gebhart/patrepeval huggingface dataset:
Increased antitumor activity of a circularly permuted interleukin 4-toxin in mice with interleukin 4 receptor-bearing human carcinoma. (1995)

We reported previously that circularly permuted interleukin-4 (IL4), composed of amino acids 38-129 of IL4 connected by a linker peptide GGNGG to amino acids 1-37, is preferable to native IL4 for fusing to the amino terminus of truncated Pseudomonas exotoxin (PE) to make a recombinant toxin, because the new ligand-toxin junction results in improved IL4 receptor (IL4R)-binding (R. J. Kreitman et al., Proc. Natl. Acad. Sci. USA, 91: 6889-6893, 1994). We now report that the improved binding of circularly permuted IL4-toxin is associated with improved antitumor activity in tumor-bearing mice. For in vivo testing, we made an improved circularly permuted IL4-toxin, termed IL4(38-37)-PE38KDEL. It contains an N38D mutation at the amino terminus, allowing improved expression and large-scale production in Escherichia coli. It also contains the truncated toxin PE38KDEL, which is composed of amino acids 253-364 and 381-608 of PE, followed by KDEL. To evaluate antitumor activity, nude mice carrying s.c. tumors composed of IL4R-bearing human A431 epidermoid carcinoma cells were injected with recombinant toxins i.v. every other day for three doses. IL4(38-37)-PE38KDEL induced complete remissions in 80% of mice receiving 50 micrograms/kg x 3 and 100% of mice receiving 100 micrograms/kg x 3, while only 70% of mice receiving 200 micrograms/kg x 3 of the native IL4-toxin IL4-PE38KDEL obtained complete remission. Disease-free survival after obtaining complete remissions was higher in mice treated with IL4(38-37)-PE38KDEL 50 micrograms/Kg QOD x 3 than with IL4-PE38KDEL 200 micrograms/Kg QOD x 3 (P < 0.03). IL4(38-37)-PE38KDEL and IL4-PE38KDEL exhibited similar toxicity and pharmacokinetics in the mice, indicating that the improved antitumor activity of the circularly permuted IL4-toxin was due to its improved binding to the IL4R on the target cells.
Dictionary of endocrinology and related biomedical sciences (1996)

Endocrinology is a vital and rapidly growing science at the interface of molecular biology, biochemistry, genetics, physiology and medicine. New terminology enters the working vocabulary of endocrinologists from a variety of other scientific disciplines. In response to the explosion of endocrine terms, this detailed reference work provides a ready source of definitions that should benefit biomedical and basic researchers and clinicians.
Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets (2001)

Although the source of embryonic stem (ES) cells presents ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of pancreatic islets. We have generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo. When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization.
Steroidal Alkaloids from the Roots and Rhizomes of Vertrum nigrum L. (2007)

Abstract Two new steroidal alkaloids, neoverapatuline ( 1 ) and (1 β ,3 α ,5 β )‐1,3‐dihydroxyjervanin‐12‐en‐11‐one ( 2 ), together with the four known compounds, veratramine ( 3 ), rubijervine ( 4 ), veratrosine ( 5 ), and veratroylzygadenine ( 6 ), were isolated from the roots and rhizomes of Veratrum nigrum L. Their structures were established through combined analyses of physicochemical properties and spectroscopic evidence. All compounds 1 – 6 were tested for their cytotoxicities in vitro against the human glioma cell line SF188.
Biochemical and Enzyme Kinetic Applications for the Characterization of β-Lactamases (2003)

For the last 20 yr thin-layer polyacrylamide isoelectric focusing (IEF) has played a major role in the identification and characterization of β-lactamases. IEF is able to distinguish enzymes that focus only 0.05 pI apart (1), but the exponential increase rin the numbers of β-lactamases discovered over the last 10 yr has meant that this method no longer provides sufficient resolution to distinguish the majority of β-lactamases. Today the pI of a β-lactamase is still an essential determinant that must be used in combination with a variety of other data. Moreover, the IEF of β-lactamases is now entering a new era as this technique can be adapted to provide important biochemical information on β-lactamases other than simply their pI values. These approaches are discussed in Subheading 3.1.
Development of clinical utility of zoledronic acid and patient considerations in the treatment of osteoporosis (2010)

