gebhart/patrepeval huggingface dataset:
Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification (2004)

MicroRNAs are approximately 22-nucleotide (nt) RNAs processed from foldback segments of endogenous transcripts. Some are known to play important gene regulatory roles during animal and plant development by pairing to the messages of protein-coding genes to direct the post-transcriptional repression of these messages. Previously, we developed a computational method called MiRscan, which scores features related to the foldbacks, and used this algorithm to identify new miRNA genes in the nematode Caenorhabditis elegans. In the present study, to identify sequences that might be involved in processing or transcriptional regulation of miRNAs, we aligned sequences upstream and downstream of orthologous nematode miRNA foldbacks. These alignments showed a pronounced peak in sequence conservation about 200 bp upstream of the miRNA foldback and revealed a highly significant sequence motif, with consensus CTCCGCCC, that is present upstream of almost all independently transcribed nematode miRNA genes. Scoring the pattern of upstream/downstream conservation, the occurrence of this sequence motif, and orthology of host genes for intronic miRNA candidates, yielded substantial improvements in the accuracy of MiRscan. Nine new C. elegans miRNA gene candidates were validated using a PCR-sequencing protocol. As previously seen for bacterial RNA genes, sequence features outside of the RNA secondary structure can therefore be very useful for the computational identification of eukaryotic noncoding RNA genes. The total number of confidently identified nematode miRNAs now approaches 100. The improved analysis supports our previous assertion that miRNA gene identification is nearing completion in C. elegans with apparently no more than 20 miRNA genes now remaining to be identified.
Comparison of speed of sound and ultrasound attenuation in the os calcis to bone density of the radius, femur and lumbar spine (1989)

Broadband ultrasonic attenuation (BUA) between 0.1 and 0.6 MHz and speed of sound (SOS) were measured on the os calcis in normal women (n = 40), and women who had mild osteoporosis (n = 36). Comparisons were made between the ultrasonic properties and bone mineral densities (BMD) obtained using photon absorptiometry on the lumbar spine, proximal femur and radius shaft. In the osteoporotic women, whose spine BMD was significantly reduced, BUA and SOS were lower, to about the same degree of significance as radius BMD; ROC analysis demonstrated that for discrimination of spinal osteopenia, the area under the ROC curve was similar for radius BMD, SOS, and BUA. There was a modest correlation (r about 0.65) between either SOS or BUA on the os calcis and BMDs of the spine and radius. Correlations of the SOS and BUA with femoral neck BMD were lower (r about 0.4 to 0.5). The standard error of estimate for both spine and femoral neck BMD was too high (about 0.14 g cm-2) for os calcis measurements to be substituted clinically for densitometry at these fracture sites.
Short technical reports. Modification of the TRI reagent procedure for isolation of RNA from polysaccharide- and proteoglycan-rich sources. (1995)

A modification of the TRI Reagent procedure has been elaborated for isolation of RNA from polysaccharide- and proteoglycan-rich material. In the modified procedure, RNA is precipitated from the aqueous phase by the combined action of isopropanol and a high-salt concentration. Under these conditions, RNA is effectively precipitated while contaminating polysaccharides and proteoglycans remain in the soluble form. The modified precipitation does not prolong or increase the complexity of the TRI Reagent procedure. The new procedure was tested by isolation of RNA from polysaccharide- and proteoglycan-rich tissues such as rat liver and aorta.
Poly‐gamma‐glutamate in bacteria (2006)

