gebhart/patrepeval huggingface dataset:
Early Meiotic Transcripts Are Highly Unstable in Saccharomyces cerevisiae (1992)

Meiosis in Saccharomyces cerevisiae requires the induction of a large number of genes whose mRNAs accumulate at specific times during meiotic development. This study addresses the role of mRNA stability in the regulation of meiosis-specific gene expression. Evidence is provided below demonstrating that the levels of meiotic mRNAs are exquisitely regulated by both transcriptional control and RNA turnover. The data show that (i) early meiotic transcripts are extremely unstable when expressed during either vegetative growth or sporulation, and (ii) transcriptional induction, rather than RNA turnover, is the predominant mechanism responsible for meiosis-specific transcript accumulation. When genes encoding the early meiotic mRNAs are fused to other promoters and expressed during vegetative growth, their mRNA half-lives, of under 3 min, are among the shortest known in S. cerevisiae. Since these mRNAs are only twofold more stable when expressed during sporulation, we conclude that developmental regulation of mRNA turnover can be eliminated as a major contributor to meiosis-specific mRNA accumulation. The rapid degradation of the early mRNAs at all stages of the yeast life cycle, however, suggests that a specific RNA degradation system operates to maintain very low basal levels of these transcripts during vegetative growth and after their transient transcriptional induction in meiosis. Studies to identify specific cis-acting elements required for the rapid degradation of early meiotic transcripts support this idea. A series of deletion derivatives of one early meiosis-specific gene, SPO13, indicate that its mRNA contains determinants, located within the coding region, which contribute to the high instability of this transcript. Translation is another component of the degradation mechanism since frameshift and nonsense mutations within the SPO13 mRNA stabilize the transcript.
Direct Conversion of Human Fibroblasts into Neuronal Restricted Progenitors (2014)

Neuronal restricted progenitors (NRPs) represent a type of transitional intermediate cells that lie between multipotent neural progenitors and terminal differentiated neurons during neurogenesis. These NRPs have the ability to self-renew and differentiate into neurons, but not into glial cells, which is considered an advantage for cellular therapy of human neurodegenerative diseases. However, difficulty in the extraction of highly purified NRPs from normal nervous tissue prevents further studies and applications. In this study, we report the conversion of human fetal fibroblasts into human induced NRPs (hiNRPs) in 11 days by using just three defined factors: Sox2, c-Myc, and either Brn2 or Brn4. The hiNRPs exhibited distinct neuronal characteristics, including cell morphology, multiple neuronal marker expression, self-renewal capacity, and a genome-wide transcriptional profile. Moreover, hiNRPs were able to differentiate into various terminal neurons with functional membrane properties but not glial cells. Direct generation of hiNRPs from somatic cells will provide a new source of cells for cellular replacement therapy of human neurodegenerative diseases.
The adult eosinophilic oesophagitis quality of life questionnaire: a new measure of health-related quality of life (2011)

The EoO-QOL-A is a valid and reliable disease-specific HRQOL measure for adult EoO patients. Developing the Adult Eosinophilic Oesophagitis Quality of Life is an important step in guiding treatment practices, improving disease education and standardising research protocols.
Clinical Studies of Cerebral Blood Flow in Alzheimer's Disease (1997)

Studies of Alzheimer's disease using single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have found reductions in blood flow and glucose metabolism in temporal and parietal cortex. In 50 AD patients who underwent neuropsychological testing and SPECT perfusion imaging, we found significant correlations between perfusion and performance on the Mini-Mental Status Examination in the frontal and parietal lobes. In addition, specific correlations between perfusion in the frontal lobes and performance on tests of frontal lobe ability were noted. These findings, while suggesting the importance of perfusion measures in determining clinical features of the disease, do not clearly define perfusion changes as primary, since similar findings have been seen when metabolism is studied. In a separate group of 5 AD patients and 16 controls, we used PET with the perfusion tracer HIPDM and examined cerebrovascular reactivity to carbon dioxide inhalation. We found that in multiple brain regions, including the temporal lobes, AD patients showed robust and significant increases in perfusion in response to carbon dioxide that did not differ from the response seen in the controls. Taken together, these results show that while perfusion changes are important in AD, they are not clearly either primary or limiting.
Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling (2006)

X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X-linked transmission are in accordance to that reported elsewhere (RP2: 15.9% vs. 6-20%; RPGR: 78.4% vs. 55-90%). Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years.
A beta turn in the cytoplasmic tail of the integrin alpha v subunit influences conformation and ligand binding of alpha v beta 3. (1994)

