gebhart/patrepeval huggingface dataset:
Genetic modifiers of otocephalic phenotypes inOtx2heterozygous mutant mice (2002)

Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most of the offspring of Otx2 knock-out chimeras, which are equivalent to the F(1) of CBA and B6 strains, backcrossed with B6 females display reduction or loss of mandible, whereas those backcrossed with CBA females do not show noticeable phenotype at birth. The availability of phenotypically disparate strains renders identification of Otx2 modifier loci possible. In this study, a backcross of chimera with B6 was generated and genome-wide scans were conducted with polymorphic markers for non-mendelian distribution of alleles in Otx2 heterozygous mutant mice displaying abnormalities in the lower jaw. We identified one significant locus, Otmf18, between D18Mit68 and D18Mit120 on chromosomes 18, linked to the mandibular phenotype (LOD score 3.33). A similar replication experiment using a second backcross (N3) mouse demonstrated the presence of another significant locus, Otmf2 between D2Mit164 and D2Mit282 on chromosome 2, linked to the mandibular phenotype (LOD score 3.93). These two modifiers account for the distribution of the craniofacial malformations by the genetic effect between B6 and CBA strains. Moreover, Otmf2 contain a candidate gene for several diseases in mice and humans. These genetic studies involving an otocephalic mouse model appear to provide new insights into mechanistic pathways of craniofacial development. Furthermore, these experiments offer a powerful approach with respect to identification and characterization of candidate genes that may contribute to human agnathia-holoprosencephaly complex diseases.
Activation of Phosphatidylinositol-3′ Kinase by Src-Family Kinase SH3 Binding to the p85 Subunit (1994)

Engagement of antigen receptor complexes induces rapid activation of Src-family kinases and association with phosphatidylinositol-3' kinase (PI-3 kinase). Here it was found that the Src homology 3 (SH3) domain of Lyn and Fyn bound to a proline-rich region (residues 84 to 99) within the 85-kilodalton subunit (p85) of PI-3 kinase. The binding of SH3 to the purified kinase led to a five- to sevenfold increase in the specific activity of PI-3 kinase. Ligand-induced receptor stimulation activated PI-3 kinase, and this activation was blocked by a peptide containing residues 84 to 99 of p85. These data demonstrate a mechanism for PI-3 kinase activation and show that binding of SH3 domains to proline-rich target sequences can regulate enzymatic activity.
Identification of the α 2 -δ-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin (2006)

Neuropathic pain is a debilitating condition affecting millions of people around the world and is defined as pain that follows a lesion or dysfunction of the nervous system. This type of pain is difficult to treat, but the novel compounds pregabalin (Lyrica) and gabapentin (Neurontin) have proven clinical efficacy. Unlike traditional analgesics such as nonsteroidal antiinflammatory drugs or narcotics, these agents have no frank antiinflammatory actions and no effect on physiological pain. Although extensive preclinical studies have led to a number of suggestions, until recently their mechanism of action has not been clearly defined. Here, we describe studies on the analgesic effects of pregabalin in a mutant mouse containing a single-point mutation within the gene encoding a specific auxiliary subunit protein (alpha2-delta-1) of voltage-dependent calcium channels. The mice demonstrate normal pain phenotypes and typical responses to other analgesic drugs. We show that the mutation leads to a significant reduction in the binding affinity of pregabalin in the brain and spinal cord and the loss of its analgesic efficacy. These studies show conclusively that the analgesic actions of pregabalin are mediated through the alpha2-delta-1 subunit of voltage-gated calcium channels and establish this subunit as a therapeutic target for pain control.
Incidence and prevalence of recognised and unrecognised myocardial infarction in women The Reykjavik Study (1998)

Myocardial infarction in women is very age-dependent with both incidence and prevalence increasing continuously and steeply with age. There was a significant trend for an increase in prevalence of recognised myocardial infarction from 1968 to 1992. The proportion of unrecognised non-fatal infarctions ranged from 27% in the oldest age group to 40% in the youngest. On average, this form of coronary heart disease is as common as in men.
Pharyngeal Selective Brain Cooling Improves Neurofunctional and Neurocognitive Outcome after Fluid Percussion Brain Injury in Rats (2009)

