gebhart/patrepeval huggingface dataset:
Source of methylmalonyl-coenzyme A for erythromycin synthesis: methylmalonyl-coenzyme A mutase from Streptomyces erythreus (1984)

Streptomyces erythreus produces erythromycin, presumably from methylmalonyl-coenzyme A (CoA), which could be generated by the isomerization of succinyl-CoA. In S. erythreus cultures, [1,4-14C,2,3-3H]succinate was incorporated into erythromycin with a doubling of the 3H/14C ratio. This result is consistent with the hypothesis that succinyl-CoA is isomerized to methylmalonyl-CoA before incorporation into the macrocyclic lactone of erythromycin. The presence of methylmalonyl-CoA mutase, which catalyzes this isomerization, was demonstrated in cell-free extracts prepared from this organism. Consistent with the suggested role for this enzyme, methylmalonyl-CoA mutase activity increased over 12-fold at the time of the most rapid antibiotic production, and the activity level drastically declined when the antibiotic production ceased. The mutase was partially purified from this organism with DEAE-cellulose, ammonium sulfate precipitation, and affinity chromatography on a B12-coenzyme Sepharose column. The enzyme was stimulated 2.5-fold by the addition of B12-coenzyme. The enzyme showed a typical Michaelis-Menten type substrate saturation patterns, with KmS of 0.31 mM and 0.09 microM for methylmalonyl-CoA and B12-coenzyme, respectively, and a V of 0.5 mumol/min per mg. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a major band with a molecular weight of 63,000. The properties of this enzyme appear to be fairly similar to those of the mutase previously obtained from other sources.
Survival or Revival: Long-Term Preservation Induces a Reversible Viable but Non-Culturable State in Methane-Oxidizing Bacteria (2012)

Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB) has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry) and culturability (via most-probable number analysis and plating) of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT) as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC) state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium.
Cleavage-site motifs in mitochondrial targeting peptides (1990)

Although mitochondrial targeting peptides lack a common consensus sequence, a certain bias in the positional distribution of amino acids has recently been found. These patterns seem to be associated with cleavage of the precursor proteins by matrix processing proteases. We have extended the previous studies and found new sequence motifs that are conserved within subgroups of mitochondrial targeting peptides. These motifs have certain common themes, indicating that they are associated with cleavage by one single protease. Two of the conserved patterns have a high predictive value, but even for sequences that do not possess these patterns, a fairly accurate prediction of the cleavage site is shown to be possible. We also suggest that a well-conserved RXY decreases (S/A) pattern may be used to engineer efficiently recognized cleavage sites into uncleaved or artificial mitochondrial targeting peptides.
Cytologically normal cells from neoplastic cervical samples display extensive structural abnormalities on IR spectroscopy: Implications for tumor biology (1998)

Fourier-transform IR (FT-IR) spectra of pelleted exfoliated cervical cells from patients with cervical cancer or dysplasia differ from those from normal women. To study the origin of these spectral changes, we obtained the FT-IR spectra of individual cervical cells from normal, dysplastic, and malignant cervical samples. Ninety five percent of normal superficial and intermediate cells displayed two distinct spectral patterns designated A and B, and 5% displayed an intermediate pattern, suggesting extensive structural heterogeneity among these cells. Parabasal and endocervical cells showed pattern B spectra. The spectra of malignant, dysplastic, and other abnormal cells also were characterized. Analysis of FT-IR spectra of over 2, 000 individual cells from 10 normal females, 7 females with dysplasia, and 5 females with squamous cell carcinoma revealed that the spectra of normal-appearing intermediate and superficial cells of the cervix from women with either dysplasia or cancer differed from those of normal women. Chemometric and classical spectroscopic analysis showed a continuum of changes paralleling the transition from normalcy to malignancy. These findings suggest that (i) the structural changes underlying the spectroscopic changes are involved in or are a product of cervical carcinogenesis and (ii) the neoplastic process may be more extensive than currently recognized with morphological criteria. This approach may be useful for the structural study of neoplasia and also may be of help in the diagnosis or classification of cervical disorders.
Gluconeogenesis and hepatic glycogenolysis during exercise at the lactate threshold (2012)

