gebhart/patrepeval huggingface dataset:
Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol (2008)

Saccharomyces cerevisiae was engineered with an n-butanol biosynthetic pathway, in which isozymes from a number of different organisms (S. cerevisiae, Escherichia coli, Clostridium beijerinckii, and Ralstonia eutropha) were substituted for the Clostridial enzymes and their effect on n-butanol production was compared. By choosing the appropriate isozymes, we were able to improve production of n-butanol ten-fold to 2.5 mg/L. The most productive strains harbored the C. beijerinckii 3-hydroxybutyryl-CoA dehydrogenase, which uses NADH as a co-factor, rather than the R. eutropha isozyme, which uses NADPH, and the acetoacetyl-CoA transferase from S. cerevisiae or E. coli rather than that from R. eutropha. Surprisingly, expression of the genes encoding the butyryl-CoA dehydrogenase from C. beijerinckii (bcd and etfAB) did not improve butanol production significantly as previously reported in E. coli. Using metabolite analysis, we were able to determine which steps in the n-butanol biosynthetic pathway were the most problematic and ripe for future improvement.
Some Relations between Reaction Rates and Equilibrium Constants. (1935)

ADVERTISEMENT RETURN TO ISSUEPREVArticleSome Relations between Reaction Rates and Equilibrium Constants.Louis P. HammettCite this: Chem. Rev. 1935, 17, 1, 125–136Publication Date (Print):August 1, 1935Publication History Published online1 May 2002Published inissue 1 August 1935https://pubs.acs.org/doi/10.1021/cr60056a010https://doi.org/10.1021/cr60056a010research-articleACS PublicationsRequest reuse permissionsArticle Views5501Altmetric-Citations727LEARN 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
Rapid Differentiation of “ Mycobacterium canettii ” from Other Mycobacterium tuberculosis Complex Organisms by PCR-Restriction Analysis of the hsp65 Gene (2001)

A total of 102 isolates of the Mycobacterium tuberculosis complex, including available "M. canettii" isolates, were studied by PCR-restriction analysis of a 441-bp fragment of the hsp65 gene. PRA upon HhaI enzyme digestion (GCGC) allowed easy differentiation of "M. canettii" from other members of the M. tuberculosis complex (three bands of 260, 105, and 60 bp for "M. canetti," compared to four bands of 185, 105, 75, and 60 bp for other members of the M. tuberculosis complex). Sequencing of the 441-bp hsp65 fragment of "M. canettii" isolates showed the disappearance of an HhaI site at position 235 due to a C-to-T transition that corresponded to position 631 of the homologous hsp65 gene of M. tuberculosis H37Rv. Considering that "M. canettii" may also exist as a stable rough morphotype, we suggest that the true number of "M. canettii" isolates may be underestimated in clinical microbiology laboratories.
Activated IGF-1R inhibits hyperglycemia-induced DNA damage and promotes DNA repair by homologous recombination (2005)

The IGF-1R is a genetic determinant of oxidative stress and longevity. Hyperglycemia induces an exponential increase in the production of a key danger signal, reactive oxygen intermediates, which target genomic DNA. Here, we report for the first time that ligand activation of the IGF-1R prevents hyperglycemia-induced genotoxic stress and enhances DNA repair, maintaining genomic integrity and cell viability. We performed single gel electrophoresis (comet assay) to evaluate DNA damage in serum-starved SV40 murine mesangial cells (MMC) and normal human mesangial cells (NHMC), maintained at high ambient glucose concentration. Hyperglycemia inflicted an impressive array of DNA damage in the form of single-strand breaks (SSBs) and double-strand breaks (DSBs). The inclusion of IGF-1 to culture media of MMC and NHMC prevented hyperglycemia-induced DNA damage. To determine whether DNA damage was mediated by reactive oxygen species (ROS), ROS generation was evaluated, in the presence of IGF-1, or the free radical scavenger n-acetyl-cysteine (NAC). IGF-1 and NAC inhibited hyperglycemic-induced ROS production and hyperglycemia-induced DNA damage. We next asked whether IGF-1 promotes the repair of DSB under hyperglycemic conditions, by homologous recombination (HRR) or nonhomologous end joining (NHEJ). Repair of DSB by NHEJ and HRR was operative in MMC maintained under hyperglycemic conditions. IGF-1 increased HRR by nearly twofold, whereas IGF-1 did not affect DNA repair by NHEJ. IGF-1R enhancement of HRR correlated with the translocation of Rad51 to foci of DNA damage. Inhibition of Rad51 expression by short interfering RNA experiments markedly decreased percentage of MMC positive for Rad51 nuclear foci and increased hyperglycemic DNA damage. We conclude that the activated IGF-1R rescues mesangial cells from hyperglycemia-induced danger signals that target genomic DNA by suppressing ROS and enhancing DNA repair by HRR.
Acamprosate in alcohol dependence: how does it work? (2003)