Therapeutic hypothermia (TH) after cardiac arrest reduces mortality and improves neurological outcome. Experimental TH after traumatic brain injury (TBI) indicated similar effects, but benefits were not reproducible in large clinical trials. Therefore, a novel approach of pharyngeal selective brain cooling (pSBC) was tested in respect to neurological outcome in a model of experimental TBI. Male Sprague-Dawley rats were subjected to lateral fluid percussion (LFP) brain injury and received pSBC for 3h post-injury. All animals were examined for neuromotor and sensorimotor dysfunction and coordination: before and after injury, and during recovery on day post-injury (DPI) 7 and 14 using (i) the standardized Composite Neuroscore (NS) test and (ii) the Rotarod test. Recovery of cognitive function was assessed on days 10-14 using (iii) the Barnes Circular Maze (BCM). In pSBC-animals, brain temperature was selectively lowered to 33 +/- 0.5 degrees C at 15 min post-injury, keeping rectal temperature at a physiologic level. All animals subjected to TBI via LFP showed an identical pattern of severe neurofunctional impairment at 24 h after injury. In the time course of the experiment, pSBC-animals showed superior neurofunctional recovery on DPI 7 (p = 0.03) and 14 (p = 0.002). Similarly, distance, time, and maximum speed on the Rota-Rod were significantly increased in pSBC-animals on DPI 7 (p < 0.01) and 14 (p < 0.01), as well as latency, distance, and mean number of errors in the BCM on DPI 14 (p < 0.01). The novel approach of pSBC was associated with improved neuromotor, sensormotor, and neurocognitive outcome after experimental TBI.
Steroidal Sapogenins. XLV. Effect of Side Chain Isomerism on Rate of Conversion to Pseudosapogenins2 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteroidal Sapogenins. XLV. Effect of Side Chain Isomerism on Rate of Conversion to Pseudosapogenins2Monroe E. Wall and Samuel SerotaCite this: J. Am. Chem. Soc. 1957, 79, 24, 6481–6483Publication Date (Print):December 1, 1957Publication History Published online1 May 2002Published inissue 1 December 1957https://pubs.acs.org/doi/10.1021/ja01581a032https://doi.org/10.1021/ja01581a032research-articleACS PublicationsRequest reuse permissionsArticle Views69Altmetric-Citations3LEARN 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
Chemical Modification of Chitosan. 3. Hyperbranched Chitosan−Sialic Acid Dendrimer Hybrid with Tetraethylene Glycol Spacer (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTChemical Modification of Chitosan. 3. Hyperbranched Chitosan−Sialic Acid Dendrimer Hybrid with Tetraethylene Glycol SpacerHitoshi Sashiwa, Yoshihiro Shigemasa, and René RoyView Author Information Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada, and Faculty of Engineering, Tottori University, Tottori, 680-8552, Japan Cite this: Macromolecules 2000, 33, 19, 6913–6915Publication Date (Web):August 22, 2000Publication History Received30 March 2000Revised18 July 2000Published online22 August 2000Published inissue 1 September 2000https://pubs.acs.org/doi/10.1021/ma0005769https://doi.org/10.1021/ma0005769rapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views908Altmetric-Citations46LEARN 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 SUBJECTS:Alcohols,Amines,Biopolymers,Dendrons,Polymers Get e-Alerts
Iodine Contrast Medium Sensitizes Cultured Mammalian Cells to X Rays but Not to γ Rays (1980)

The influence of an iodine contrast medium on several responses to radiation was examined in mammalian cells in culture (L5178Y). The presence of the medium at the time of irradiation enhanced cell killing, frequency of micronuclei, and yield of DNA single-strand breaks induced by x rays, depending on the concentration used, whereas no such effect was found with ..gamma.. rays. It was concluded that the contrast medium sensitizes mammalian cells in culture primarily by means of the photoelectric effect, thereby increasing the absorbed dose of x rays in the cells.
Lithium induces clearance of protease resistant prion protein in prion‐infected cells by induction of autophagy (2009)

Abstract Lithium is used for several decades to treat manic‐depressive illness (bipolar affective disorder). Recently, it was found that lithium induces autophagy, thereby promoting the clearance of mutant huntingtin and α‐synucleins in experimental systems. We show here for the first time that lithium significantly reduces the amount of pathological prion protein (PrP Sc ) in prion‐infected neuronal and non‐neuronal cultured cells by inducing autophagy. Treatment of prion‐infected cells with 3‐methyladenine, a potent inhibitor of autophagy, counteracted the anti‐prion effect of lithium, demonstrating that induction of autophagy mediates degradation of PrP Sc . Co‐treatment with lithium and rapamycin, a drug widely used to induce autophagy, had an additive effect on PrP Sc clearance compared to treatment with either drug alone. In addition, we provide evidence that the ability to reduce PrP Sc and to induce autophagy is common for diverse lithium compounds, not only for the drug lithium chloride, usually administered in clinical therapy. Furthermore, we show here that besides reduction of PrP Sc ‐aggregates, lithium‐induced autophagy also slightly reduces the levels of cellular prion protein. Limiting the substrate available for conversion of cellular prion protein into PrP Sc may provide an additional mechanism for reduction of PrP Sc by lithium‐induced autophagy.
A Live Attenuated Dengue-L Vaccine Candidate (45AZ5) Passaged In Primary Dog Kidney Cell Culture Is Attenuated And Immunogenic For Humans (1994)

A dengue-1 candidate vaccine (45AZ5), previously found to be underattenuated in 2 volunteers, was further attenuated by passage in primary dog kidney (PDK) cell cultures. New candidate vaccines prepared from three levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were each injected into 9 or 10 volunteers. There was a significant, progressive decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees and induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for < or = 1 day in 4, and neutralizing antibody in all 10, which persisted for > or = 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 45AZ5 for humans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted.
Growth Suppression of Pre-T Acute Lymphoblastic Leukemia Cells by Inhibition of Notch Signaling (2003)

