gebhart/patrepeval huggingface dataset:
Lysine to arginine mutagenesis of chlorotoxin enhances its cellular uptake (2017)

Chlorotoxin (CTX), a disulfide-rich peptide from the scorpion Leiurus quinquestriatus, has several promising biopharmaceutical properties, including preferential affinity for certain cancer cells, high serum stability, and cell penetration. These properties underpin its potential for use as a drug design scaffold, especially for the treatment of cancer; indeed, several analogs of CTX have reached clinical trials. Here, we focus on its ability to internalize into cells-a trait associated with a privileged subclass of peptides called cell-penetrating peptides-and whether it can be improved through conservative substitutions. Mutants of CTX were made using solid-phase peptide synthesis and internalization into human cervical carcinoma (HeLa) cells was monitored by fluorescence and confocal microscopy. CTX_M1 (ie, [K15R/K23R]CTX) and CTX_M2 (ie, [K15R/K23R/Y29W]CTX) mutants showed at least a twofold improvement in uptake compared to CTX. We further showed that these mutants internalize into HeLa cells largely via an energy-dependent mechanism. Importantly, the mutants have high stability, remaining intact in serum for over 24 h; thus, retaining the characteristic stability of their parent peptide. Overall, we have shown that simple conservative substitutions can enhance the cellular uptake of CTX, suggesting that such type of mutations might be useful for improving uptake of other peptide toxins.
Role of Caspases in Immunotoxin-Induced Apoptosis of Cancer Cells (1998)

Immunotoxins composed of antibodies linked to plant or bacterial toxins are being evaluated in the treatment of cancer. It is known that the toxin moieties of immunotoxins, including Pseudomonasexotoxin A (PE), diphtheria toxin, and ricin, are capable of inducing apoptosis. Since the efficiency of induction of apoptosis and the apoptosis pathway may have direct effects on the therapeutic usefulness of immunotoxins, we have studied how B3(Fv)-PE38, a genetically engineered immunotoxin in which the Fv fragment of an antibody is fused to a mutated form of PE, induces apoptosis of the MCF-7 breast cancer cell line. We show for the first time that a PE-containing immunotoxin activates ICE/ced-3 proteases, now termed caspases, and causes characteristic cleavage of the "death substrate" poly(ADP)-ribose polymerase (PARP) to an 89 kDa fragment with a time course of cleavage comparable to that induced by TNFalpha. Also the fluorescent substrate, DEVD-AFC, is cleaved 2-4-fold more rapidly by lysates from B3(Fv)-PE38 treated MCF-7 cells than untreated control cells, suggesting that a CPP32-like caspase is involved in B3(Fv)-PE38-mediated apoptosis. B3(Fv)-PE38-induced PARP cleavage is inhibited by several protease inhibitors known to inhibit caspases (zVAD-fmk, zDEVD-fmk, zIETD-fmk) as well as by overexpression of Bcl-2 providing additional evidence for caspase involvement. zVAD-fmk, a broad spectrum inhibitor of most mammalian caspases, prevents the early morphological changes and loss of cell membrane integrity produced by B3(Fv)-PE38, but not its ability to inhibit protein synthesis, arrest cell growth, and subsequently kill cells. Despite inhibition of apoptosis, the immunotoxin is still capable of selective cell killing, which indicates that B3(Fv)-PE38 kills cells by two mechanisms: one requires caspase activation, and the other is due to the arrest of protein synthesis caused by inactivation of elongation factor 2. The fact that an immunotoxin can specifically kill tumor cells without the need of inducing apoptosis makes such agents especially valuable for the treatment of cancers that are protected against apoptosis, e.g., by overexpression of Bcl-2.
Anticoagulant and Fibrinolytic Properties of Salivary Proteins from the Leech Haementeria ghilianii (1981)