Osteoporosis is a major health concern, which results in the increased risk of fractures. There is a high risk for the first or consecutive fractures leading to considerable morbidity and debilitating consequences if osteoporosis is untreated. Currently, bisphosphonates are the mainstay of treatment for osteoporosis though long-term persistence and adherence to bisphosphonates, especially those taken orally, remain low. This medication noncompliance has serious consequences on osteoporotic patients as it is associated with a significantly higher fracture risk. Intravenous (IV) zoledronic acid (ZOL), developed to increase compliance by overcoming the frequent and burdensome dosing requirements of oral bisphosphonates, is the first and the only once-yearly bisphosphonate globally approved for use in the treatment of up to 6 indications of osteoporosis. Several clinical studies have documented that a single infusion of IV ZOL resulted in decreased bone turnover and improved bone density for at least 12 months post infusion. This article traces the development of ZOL's clinical utility and evaluates its patient preference by collating data from all major clinical trials, studying the efficacy and safety of ZOL in the treatment of osteoporosis and other benign bone disorders.
Structures of Immunophilins and their Ligand Complexes (2003)

This review includes an analysis of available X-ray and NMR structures of both members of the immunophilin family; cyclophilins and the FK-506 binding proteins (FKBPs). Available structures are compared and contrasted to highlight different structural features seen both within and between species. Each immunophilin family has been structurally characterised with a variety of small molecule ligands, principally immunosuppressive drugs and their analogues and an overview of these complexes is also presented. Currently the Protein Data Base contains over 60 entries for cyclophilins and over 40 entries for FKBPs. A number of FKBP related structures are also available including structures of MIP (Macrophage Infectivity Potentiator protein) from Legionella pneumophila and Trypanosoma cruzi and Trigger Factor from Mycoplasma genitalium. For all structures discussed in the review a summary of the available biological data is also presented.
On a decentralized active sensing strategy using mobile sensor platforms in a network (2004)

In this paper, we consider the problem of active sensing using mobile nodes as a sensor network to estimate the state of a dynamic target. We propose a gradient-search-based decentralized algorithm that demonstrates the benefits of distributed sensing. We then examine the task of tracking multiple targets, and address it via a simple extension to our algorithm. Simulation results show that our simple decentralized approach performs quite well and leads to interesting cooperative behavior.
Contribution of Epithelial-derived Fibroblasts to Bleomycin-induced Lung Fibrosis (2009)

Both EMT and bone marrow progenitors contribute to S100A4-positive fibroblasts in bleomycin-induced lung fibrosis. However, neither origin is a principal contributor to lung myofibroblasts.
Extraction of Human Body Skeleton Based on Silhouette Images (2010)

Skeleton extraction is essential for general shape representation. A typical skeletonization algorithm should obtain the ability to preserve original object’s topological and hierarchical properties. However, most of current methods are high memory cost, computationally intensive, and also require complex data structures. In this paper, we propose an efficient and accurate skeletonization method for the skeleton feature points extracted from human body based on silhouette images. First, the gradient of distance transform is used to detect critical points inside the foreground. Then, we converge and simplify critical points in order to generate the most important and elegant skeleton feature points. Finally, we present an algorithm which connects the skeleton feature points and estimates the position of skeleton joints.
Isolation and characterization of a mutant from Saccharomyces cerevisiae lacking fructose 1,6‐bisphosphatase (1984)

Mutants lacking fructose 1,6-bisphosphatase activity have been isolated from Saccharomyces cerevisiae and genetically purified. Mutants were unable to grow on gluconeogenic carbon sources. Revertants that grew on glycerol have regained the fructose 1,6-bisphosphatase activity, showing that there is no bypass in yeast for this enzymatic step. No significant differences were found in the growth of the mutants and the parental strains in other carbon sources. Other mutants lacking fructose 1,6-bisphosphatase activity but pleiotropically affected in the derepression of several enzymes sensitive to catabolite repression were also isolated. All the mutants isolated were of nuclear origin and defined three complementation groups.
Reduced Excitatory Neurotransmission and Mild Autism-Relevant Phenotypes in AdolescentShank3Null Mutant Mice (2012)

