gebhart/patrepeval huggingface dataset:
Nitric oxide-based protein modification: formation and site-specificity of protein S-nitrosylation (2013)

Nitric oxide (NO) is a reactive free radical with pleiotropic functions that participates in diverse biological processes in plants, such as germination, root development, stomatal closing, abiotic stress, and defense responses. It acts mainly through redox-based modification of cysteine residue(s) of target proteins, called protein S-nitrosylation.In this way NO regulates numerous cellular functions and signaling events in plants. Identification of S-nitrosylated substrates and their exact target cysteine residue(s) is very important to reveal the molecular mechanisms and regulatory roles of S-nitrosylation. In addition to the necessity of protein-protein interaction for trans-nitrosylation and denitrosylation reactions, the cellular redox environment and cysteine thiol micro-environment have been proposed important factors for the specificity of protein S-nitrosylation. Several methods have recently been developed for the proteomic identification of target proteins. However, the specificity of NO-based cysteine modification is still less defined. In this review, we discuss formation and specificity of S-nitrosylation. Special focus will be on potential S-nitrosylation motifs, site-specific proteomic analyses, computational predictions using different algorithms, and on structural analysis of cysteine S-nitrosylation.
VLSI Implementation of a Multi-Mode Turbo/LDPC Decoder Architecture (2012)

Flexible and reconfigurable architectures have gained wide popularity in the communications field. In particular, reconfigurable architectures for the physical layer are an attractive solution not only to switch among different coding modes but also to achieve interoperability. This work concentrates on the design of a reconfigurable architecture for both turbo and LDPC codes decoding. The novel contributions of this paper are: i) tackling the reconfiguration issue introducing a formal and systematic treatment that, to the best of our knowledge, was not previously addressed and ii) proposing a reconfigurable NoC-based turbo/LDPC decoder architecture and showing that wide flexibility can be achieved with a small complexity overhead. Obtained results show that dynamic switching between most of considered communication standards is possible without pausing the decoding activity. Moreover, post-layout results show that tailoring the proposed architecture to the WiMAX standard leads to an area occupation of 2.75 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and a power consumption of 101.5 mW in the worst case.
Rational chemical design of the carbohydrate in a glycoconjugate vaccine enhances IgM-to-IgG switching (2008)

Many pathogens are sheltered from host immunity by surface polysaccharides that would be ideal as vaccines except that they are too similar to host antigens to be immunogenic. The production of functional IgG is a desirable response to vaccines; because IgG is the only isotype that crosses the placenta, it is of particular importance in maternal vaccines against neonatal disease due to group B Streptococcus (GBS). Clinical studies found a substantially lower proportion of IgG-relative to IgM-among antibodies elicited by conjugates prepared with purified GBS type V capsular polysaccharide (CPS) than among those evoked by CPSs of other GBS serotypes. The epitope specificity of IgG elicited in humans by a conjugate prepared with type V CPS is for chemically desialylated type V CPS (dV CPS). We studied desialylation as a mechanism for enhancing the ability of type V CPS to induce IgM-to-IgG switching. Desialylation did not affect the structural conformation of type V CPS. Rhesus macaques, whose isotype responses to GBS conjugates match those of humans, produced functionally active IgG in response to a dV CPS-tetanus toxoid conjugate (dV-TT), and 98% of neonatal mice born to dams vaccinated with dV-TT survived lethal challenge with viable GBS. Targeted chemical engineering of a carbohydrate to create a molecule less like host self may be a rational approach for improving other glycoconjugates.
Perfect Eyes (1999)

Abstract It is extremely difficult to remove artifacts common to eye tissue such as folds, shrinking raisin effect, and parched earth effect. By adjusting our fixation and processing procedures, we attempted to reduce or eliminate these artifacts. We tested the fixatives from various vendors to determine which of them is most compatible with eye tissue and which would eliminate artifacts. We found Pen-Fix (alcoholic formalin; Richard Allen, Richland, Ml) produced optimal fixation (well defined nuclear detail, without bubbling artifact). In similar testing, we found Peel-a-way (Shandon-Lipshaw, Pittsburgh, PA) to be the optimal paraffin for processing and embedding ocular tissues.
PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules (2004)