Acamprosate is a relatively new drug that appears to be clinically useful in the treatment of alcohol dependence. Although it has proved effective in reducing relapse into drinking in clinical trials its exact mechanism of action is uncertain. Evidence is presented that the drug does not act in any of the conventional ways to reduce alcohol intake and it is proposed that it may be a novel kind of agent that suppresses "craving". On the basis of its known pharmacological effects in pre-clinical studies it is suggested that acamprosate may reduce craving that is associated with conditioned withdrawal. In addition to the potential therapeutic value of acamprosate, the drug may be useful because work directed toward understanding its mechanism of action may shed light on some of the fundamental processes that govern alcohol abuse and relapse in weaned alcohol dependent patients.
Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8 (2006)

Mammalian oogenesis requires oocyte-specific transcriptional regulators. The full complement of oocyte-specific transcription factors is unknown. Here, we describe the finding that Sohlh1, a spermatogenesis and oogenesis basic helix-loop-helix transcription factor in females, is preferentially expressed in oocytes and required for oogenesis. Sohlh1 disruption perturbs follicular formation in part by causing down-regulation of two genes that are known to disrupt folliculogenesis: newborn ovary homeobox gene (Nobox) and factor in the germ-line alpha (Figla). In addition, we show that Lhx8 is downstream of Sohlh1 and critical in fertility. Thus, Sohlh1 and Lhx8 are two germ cell-specific, critical regulators of oogenesis.
Ecology and evolution of bacterial microdiversity (2000)

Using high resolution molecular fingerprinting techniques like random amplification of polymorphic DNA, repetitive extragenic palindromic PCR and multilocus enzyme electrophoresis, a high bacterial diversity below the species and subspecies level (microdiversity) is revealed. It became apparent that bacteria of a certain species living in close association with different plants either as associated rhizosphere bacteria or as plant pathogens or symbiotic organisms, typically reflect this relationship in their genetic relatedness. The strain composition within a population of soil bacterial species at a given field site, which can be identified by these high resolution fingerprinting techniques, was markedly influenced by soil management and soil features. The observed bacterial microdiversity reflected the conditions of the habitat, which select for better adapted forms. In addition, influences of spatial separation on specific groupings of bacteria were found, which argue for the occurrence of isolated microevolution. In this review, examples are presented of bacterial microdiversity as influenced by different ecological factors, with the main emphasis on bacteria from the natural environment. In addition, information available from some of the first complete genome sequences of bacteria (Helicobacter pylori and Escherichia coli) was used to highlight possible mechanisms of molecular evolution through which mutations are created; these include mutator enzymes. Definitions of bacterial species and subspecies ranks are discussed in the light of detailed information from whole genome typing approaches.
Flip and Flop: A Cell-Specific Functional Switch in Glutamate-Operated Channels of the CNS (1990)

In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.
The effect of solar ultraviolet radiation (UVR) on induction of skin cancers (2016)