Integrins undergo conformational alterations in response to extracellular or intracellular stimuli, suggesting that structural elements within their exo- and cytoplasmic domains cooperate during transmembrane signaling. In this report, we identify a beta turn in the cytoplasmic tail of the alpha v subunit that impacts the ligand binding and conformation of the alpha v beta 3 heterodimer. Cells expressing a mutant alpha v beta 3 heterodimer composed of a truncated alpha v subunit, alpha v1000, lacking 18 carboxyl-terminal amino acids exhibits wild-type receptor structure and function. However, a truncation mutant, alpha v995, lacking five additional residues (PPQEE), which define a beta turn, is deficient in vitronectin and fibrinogen adhesion. This alteration in adhesive function is associated with two detectable structural changes in the alpha v beta 3 heterodimer. First, the alpha v995 membrane-spanning light chain exhibits retarded electrophoretic mobility on SDS-polyacrylamide gels. Second, the alpha v995 beta 3 receptor shows an altered chymotryptic profile as measured by the loss of a 39-kDa proteolytic fragment from its ectodomain. These findings demonstrate that the ligand binding and structural properties of the intact alpha v beta 3 heterodimer can be influenced by a beta turn within the cytoplasmic tail of its alpha v subunit. The presence of homologous beta turns within other alpha subunit cytoplasmic tails suggests that this structural motif may play a role in regulating integrin-mediated bidirectional transmembrane signals.
ABC of oral health: Periodontal disease (2000)

Most periodontal disease arises from, or is aggravated by, accumulation of plaque, and periodontitis is associated particularly with anaerobes such as Porphyromonas gingivalis, Bacteroides forsythus, and Actinobacillus actinomycetemcomitans. Calculus (tartar) may form from calcification of plaque above or below the gum line, and the plaque that collects on calculus exacerbates the inflammation. The inflammatory reaction is associated with progressive loss of periodontal ligament and alveolar bone and, eventually, with mobility and loss of teeth. 

Periodontal diseases are ecogenetic in the sense that, in subjects rendered susceptible by genetic or environmental factors (such as polymorphisms in the gene for interleukin 1, cigarette smoking, immune depression, and diabetes), the infection leads to more rapidly progressive disease. Osteoporosis also seems to have some effect on periodontal bone loss. 

The possible effects of periodontal disease on systemic health, via pro-inflammatory cytokines, have been the focus of much attention. Studies to test the strength of associations with atherosclerosis, hypertension, coronary heart disease, cerebrovascular disease, and low birth weight, and any effects on diabetic control, are ongoing.
Template stripping using cold welding (2004)

A method for fabricating ultra-flat template-stripped (TS) metal surfaces on standard silicon/silicon-oxide wafers by means of gold cold-welding is presented, and cold-welded template-stripped (CWTS) platinum surfaces are demonstrated as an example. Due to the lack of any adhesives, the final TS metal “sandwiches” are fully compatible with all organic solvents, as well as ultra-high vacuum (UHV). The produced CWTS platinum surfaces are demonstrated to have the same surface properties—most importantly single-angstrom rms roughness—as previously studied TS platinum. The effectiveness of the cold-welding technique is shown to decrease as a function of time exposed to ambient laboratory conditions after removal from vacuum and prior to pressurized cold-welding. Contact angle measurements demonstrate this decrease to be due to a gradual increase in surface contamination of the evaporated gold layers prior to their being joined by cold-welding. The potential versatility and scalability of the CWTS fabrication process is briefly discussed.
Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma (2012)

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the prevalence of HCC, there is no effective, systemic treatment. The transcription factor LSF is a promising protein target for chemotherapy; it is highly expressed in HCC patient samples and cell lines, and promotes oncogenesis in rodent xenograft models of HCC. Here, we identify small molecules that effectively inhibit LSF cellular activity. The lead compound, factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity both in vitro, as determined by electrophoretic mobility shift assays, and in cells, as determined by ChIP. Consistent with such inhibition, FQI1 eliminates transcriptional stimulation of LSF-dependent reporter constructs. FQI1 also exhibits antiproliferative activity in multiple cell lines. In LSF-overexpressing cells, including HCC cells, cell death is rapidly induced; however, primary or immortalized hepatocytes are unaffected by treatment with FQI1. The highly concordant structure-activity relationship of a panel of 23 quinolinones strongly suggests that the growth inhibitory activity is due to a single biological target or family. Coupled with the striking agreement between the concentrations required for antiproliferative activity (GI(50)s) and for inhibition of LSF transactivation (IC(50)s), we conclude that LSF is the specific biological target of FQIs. Based on these in vitro results, we tested the efficacy of FQI1 in inhibiting HCC tumor growth in a mouse xenograft model. As a single agent, tumor growth was dramatically inhibited with no observable general tissue cytotoxicity. These findings support the further development of LSF inhibitors for cancer chemotherapy.
A Sequence in M13 Phage Detects Hypervariable Minisatellites in Human and Animal DNA (1987)

