gebhart/patrepeval huggingface dataset:
Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment (2015)

The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D) via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA), protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO) and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103(+) DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN) of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.
Abstract 346: Integrative genomic analysis of sporadic clear cell renal cell carcinoma (2011)

Abstract Sporadic clear cell Renal Cell Carcinoma (ccRCC) is the most common type of adult kidney cancer. Using high-density copy-number profiling and gene expression profiles, we performed an integrated genomic analysis of 54 sporadic tumor samples. We took a two pronged approach, focusing on 1) all samples and 2) comparing ccRCCs that express both HIF1α and HIF2α (H1H2) and those that express only HIF2α (H2), sub-types of ccRCC that we previously described. For all samples at a frequency over 10%, we identified regions of amplification on 1q, 5q, 7q, 8q, 12p, and 20q, and regions of deletion on 1p, 3p, 6q, 8p, 9p, and 14q, as previously described. We used our integrative analysis to identify target genes that had consistent copy-number and gene expression changes (e.g. amplified and upregulated or deleted and downregulated) within regions on chromosomes 5 and 7. Combining our data with an independent dataset (Beroukhim et al., 2009) and including a literature based analysis, we were able to narrow down to three target genes, which we subsequently validated using a renal cancer cell line. We then compared genomic changes in H1H2 and H2 ccRCCs. Prior data suggested that H2 ccRCCs have increased expression of genes involved in double strand break repair, thus potentially greater genomic stability. Using high-density copy-number data, we have confirmed that H2 tumors have significantly fewer genomic aberrations compared to H1H2 tumors (for amplifications p=0.032 and for deletions p=0.003). In addition, using GISTIC, we found that deletion of chromosome 6 is significantly more common in H1H2 tumors (p&amp;lt;0.001), whereas deletion of chromosome 9 is significantly more common in H2 tumors (p&amp;lt;0.001). Of note, deletion of chromosome 9 previously has been associated with poor prognosis. Thus, correlations between the copy-number data and gene expression profiles indicate that the H1H2 and H2 classes of ccRCC tumors may each have a distinct set of drivers of tumorigenesis; target gene validation for these groups is underway. These experiments provide novel insights into the biology of clear cell Renal Cell Carcinoma (ccRCC). Beroukhim et al. Patterns of Gene Expression and Copy-Number Alternations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney. Can Res 2009; 69: (11):4674-81. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 346. doi:10.1158/1538-7445.AM2011-346
Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides (2017)

Colorectal cancer (CRC) is the third most common solid internal malignancy among cancers. Early detection of cancer is key to increasing the survival rate of colorectal cancer patients. Overexpression of the EGFR protein is associated with CRC. We have designed a series of peptides that are highly specific for the extracellular domain of EGFR, based on our earlier studies on linear peptides. The previously reported linear peptide LARLLT, known to bind to EGFR, was modified with the goals of increasing its stability and its specificity toward EGFR. Peptide modifications, including D-amino acid substitution, cyclization, and chain reversal, were investigated. In addition, to facilitate labeling of the peptide with a fluorescent dye, an additional lysine residue was introduced onto the linear (KLARLLT) and cyclic peptides cyclo(KLARLLT) (Cyclo.L1). The lysine residue was also converted into an azide group in both a linear and reversed cyclic peptide sequences cyclo(K(N3)larllt) (Cyclo.L1.1) to allow for subsequent "click" conjugation. The cyclic peptides showed enhanced binding to EGFR by SPR. NMR and molecular modeling studies suggest that the peptides acquire a β-turn structure in solution. In vitro stability studies in human serum show that the cyclic peptide is more stable than the linear peptide.
Site‐specific integration of DNA into wild‐type and mutant lox sites placed in the plant genome (1995)

The bacteriophage P1 Cre-lox site-specific recombination system has been used to integrate DNA specifically at lox sites previously placed in the tobacco genome. As integrated molecules flanked by wild-type lox sites can readily excise in the presence of Cre recombinase, screening for mutant lox sites that can resist excisional recombination was performed. In gene integration experiments, wild-type and mutant lox sites were used in conjunction with two strategies for abolishing post-integration Cre activity: (i) promoter displacement of a cre-expression construct present in the target genome; and (ii) transient expression of cre. When the promoter displacement strategy was used, integrant plants were recovered after transformation with constructs containing mutant lox sequences, but not with constructs containing wild-type lox sites. When cre was transiently expressed, integrant plants were obtained after transformation with either mutant or wild-type lox sites. DNA rearrangements at the target locus were less frequent when mutant lox sites were used. DNA integration at the genomic lox site was usually without additional insertions in the genome. Thus, the Cre-lox site-specific recombination system is useful for the single-copy integration of DNA into a chromosomal lox site.
Therapeutic Angiogenesis Induced by Human Recombinant Hepatocyte Growth Factor in Rabbit Hind Limb Ischemia Model as Cytokine Supplement Therapy (1999)

