergic conjunctivitis. Mounting evidence suggests that IFN-gamma is crucial for optimum expression of allergic conjunctivitis. Costimulatory molecules influence the induction of Th2 immune responses and the early phase reaction, whereas regulatory T cells shape the expression of the late phase reaction of allergic conjunctivitis.
Commissioning a small‐field biological irradiator using point, 2D, and 3D dosimetry techniques (2011)

The combination of independent 2D and 3D measurements was found to be valuable to ensure accurate and comprehensive commissioning. Film measurements were time consuming and challenging due to the difficulty of film alignment in small fields. PRESAGE® 3D measurements were comprehensive and efficient, because alignment errors are negligible, and all parameters for multiple fields could be obtained from a single dosimeter and scan. However, achieving accurate superficial data (within 4 mm) is not yet feasible due to optical surface artifacts.
Adult stem cell plasticity (2004)

This chapter reviews several reports on adult stem cell plasticity. It addresses the strengths and concerns of each report. The chapter addresses the different possibilities and explanations for stem cell plasticity, which apply to multipotent adult progenitor cell and the field in general. Human and mouse embryonic stem (ES) cells are the quintessential pluri-potent stem cells and fulfil all of these criteria. Both mouse and human ES cells are capable of 300-400 cell doublings in culture while maintaining a stable karyotype and phenotype. Adult stem cells also fulfil these criteria. However, the degree of self-renewal and differentiation potential is far more restricted when compared with embryonic stem cells. Pluripotent stem cells are exemplified by embryonic stem cells. Embryonic stem cells have been characterized based on cell surface markers including stage specific embryonic antigens, expression of the transcription factors Oct4 and Rex1.