The term "DNA fingerprint" has been used to describe the extensive restriction fragment length polymorphism associated with hypervariable minisatellites present in the human genome. Until now, it was necessary to hybridize Southern blots to specific probes cloned from human genomic DNA in order to obtain individual-specific restriction patterns. The present study describes the surprising finding that the insert-free, wild-type M13 bacteriophage detects hypervariable minisatellites in human and in animal DNA, provided no competitor DNA is used during hybridization. The effective sequence in M13 was traced to two clusters of 15-base pair repeats within the protein III gene of the bacteriophage. This unexpected use of M13 renders the DNA fingerprinting technology more readily available to molecular biology laboratories.
Sunscreens: are they beneficial for health? An overview of endocrine disrupting properties of UV‐filters (2012)

Today, topical application of sunscreens, containing ultraviolet-filters (UV-filters), is preferred protection against adverse effects of ultraviolet radiation. Evidently, use of sunscreens is effective in prevention of sunburns in various models. However, evidence for their protective effects against melanoma skin cancer is less conclusive. Three important observations prompted us to review the animal data and human studies on possible side effects of selected chemical UV-filters in cosmetics. (1) the utilization of sunscreens with UV-filters is increasing worldwide; (2) the incidence of the malignant disorder for which sunscreens should protect, malignant melanoma, is rapidly increasing and (3) an increasing number of experimental studies indicating that several UV-filters might have endocrine disruptive effects. The selected UV-filters we review in this article are benzophenone-3 (BP-3), 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), Homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) and 4-aminobenzoic acid (PABA). The potential adverse effects induced by UV-filters in experimental animals include reproductive/developmental toxicity and disturbance of hypothalamic-pituitary-thyroid axis (HPT). Few human studies have investigated potential side effects of UV-filters, although human exposure is high as UV-filters in sunscreens are rapidly absorbed from the skin. One of the UV-filters, BP-3, has been found in 96% of urine samples in the US and several UV-filters in 85% of Swiss breast milk samples. It seems pertinent to evaluate whether exposure to UV-filters contribute to possible adverse effects on the developing organs of foetuses and children.
Growth Factor Mediated Assembly of Cell Receptor-Responsive Hydrogels (2007)

The design of materials in which assembly, mechanical response, and biological properties are controlled by protein-polysaccharide interactions may mimic the biological environment, be responsive to appropriate biological cues, and find use in many biomedical applications. Here we report the assembly of hydrogels via the noncovalent interaction of heparin-functionalized, star-PEG polymers and the therapeutically relevant, heparin-binding protein VEGF (vascular endothelial growth factor). The viscoelastic properties of these hydrogels, and the specificity of VEGF in crosslinking, were assessed via laser tweezer microrheology. The receptor-mediated delivery of VEGF, with concurrent erosion of the hydrogels, was indicated via radiometry assays of the hydrogels in the presence of VEGFR-2-modified particles, and the specificity of this interaction was indicated by a lack of erosion of the hydrogels when incubated with particles modified with a protein lacking affinity for VEGF. The VEGF delivered from the hydrogels is bioactive as assessed via cell proliferation and live/dead assays. These results indicate the potential for targeted delivery of growth factors and erosion of hydrogels on the basis of ligand-receptor interactions that occur between cells and the extracellular matrix. The therapeutic relevance of other dimeric heparin-binding growth factors, as well as opportunities for designing peptides with specific affinities and therapeutic action, suggests broader opportunities for these strategies in the production of responsive matrices for biomedical applications.
Passive Inhalation of Marijuana Smoke: Urinalysis and Room Air Levels of Delta-9-Tetrahydrocannabinol (1987)

In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [THC]) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.
Pyrvinium Targets the Unfolded Protein Response to Hypoglycemia and Its Anti-Tumor Activity Is Enhanced by Combination Therapy (2008)