The salivary glands of the blood-sucking leech Haementeria ghilianii contain an anticoagulant that not only inhibits the clotting of human and bovine plasma, but also dissolves previously formed fibrin clots. This anticoagulant activity is attributable to an enzyme, for which the name hementin is proposed. Hementin catalyzes the proteolytic degradation of fibrinogen and fibrin, even in the presence of the inhibitors of proteases occurring in human plasma. The enzyme has the same affinity for human fibrinogen and fibrin. In human fibrinogen cleaves the Act chain initially and then the γ chain to yield characteristic fragments of high molecular weight that are different from the fragments resulting from the digestion of fibrinogen by plasmin. The salivary extracts do not contain any appreciable amounts of an activator of human plasminogen or an inhibitor of human or bovine thrombin. Thus, H. ghilianii prevents coagulation of its host blood through a fibrinogenolytic mechanism that is entirely different from that of hirudin, a thrombin-inactivating polypeptide present in the saliva of another leech, Hirudo medicinalis.
PHOTODYNAMIC RESPONSES IN RHODOTORULA GLUTINIS IN THE ABSENCE OF ADDED SENSITIZERS* (1971)

Abstract— –The lethal effect of a continuous spectrum of light at wavelengths longer than 300 nm has been examined for the yeast Rhodotorula glutinis. A survival curve consisting of a shoulder, an exponential phase of death, and a “tailing off” phase was shown to occur when cells were irradiated in the absence of a sensitizing dye. An action spectrum showed that the portion of the light used for irradiation which is lethal to the cells lies between 310 and 430 nm. It was found that carotenoid pigments were not able to provide any protection against this endogenously photosensitized oxidation. Exponentially growing cells were the most sensitive to killing and, as cells approached and entered into the stationary phase of growth, they became more resistant until a constant level of sensitivity was reached. A primary temperature effect on the length of the shoulder prior to the death of the cell has been observed. The sensitivity was greatest at low temperatures with an optimum resistance occurring at 22.5°C and an increasing sensitivity occurring at higher temperatures. Various sites have been examined for cellular damage which might lead to the death of the cell. Damage was found to impair the function of the plasma‐lemma, the glycolytic and respiratory system, the nucleus, and to be observable cytologically.
Novel human G protein‐coupled receptors with long N‐terminals containing GPS domains and Ser/Thr‐rich regions (2002)

We report eight novel members of the superfamily of human G protein-coupled receptors (GPCRs) found by searches in the human genome databases, termed GPR97, GPR110, GPR111, GPR112, GPR113, GPR114, GPR115 and GPR116. Phylogenetic analysis shows that these are additional members of a family of GPCRs with long N-termini, previously termed EGF-7TM, LNB-7TM, B2 or LN-7TM. Five of the receptors form their own phylogenetic cluster, while three others form a cluster with the previously reported HE6 and GPR56 (TM7XN1). All the receptors have a GPS domain in their N-terminus and long Ser/Thr-rich regions forming mucin-like stalks. GPR113 has a hormone binding domain and one EGF domain. GPR112 has over 20 Ser/Thr repeats and a pentraxin domain. GPR116 has two immunoglobulin-like repeats and a SEA box. We found several human EST sequences for most of the receptors showing differential expression patterns, which may indicate that some of these receptors participate in reproductive functions while others are more likely to have a role in the immune system.
Impaired rejection and mucosal injury of small intestinal allografts lacking the interferon‐γ receptor (2003)

Small intestinal mucosal T cell activation results in villous atrophy and crypt hyperplasia. There is conflicting evidence as to whether a Th1 IFN-gamma response may be involved. Using a murine intestinal transplant model of T cell-mediated enteropathy we aimed to study the role of IFN-gamma on the development of villous atrophy and crypt hyperplasia. Isografts or allografts of foetal small intestine from 129SV-/- IFN-gamma receptor knockout mice or wild type mice were implanted under the kidney capsule of Balb/c recipient mice. Grafts were examined histologically at intervals from 2 to 9 days post implantation for signs of rejection. Quantitative rtPCR for IFN-gamma, TNFalpha and IL-4 was conducted on grafts at 5 and 9 days post implantation. In allografts, rejection accompanied by the development of villous atrophy and crypt hyperplasia, occurred in a time-dependent manner. However this process was markedly slower in the IFN-gamma receptor knockout grafts compared to the wild type grafts at 5 days (chi2 = 10.08, P = 0.007) and 9 days post implantation (chi2 = 13.25, P = 0.004). There were also significantly fewer TNFalpha transcripts in allografts of IFN-gamma-/- intestine than in wild type allografts (P = 0.02). IFN-gamma has a partial, but not obligatory, role in the development of villous atrophy and crypt hyperplasia during T cell mediated rejection of intestinal allografts.
A novel gestural input device for virtual reality (2002)