Because the maintenance of glycemia is essential during prolonged exercise, we examined the effects of endurance training, exercise intensity, and plasma lactate concentration ([lactate]) on gluconeogenesis (GNG) and hepatic glycogenolysis (GLY) in fasted men exercising at, and just below, the lactate threshold (LT), where GNG precursor lactate availability is high. Twelve healthy men (6 untrained, 6 trained) completed 60 min of constant-load exercise at power outputs corresponding to their individual LT. Trained subjects completed two additional 60-min sessions of constant-load exercise: one at 10% below the LT workload (LT-10%), and the other with a lactate clamp (LT-10%+LC) to match the [lactate] of the LT trial. Flux rates were determined by primed continuous infusion of [6,6-(2)H(2)]glucose, [3-(13)C]lactate, and [(13)C]bicarbonate tracers during 90 min of rest and 60 min of cycling. Exercise at LT corresponded to 67.6 ± 1.3 and 74.8 ± 1.7% peak O(2) consumption in the untrained and trained subjects, respectively (P < 0.05). Relative exercise intensity was matched between the untrained group at LT and the trained group at LT-10%, and [lactate] during exercise was matched in the LT and LT-10%+LC trials via exogenous lactate infusion. Glucose kinetics (rate of appearance, rate of disposal, and metabolic clearance rate) were augmented with the lactate clamp. GNG was decreased in the trained subjects exercising at LT and LT-10% compared with the untrained subjects, but increasing [lactate] in the LT-10%+LC trial significantly increased GNG (4.4 ± 0.9 mg·kg(-1)·min(-1)) compared with its corresponding control (1.7 ± 0.4 mg·kg(-1)·min(-1), P < 0.05). Hepatic GLY was higher in the trained than untrained subjects, but not significantly different across conditions. We conclude that GNG plays an essential role in maintaining total glucose production during exercise in fasted men, regardless of training state. However, endurance training increases the ability to achieve a higher relative exercise intensity and absolute power output at the LT without a significant decrease in GNG. Furthermore, raising systemic precursor substrate availability increases GNG during exercise, but not at rest.
Integrated Photonics: Fundamentals (2003)

All integrated optical components and devices make use of where light is confined by total internal reflection. The elements in such chip are interconnected through waveguides, and also the integrated optics components themselves are fabricated using waveguide configuration, such as couplers, switches, modulators, multiplexors, amplifiers and lasers, etc. These components are integrated in a single substrate, thus resulting in a compact and robust photonic device, which can be optically connected through optical fibres. With and increase in the number of integrated optical components and devices emerging from the research laboratories to the market place an up-to-date book is essential in collecting, summarizing and presenting the new developed photonic devices. This includes fundamental aspects, technical aspects (such as fabrication techniques and materials) and characterisation and performance. This is an advanced text aimed at specialists in the field of photonics, but who may be new to the field of integrated photonics. The fundamental aspects have been carefully considered, and all the topics covered by the book start at a medium level, making it highly relevant for undergraduate and post-graduate students following this discipline.
Recent Advances in Stress Signaling in Cancer (2004)

This meeting brought together some of the world's leading scientists in the field of stress signaling, apoptosis, and cancer. This resulted in a productive interaction that updated our current knowledge on "Stress Signaling in Cancer." It comes out that subtle disturbances in cell signaling can be associated with and even lead to cancer. As a corollary, it appears that correcting the signaling defects associated with cancer constitutes a new approach to the treatment and control of neoplastic diseases. The meeting also raised several questions that should be addressed. In particular, it is of the utmost importance to better understand the mechanisms that underlie the specificity of the cellular response with regard to different ligands. For example, why does Gadd45b prevent apoptotic cell death in response to tumor necrosis factor alpha, whereas it favors apoptosis after transforming growth factor beta (E. De Smaele et al.). Other questions concern the understanding of the cross-talk mechanisms between different stress and apoptotic pathways and how the strength and the position and timing of a signal may affect different pathways. The next few years of research in this field should be enlightening and fruitful.
Ca2+-dependent protein kinase C isoforms are critical to estradiol 17β-d-glucuronide–induced cholestasis in the rat (2008)

Our findings support a central role for cPKC isoforms in E(2)17G-induced cholestasis, by inducing both transporter retrieval from the canalicular membrane and opening of the paracellular route.
Curcumin Induced Suicidal Erythrocyte Death (2007)