Ultraviolet radiation is a physical mutagenic and cancerogenic factor. About 95% of ultraviolet A (UVA) (320-400 nm) and 5% of UVB (280-320 nm) reach the Earth's surface. Melanin is a natural skin protective factor against UV radiation. Skin cancers associated with long-term exposure to UV radiation are: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). The high risk of BCC development is related to acute and repeated exposure to UV causing sunburn. Molecular studies of BBC demonstrated disorders in sonic hedgehog (SHH) cell signaling regulation pathway, associated with the suppressor protein patched homolog 1 gene (PTCH1) mutations. The risk of the BCC development is related to the polymorphism of melanokortin-1 receptor gene (MC1R). Tumor P53 gene mutations observed in BCC cells has been classified as secondary genetic changes. In SCC cells UV-induced mutations were mostly related to P53 gene. Increased expression of cyclooxigenase- 2 gene (COX-2) plays a significant role in the development of SCC. Other pathogenetic factors include intensification of the synthesis of pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1β and IL-6). Currently, the role of UVB has been recognized in the pathogenesis of CMM. In CMM cells the following gene mutations were noted: cyclindependent kinase inhibitor 2A INK4A (p16INK4A), cyclin-dependent kinase 4 (CDK4), Ras, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and proto-oncogene B-Raf (BRAF). The BRAF gene mutations were observed in ~50% of CMM cases. Mutations of P53 gene are not characteristic of CMM cells. Med Pr 2016;67(2):255-266.
Cloned, stably expressed parathyroid hormone (PTH)/PTH-related peptide receptors activate multiple messenger signals and biological responses in LLC-PK1 kidney cells. (1993)

PTH elicits multiple second messenger signals in target cells. This signaling diversity may reflect coupling of a single species of PTH receptors to multiple effectors, the action of different subtypes of PTH receptors, or both. We recently reported the expression cloning, from rat and opossum cells, of closely related cDNAs encoding receptors for PTH [and PTH-related peptide (PTHRP)]. To determine if these cloned PTH/PTHRP receptors can activate multiple intracellular effectors when present at near-physiological levels in intact target cells, we have stably expressed the rat and opossum PTH/PTHRP receptor cDNAs in LLC-PK1 porcine renal epithelial cells. These cells lack endogenous PTH/PTHRP receptors, but do express abundant calcitonin receptors and many features of a proximal tubular phenotype. Subclones of transfected LLC-PK1 cells exhibited high affinity binding (Kd, 1-5 nM) of [Nle8.18,Tyr34]bovine PTH-(1-34)amide (PTH) and dose-dependent activation by PTH of both cAMP accumulation (EC50, 1 nM) and increased release of cytosolic free calcium from intracellular stores (EC50, > or = 20-50 nM) across a wide range of receptor expression. Expressed rat and opossum receptors exhibited similar properties, except for a 5-fold lower binding affinity of the rat receptor for PTH-(7-34). Stimulation by PTH of both cAMP accumulation and elevated cytosolic free calcium was augmented in cells expressing higher numbers of PTH/PTHRP receptors. Like calcitonin, PTH (1-100 nM) reduced the rate of cell proliferation and augmented the rate of inorganic phosphate transport after 24 and 5 h of preincubation, respectively. The growth effect was mimicked by cAMP analogs, forskolin, phorbol esters, and calcium ionophores. Regulation of phosphate transport, however, was mimicked by phorbols, but not by cAMP analogs or forskolin. We conclude that LLC-PK1 cells provide a useful model in which to study the function of cloned PTH/PTHRP receptors. In these cells, a single species of cloned PTH/PTHRP receptors, stably expressed at near-physiological numbers, activates multiple second messenger responses and regulates subsequent biological responses, including at least one (phosphate transport) that is mediated by mechanisms independent of cAMP.
Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. (1993)

