gebhart/patrepeval huggingface dataset:
Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization (1999)

Our findings demonstrate that expression of VEGF and its receptor KDR may play a role in the formation of experimentally induced choroidal neovascularization. In this study, VEGF and its receptor were co-localized, suggesting that an autocrine and/or paracrine mechanism may be operative.
Neuregulin-3 (NRG3): A novel neural tissue-enriched protein that binds and activates ErbB4 (1997)

We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4.
Pot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans (2001)

Telomere proteins from ciliated protozoa bind to the single-stranded G-rich DNA extensions at the ends of macronuclear chromosomes. We have now identified homologous proteins in fission yeast and in humans. These Pot1 (protection of telomeres) proteins each bind the G-rich strand of their own telomeric repeat sequence, consistent with a direct role in protecting chromosome ends. Deletion of the fission yeast pot1+ gene has an immediate effect on chromosome stability, causing rapid loss of telomeric DNA and chromosome circularization. It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom.
Complementary and Alternative Veterinary Medicine: Principles and Practice (1998)

Unit I: Fundamentals. Fundamentals of Complementary and Alternative Veterinary Medicine. Evidence-Based Medicine: Critical Evaluation of New and Existing Therapies. Unit II: Nutrition. Basic and Preventive Nutrition for the Dog, Cat, And Horse. Therapeutic Nutrition for the Dog, Cat, And Horse. Pet Food Additives. Glandular Therapy, Cell Therapy, And Oral Tolerance. Nutritional Approaches to Cancer Therapy. Orthomolecular Medicine: A Practitioner's Perspective. Unit III: Physical Medicine. Traditional Chinese Medical Theory. Small Animal Acupuncture: Scientific Basis and Clinical Applications. Equine Acupuncture. Chiropractic Care. Physical Therapy. Massage Therapy. TEAM Approach. Unit IV: Energetic Medicine. Introduction to Bioenergetic Medicine. Low-Level Photon Therapy. Magnetic Field Therapy. Unit V: Botanical Medicine. Western Herbal Medicine: Materia Medica. Western Herbal Medicine: Clinical Applications. Chinese Herbal Medicine: Pharmacologic Basis. Chinese Herbal Veterinary Medicine in China. Chinese Herbal Medicine in Small Animal Practice. Ayurvedic Veterinary Medicine. Unit VI: Homeopathy. Homeopathic Medicine: Principles and Research. Veterinary Homeopathy: Principles and Practice. Homeopathy in Food Animal Practice. Homeopathy in Equine Practice. Unit VII: Miscellaneous Therapies. Environmental Medicine. Aromatherapy. Bach Flower Therapy: A Practitioner's Perspective. Unit VIII: Integration Into Veterinary Practice. Integration Into Small Animal Practice. Holistic Approach to Equine Practice. Integration Into Equine Practice. Integration Into Exotic Species Practice. Integration Into Surgical Practice. Unit IX: Complementary and Alternative Perspectives. Veterinary Bioethics. The Human-Companion Animal Bond. Small Animal Euthanasia: Behavioural Perspective. Vaccine-Related Issues. Ethnoveterinary Medicine. Legal Perspective of Holistic Veterinary Practice. Appendices.
Identification and Characterization of a Novel MAP Kinase Kinase Kinase, MLTK (2001)

The MAPK cascades regulate a wide variety of cellular functions, including cell proliferation, differentiation, and stress responses. Here we have identified a novel MAP kinase kinase kinase (MAPKKK), termed MLTK (for MLK-like mitogen-activated protein triple kinase), whose expression is increased by activation of the ERK/MAPK pathway. There are two alternatively spliced forms of MLTK, MLTKalpha and MLTKbeta. When overexpressed in cells, both MLTKalpha and MLTKbeta are able to activate the ERK, JNK/SAPK, p38, and ERK5 pathways. Moreover, both MLTKalpha and MLTKbeta are activated in response to osmotic shock with hyperosmolar media through autophosphorylation. Remarkably, expression of MLTKalpha, but not MLTKbeta, in Swiss 3T3 cells results in the disruption of actin stress fibers and dramatic morphological changes. A kinase-dead form of MLTKalpha does not cause these phenomena. Inhibition of the p38 pathway significantly blocks MLTKalpha-induced stress fiber disruption and morphological changes. These results suggest that MLTK is a stress-activated MAPKKK that may be involved in the regulation of actin organization.
Changes in intraocular pressure and pupil size following intramuscular administration of hydromorphone hydrochloride and acepromazine in clinically normal dogs (2003)