Poly-gamma-glutamate (PGA), a natural polymer, is synthesized by several bacteria (all Gram-positive), one archaea and one eukaryote. PGA has diverse biochemical properties, enabling it to play different roles, depending on the organism and its environment. Indeed, PGA allows bacteria to survive at high salt concentrations and may also be involved in virulence. The minimal gene sets required for PGA synthesis were recently defined. There are currently two nomenclatures depending on the PGA final status: cap, for 'capsule', when PGA is surface associated or pgs, for 'polyglutamate synthase', when PGA is released. The minimal gene sets contain four genes termed cap or pgs B, C, A and E. The PGA synthesis complex is membrane-anchored and uses glutamate and ATP as substrates. Schematically, the reaction may be divided into two steps, PGA synthesis and PGA transport through the membrane. PGA synthesis depends primarily on CapB-CapC (or PgsB-PgsC), whereas PGA transport requires the presence, or the addition, of CapA-CapE (or PgsAA-PgsE). The synthesis complex is probably responsible for the stereochemical specificity of PGA composition. Finally, PGA may be anchored to the bacterial surface or released. An additional enzyme is involved in this reaction: either CapD, a gamma-glutamyl-transpeptidase that catalyses anchorage of the PGA, or PgsS, a hydrolase that facilitates release. The anchoring of PGA to the bacterial surface is important for virulence. All cap genes are therefore potential targets for inhibitors specifically blocking PGA synthesis or anchorage.
Endoglin Regulates Trophoblast Differentiation along the Invasive Pathway in Human Placental Villous Explants* (1997)

Successful invasion of the maternal vascular system by trophoblast cells is a prerequisite for the establishment of a normal hemochorial placenta. Transforming growth factor-beta (TGFbeta) has been implicated in the regulation of trophoblast invasiveness into the uterus. Endoglin is a component of the TGFbeta receptor complex that binds beta1 and beta3 isoforms and is expressed at high levels on syncytiotrophoblast throughout pregnancy and is also transiently up-regulated on extravillous trophoblasts differentiating along the invasive pathway. We investigated the role of endoglin in a serum-free human villous explant culture system that allows the study of trophoblast outgrowth, migration, and invasion and mimics events occurring in anchoring villi during the first trimester of gestation. Addition to explant cultures from 5-8 weeks gestation of a monoclonal antibody to endoglin or of antisense endoglin oligonucleotides significantly stimulated trophoblast outgrowth and migration. These responses were specific, as incubation of explants with nonimmune IgG or sense and scrambled oligonucleotides had no effect. Antisense endoglin-induced trophoblast outgrowth and migration were accompanied by cell division of villous-associated trophoblasts within the proximal region of the forming column and by the characteristic switch in integrins observed in anchoring villi in situ. Treatment of villous explants with antibody and antisense oligonucleotides to endoglin also resulted in an increased fibronectin release into the culture medium. The stimulatory effect of antisense endoglin on fibronectin production was overcome by the addition of exogenous TGFbeta2, but not TGFbeta1 and -beta3. These findings suggest that endoglin expression in the transition from polarized to nonpolarized trophoblasts in anchoring villi is necessary for mediation of the inhibitory effect of TGFbeta1 and/or TGFbeta3 on trophoblast differentiation along the invasive pathway.
Site-specific interaction of vaccinia virus topoisomerase I with duplex DNA. Minimal DNA substrate for strand cleavage in vitro. (1991)

Site-specific interaction of vaccinia virus topoisomerase I with duplex DNA.Minimal DNA substrate for strand cleavage in vitro.
A facility for characterizing the steady-state and dynamic thermal performance of microelectromechanical system thermal switches (2008)

A facility to characterize microelectromechanical system (MEMS) thermal switches by measuring two pertinent figures of merit is described. The two figures of merit measured are the ratio of thermal resistance of the switch in the off and on states, Roff/Ron, and the time required to switch from the off to the on state, tauswitch. The facility consists of two pieces of equipment. A guard-heated calorimeter is used to measure heat transfer across the thermal switch under steady-state conditions. Measuring heat transfer across a thermal switch in both the off and on states then gives the thermal resistance ratio Roff/Ron. A thin-film radial heat-flux sensor is used to measure heat transfer across the thermal switch under dynamic conditions. Measuring heat transfer across a thermal switch as the switch changes from the off to the on state gives the thermal switching time tauswitch. The test facilities enable the control of the applied force on the thermal switch when the thermal switch is on, the thickness of the gas gap when the thermal switch is off, and the gas species and pressure in the thermal switch gas gap. The thermal performance of two MEMS thermal switches employing two different thermal contact materials, a polished silicon surface and an array of liquid-metal microdroplets, is characterized and compared.
RNA sorting in Xenopus oocytes and embryos (1999)