The natural nutrient component Curcumin with anti-inflammatory and antitumor activity has previously been shown to stimulate apoptosis of several nucleated cell types. The present study has been performed to explore whether Curcumin could similarly induce suicidal death of erythrocytes or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing cells are phagocytosed and thus rapidly cleared from circulating blood. Erythrocyte membrane scrambling may be triggered by increase of cytosolic Ca(2+) activity or formation of ceramide. To test for eryptosis, erythrocyte phosphatidylserine exposure has been estimated from annexin V binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to Curcumin (= 1 microM) increased annexin V binding and decreased forward scatter, pointing to phosphatidylserine exposure at the cell surface and cell shrinkage. According to Fluo3 fluorescence Curcumin increased cytosolic Ca(2+) activity and according to immunofluorescence Curcumin increased ceramide formation. As shown previously, hypertonic shock (addition of 550mM sucrose), chloride removal and glucose depletion decreased the forward scatter and increased annexin V binding. The effects on annexin binding were enhanced in the presence of Curcumin. Exposure to Curcumin did, however, not significantly enhance the shrinking effect of hypertonic shock or Cl(-) removal and reversed the shrinking effect of glucose withdrawal. The present observations disclose a proeryptotic effect of Curcumin which may affect the life span of circulating erythrocytes.
Cell Growth in Response to Mechanical Stiffness is Affected by Neuron- Astroglia Interactions (2007)

Cell adhesion and morphology are affected by the mechanical properties of the extracellular matrix.Using polyacrylamide gels as cell substrates, the cellular response to substrate compliance was investigated in pure neuronal, pure astroglial, or mixed co-cultures.Substrates used spanned a large range of stiffnesses including that of brain tissue.In both pure and mixed cultures, immature (vimentin+) astroglia adhered best to stiffest gels.Mature (GFAP+) astrocyte adhesion peaked on intermediate stiffness, while pure GFAP+ astroglial adhesion displayed no intermediate preference and increased with stiffness.Neurite length was constant with stiffness; however, primary dendrite number was lowest on intermediate gels.Pure neuronal cultures were more adherent to hard gels, while mixed cultures had no stiffness preference.Furthermore, we investigated the role of stiffness in the modulation of the neurotoxic effect of glutamate.Exposure to two glutamate concentrations (500 and 1000 M) of cultured spinal cord neurons induced cell death.The damage elicited by 500 m glutamate to neurons in a mixed culture of spinal cord cells is most severe on soft 300 Pa gels.The neurotoxic effect of glutamate on neurons cultured on hard gels where astrocytes are present was strongly attenuated compared with that observed on soft gels, where there is a relatively low number of astrocytes.Our data suggest that mechanical stiffness of the substrate affects the response of both neurons and astroglia, and this response is varied by interaction between the two cell types.
Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial (2011)

Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55-84 years, in the Prostate Cancer Prevention Trial during 1994-2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk.
Bacillus anthracis peptidoglycan activates human platelets through FcγRII and complement (2013)

Platelet activation frequently accompanies sepsis and contributes to the sepsis-associated vascular leakage and coagulation dysfunction. Our previous work has implicated peptidoglycan (PGN) as an agent causing systemic inflammation in gram-positive sepsis. We used flow cytometry and fluorescent microscopy to define the effects of PGN on the activation of human platelets. PGN induced platelet aggregation, expression of the activated form of integrin αIIbβ3, and exposure of phosphatidylserine (PS). These changes were dependent on immunoglobulin G and were attenuated by the Fcγ receptor IIa-blocking antibody IV.3, suggesting they are mediated by PGN-anti-PGN immune complexes signaling through Fcγ receptor IIa. PS exposure was not blocked by IV.3 but was sensitive to inhibitors of complement activation. PGN was a potent activator of the complement cascade in human plasma and caused deposition of C5b-9 on the platelet surface. Platelets with exposed PS had greatly accelerated prothrombinase activity. We conclude that PGN derived from gram-positive bacteria is a potent platelet agonist when complexed with anti-PGN antibody and could contribute to the coagulation dysfunction accompanying gram-positive infections.
Amplifier-Free Bias-Free Receiver Based on Low-Capacitance Nanophotodetector (2017)

The substantial energy dissipation of photoreceivers will obstruct dense photonic-electronic integration in keeping the development of processors and communications on a chip. Nanophotodetectors offer the opportunity to overcome this problem by allowing us to realize an amplifier-free bias-free receiver. Low device capacitance and forward-biased operation are the keys to achieving such a receiver, which can operate with signal light alone, namely without extra electrical energy. A photonic-crystal waveguide combined with an embedded absorber is a good candidate for this purpose, since our simulation reveals that light confinement and carrier depletion in a narrow dimension lead to fast and efficient operation. We also carry out circuit analyses to investigate the receiver performance and compare it with that of a conventional receiver with amplifiers. We show that an amplifier-free bias-free receiver can be expected to offer advantages in terms of energy consumption, signal-to-noise ratio, footprint, and delay.
Thrombospondin promotes platelet aggregation (1988)