Nitric oxide (NO) has antimicrobial activity against a wide spectrum of infectious pathogens, but an antiviral effect has not been reported. The impact of NO, from endogenous and exogenous sources, on herpes simplex virus type 1 (HSV 1) replication was studied in vitro. HSV 1 replication in RAW 264.7 macrophages was reduced 1,806-fold in monolayers induced to make NO by activation with gamma IFN and LPS. A competitive and a noncompetitive inhibitor of nitric oxide synthetase substantially reduced the antiviral effect of activated RAW macrophages. S-nitroso-L-acetyl penicillamine (SNAP) is a donor of NO and was added to the media of infected monolayers to assess the antiviral properties of NO in the absence of gamma IFN and LPS. A single dose of S-nitroso-L-acetyl penicillamine 3 h after infection inhibited HSV 1 replication in Vero, HEp2, and RAW 264.7 cells in a dose-dependent manner. Neither virucidal nor cytocidal effects of NO were observed under conditions that inhibited HSV 1 replication. Nitric oxide had inhibitory effects, comparable to that of gamma IFN/LPS, on protein and DNA synthesis as well as on cell replication. This report demonstrates that, among its diverse properties, NO has an antiviral effect.
miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury (2012)

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Their roles in regulating the responses of Schwann cells (SCs) to injury stimuli remain unexplored. Here we report dynamic alteration of miRNA expression following rat sciatic nerve injury using microarray analysis. We harvested the proximal nerve stumps and identified 77 miRNAs that showed significant changes at four time points after nerve transection. Subsequently, we analyzed the expression pattern of miRNA, selected one significant profile, and then integrated putative miRNA targets with differentially expressed mRNA yielding 274 potential targets. The 274 targets were mainly involved in cell proliferation, cell locomotion and cellular homeostasis that were known to play important roles in modulating cell phenotype. The upregulation of the miR-221 and miR-222 cluster (miR-221/222) was found to correlate with the injury-induced SC phenotypic modulation. Enhanced expression of miR-221/222 could promote SC proliferation and migration in vitro, whereas silencing their expression resulted in a reduced proliferation and migration. Further studies revealed that longevity assurance homologue 2 (LASS2) was a direct target of miR-221/222 in SCs because miR-221/222 bound directly to the 3'-untranslated region of LASS2, thus reducing both mRNA and protein levels of LASS2. Silencing of LASS2 recapitulated the effects of miR-221/222 mimics, whereas enforced knockdown of LASS2 reversed the suppressive effects of miR-221/222 inhibitors. Our findings indicate that injury promotes SC proliferation and migration through the regulation of miR-221/222 by targeting LASS2, and provide new insights into the role of miRNAs in nerve regeneration.
Identification of a novel first exon in the human dystrophin gene and of a new promoter located more than 500 kb upstream of the nearest known promoter. (1994)

The dystrophin gene, which is mutated in patients with Duchenne and Becker muscular dystrophies, is the largest known human gene. Five alternative promoters have been characterized until now. Here we show that a novel dystrophin isoform with a different first exon can be produced through transcription initiation at a previously unidentified alternative promoter. The case study presented is that of a patient with Duchenne muscular dystrophy who had a deletion extending from the 5' end of the dystrophin gene to exon 2, including all promoters previously mapped in the 5' part of the gene. Transcripts from lymphoblastoid cells were found to contain sequences corresponding to exon 3, indicating the presence of new promoter upstream of this exon. The nucleotide sequence of amplified cDNA corresponding to the 5' end of the new transcript indicated that the 5' end of exon 3 was extended by 9 codons, only the last (most 3') of which codes for methionine. The genomic nucleotide sequence upstream from the new exon, as determined using inverse polymerase chain reaction, revealed the presence of sequences similar to a TATA box, an octamer motif and an MEF-2 element. The identified promoter/exon did not map to intron 2, as might have been expected, but to a position more than 500 kb upstream of the most 5' of the previously identified promoters, thereby adding 500 kb to the dystrophin gene. The sequence of part of the new promoter region is very similar to that of certain medium reiteration frequency repetitive sequences. These findings may help us understand the molecular evolution of the dystrophin gene.
Arg‐Gly‐Asp constrained within cyclic pentapoptides Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1 (1991)