Kir5.1, a nonfunctional inwardly rectifying K(+) channel by itself, can form functional channels by assembling with other proteins. We previously showed that Kir5.1 assembled with Kir4.1 and functioned as an acid-base regulator in the kidney. In this study, we examined the intrarenal distribution of Kir5.1 by RT-PCR analysis on dissected nephron segments and immunohistochemical analysis with the specific anti-Kir5.1 antibody. Strong expression of Kir5.1 was detected in distal convoluted tubules, and weak expression was also detected in thick ascending limb of Henle's loop. Colocalization of Kir5.1 with Kir4.1 indicated expression of Kir5.1/Kir4.1 heteromer in these nephron segments. In a renal epithelial cell line, Madin-Darby canine kidney cells, heteromer formation with Kir4.1 changed the localization of Kir5.1 from intracellular components to the cell surface. The COOH-terminal cytoplasmic portion that includes the PDZ binding motif of Kir4.1 was responsible for this intracellular localization. These data suggest the signals on the COOH terminus of Kir4.1, including PDZ binding motif, determine the intracellular localization of Kir5.1/Kir4.1 heteromer in distal tubules.
A Sporozoite Asparagine-Rich Protein Controls Initiation of Plasmodium Liver Stage Development (2008)

Plasmodium sporozoites invade host hepatocytes and develop as liver stages (LS) before the onset of erythrocytic infection and malaria symptoms. LS are clinically silent, and constitute ideal targets for causal prophylactic drugs and vaccines. The molecular and cellular mechanisms underlying LS development remain poorly characterized. Here we describe a conserved Plasmodium asparagine-rich protein that is specifically expressed in sporozoites and liver stages. Gene disruption in Plasmodium berghei results in complete loss of sporozoite infectivity to rodents, due to early developmental arrest after invasion of hepatocytes. Mutant sporozoites productively invade host cells by forming a parasitophorous vacuole (PV), but subsequent remodelling of the membrane of the PV (PVM) is impaired as a consequence of dramatic down-regulation of genes encoding PVM-resident proteins. These early arrested mutants confer only limited protective immunity in immunized animals. Our results demonstrate the role of an asparagine-rich protein as a key regulator of Plasmodium sporozoite gene expression and LS development, and suggest a requirement of partial LS maturation to induce optimal protective immune responses against malaria pre-erythrocytic stages. These findings have important implications for the development of genetically attenuated parasites as a vaccine approach.
Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells (2004)

Bortezomib (PS-341), a selective inhibitor of proteasomes, induces apoptosis in multiple myeloma (MM) cells; however, prolonged drug exposure may result in cumulative toxicity and the development of chemoresistance. Here we show that combining PK-11195 (PK), an antagonist to mitochondrial peripheral benzodiazepine receptors (PBRs), with bortezomib triggers synergistic anti-MM activity even in doxorubicin-, melphalan-, thalidomide-, dexamethasone-, and bortezomib-resistant MM cells. No significant cytotoxicity was noted in normal lymphocytes. Low-dose combined PK and bortezomib treatment overcomes the growth, survival, and drug resistance conferred by interleukin-6 or insulin growth factor within the MM bone marrow milieu. The mechanism of PK + bortezomib-induced apoptosis includes: loss of mitochondrial membrane potential; superoxide generation; release of mitochondrial proteins cytochrome-c (cyto-c) and Smac; and activation of caspases-8/-9/-3. Furthermore, PK + bortezomib activates c-Jun NH2 terminal kinase (JNK), which translocates to mitochondria, thereby facilitating release of cyto-c and Smac from mitochondria to cytosol. Blocking JNK, by either dominant-negative mutant (DN-JNK) or cotreatment with a specific JNK inhibitor SP600125, abrogates both PK + bortezomib-induced release of cyto-c/Smac and induction of apoptosis. Together, these preclinical studies suggest that combining bortezomib with PK may enhance its clinical efficacy, reduce attendant toxicity, and overcome conventional and bortezomib resistance in patients with relapsed refractory MM.
Pseudomonas aeruginosa secretes and correctly processes human growth hormone (1984)