Cytoplasmic localization of mRNA molecules has emerged as a powerful mechanism for generating spatially restricted gene expression. This process is an important contributor to cell polarity in both somatic cells and oocytes, and can provide the basis for patterning during embryonic development. In vertebrates, this phenomenon is perhaps best documented in the frog, Xenopus laevis, where polarity along the animal-vegetal axis coincides with the localization of numerous mRNA molecules. Research over the last several years has made exciting progress toward understanding the molecular mechanisms underlying cytoplasmic mRNA localization.
The CtBP binding domain in the adenovirus E1A protein controls CR1- dependent transactivation (1996)

The adenovirus E1A-243R protein has the ability to force a resting cell into uncontrolled proliferation by modulating the activity of key targets in cell cycle control. Most of these regulatory mechanisms are dependent on activities mapping to conserved region 1 (CR1) and the non-conserved N-terminal region of E1A. We have previously shown that CR1 functions as a very patent transactivator when it is tethered to a promoter through a heterologous DNA binding domain. However, artificial DNA binding was not sufficient to convert full-length E1A-243R to a transactivator. Thus, an additional function(s) of the E1A-243R protein modulates the effect of CR1 in transcription regulation. Here we demonstrate that a 44 amino acid region at the extreme C-terminus of ElA inhibited transactivation by a Gal4-CR1 fusion protein. Inhibition correlated with binding of the nuclear 48 kDa C-terminal binding protein (CtBP), which has been implicated in E1A-mediated suppression of the metastazing potential of tumour cells. This might suggest that CtBP binding can regulate E1A-mediated transformation by modulating CR1-dependent control of transcription.
Expression of homeobox genes, including an insulin promoting factor, in the murine yolk sac at the time of hematopoietic initiation (1997)

The visceral yolk sac (YS), a simple bilayer structure formed during gastrulation, supplies blood cells and intestine- and liver-like functions to support embryonic growth. To better understand gene regulation in extraembryonic tissues, we examined the early murine YS for expression of the homeobox family of developmental transcription regulators. We identified a subset of known homeobox sequences (Hox a1, b1, a9, c9, a7, b7, b8, a10, cdx-1, and PDX-1), as well as two novel homeodomains consisting of a fourth labial class Hox genes and one that matches the Antennapedia class on the amino acid level. The two most frequently isolated YS Hox genes, a9 and c9, are initially expressed only in the YS (E7.5) and subsequently expressed in both the embryo and YS (E8.5). Another of the identified genes, PDX-1, is involved in pancreatic development and insulin regulation. Whereas the rodent YS is known to produce insulin from mid to late gestation, YS insulin expression had not been examined earlier in development. We detected insulin mRNA in the YS at both E7.5 and E8.5, prior to expression in the embryo proper or formation of the pancreas. However, other pancreatic products, such as glucagon, somatostatin, and carboxypeptidase A, are not expressed in the YS. In situ analysis indicates insulin is produced in YS mesothelial cells and endoderm cells, but not in blood cells. We hypothesize the early expression of insulin in the YS is required for the expansion of insulin responsive cells including primitive erythroblasts. Mol. Reprod. Dev. 48:145–153, 1997. © 1997 Wiley-Liss, Inc.
Design and development of BACE-1 inhibitors. (2004)

In early 1999, beta-amyloid cleaving enzyme-1 (BACE-1) was identified as the protease responsible for the critical first step in the processing of beta-amyloid precursor protein that ultimately leads to the production of Abeta peptides in the brain. Accumulation of these peptides has been implicated in the pathology of Alzheimer's disease (AD). An inhibitor of BACE-1 would therefore have therapeutic potential to slow or halt the progression of this debilitating and ultimately fatal disease. This review provides a perspective on the recent developments in the design of BACE-1 inhibitors. An overview of early research is also included, with particular emphasis on a comprehensive survey of the patent literature.
Sjögren's syndrome-like disease in mice with T cells lacking class 1A phosphoinositide-3-kinase (2006)