Hepatocyte growth factor (HGF) exclusively stimulates the growth of endothelial cells without replication of vascular smooth muscle cells and acts as a survival factor against endothelial cell death. Therefore we hypothesized that a decrease in local vascular HGF might be related to the pathogenesis of peripheral arterial disease. We initially evaluated vascular HGF concentration in the vessels of patients with arteriosclerosis obliterans. Consistent with in vitro findings that hypoxia downregulated vascular HGF production, vascular HGF concentration in the diseased segments of vessels from patients with arteriosclerosis obliterans was significantly decreased as compared with disease-free segments from the same patients (P<0.05), accompanied by a marked reduction in HGF mRNA. On the other hand, a novel therapeutic strategy for ischemic diseases that uses angiogenic growth factors to expedite and/or augment collateral artery development has recently been proposed. Thus in view of the decreased endogenous vascular HGF, rhHGF (500 micrograms/animal) was intra-arterially administered through the internal iliac artery of rabbits in which the femoral artery was excised to induce unilateral hind limb ischemia, to evaluate the angiogenic activity of HGF, which could potentially have a beneficial effect in hypoxia. Administration of rhHGF twice on days 10 and 12 after surgery produced significant augmentation of collateral vessel development on day 30 in the ischemic model as assessed by angiography (P<0.01). Serial angiograms revealed progressive linear extension of collateral arteries from the origin stem artery to the distal point of the reconstituted parent vessel in HGF-treated animals. In addition, we examined the feasibility of intravenous administration of rhHGF in a moderate ischemia model. Importantly, intravenous administration of rhHGF also resulted in a significant increase in angiographic score as compared with vehicle (P<0.01). Overall, a decrease in vascular HGF might be related to the pathogenesis of peripheral arterial disease. In the presence of decreased endogenous HGF, administration of rhHGF induced therapeutic angiogenesis in the rabbit ischemic hind limb model, as potential cytokine supplement therapy for peripheral arterial disease.
Restorative Increases in Serum Testosterone Levels Are Significantly Correlated to Improvements in Sexual Functioning (2004)

It is recognized that testosterone (T) levels decrease in men with age, as does sexual function. We hypothesize that T supplementation in hypogonadal men with sexual dysfunction will restore certain elements of sexual function. Hypogonadal male subjects (total T < or = 300 ng/dL, n = 406, mean age 58 years) reporting one or more symptoms of low testosterone were randomized to T gel (50 mg/d and 100 mg/d), T patch, or placebo. Twenty-four-hour pharmacokinetic profiles for T were obtained. The 3 primary end points evaluated at 30 and 90 days posttreatment included a significant change in the frequency of intercourse and nighttime erections per 7-day week as well as a change in sexual desire measured on a Likert-type scale and calculated as a mean daily score. At day 30, a significant increase from baseline in sexual desire was noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel, T patch, or placebo (1.2 vs 0.4, 0.7, and 0.4, respectively). A significant increase from baseline in the frequency of nighttime erections was also noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel or placebo (51% of subjects in the 100 mg/d T gel group had an increase in frequency vs 30% for the 50 mg/d T gel group and 26% in the placebo group). Finally, a significant increase from baseline in the frequency of intercourse was evidenced for those on 100 mg/d T gel compared with those on T patch or placebo (39% of subjects in the 100 mg/d T gel group had an increase in frequency vs 21% for the T patch group and 24% in the placebo group). Similar results were seen for 100 mg/d T gel at day 90 for sexual desire and nighttime erections vs placebo. These data demonstrate a clear relationship between restoring serum T concentrations and improvement in certain parameters of sexual function. We propose that threshold T levels are needed in order to significantly affect improvements in sexual functioning.
Molecular and culture-dependent analyses revealed similarities in the endophytic bacterial community composition of leaves from three rice (Oryza sativa) varieties (2012)