The ImageGlove is 3D input device with six degrees-of-freedom that can be used to interface with non-immersive virtual environments. It is possible to detect the position and orientation of the human hand in real time. The author's device can be used as a wireless replacement for the Polhemus position sensor. The system allows one to use the human hand as an input device to interact with 3D virtual-reality applications in a very natural way.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Role of ER Export Signals in Controlling Surface Potassium Channel Numbers (2001)

Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steady-state distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein-coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals.
Hybrid Optical WDM Networks Utilizing Optical Waveband and Electrical Wavelength Cross-connects (2011)

We propose an optical waveband and electrical OTN hybrid-HOXC node configuration, and a suitable network design algorithm. The proposed hybrid-HOXC network is verified as being very cost effective over a wide range of parameter values.
In Vitro Activities of Voriconazole, Itraconazole, and Amphotericin B against Blastomyces dermatitidis , Coccidioides immitis , and Histoplasma capsulatum (2000)

The in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorphic fungi, Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. MICs were determined by a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M27-A procedure. RPMI 1640 medium was used for tests with voriconazole and itraconazole, whereas Antibiotic Medium 3 with 2% glucose was used for amphotericin B. Minimum fungicidal concentrations (MFCs) were also determined. Amphotericin B was active against all three dimorphic fungi, with MICs at which 90% of the isolates tested are inhibited (MIC(90)s) of 0.5 to 1 microg/ml. Itraconazole had MIC(90)s of 0.06 microg/ml for H. capsulatum, 0.125 microg/ml for B. dermatitidis, and 1 microg/ml for C. immitis. The MIC(90)s of voriconazole were 0.25 microg/ml for all three fungi. Amphotericin B was fungicidal for B. dermatitidis and H. capsulatum with MFCs at which 90% of strains tested are killed (MFC(90)s) of 0.5 and 2 microg/ml, respectively. It was less active against C. immitis, with MFCs ranging from 0.5 to >16 microg/ml. Voriconazole and itraconazole were lethal for most isolates of B. dermatitidis, with MFC(50)s and MFC(90)s of 0.125 and 4 microg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC(50)s of 2 and 8 microg/ml for itraconazole and voriconazole, respectively; neither had a lethal effect upon C. immitis. Our results suggest that voriconazole possesses promising activity against these important human pathogens.
Polypeptides of the Maize Amyloplast Stroma1 (1998)

In the developing endosperm of monocotyledonous plants, starch granules are synthesized and deposited within the amyloplast. A soluble stromal fraction was isolated from amyloplasts of immature maize (Zea mays L.) endosperm and analyzed for enzyme activities and polypeptide content. Specific activities of starch synthase and starch-branching enzyme (SBE), but not the cytosolic marker alcohol dehydrogenase, were strongly enhanced in soluble amyloplast stromal fractions relative to soluble extracts obtained from homogenized kernels or endosperms. Immunoblot analysis demonstrated that starch synthase I, SBEIIb, and sugary1, the putative starch-debranching enzyme, were each highly enriched in the amyloplast stroma, providing direct evidence for the localization of starch-biosynthetic enzymes within this compartment. Analysis of maize mutants shows the deficiency of the 85-kD SBEIIb polypeptide in the stroma of amylose extender cultivars and that the dull mutant lacks a >220-kD stromal polypeptide. The stromal fraction is distinguished by differential enrichment of a characteristic group of previously undocumented polypeptides. N-terminal sequence analysis revealed that an abundant 81-kD stromal polypeptide is a member of the Hsp70 family of stress-related proteins. Moreover, the 81-kD stromal polypeptide is strongly recognized by antibodies specific for an Hsp70 of the chloroplast stroma. These findings are discussed in light of implications for the correct folding and assembly of soluble, partially soluble, and granule-bound starch-biosynthetic enzymes during import into the amyloplast.
Isoprenyl diphosphate synthases: Protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure (1994)