Abstract Objective To investigate the effects of intramuscularly administered hydromorphone hydrochloride and acepromazine on intraocular pressure (IOP) and pupil size (PS). Animals studied Seventeen dogs free of clinically relevant ocular abnormalities. Procedure Measurements of IOP and PS were obtained and the dogs were injected intramuscularly with hydromorphone (0.04–0.08 mg/kg) and acepromazine (0.04 mg/kg). Measurements of IOP and PS were repeated 10 min and 25 min later. Results Though a decreasing trend in IOP values was demonstrated, no significant difference was noted in IOP from the initial examination to examination following intramuscular administration of hydromorphone and acepromazine. Significant miosis was present in 16 of 17 dogs at 10 min and 25 min following administration of hydromorphone and acepromazine. Conclusion Hydromorphone (0.04–0.08 mg/kg) and acepromazine (0.04 mg/kg) cause significant miosis in dogs at 10 and 25 min following intramuscular administration.
Refractive Index Tuning of Hybrid Materials for Highly Transmissive Luminescent Lanthanide Particle–Polymer Composites (2018)

High-refractive-index ZrO<sub>2</sub> nanoparticles were used to tailor the refractive index of a polymer matrix to match that of luminescent lanthanide-ion-doped (La<sub>0.92</sub>Yb<sub>0.075</sub>Er<sub>0.005</sub>F<sub>3</sub>) light-emitting particles, thereby reducing scattering losses to yield highly transparent emissive composites. Photopolymerization of blends of an amine-modified poly(ether acrylate) oligomer and tailored quantities of ZrO<sub>2</sub> nanoparticles yielded optically transparent composites with tailored refractive indices between 1.49 and 1.69. By matching the refractive index of the matrix to that of La<sub>0.92</sub>Yb<sub>0.075</sub>Er<sub>0.005</sub>F<sub>3</sub>, composites with high transmittance (>85%) and low haze from the visible to infrared regions, bright 1530 nm optical emissions were achieved at solids loadings of La<sub>0.92</sub>Yb<sub>0.075</sub>Er<sub>0.005</sub>F<sub>3</sub>, ranging from 5 to 30 vol %. These optical results suggest that a hybrid matrix approach is a versatile strategy for the fabrication of functional luminescent optical composites of high transparency.
Immunotherapy of Acute Myeloid Leukemia (2001)

Most patients with acute myeloid leukemia (AML) respond initially to combination chemotherapy but later relapse. These patients often die from progressive disease or toxicities of further chemotherapy. At relapse, the patients' blasts are usually resistant to the drugs to which the patient has been exposed and frequently to other cytotoxic agents as well. Nevertheless, a number of these patients may be salvaged and achieve remissions with allogeneic stem cell transplants. In such cases, the pre-transplant conditioning regimens do not appear to account for the entire anti-leukemic efficacy. Immunological mechanisms for blast killing appear critical. There is tissue culture, animal and clinical evidence that stimulated donor T cells can recognize and kill leukemic blasts through recognition of alloantigens, differentiation antigens or leukemia-specific antigens as targets. We will review the molecular mechanisms for the generation of anti-leukemic T cells and discuss methods to improve the specificity and intensity of anti-leukemic T cell responses in the setting of allogeneic stem cell transplants, donor lymphocyte infusions, autologous anti-leukemic T cell infusions, and vaccine use in AML patients.
Mucosal and Systemic T Helper Cell Function after Intragastric Colonization of Adult Mice with Candida albicans (1993)

In 85% of adult DBA/2 mice inoculated intragastrically with Candida albicans, significant numbers of yeast cells were recovered from the gastrointestinal tract for up to 4 weeks, with the animals eventually clearing infection in the absence of systemic disease despite the occurrence of localized, self-limiting foci of mucosal involvement in their stomachs. Two major findings in colonized mice were defective production of IgA, interleukin (IL)-4, and IL-5 by Peyer's patches lymphocytes and increased numbers of interferon-gamma-producing T cells in mesenteric lymph nodes and spleens. Relatively low levels of circulating antibodies of T helper type 2 (Th2)-dependent isotypes were also found in colonized mice, which exhibited strong footpad responses and increased resistance to systemic reinfection. Unlike systemic challenge, gastrointestinal colonization of adult immunocompetent DBA/2 mice with C. albicans appears to be an effective stimulus for the systemic development of protective Th1 responses.
Dramatically stabilized phosphotriesterase—polymers for nerve agent degradation (1997)

Phosphotriesterase (EC 3.1.8.1) was immobilized within a polyurethane foam matrix during polymer synthesis using a prepolymer synthesis strategy. In addition to retaining greater than 50% of the enzyme specific activity, numerous benefits were incurred upon immobilization. Orders of magnitude increases in storage and thermal stability (net stabilization energy = 12.5 kJ/mol) were observed without the need for enzyme premodification. The immobilized enzyme system was protease resistant and seemed to display no adverse effects from immobilization, such as an alteration of enzyme function. The organic solvent, dimethyl sulfoxide, also exhibited a stabilizing effect on phosphotriesterase enzyme systems over a range of intermediate concentrations. We attribute these effects in part to direct interaction between the aprotic solvent and metal containing residues present at the enzyme's active site. Our data demonstrate that just 2.5 kg of immobilized enzyme may be sufficient to degrade 30,000 tons of nerve agent in just 1 year.
Posttesticular Antifertility Action of Triptolide in the Male Rat: Evidence for Severe Impairment of Cauda Epididymal Sperm Ultrastructure (2000)