The endophytic bacterial communities of the three most important rice varieties cultivated in Uruguay were compared by a multiphasic approach. Leaves of mature plants grown in field experiments for two consecutive crop seasons were studied. No significant differences were found in the heterotrophic bacterial density for the three varieties. Pantoea ananatis and Pseudomonas syringae constituted 51% of the total of the isolates. These species were always present regardless of the variety or the season. Molecular analysis based on the 16S rRNA gene was performed by terminal restriction fragment length polymorphism (T-RFLP) and cloning. T-RFLP analysis revealed that bacterial communities grouped according to the variety, although the three varieties presented communities that showed 74% or higher similarities. Brevundimonas, the dominant genus in the clone library (18% of the clones), which might be present in all varieties according to T-RFLP profiles, was not recovered by cultivation. Conversely, bacteria from the genus Pseudomonas were not detected in the clone library. These results indicate that communities established in leaves of physiologically different rice varieties were highly similar and composed by a reduced group of strongly associated and persistent bacteria that were partially recovered by cultivation.
Inhibition, Escape, and Attenuated Growth of Severe Acute Respiratory Syndrome Coronavirus Treated with Antisense Morpholino Oligomers (2005)

The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) is a potent pathogen of humans and is capable of rapid global spread. Peptide-conjugated antisense morpholino oligomers (P-PMO) were designed to bind by base pairing to specific sequences in the SARS-CoV (Tor2 strain) genome. The P-PMO were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral RNA motifs and secondary structures. Several virus-targeted P-PMO and a random-sequence control P-PMO showed low inhibitory activity against SARS coronavirus. Certain other virus-targeted P-PMO reduced virus-induced cytopathology and cell-to-cell spread as a consequence of decreasing viral amplification. Active P-PMO were effective when administered at any time prior to peak viral synthesis and exerted sustained antiviral effects while present in culture medium. P-PMO showed low nonspecific inhibitory activity against translation of nontargeted RNA or growth of the arenavirus lymphocytic choriomeningitis virus. Two P-PMO targeting the viral transcription-regulatory sequence (TRS) region in the 5' untranslated region were the most effective inhibitors tested. After several viral passages in the presence of a TRS-targeted P-PMO, partially drug-resistant SARS-CoV mutants arose which contained three contiguous base point mutations at the binding site of a TRS-targeted P-PMO. Those partially resistant viruses grew more slowly and formed smaller plaques than wild-type SARS-CoV. These results suggest PMO compounds have powerful therapeutic and investigative potential toward coronavirus infection.
A physiological strain index to evaluate heat stress (1998)

A physiological strain index (PSI), based on rectal temperature (Tre) and heart rate (HR), capable of indicating heat strain online and analyzing existing databases, has been developed. The index rates the physiological strain on a universal scale of 0-10. It was assumed that the maximal Tre and HR rise during exposure to exercise heat stress from normothermia to hyperthermia was 3 degrees C (36.5-39.5 degrees C) and 120 beats/min (60-180 beats/min), respectively. Tre and HR were assigned the same weight functions as follows: PSI = 5(Tret - Tre0) . (39.5 - Tre0)-1 + 5(HRt - HR0) . (180 - HR0)-1, where Tret and HRt are simultaneous measurements taken at any time during the exposure and Tre0 and HR0 are the initial measurements. PSI was applied to data obtained from 100 men performing exercise in the heat (40 degrees C, 40% relative humidity; 1.34 m/s at a 2% grade) for 120 min. A separate database representing seven men wearing protective clothing and exercising in hot-dry and hot-wet environmental conditions was applied to test the validity of the present index. PSI differentiated significantly (P < 0.05) between the two climates. This index has the potential to be widely accepted and to serve universally after extending its validity to women and other age groups.
The Human Antibacterial Cathelicidin, hCAP-18, Is Synthesized in Myelocytes and Metamyelocytes and Localized to Specific Granules in Neutrophils (1997)

hCAP-18 is the only human member of the antibacterial and endotoxin-binding family of proteins known as cathelicidins. The antibacterial and endotoxin binding domains reside in the C-terminal 37 amino acids of the protein (LL-37) and this is believed to be unleashed from the neutralizing N-terminus by proteases from peroxidase positive granules. In human neutrophils, peroxidase positive and peroxidase negative granules can be subdivided into granule subsets that differ in protein content and ability to be exocytosed. To determine the localization of hCAP-18, we performed high-resolution immuno-electron microscopy and subcellular fractionation on Percoll density gradients. Biosynthesis of hCAP-18 was investigated in isolated human bone marrow cells. hCAP-18 was found to colocalize and comobilize with lactoferrin, but not with gelatinase in subcellular fractions. This was confirmed by electron microscopy. hCAP-18 is synthesized at the same stage of myeloid cell maturation as lactoferrin, and is efficiently targeted to granules. Like the peroxidase negative granule's matrix metalloproteinases, collagenase and gelatinase, hCAP-18 is also stored in unprocessed form. hCAP-18 is a major protein of specific granules where it is present in equimolar ratio with lactoferrin.
Safety and Immunogenicity of Glycoprotein D--Adjuvant Genital Herpes Vaccine (2005)