We identified pyrvinium pamoate, an old anthelminthic medicine, which preferentially inhibits anchorage-independent growth of cancer cells over anchorage-dependent growth (approximately 10 fold). It was also reported by others to have anti-tumor activity in vivo and selective toxicity against cancer cells under glucose starvation in vitro, but with unknown mechanism. Here, we provide evidence that pyrvinium suppresses the transcriptional activation of GRP78 and GRP94 induced by glucose deprivation or 2-deoxyglucose (2DG, a glycolysis inhibitor), but not by tunicamycin or A23187. Other UPR pathways induced by glucose starvation, e.g. XBP-1, ATF4, were also found suppressed by pyrvinium. Constitutive expression of GRP78 via transgene partially protected cells from pyrvinium induced cell death under glucose starvation, suggesting that suppression of the UPR is involved in pyrvinium mediated cytotoxicity under glucose starvation. Xenograft experiments showed rather marginal overall anti-tumor activity for pyrvinium as a monotherapy. However, the combination of pyrvinium and Doxorubicin demonstrated significantly enhanced efficacy in vivo, supporting a mechanistic treatment concept based on tumor hypoglycemia and UPR.
Separation-Free Sandwich Enzyme Immunoassays Using Microporous Gold Electrodes and Self-Assembled Monolayer/Immobilized Capture Antibodies (1994)

A novel separation-free sandwich-type enzyme immunoassay for proteins is performed by designing an electrochemical detection system that enables preferential measurement of surface-bound enzyme-labeled antibody relative to the excess enzyme-labeled reagent in the bulk sample solution. In this initial model system, the assay is carried out using gold-coated microporous nylon membranes (pore size 0.2 micron) which are mounted between two chambers of a diffusion cell. The membrane serves as both a solid phase for the sandwich assay and the working electrode in the three-electrode amperometric detection system. The capture monoclonal antibody is immobilized covalently on the gold side of the membrane via a self-assembled monolayer of thioctic acid. In the separation-free sandwich assay, both model analyte protein (human chorionic gonadotropin; hCG) and alkaline phosphatase labeled anti-hCG (ALP-Ab) are incubated simultaneously with the immobilized capture anti-hCG antibody. Surface-bound ALP-Ab is spatially resolved from the excess conjugate in the bulk sample solution by introducing the enzyme substrate (4-aminophenyl phosphate) through the back side of the porous membrane. The substrate diffuses rapidly through the porous membrane where it first encounters bound ALP-Ab at the gold surface. The enzymatically generated product, aminophenol, is detected immediately by oxidation at the gold electrode (at +0.19 V vs Ag/AgCl), and the magnitude of current is directly proportional to the concentration of hCG in the sample. The response time after substrate addition is less than 1 min, although maximum response toward the analyte protein requires a sample/conjugate preincubation time of 30 min with the porous electrode.(ABSTRACT TRUNCATED AT 250 WORDS)
Insertional inactivation of binding determinants of Streptococcus crista CC5b using Tn916 (1995)

Intermicrobial binding plays an important role in the ecology of the oral cavity because it represents one mechanism by which specific bacteria colonize dental plaque. The formation of "corncobs", a morphologically distinct microbial unit composed of Streptococcus crista and Fusobacterium nucleatum, is a highly specific binding interaction that depends on the presence of polar tufts of fimbriae on the streptococci. We have used a genetic approach to examine the role of streptococcal cell surface components involved in the binding of S. crista to F. nucleatum. Such binding may be an important component of corncob formation. A method for the genetic transformation of S. crista was used to transfer the broad host range transposon, Tn916, into the bacteria. Cells were grown to early log phase in brain heart infusion broth containing 10% fetal calf serum. The competent cells were mixed with purified DNA from pDL916, a plasmid construct consisting of Tn916 and the streptococcal/Escherichia coli shuttle vector pDL278. Over 300 transformants were screened for a reduction in binding to F. nucleatum. Five of the transformants showed a change in binding ranging from 59% to 29% of the positive control values. Southern blots revealed that the binding-deficient transformants contained the Tn916 element integrated into one of 4 different sites in the chromosome. The transposon, integrated into 4 different sites, appeared to be stable in the absence of selective pressure. Based on these findings, it appears that some strains of S. crista are naturally competent and that insertional inactivation methods can be used to facilitate the study of binding receptors in this group of oral streptococci.