Pseudomonas aeruginosa transformed with a plasmid containing a gene encoding the mature form of human growth hormone (hGH) preceded by an ATG codon to initiate translation expresses methionyl-hGH its cytoplasm. hGH produced in P. aeruginosa cells transformed with a plasmid containing a gene for the natural hGH precursor is transported across the inner membrane and has the NH2-terminal amino acid sequence of authentic mature hGH.
Standardized Peptidome Profiling of Human Urine by Magnetic Bead Separation and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (2007)

This reliable pretreatment protocol allows standardization of preanalytical modalities and facilitates reproducible peptidome profiling of human urine by means of MB separation in combination with MALDI-TOF MS.
Structure/function relationships in hexokinase. Site-directed mutational analyses and characterization of overexpressed fragments implicate different functions for the N- and C-terminal halves of the enzyme. (1993)

Hexokinases are comprised of two highly homologous approximately 50-kDa halves and are product-inhibited by glucose-6-P. Four amino acid residues, Ser603, Asp657, Glu708, and Glu742, located in the C-terminal half of the tumor mitochondrial enzyme have been shown to be essential for enzyme function (Arora, K. K., Filburn, C. R., and Pedersen, P. L. (1991) J. Biol. Chem. 266, 5359-5362). Here we have assessed also the role of the N-terminal half of the same enzyme. Site-directed mutagenesis of residues predicted to interact with glucose in the N-terminal half, i.e. Ser155, Asp209, and Glu260, to Ala, have no effect on hexokinase activity. In addition, inhibition by hexose mono- and bisphosphates is unchanged for each of the mutant enzymes. Significantly, the overexpressed N-terminal polypeptide is devoid of catalytic activity but does have the capacity to bind ATP-agarose and be released with ATP and glucose-6-P. In contrast, the overexpressed C-terminal polypeptide is catalytically active and shows the same product inhibition pattern as the complete 100-kDa parent enzyme. These results emphasize that the N-terminal half of tumor hexokinase is essential neither for catalysis nor product modulation. Rather, the N-terminal half may play another role, perhaps in modulation of the ATP/glucose-6-P-dependent binding of the enzyme to tumor mitochondria or by acting as a spacer between the outer mitochondrial membrane and the C-terminal catalytic unit.
The B7/CD28 costimulatory family in autoimmunity (2005)

Host defense is dependent on the appropriate induction of immune responses. A central concept in immunology is the ability of the immune system to differentiate foreign from self-antigens. The failure of the immune response to recognize foreign pathogens can result in infection and disease in the host. The inappropriate response of the immune system to self-antigens is equally problematic, leading to autoimmune disease. Central and peripheral tolerance mechanisms control self-reactive T-cell responses and protect peripheral tissues from autoimmune attack. This review examines the roles of B7/CD28 family members, which can augment or antagonize T-cell receptor signaling, in the regulation of central and peripheral T-cell tolerance. We also discuss how B7/CD28 pathways influence both T-cell-intrinsic and -extrinsic mechanisms of regulation.
Diabetes Bars and Beverages: The Benefits and the Controversies (2002)

The couple in the advertisement, a pair of retirees, is enjoying a vigorous outing on the beach. They walk briskly through the surf as waves roll in over their feet. We find out that the couple faces having diabetes. However, they use a special food product the ad tells us is “designed for people with diabetes.” The product helps them control their blood glucose and maintain optimal health. The scene is hopeful and reassuring that, with the help of this product, it is possible to have good diabetes control, look good, and feel great and to do so without an overwhelming amount of effort.