A variety of active diterpene epoxides, including the triptolide (isolated from Tripterygium wilfordii) have been reported to cause infertility in male rats. Previously, we showed that oral administration of triptolide at a dosage of 100 microg/kg per body weight for 70 days completely inhibited fertility in male rats, with little or no demonstrable detrimental effect on spermatogenesis and Leydig cell function as determined by testicular light microscopic appearance and serum and intratesticular testosterone levels. Despite the apparent absence of effects on the testes, cauda epididymal sperm were abnormal, with complete cessation of sperm motility and some reduction in sperm numbers. This study was undertaken to provide additional insight into the subcellular sites and possible mechanisms of action of this compound using ultrastructural analysis of the testes and epididymidis. The most striking effect of triptolide treatment was observed in sperm in the epididymis. In rats rendered infertile with 100 microg/kg per body weight of triptolide daily for 70 days, virtually all cauda epididymal sperm exhibited complete absence of plasma membrane over the entire middle and principal piece, premature decondensation of the nuclei, and disorganization of the mitochondrial sheath with many vacuolated mitochondria. No ultrastructural differences in the epididymal epithelium were observed between control and triptolide-treated rats. The testes appeared to be mildly affected after triptolide treatment but exhibited only subtle ultrastructural defects in the germ cells. The findings of severe impairment of cauda epididymal sperm ultrastructure, along with minimal discernible abnormalities in the fine structural cytology of the testes, further suggest that the site of action of this compound is posttesticular and may be confined to the cauda epididymal sperm. However, we cannot rule out an effect of triptolide that occurs during germ cell maturation but is delayed in its manifestation or triggered at the rete testis and epididymal level.
Subcellular localization of H2O2 in plants. H2O2 accumulation in papillae and hypersensitive response during the barley—powdery mildew interaction (1997)

Active oxygen species (AOS) are believed to have important roles in plants in general and in plant—pathogen interactions in particular. They are believed to be involved in signal transduction, cell wall reinforcement, hypersensitive response (HR) and phytoalexin production, and to have direct antimicrobial effects. Since current methods are inadequate for localizing AOS in intact plant tissue, most studies have been conducted using cell suspension culture/elicitors systems. 3,3‐diaminobenzidine (DAB) polymerizes instantly and locally as soon as it comes into contact with H 2 O 2 in the presence of peroxidase, and it was found that, by allowing the leaf to take up this substrate, in‐vivo and in‐situ detection of H 2 O 2 can be made at subcellular levels. This method was successfully used to detect H 2 O 2 in developing papillae and surrounding haloes (cell wall appositions) and whole cells of barley leaves interacting with the powdery mildew fungus. Thus, H 2 O 2 can be detected in the epidermal cell wall subjacent to the primary germ tube from 6 h after inoculation, and subjacent to the appressorium from 15 h. The earliest time point for observation of H 2 O 2 in relation to epidermal cells undergoing HR is 15 h after inoculation, first appearing in the zones of attachment to the mesophyll cells underneath, and eventually in the entire epidermal cell. Furthermore, it was observed that proteins in papillae and HR cells are cross‐linked, a process believed to be fuelled by H 2 O 2 . This cross‐linking reinforces the apposition, presumably assisting the arrest of the pathogen.
Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning (2005)

Protein synthesis has long been known to be required for associative learning to consolidate into long-term memory. Here we demonstrate that PKC isozyme activation on days before training can induce the synthesis of proteins necessary and sufficient for subsequent long-term memory consolidation. Bryostatin (Bryo), a macrolide lactone with efficacy in subnanomolar concentrations and a potential therapeutic for Alzheimer's disease, is a potent activator of PKC, some of whose isozymes undergo prolonged activation after associative learning. Under normal conditions, two training events with paired visual and vestibular stimuli cause short-term memory of the mollusc Hermissenda that lasts approximately 7 min. However, after 4-h exposures to Bryo (0.25 ng/ml) on two preceding days, the same two training events produced long-term conditioning that lasted >1 week and that was not blocked by anisomycin (1 mug/ml). Anisomycin, however, eliminated long-term memory lasting at least 1 week after nine training events. Both the nine training events alone and two Bryo exposures plus two training event regimens caused comparably increased levels of the PKC alpha-isozyme substrate calexcitin in identified type B neurons and enhanced PKC activity in the membrane fractions. Furthermore, Bryo increased overall protein synthesis in cultured mammalian neurons by up to 60% for >3 days. The specific PKC antagonist Ro-32-0432 blocked much of this Bryo-induced protein synthesis as well as the Bryo-induced enhancement of the behavioral conditioning. Thus, Bryo-induced PKC activation produces those proteins necessary and sufficient for long-term memory on days in advance of the training events themselves.
Composition of Colostrum from Dairy Heifers Exposed to High Air Temperatures During Late Pregnancy and the Early Postpartum Period (1997)