Mutations in the synaptic scaffolding protein gene SHANK3 are strongly implicated in autism and Phelan-McDermid 22q13 deletion syndrome. The precise location of the mutation within the Shank3 gene is key to its phenotypic outcomes. Here, we report the physiological and behavioral consequences of null and heterozygous mutations in the ankyrin repeat domain in Shank3 mice. Both homozygous and heterozygous mice showed reduced glutamatergic transmission and long-term potentiation in the hippocampus with more severe deficits detected in the homozygous mice. Three independent cohorts were evaluated for magnitude and replicability of behavioral endophenotypes relevant to autism and Phelan-McDermid syndrome. Mild social impairments were detected, primarily in juveniles during reciprocal interactions, while all genotypes displayed normal adult sociability on the three-chambered task. Impaired novel object recognition and rotarod performance were consistent across cohorts of null mutants. Repetitive self-grooming, reduced ultrasonic vocalizations, and deficits in reversal of water maze learning were detected only in some cohorts, emphasizing the importance of replication analyses. These results demonstrate the exquisite specificity of deletions in discrete domains within the Shank3 gene in determining severity of symptoms.
Fusarin C Biosynthesis in Fusarium moniliforme and Fusarium venenatum (2004)

Fragments of polyketide synthase (PKS) genes were amplified from complementary DNA (cDNA) of the fusarin C producing filamentous fungi Fusarium moniliforme and Fusarium venenatum by using degenerate oligonucleotides designed to select for fungal PKS C-methyltransferase (CMeT) domains. The PCR products, which were highly homologous to fragments of known fungal PKS CMeT domains, were used to probe cDNA and genomic DNA (gDNA) libraries of F. moniliforme and F. venenatum. A 4.0 kb cDNA clone from F. venenatum was isolated and used to prepare a hygromycin-resistance knockout cassette, which was used to produce a fusarin-deficient strain of F. venenatum (kb = 1000 bp). Similarly, a 26 kb genomic fragment, isolated on two overlapping clones from F. moniliforme, encoded a complete iterative Type I PKS fused to an unusual nonribosomal peptide synthase module. Once again, targeted gene disruption produced a fusarin-deficient strain, thereby proving that this synthase is responsible for the first steps of fusarin biosynthesis.
Characterization of bonds formed between platelet factor 4 and negatively charged drugs using single molecule force spectroscopy (2014)

Immunogenicity (i.e., the ability to initiate immune reactions) is one of the major challenges for the development of new drugs, as it may turn the developed drug therapeutically ineffective or cause severe immune-related effects. Using single molecule force spectroscopy, we study rupture forces between the positively charged, endogenous protein platelet factor 4 (PF4; also known as CXC chemokine ligand 4, CXCL4) and the antithrombotic drug heparin and other negatively charged glycosaminoglycans (GAGs), which are known to form immunogenic PF4/GAG-complexes (e.g., heparin and dextran sulfate) as well as non-immunogenic complexes (e.g., chondroitin sulfate A). Our measurements suggest that the average number of sulfate groups per monosaccharide unit (i.e., the degree of sulfation DS) does not affect the unbinding characteristics of single PF4/GAG-bonds (reaction coordinate x0 = 2.2 ± 0.2 Å, energy barrier ΔG ≈ -1 kBT). However, the average number of GAG bonds formed to a single PF4 molecule increases with increasing DS as indicated by a rising frequency of unbinding events, suggesting a multivalent binding scheme between PF4 and GAGs. Our studies show that at least three GAG bonds have to be formed to each PF4 molecule to induce epitope formation on the PF4/GAG-complex to which PF4/GAG-complex specific antibodies bind. Hence, GAG-based drugs that form less than three bonds per PF4 molecule are unlikely to constitute PF4/drug-complexes that are of immunologic relevance.
The sodium ion translocating glutaconyl‐CoA decarboxylase from Acidaminococcus fermentans: cloning and function of the genes forming a second operon (1999)