This ad was no doubt produced to capture the attention of the burgeoning market of individuals with diabetes—16 million adults in the United States.1 Through visual suggestion, the ad offers an important message about positive lifestyle choices, such as doing moderate physical activity, eating right, maintaining a healthy weight, managing stress, and enjoying life. However, at the end of the scene, a significant oversight becomes obvious. When the waves wash back, we see the couple, otherwise seemingly doing things right, walking along barefooted , thereby leaving themselves vulnerable to potentially undesirable consequences.

The food item advertised is one of a growing number of products known as “functional” or “medical” foods that are formulated to address the nutrition concerns of people with diabetes or abnormal glucose tolerance. These products, in the form of beverages and snack bars, are developed to meet society’s demand for convenience, portability, and good taste. At the same time, they are promoted as healthy foods that help people with diabetes manage their disease by improving glycemic control and lowering risk factors for long-term complications, especially cardiovascular disease.

This article offers information about currently available diabetes bars and beverages, the research that has …
Stress in silicon dioxide films deposited using chemical vapor deposition techniques and the effect of annealing on these stresses (1990)

Using an in situ stress measurement technique that measures stress as a function of annealing temperature, instabilities in mechanical stress induced by heat treatment in a variety of doped/undoped SiO2 films deposited by atmospheric-pressure chemical vapor deposition (APCVD), low-pressure chemical vapor deposition (LPCVD), and plasma-enhanced chemical vapor deposition (PECVD) techniques have been investigated. A large hysteresis in mechanical stress, caused by first heat treatment to which the as-deposited films are subjected, has been observed in films deposited by APCVD/LPCVD techniques. No such hysteresis is observed in films deposited by PECVD technique. Hysteresis in APCVD/LPCVD films is found to vanish once the films are heat treated at or above 800 °C. Stress behavior of heat treated (≥800 °C) films is found to resemble that of thermally grown SiO2 films and can be described by simple elastic theory. During the first annealing cycle, APCVD/LPCVD films have been found to develop stress levels as large as an order of magnitude higher than their as-deposited stress value. Maximum stress developed in the film during heat treatment and the temperature TR at which maximum stress occurs have been found to be dependent on phosphorous content in the film. For heat treatment below this temperature TR, the stress on cooling becomes significantly larger than the as-deposited stress. The results are discussed in terms of oxide densification, the presence of hydrogenous species, and phosphorous.
Strategies for the Development of Vaccines for Typhoid Fever, Shigellosis, and Cholera (1989)

Enteric fevers and diarrheal diseases are major causes of morbidity and mortality throughout the developing world. 1 Traditional approaches to the development of vaccines for bacterial diseases include the parenteral injection of purified components or killed organisms. 2 These methods require technologically advanced preparation and are relatively expensive despite their proven benefits. Live oral vaccine strains have several advantages over parenteral vaccines: low cost, ease of administration, and simple preparation. The development of live vaccines has been limited by lack of understanding of the pathogenesis of disease on a molecular level. Candidate live vaccine strains require nonrevertable genetic alterations that affect the virulence of the organism, but not its induction of an immune response. Work defining the mechanisms of toxigenesis of Vibrio cholerae has made it possible to create live vaccine strains based on deletion of the toxin genes. 3,4 We will discuss below recent studies that have begun to define the molecular basis of Salmonella typhimurium macrophage survival and virulence. This may lead to the development of a live oral Salmonella typhi vaccine that can be used as a carrier for heterologous antigens. This approach has the advantage that immunity to multiple diseases could be generated with a single vaccine strain. Attenuated Salmonella typhi would deliver heterologous antigens directly to the immune effector cell, the macrophage, and generate cell‐mediated as well as humoral immune response. 5
Co‐ordinated expression of multiple enzymes in different subcellular compartments in plants (1998)