Sjögren's syndrome (SS) is an autoimmune disease that is characterized by infiltration of exocrine tissues, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Here, we show that mice with T cell-specific loss of class IA phosphoinositide 3-kinase function develop organ-specific autoimmunity that resembles the human disease SS. Most mutant mice aged 3-8 months develop corneal opacity and eye lesions due to irritation and constant scratching. These mice display cardinal signs of primary SS such as marked lymphocytic infiltration of the lacrimal glands, antinuclear antibodies in the serum, and elevated titer of anti-SS-A antibody, in the absence of kidney pathology. Immunofluorescence studies show the presence of numerous CD4+ T cells with a smaller number of CD8+ T cells and B cells in the lacrimal glands. CD4+ T cells from these mice exhibit aberrant differentiation in vitro. These results indicate that aberrant T cells with impaired class IA phosphoinositide 3-kinase signaling can lead to organ-specific autoimmunity. In addition, the mouse model described here represents a tool to study the pathogenesis and treatment of SS.
Targeting chaperones in transformed systems – a focus on Hsp90 and cancer (2006)

The molecular chaperone Hsp90 is a protein with important roles in maintaining the functional stability and viability of cells under a transforming pressure. Cancer cells harbour mutated oncogenic proteins or proteins with dysregulated function and the chaperone is required to maintain their folded and functionally active conformation. In addition, by chaperoning key proteins such as Raf-1, Akt, survivin and hTERT, Hsp90 regulates signalling pathways necessary for the growth, survival and limitless replicative potential of most tumours. Important elements of the apoptotic pathways are also regulated by Hsp90. Overall, these characteristics propose Hsp90 as an important target of whose inhibition may aim at a wide-range of oncogenic transformations. Several years into Hsp90 research have shed light into the feasibility, but also the limitations, of such an approach. In this review, the authors present the current understanding on the relevance and possibility of translating Hsp90 inhibitors into therapeutic agents in cancer therapy.
Diffusion-Limited Aggregation, a Kinetic Critical Phenomenon (1981)

A model for random aggregates is studied by computer simulation. The model is applicable to a metal-particle aggregation process whose correlations have been measured previously. Density correlations within the model aggregates fall off with distance with a fractional power law, like those of the metal aggregates. The radius of gyration of the model aggregates has power-law behavior. The model is a limit of a model of dendritic growth.
Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers (2008)

The cell surface protein Trop-2 is highly expressed in a wide variety of epithelial cancers. In contrast, there is little or no expression of Trop-2 in adult somatic tissue. Because it is a cell surface protein that is selectively expressed in tumor cells, Trop-2 is a potential therapeutic target. However, whether Trop-2 is actively involved in tumorigenesis and whether its targeting for treatment would be effective have not been examined. Here, we show that Trop-2 expression is necessary for tumorigenesis and invasiveness of colon cancer cells, as both are inhibited when Trop-2 expression is suppressed by RNA interference. Conversely, ectopic expression of Trop-2 in colon cancer cells enhances their capacity for anchorage-independent growth and ectopic expression of Trop-2 in NIH3T3 cells is sufficient to promote both anchorage-independent growth and tumorigenesis. Importantly, we show that an antibody against the extracellular domain of Trop-2 reduces tumor cell invasiveness. Therefore, we have identified Trop-2 as an oncogene that has potential as a therapeutic target. Given the restricted expression of Trop-2 in normal tissue, anti-Trop-2 therapeutics would be predicted to have limited toxicity.
Vitamin A (retinol) status of first nation adults with non-insulin-dependent diabetes mellitus. (1997)