The vaccine was generally safe, well tolerated, and immunogenic.
T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road (2020)

T-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their effectiveness. This process can involve introducing a receptor that has high affinity for a tumour antigen, with two promising candidates known as chimeric-antigen receptors (CARs), or T-cell receptors (TCRs) with high tumour specificity. This review focuses on the editing of immune cells to introduce such novel receptors to improve immune responses to cancer. These new receptors redirect T-cells innate killing abilities to the appropriate target on cancer cells. CARs are modified receptors that recognise whole proteins on the surface of cancer cells. They have been shown to be very effective in haematological malignancies but have limited documented efficacy in solid cancers. TCRs recognise internal antigens and therefore enable targeting of a much wider range of antigens. TCRs require major histocompatibility complex (MHC) restriction but novel TCRs may have broader antigen recognition. Moreover, there are multiple cell types which can be used as targets to improve the "off-the-shelf" capabilities of these genetic engineering methods.
Generation of High Titre Antibodies to Pokeweed Antiviral Protein (PAP) in Rabbits Using Synthetic Peptides and their Use in Detecting PAP in Transgenic Petunia and Yeast (2012)

Abstract Antibodies are important for the study of pokeweed antiviral protein (PAP), an important antiviral agent against many plant, animal and human viruses. As PAP is expressed only at a low level in pokeweed plants ( Phytolacca americana L.), it is complex and time‐consuming to extract PAP from pokeweed plants for antibody preparation. Here, we describe an antigen‐designed method according to the amino acid sequence that translated from PAP gene cleaving the C‐terminus toxic region and N‐terminus signal peptide (Genbank No. AF338910 ); the two peptides, DC15: DISGTERQDVETTLC and CR15: CRYPTLESKAGVKSR, were synthesized for generation of antibodies. The design strategy enabled straightforward antigen production and antibody generation. The antibodies can be used to detect PAP in transgenic petunia plants ( Petunia hybrid a Vilm.), pokeweed plants ( P. americana ) and transformed yeast ( Pachia pastoris ), which can express the PAP gene by western blotting. These antibodies generated against synthetic peptides will be useful for various assays such as for PAP detection, immunoprecipitation, protein purification and western blot analysis.
The influence of basal lamina on the accumulation of acetylcholine receptors at synaptic sites in regenerating muscle. (1984)

If skeletal muscles are damaged in ways that spare the basal lamina sheaths of the muscle fibers, new myofibers develop within the sheaths and neuromuscular junctions form at the original synaptic sites on them. At the regenerated neuromuscular junctions, as at the original ones, the muscle fiber plasma membrane is characterized by infoldings and a high concentration of acetylcholine receptors (AChRs). The aim of this study was to determine whether or not the synaptic portion of the myofiber basal lamina sheath plays a direct role in the formation of the subsynaptic apparatus on regenerating myofibers, a question raised by the results of earlier experiments. The junctional region of the frog cutaneous pectoris muscle was crushed or frozen, which resulted in disintegration and phagocytosis of all cells at the synapse but left intact much of the myofiber basal lamina. Reinnervation was prevented. When new myofibers developed within the basal lamina sheaths, patches of AChRs and infoldings formed preferentially at sites where the myofiber membrane was apposed to the synaptic region of the sheaths. Processes from unidentified cells gradually came to lie on the presynaptic side of the basal lamina at a small fraction of the synaptic sites, but there was no discernible correlation between their presence and the effectiveness of synaptic sites in accumulating AChRs. We therefore conclude that molecules stably attached to the myofiber basal lamina at synaptic sites direct the formation of subsynaptic apparatus in regenerating myofibers. An analysis of the distribution of AChR clusters at synaptic sites indicated that they formed as a result of myofiber-basal lamina interactions that occurred at numerous places along the synaptic basal lamina, that their presence was not dependent on the formation of plasma membrane infoldings, and that the concentration of receptors within clusters could be as great as the AChR concentration at normal neuromuscular junctions.
<title>Effect of molecular weight distribution on the dissolution properties of novolac blends</title> (1995)

The dissolution properties of nearly monodisperse fractions of metacresol novolac resin in aqueous potassium hydroxide solutions has been investigated. A relationship between the molecular weight of the fractions and dissolution rate was examined for a range of developer concentrations. Deliberate and calculated blending of the various fractions afforded an opportunity to investigate the fundamental relationship between molecular weight and dissolution characteristics over a range of developer concentrations.