Isoprenyl diphosphate synthases are ubiquitous enzymes that catalyze the basic chain-elongation reaction in the isoprene biosynthetic pathway. Pairwise sequence comparisons were made for 6 farnesyl diphosphate synthases, 6 geranylgeranyl diphosphate synthases, and a hexaprenyl diphosphate synthase. Five regions with highly conserved residues, two of which contain aspartate-rich DDXX(XX)D motifs found in many prenyltransferases, were identified. A consensus secondary structure for the group, consisting mostly of alpha-helices, was predicted for the multiply aligned sequences from amino acid compositions, computer assignments of local structure, and hydropathy indices. Progressive sequence alignments suggest that the 13 isoprenyl diphosphate synthases evolved from a common ancestor into 3 distinct clusters. The most distant separation is between yeast hexaprenyl diphosphate synthetase and the other enzymes. Except for the chromoplastic geranylgeranyl diphosphate synthase from Capsicum annuum, the remaining farnesyl and geranylgeranyl diphosphate synthases segregate into prokaryotic/archaebacterial and eukaryotic families.
Realization of Ultrahigh Photovoltages with Organic Photovoltaic Nanomodules (2008)

The series interconnection of organic photovoltaic cells on the scale of several hundred nanometres results in 1390 interconnected elementary cells per mm. This organic photovoltaic nanomodule generates the highest reported voltage per length for an organic photovoltaic device. As a first application we demonstrate the switching of an organic field effect transistor with a 590 µm wide photovoltaic nanomodule providing a sufficiently high gate voltage.
Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. (1983)

The binding of apotransferrin to the transferrin receptor on the surface of human leukemic K562 cells was found to be significantly less tight than that of the holoprotein, diferric transferrin. The finding that both ligands displayed linear Scatchard plots with similar receptor number (approximately equal to 150,000 per cell) and mutually inhibit each other's binding suggested that they bind to the same receptor. Both the dissociation and association rate of apotransferrin were markedly increased (28-fold and 15-fold, respectively) at pH 7.2 compared to pH 4.8. Using the values of these binding parameters, we propose a mechanism to account for the recycling of transferrin subsequent to internalization and residence within an acidic nonlysosomal organelle where iron is removed.
Crystallographic Structure of the Nitrogenase Iron Protein from Azotobacter vinelandii (1992)

The nitrogenase enzyme system catalyzes the ATP (adenosine triphosphate)-dependent reduction of dinitrogen to ammonia during the process of nitrogen fixation. Nitrogenase consists of two proteins: the iron (Fe)-protein, which couples hydrolysis of ATP to electron transfer, and the molybdenum-iron (MoFe)-protein, which contains the dinitrogen binding site. In order to address the role of ATP in nitrogen fixation, the crystal structure of the nitrogenase Fe-protein from Azotobacter vinelandii has been determined at 2.9 angstrom (A) resolution. Fe-protein is a dimer of two identical subunits that coordinate a single 4Fe:4S cluster. Each subunit folds as a single alpha/beta type domain, which together symmetrically ligate the surface exposed 4Fe:4S cluster through two cysteines from each subunit. A single bound ADP (adenosine diphosphate) molecule is located in the interface region between the two subunits. Because the phosphate groups of this nucleotide are approximately 20 A from the 4Fe:4S cluster, it is unlikely that ATP hydrolysis and electron transfer are directly coupled. Instead, it appears that interactions between the nucleotide and cluster sites must be indirectly coupled by allosteric changes occurring at the subunit interface. The coupling between protein conformation and nucleotide hydrolysis in Fe-protein exhibits general similarities to the H-Ras p21 and recA proteins that have been recently characterized structurally. The Fe-protein structure may be relevant to the functioning of other biochemical energy-transducing systems containing two nucleotide-binding sites, including membrane transport proteins.
Recombinant Human Growth Hormone in Abstinent Androgenic-Anabolic Steroid Use: Psychological, Endocrine and Trophic Factor Effects (2007)