Thrombospondin (TSP), isolated from human platelets, promotes aggregation of both nonstimulated platelets and platelets stimulated with thrombin or ADP. The TSP-promoted aggregation is specific since a monoclonal antibody against TSP inhibits the effect of exogenously added TSP and inhibits thrombin-induced platelet aggregation in the absence of added TSP. Several lines of evidence suggest that TSP mediates its effect on aggregation of nonstimulated and stimulated platelets through different platelet-surface receptor systems. The TSP-promoted aggregation of nonstimulated platelets was inhibited by a monoclonal antibody to platelet glycoprotein IV (GPIV), but not by a monoclonal antibody to the fibrinogen receptor, GPIIb-IIIa. In contrast, the antibody to GPIIb-IIIa totally inhibited the TSP-potentiated aggregation of thrombin-stimulated platelets, whereas the antibody to GPIV has no effect. Thus, these studies suggest that TSP promotes platelet aggregation by at least two mechanisms--one dependent on and one independent of the platelet fibrinogen receptor system.
Palmitic Acid-Conjugated 21-Nucleotide siRNA Enhances Gene-Silencing Activity (2011)

Short interfering RNA (siRNA) technology is a powerful tool for suppressing gene expression in mammalian cells. In this study, we focused on the development of siRNAs conjugated with palmitic acid at the 5'-end of the sense strand (C16-siRNAs) using our novel synthesis strategy in order to improve the potency of siRNA. The C16-siRNAs exhibited enhanced nuclease stability. In addition, they showed potent gene-silencing efficacy against exogenous Renilla luciferase in HeLa cells compared with a nonmodified siRNA in the presence of Lipofectamine 2000. The C16-siRNAs also had a more potent inhibitory effect on Renilla luciferase activity than the other siRNA conjugated with lipids at the 5'-end and the 3'-end by palmitoyl conjugation. For further improvement, the gene silencing potency of the C16-siRNAs against the endogenous vascular endothelial growth factor (VEGF) gene in HeLa cells was investigated. In this investigation, the siRNAs were prepared not only with the normal RNA sequence but also coupled with an inverted thymidine (idT) at the 3'-ends of both the sense and antisense strands (siRNA-idT), including palmitic acid conjugations at the 5'-end of the sense strand, to improve stability. The C16-siRNA including idT modifications exhibited a significantly greater inhibitory effect on the VEGF gene in the presence of Lipofectamine 2000. It is noteworthy that C16-siRNA-idT demonstrated long-term gene-silencing efficacy of up to 5 days. Interestingly, the C16-siRNAs, including that with idT modifications, exhibited strong RNAi potency in the absence of any transfection reagents, although only at high concentrations. Both the C16-siRNAs and C16-siRNA-idT induced a high level of membrane permeability in HeLa cells. Our developed C16-siRNAs, particularly C16-siRNA-idT, are thus among the promising candidates for a new generation of modified siRNAs that can solve the many problems associated with siRNA technology.
N‐Terminal Protein Modification by Substrate‐Activated Reverse Proteolysis (2014)

Abstract Although site‐specific incorporation of artificial functionalities into proteins is an important tool in both basic and applied research, it can be a major challenge to protein chemists. Enzymatic protein modification is an attractive goal due to the inherent regio‐ and stereoselectivity of enzymes, yet their specificity remains a problem. As a result of the intrinsic reversibility of enzymatic reactions, proteinases can in principle catalyze ligation reactions. While this makes them attractive tools for site‐specific protein bioconjugation, competing hydrolysis reactions limits their general use. Here we describe the design and application of a highly specific trypsin variant for the selective modification of N‐terminal residues of diverse proteins with various reagents. The modification proceeds quantitatively under native (aqueous) conditions. We show that the variant has a disordered zymogen‐like activation domain, effectively suppressing the hydrolysis reaction, which is converted to an active conformation in the presence of appropriate substrates.
Involvement of the neuregulins and their receptors in cardiac and neural development (1996)

The neuregulin gene encodes a series of polypeptide growth factors that can influence the growth state of target vertebrate cells in culture. Recently, three studies have explored the in vivo function of the neuregulin signaling system in mice by disrupting the genes encoding the neuregulin ligand(1) and two of its receptors, ErbB2(2) and ErbB4(3). Each of the genes is essential for development, and aberrations in cardiac and neural development are particularly prominent in mutant embryos. The observed defects, together with the localization of expression of the neuregulin signaling components within these tissues, highlight a paracrine mechanism for neuregulin-mediated intercellular communication.