Glutaconyl-CoA decarboxylase from Acidaminococcus fermentans (clostridal cluster IX), a strict anaerobic inhabitant of animal intestines, uses the free energy of decarboxylation (delta G(o) approximately -30 kJ mol-1) in order to translocate Na+ from the inside through the cytoplasmic membrane. The proton, which is required for decarboxylation, most probably comes from the outside. The enzyme consists of four different subunits. The largest subunit, alpha or GcdA (65 kDa), catalyses the transfer of CO2 from glutaconyl-CoA to biotin covalently attached to the gamma-subunit, GcdC. The beta-subunit, GcdB, is responsible for the decarboxylation of carboxybiotin, which drives the Na+ translocation (approximate K(m) for Na+ 1 mM), whereas the function of the smallest subunit, delta or GcdD, is unclear. The gene gcdA is part of the 'hydroxyglutarate operon', which does not contain genes coding for the other three subunits. This paper describes that the genes, gcdDCB, are transcribed in this order from a distinct operon. The delta-subunit (GcdD, 12 kDa), with one potential transmembrane helix, probably serves as an anchor for GcdA. The biotin carrier (GcdC, 14 kDa) contains a flexible stretch of 50 amino acid residues (A26-A75), which consists of 34 alanines, 14 prolines, one valine and one lysine. The beta-subunit (GcdB, 39 kDa) comprising 11 putative transmembrane helices shares high amino acid sequence identities with corresponding deduced gene products from Veillonella parvula (80%, clostridial cluster IX), Archaeoglobus fulgidus (61%, Euryarchaeota), Propionigenium modestum (60%, clostridial cluster XIX), Salmonella typhimurium (51%, enterobacteria) and Klebsiella pneumoniae (50%, enterobacteria). Directly upstream of the promoter region of the gcdDCB operon, the 3' end of gctM was detected. It encodes a protein fragment with 73% sequence identity to the C-terminus of the alpha-subunit of methylmalonyl-CoA decarboxylase from V. parvula (MmdA). Hence, it appears that A. fermentans should be able to synthesize this enzyme by expression of gctM together with gdcDCB, but methylmalonyl-CoA decarboxylase activity could not be detected in cell-free extracts. Earlier observations of a second, lower affinity binding site for Na+ of glutaconyl-CoA decarboxylase (apparent K(m) 30 mM) were confirmed by identification of the cysteine residue 243 of GcdB between the putative hellces VII and VIII, which could be specifically protected from alkylation by Na+. The alpha-subunit was purified from an overproducing Escherichia coli strain and was characterized as a putative homotrimer able to catalyse the carboxylation of free biotin.
Schizosaccharomyces pombe Spk1 is a tyrosine-phosphorylated protein functionally related to Xenopus mitogen-activated protein kinase. (1993)

Mitogen-activated protein kinase (MAPK) and its direct activator, MAPK kinase (MAPKK), have been suggested to play a pivotal role in a variety of signal transduction pathways in higher eukaryotes. The fission yeast Schizosaccharomyces pombe carries a gene, named spk1, whose product is structurally related to vertebrate MAPK. Here we show that Spk1 is functionally related to Xenopus MAPK. (i) Xenopus MAPK partially complemented a defect in the spk1- mutant. An spk1- diploid strain could not sporulate, but one carrying Xenopus MAPK could. (ii) Both Spk1 and Xenopus MAPK interfered with sporulation if overexpressed in S. pombe cells. (iii) Spk1 underwent tyrosine phosphorylation as does Xenopus MAPK. Tyrosine phosphorylation of Spk1 appeared to be dependent upon mating signals because it occurred in homothallic cells but not in heterothallic cells. Furthermore, this phosphorylation was diminished in a byr1 disruptant strain, suggesting that spk1 lies downstream of byr1, which encodes a MAPKK homolog in S. pombe. Taken together, the MAPKK-MAPK cascade may be evolutionarily conserved in signaling pathways in yeasts and vertebrates.
An Implantable MOSFET Dosimeter for the Measurement of Radiation Dose in Tissue During Cancer Therapy (2008)