A gene expression system designed for coordinated expression of multiple genes in plants and their targeting to specified subcellular locations was tested. A series of genes encoding polyproteins containing the tobacco vein mottling virus (TVMV) Nla proteinase along with two other reporter genes (those encoding the Escherichia coli acetate kinase (ACK) and Tn9 chloramphenicol, acetyl transferase (CAT) enzymes) were assembled. The respective coding sequences of these genes were separated by a TVMV Nla proteinase recognition sequence. In addition, in some instances, chloroplast targeting information (a transit peptide (TP) from a pea rbcS gene) was incorporated into the polyprotein. We found that the Nla proteinase can be used to express, as individual polypeptides, the ACK and CAT proteins, and that these proteins retain enzymatic activity. Polyproteins with the structure TP-Nla-ACK-CAT or TP-ACK-CAT-Nla failed to yield chloroplast-localized ACK and CAT proteins, although the latter did give rise to a chloroplast-localized ACK-CAT polyprotein. These results indicate that the Nla proteinase acts in cis more rapidly than transport of proteins into the chloroplast, but that chloroplast localization can take place before complete processing of the polyprotein. Polyproteins with the structures ACK-Nla-TP-CAT and TP-ACK-Nla-TP-CAT yielded appropriately processed and targeted ACK and CAT. Our results show that subcellular localization signals can be effectively recognized in the context of a polyprotein, and they suggest an appropriate strategy for simultaneous engineering of multiple subcellular compartments in plants.
Treatment of nonalcoholic fatty liver disease: role of AMPK (2016)

Nonalcoholic fatty liver disease (NAFLD) is a growing worldwide epidemic and an important risk factor for the development of insulin resistance, type 2 diabetes, nonalcoholic steatohepatitis (NASH), and hepatic cellular carcinoma (HCC). Despite the prevalence of NAFLD, lifestyle interventions involving exercise and weight loss are the only accepted treatments for this disease. Over the last decade, numerous experimental compounds have been shown to improve NAFLD in preclinical animal models, and many of these therapeutics have been shown to increase the activity of the cellular energy sensor AMP-activated protein kinase (AMPK). Because AMPK activity is reduced by inflammation, obesity, and diabetes, increasing AMPK activity has been viewed as a viable therapeutic strategy to improve NAFLD. In this review, we propose three primary mechanisms by which AMPK activation may improve NAFLD. In addition, we examine the mechanisms by which AMPK is activated. Finally, we identify 27 studies that have used AMPK activators to reduce NAFLD. Future considerations for studies examining the relationship between AMPK and NAFLD are highlighted.
Contraction‐mediated pinocytosis of RGD‐peptide by dermal fibroblasts: Inhibition of matrix attachment blocks contraction and disrupts microfilament organisation (2002)

Force generation in collagen and matrix contraction are basic functions of fibroblasts and important elements of tissue repair. Cell-matrix attachment is critical to this contraction, involving RGD-binding integrins. We have investigated how this process operates, in terms of force generation (in the Culture Force Monitor) and cytoskeletal structure, using a synthetic RGD-decapeptide. The RGD-peptide blocked force generation over the first 6 h, followed by near complete recovery by 20 h. However, dose response was complex indicating multiple processes were operating. Analysis of cytoskeletal structure after treatment with RGD-peptide indicated major disruption with condensed aggregates of actin and microtubular fragmentation. Fluorescent labeling and tracking of the RGD-peptide demonstrated intracellular uptake into discrete cytoplasmic aggregates. Critically, these RGD-peptide pools co-localised with the condensed actin microfilament aggregates. It is concluded that RGD-peptide uptake was by a form of contraction-mediated pinocytosis, resulting from mechanical tension applied to the untethered RGD-peptide-integrin, as contractile microfilament were assembled. These findings emphasize the importance of sound mechanical attachment of ligand-occupied integrins (e.g., to extracellular matrix) for normal cytoskeletal function. Conversely, this aspect of unrestrained cytoskeletal contraction may have important pathogenic and therapeutic applications.
Assessment of a Vesicular Stomatitis Virus–Based Vaccine by Use of the Mouse Model of Ebola Virus Hemorrhagic Fever (2007)

Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.