This study examined the effects of heat stress on composition of colostrum from primiparous cows during late pregnancy and the early postpartum period. Two groups of 6 Holstein heifers were utilized. During the last 3 wk of pregnancy and during the first 36 h after calving, one group was exposed to thermal comfort (temperature-humidity index = 65); the other group was exposed to high air temperatures (temperature-humidity index = 82 from 0900 to 2000 h and temperature-humidity index = 76 from 2100 to 0800 h). Heifers under heat stress had higher rectal temperatures and respiratory rates; lower plasma triiodothyronine and glucose; higher plasma nonesterified fatty acids and beta-hydroxybutyrate; lower intakes of dry matter, net energy for lactation, and crude protein; higher water intakes; and lower body condition scores. The decline of plasma immunoglobulins (Ig) over the final 2 wk of pregnancy was less pronounced for heifers under heat stress. For the first four milkings, colostrum of cows exposed to high air temperatures had lower mean concentrations of IgG and IgA; lower mean percentages of total protein, casein, lactalbumin, fat, and lactose; lower contents (grams per liter) of short- and medium-chain fatty acids; lower energy; lower titratable acidity; and higher pH. Thus, high air temperatures during late pregnancy and the early postpartum period markedly affected the composition of colostrum from primiparous dairy cows.
Molecular networks regulating Arabidopsis seed maturation, after‐ripening, dormancy and germination (2008)

The transition between dormancy and germination represents a critical stage in the life cycle of higher plants and is an important ecological and commercial trait. In this review we present current knowledge of the molecular control of this trait in Arabidopsis thaliana, focussing on important components functioning during the developmental phases of seed maturation, after-ripening and imbibition. Establishment of dormancy during seed maturation is regulated by networks of transcription factors with overlapping and discrete functions. Following desiccation, after-ripening determines germination potential and, surprisingly, recent observations suggest that transcriptional and post-transcriptional processes occur in the dry seed. The single-cell endosperm layer that surrounds the embryo plays a crucial role in the maintenance of dormancy, and transcriptomics approaches are beginning to uncover endosperm-specific genes and processes. Molecular genetic approaches have provided many new components of hormone signalling pathways, but also indicate the importance of hormone-independent pathways and of natural variation in key regulatory loci. The influence of environmental signals (particularly light) following after-ripening, and the effect of moist chilling (stratification) are increasingly being understood at the molecular level. Combined postgenomics, physiology and molecular genetics approaches are beginning to provide an unparalleled understanding of the molecular processes underlying dormancy and germination.
Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations (2000)

Two young males with limb-girdle muscular dystrophy (LGMD) resulting from sarcoglycan deficiency died at 27 (patient 1) and 18 years (patient 2) of severe cardiomyopathy. Genetic analysis showed that they were compound heterozygotes for mutations in the beta sarcoglycan gene. One of these mutations, an 8 bp duplication in exon 3, was common to both patients. The second mutation in patient 2 was a 4 bp deletion at the splice donor site of intron 2, not reported previously. Patient 2 had more severe heart and skeletal muscle defects with faster deterioration; no sarcoglycans were detected in his skeletal muscle. The second mutation in patient 1, inferred because the unaffected father carries the 8 bp duplication, was not found. In patient 1, both heart and skeletal muscle were analysed and showed reduction of all sarcoglycans in both tissues and incorrect localisation of alpha and gamma sarcoglycans in heart. Therefore mutations in one sarcoglycan gene can disrupt the entire sarcoglycan complex in both skeletal and cardiac muscle. Differing expression patterns of sarcoglycan components in heart and skeletal muscle could be the result of alternatively spliced transcripts in these tissues. By sequencing an alternative transcript, highly expressed in the heart and skeletal muscle of patient 1, we found an 87 bp cryptic exon not previously reported. Although cardiomyopathy can result from mutations in alpha and gamma sarcoglycans, we show for the first time that the condition can also be caused by mutations in the beta sarcoglycan gene. This report therefore expands the phenotype of sarcoglycanopathies and suggests that cardiac function in LGMD patients with defective sarcoglycan expression should be monitored.
Nasal Delivery of High Molecular Weight Drugs (2009)

Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW) of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nano- and micro-particulate carrier systems will be summarised.