This paper describes the functionality, radiation characteristics, and clinical implementation of an implantable MOSFET radiation detector (dosimeter). The dosimeter is powered by radio frequency telemetry eliminating the need for a power source inside the dosimeter. The data can be accessed telemetrically for each treatment day during the course of therapy. The detector has been validated in vitro to confirm its accuracy. Variance between predicted and measured dose in patients is discussed. Factors such as patient setup, treatment plan error, and physiologic motion can affect the accuracy of dose delivery in moving from in vitro to in vivo dose measurements. The initial data suggests that the dosimeters can play a useful role in tracking dose discrepancies, both random and systematic, in patients treated with external beam radiation therapy. The implantable dosimeter can be used, together with the current radiation delivery and planning techniques, to optimize radiation treatment on an individual basis.
Ectopic Overexpression of Asparagine Synthetase in Transgenic Tobacco (1993)

Here, we monitor the effects of ectopic overexpression of genes for pea asparagine synthetase (AS1) in transgenic tobacco (Nicotiana tabacum). The AS genes of pea and tobacco are normally expressed only during the dark phase of the diurnal growth cycle and specifically in phloem cells. A hybrid gene was constructed in which a pea AS1 cDNA was fused to the cauliflower mosaic virus 35S promoter. The 35S-AS1 gene was therefore ectopically expressed in all cell types in transgenic tobacco and constitutively expressed at high levels in both the light and the dark. Northern analysis demonstrated that the 35S-AS1 transgene was constitutively expressed at high levels in leaves of several independent transformants. Furthermore, amino acid analysis revealed a 10- to 100-fold increase in free asparagine in leaves of transgenic 35S-AS1 plants (construct z127) compared with controls. Plant growth analyses showed increases (although statistically insignificant) in growth phenotype during the vegetative stage of growth in 35S-AS1 transgenic lines. The 35S-AS1 construct was further modified by deletion of the glutamine-binding domain of the enzyme (gln[delta]AS1; construct z167). By analogy to animal AS, we reasoned that inhibition of glutamine-dependent AS activity might enhance the ammonia-dependent AS activity. The 3- to 19-fold increase in asparagine levels in the transgenic plants expressing gln[delta]AS1 compared with wild type suggests that the novel AS holoenzyme present in the transgenic plants (gln[delta]AS1 homodimer) has enhanced ammonia-dependent activity. These data indicate that manipulation of AS expression in transgenic plants causes an increase in nitrogen assimilation into asparagine, which in turn produces effects on plant growth and asparagine biosynthesis.
New insight into the structures and formation of anthocyanic vacuolar inclusions in flower petals. (2006)

Our results strongly suggest the existence of mass transport for anthocyanins from biosynthetic sites in the cytoplasm to the central vacuole. Anthocyanin-containing PVCs are important intracellular vesicles during the anthocyanin sequestration to the central vacuole and these specific PVCs are likely derived directly from endoplasmic reticulum (ER) in a similar manner to the transport vesicles of vacuolar storage proteins. The membrane-like and thread structures of AVIs point to the involvement of intravacuolar membranes and/or anthocyanin intermolecular association in the central vacuole.
Membrane protein folding and oligomerization: the two-stage model (1990)

We discuss the view that the folding of many, perhaps most, integral membrane proteins can be considered as a two-stage process. In stage I, hydrophobic alpha-helices are established across the lipid bilayer. In stage II, they interact to form functional transmembrane structures. This model is suggested by the nature of transmembrane segments in known structures, refolding experiments, the assembly of integral membrane protein from fragments, and the existence of very small integral membrane protein subunits. It may extend to proteins with a variety of functions, including the formation of transmembrane aqueous channels. The model is discussed in the context of the forces involved in membrane protein folding and the interpretation of sequence data.