The plasma concentration of RBP was elevated in diabetic subjects and was associated with normal circulatory availability of retinol. The subjects with NIDDM, characterized by insulin resistance without insulin deficiency, thus, appear to be associated with normal vitamin A status.
Inhibition of Antigen-Induced Lymphocyte Proliferation by Tat Protein from HIV-1 (1989)

The purified human immunodeficiency virus type-l (HIV-l) Tat protein inhibited lymphocyte proliferation induced by tetanus toxoid or Candida antigens by 66 to 97% at nanomolar concentrations of Tat. In contrast, Tat did not cause a significant reduction of lymphocyte proliferation in response to mitogens such as phytohemagglutinin or pokeweed mitogen. Inhibition was blocked by oxidation of the cysteine-rich region of Tat or by incubation with an antibody to Tat before the assay. A synthetic Tat peptide (residues 1 to 58) also inhibited antigen-stimulated proliferation. Experiments with H9 and U937 cell lines showed that Tat can easily enter both lymphocytes and monocytes. The specific inhibition of antigen-induced lymphocyte proliferation by Tat mimics the effect seen with lymphocytes from HIV-infected individuals and suggests that Tat might directly contribute to the immunosuppression associated with HIV infection.
Biological Response to ErbB Ligands in Nontransformed Cell Lines Correlates with a Specific Pattern of Receptor Expression (1998)

The human epidermal growth factor receptor (HER or ErbB) family consists of four distinct members, including the epidermal growth factor (EGF) receptor (EGFR, HER1, or ErbB1), ErbB2 (HER2 or neu), ErbB3 (HER3), and ErbB4 (HER4). Activation of these receptors plays an important role in the regulation of cell proliferation, differentiation, and survival in several different tissues. Binding of a specific ligand to one of the ErbB receptors triggers the formation of specific receptor homo- and heterodimers, with ErbB2 being the preferred signaling partner. We analyzed the levels of various ErbB receptor messenger RNAs in a series of nontransformed cell lines by real time quantitative RT-PCR. The cell lines chosen were derived from a variety of tissues, including pancreas, lung, heart, and nervous system. Further, we measured biological responses in these cell lines upon treatment with EGF, betacellulin, and two types of neuregulins, heregulin and sensory and motor neuron-derived factor. All cell lines examined expressed detectable levels of ErbB2. High levels of expression of ErbB3 were correlated with responsiveness to heregulin and sensory and motor neuron-derived factor, whereas high levels of EGFR expression were correlated with responsiveness to EGF and betacellulin. Moreover, the sensitivity of a cell line to ErbB ligands was also correlated with the levels of expression of the appropriate ErbB receptors in that cell line. These results are consistent with our hypothesis that appropriate biological responsiveness to ErbB ligands is determined by the levels of expression of specific ErbB receptor combinations within a given tissue.
Development of a Carbon Dioxide-Based Microencapsulation Technique for Aqueous and Ethanol-Based Latexes (2002)

A new microencapsulation technique is presented in which carbon dioxide is used to facilitate the transport of additives into colloidal polymer particles. Aqueous latexes were impregnated with additives by emulsifying carbon dioxide and water with the aid of a surfactant, Pluronic F108. Ethanol-based latexes were also successfully impregnated by dispersing additives into an ethanol−carbon dioxide solution. Preexisting size monodisperse polystyrene microspheres were impregnated with dyes with varying solubility characteristics. The effects of particle size, surfactant concentration, dye amount, impregnation time, and pressure on the dye loadings were studied. Partitioning of the dye between the polymer phase and the medium surrounding the polymer particles is the driving force for the dye to enter the polymer phase. Consequently, the partition coefficient is the most important factor that determines the maximum dye loading at the thermodynamic equilibrium. Increasing the solubility of the dye in the medium improves the kinetics but results in low dye loading. Dye loading is improved by increasing the interfacial area, either by increasing surfactant concentration or by lowering particle size. Data reported in this paper illustrate high potential of this technique for microencapsulation at room temperature without organic solvents and with precise control of particle size.