This study examined whether six days recombinant human growth hormone (rhGH) affected psychological profile in an abstinent androgenic-anabolic steroid (AAS) abusing group, compared with an abstinent AAS control group. Male subjects (n = 48) were assigned in a random fashion into one of two groups: (1): (n=24) control group (C); (2): (n=24) rhGH group (GH). A hospital anxiety scale (HADS) questionnaire was completed by all subjects. Physiological responses investigated included anthropometry. Biochemical markers examined included; serum glucose, sodium, urea, lipid profile, high sensitivity C-reactive protein (hsCRP), homocysteine (HCY), tetra-iodothyronine (T4), thyroid stimulating (TSH), luteinising (LH) and follicle stimulating (FSH) hormones, testosterone (T), prolactin (PRL), cortisol and insulin like growth factor-1 (IGF-I). HADS questionnaire significantly decreased in both anxiety (A) and depression (D) symptoms within GH (P<0.017) and compared with C (P<0.05). Body mass index (BMI) and fat-free mass index (FFMI) significantly increased (both P<0.017) while body fat significantly decreased within GH (P<0.017). IGF-I significantly increased within GH (P<0.017) and significantly increased compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum HCY, hsCRP, TSH and T4, significantly decreased within GH (all P<0.017). PRL significantly increased and T4 significantly decreased compared with C (both P<0.05). The findings of this study suggest that short term use of rhGH has beneficial effects on mental state in individuals who were previous abusers of AAS and appeared to have a beneficial effect on cardiovascular risk markers associated with adverse mental health.
Novel sulfonamides as potential, systemically active antitumor agents (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel sulfonamides as potential, systemically active antitumor agentsHiroshi Yoshino, Norihiro Ueda, Jun Niijima, Hiroyuki Sugumi, Yoshihiko Kotake, Nozomu Koyanagi, Kentaro Yoshimatsu, Makoto Asada, Tatsuo Watanabe, Takeshi Nagasu, Kappei Tsukahara, Atsumi Iijima, and Kyosuke KitohCite this: J. Med. Chem. 1992, 35, 13, 2496–2497Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue 1 June 1992https://pubs.acs.org/doi/10.1021/jm00091a018https://doi.org/10.1021/jm00091a018research-articleACS PublicationsRequest reuse permissionsArticle Views901Altmetric-Citations193LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier. (1997)

Members of the superfamily of nuclear hormone receptors which are obligate heterodimeric partners of the retinoid X receptor may be important in epidermal development. Here, we examined the effects of activators of the receptors for vitamin D3 and retinoids, and of the peroxisome proliferator activated receptors (PPARs) and the farnesoid X-activated receptor (FXR), on the development of the fetal epidermal barrier in vitro. Skin explants from gestational day 17 rats (term is 22 d) are unstratified and lack a stratum corneum (SC). After incubation in hormone-free media for 3-4 d, a multilayered SC replete with mature lamellar membranes in the interstices and a functionally competent barrier appear. 9-cis or all-trans retinoic acid, 1,25 dihydroxyvitamin D3, or the PPARgamma ligands prostaglandin J2 or troglitazone did not affect the development of barrier function or epidermal morphology. In contrast, activators of the PPARalpha, oleic acid, linoleic acid, and clofibrate, accelerated epidermal development, resulting in mature lamellar membranes, a multilayered SC, and a competent barrier after 2 d of incubation. The FXR activators, all-trans farnesol and juvenile hormone III, also accelerated epidermal barrier development. Activities of beta-glucocerebrosidase and steroid sulfatase, enzymes previously linked to barrier maturation, also increased after treatment with PPARalpha and FXR activators. In contrast, isoprenoids, such as nerolidol, cis-farnesol, or geranylgeraniol, or metabolites in the cholesterol pathway, such as mevalonate, squalene, or 25-hydroxycholesterol, did not alter barrier development. Finally, additive effects were observed in explants incubated with clofibrate and farnesol together in suboptimal concentrations which alone did not affect barrier development. These data indicate a putative physiologic role for PPARalpha and FXR in epidermal barrier development.