Cyclic Arg-Gly-Asp-Phe-Val peptides with either D-Phe or D-Val residues were 20- to more than 100-fold better inhibitors of cell adhesion to vitronectin and/or laminin fragment P1 when compared to a linear variant or Gly-Arg-Gly-Asp-Ser. No or only little increase in inhibitory capacity was observed for fibronectin adhesion and for the binding of platelet receptor alpha IIb beta 3 to fibrinogen. NMR studies of the two most active cyclic peptides showed for both an all-trans conformation with a beta II' and gamma turn. Subtle conformational differences, however, exist between both peptides and may contribute to selectivity of inhibition.
Chronic Fluoxetine Increases Extra-Hippocampal Neurogenesis in Adult Mice (2014)

By identifying novel cellular targets of fluoxetine, our results may provide new insight into the mechanisms underlying antidepressant responses.
Chemotherapeutic properties of prominent nitrofurans (1976)

Nitrofurazone, nitrofurantoin and furazolidone are rather broad spectrum antimicrobial agents effective against both Gram-positive and Gram-negative bacteria. Nitrofurazone has been found to be effective also against certain trypanosomes and furazolidone against trichomonads and Giardia. Resistance to these nitrofurans develops rather slowly and is seldom complete. In practice, resistance development has not been a significant problem over the many years that these compounds have been in use. Cross-resistance with antibiotics and sulphonamides has not been observed and transferable resistance is at most a very rare phenomenon. The precise mode of action of the nitrofurans has not been elucidated, however, they are known to inhibit the actions of a number of bacterial enzymes. Adverse reactions to these compounds have been observed but the incidence of severe reactions is relatively low. At present nitrofurazone is used primarily as a topical agent, furazolidone as a gastrointestinal agent and nitrofurantoin for infections of the urinary tract. Of the three, nitrofurantoin is currently the one most extensively used in human medicine.
Evaluation of vinorelbine-based chemotherapy as the second or further-line treatment in patients with metastatic breast cancer (2013)

Vinorelbine alone or in combination with 5-FU is an effective and safe treatment for pretreated advanced/ metastatic breast cancer patients. The combination of vinorelbine with 5-FU appears to be a more efficacious regimen than vinorelbine alone.
The Impact of Tower Shadow, Yaw Error, and Wind Shears on Power Quality in a Wind–Diesel System (2009)

To study the impact of aerodynamic aspects of a wind turbine (WT) (i.e., tower shadow, wind shears, yaw error, and turbulence) on the power quality of a wind-diesel system, all electrical, mechanical, and aerodynamic aspects of the WT must be studied. Moreover, the contribution of the diesel generator system and its controllers should be considered. This paper describes how the aerodynamic and mechanical aspects of a WT can be simulated using TurbSim, AeroDyn, and FAST where the electrical parts of WT, diesel generator, its controllers, and electrical loads are modeled by Simulink blocks. Simulation results obtained from the model are used to observe the power and voltage variations at the WT generator terminals under different operating conditions. Furthermore, the effects of tower shadow, wind shears, yaw error, and turbulence on the power quality in a stand-alone wind-diesel system utilizing a fixed-speed WT are studied.
Vλ and Jλ‐Cλ gene segments of the human immunoglobulin λ light chain locus are separated by 14 kb and rearrange by a deletion mechanism (1991)

We have cloned a region of 124 kb of the human immunoglobulin lambda light chain locus on chromosome 22 encompassing seven V lambda and seven J-C lambda gene segments. No further C lambda gene segment was found in a region of 35 kb downstream of C lambda 7, which encodes the Ke+Oz- isotype. The C lambda proximal V lambda gene segment V lambda III. 1 is located 14.5 kb upstream of C lambda 1. The five sequenced V lambda genes have the same transcriptional orientation as the J-C lambda gene segments which is likely to be true for the majority of the V lambda gene segments in the human lambda locus and which suggests a deletion mechanism for DNA rearrangement. This is supported by hybridization of V lambda gene probes to germ-line and rearranged DNA from lambda light chain-producing cell lines. Sequences of 23 cDNA clones allow to establish a V lambda subgroup classification based on nucleic acid sequence data and an estimate of the J-C lambda usage.