Constitutive NOTCH signaling in lymphoid progenitors promotes the development of immature T-cell lymphoblastic neoplasms (T-ALLs). Although it is clear that Notch signaling can initiate leukemogenesis, it has not previously been established whether continued NOTCH signaling is required to maintain T-ALL growth. We demonstrate here that the blockade of Notch signaling at two independent steps suppresses the growth and survival of NOTCH1-transformed T-ALL cells. First, inhibitors of presenilin specifically induce growth suppression and apoptosis of a murine T-ALL cell line that requires presenilin-dependent proteolysis of the Notch receptor in order for its intracellular domain to translocate to the nucleus. Second, a 62-amino-acid peptide derived from a NOTCH coactivator, Mastermind-like-1 (MAML1), forms a transcriptionally inert nuclear complex with NOTCH1 and CSL and specifically inhibits the growth of both murine and human NOTCH1-transformed T-ALLs. These studies show that continued growth and survival of NOTCH1-transformed lymphoid cell lines require nuclear access and transcriptional coactivator recruitment by NOTCH1 and identify at least two steps in the Notch signaling pathway as potential targets for chemotherapeutic intervention.
Distributed compression in a dense microsensor network (2002)

Distributed nature of the sensor network architecture introduces unique challenges and opportunities for collaborative networked signal processing techniques that can potentially lead to significant performance gains. Many evolving low-power sensor network scenarios need to have high spatial density to enable reliable operation in the face of component node failures as well as to facilitate high spatial localization of events of interest. This induces a high level of network data redundancy, where spatially proximal sensor readings are highly correlated. We propose a new way of removing this redundancy in a completely distributed manner, i.e., without the sensors needing to talk, to one another. Our constructive framework for this problem is dubbed DISCUS (distributed source coding using syndromes) and is inspired by fundamental concepts from information theory. We review the main ideas, provide illustrations, and give the intuition behind the theory that enables this framework.We present a new domain of collaborative information communication and processing through the framework on distributed source coding. This framework enables highly effective and efficient compression across a sensor network without the need to establish inter-node communication, using well-studied and fast error-correcting coding algorithms.
Mycobacterium tuberculosis Strains Possess Functional Cellulases (2005)

The genomes of various Mycobacterium tuberculosis strains encode proteins that do not appear to play a role in the growth or survival of the bacterium in its mammalian host, including some implicated in plant cell wall breakdown. Here we show that M. tuberculosis H37Rv does indeed possess a functional cellulase. The x-ray crystal structure of this enzyme, in ligand complex forms, from 1.9 to 1.1A resolution, reveals a highly conserved substrate-binding cleft, which affords similar, and unusual, distortion of the substrate at the catalytic center. The endoglucanase activity, together with the existence of a putative membrane-associated crystalline polysaccharide-binding protein, may reflect the ancestral soil origin of the Mycobacterium or hint at a previously unconsidered environmental niche.
Enteric nervous system development: Analysis of the selective developmental potentialities of vagal and sacral neural crest cells using quail-chick chimeras (2001)

The majority of the enteric nervous system (ENS) is derived from vagal neural crest cells (NCC). For many years, the contribution from a second region of the neuraxis (the sacral neural crest) to the ENS has been less clear, with conflicting reports appearing in the literature. To resolve this longstanding issue, we documented the spatiotemporal migration and differentiation of vagal and sacral-derived NCC within the developing chick embryo using quail-chick grafting and antibody labelling. Results showed that vagal NCC colonised the entire length of the gut in a rostrocaudal direction. The hindgut, the region of the gastrointestinal tract most frequently affected in developmental disorders, was found to be colonised in a complex manner. Vagal NCC initially migrated within the submucosa, internal to the circular muscle layer, before colonising the myenteric plexus region. In contrast, sacral NCC, which colonised the hindgut in a caudorostral direction, were primarily located in the myenteric plexus region from where they subsequently migrated to the submucosa. We also observed that sacral NCC migrated into the hindgut in significant numbers only after vagal-derived cells had colonised the entire length of the gut. This suggested that to participate in ENS formation, sacral cells may require an interaction with vagal-derived cells, or with factors or signalling molecules released by them or their progeny. To investigate this possible inter-relationship, we ablated sections of vagal neural crest (NC) to prevent the rostrocaudal migration of ENS precursors and, thus, create an aganglionic hindgut model. In the same NC ablated animals, quail-chick sacral NC grafts were performed. In the absence of vagal-derived ganglia, sacral NCC migrated and differentiated in an apparently normal manner. Although the numbers of sacral cells within the hindgut was slightly higher in the absence of vagal-derived cells, the increase was not sufficient to compensate for the lack of enteric ganglia. As vagal NCC appear to be more invasive than sacral NCC, since they colonise the entire length of the gut, we investigated the ability of transplanted vagal cells to colonise the hindgut by grafting the vagal NC into the sacral region. We found that when transplanted, vagal cells retained their invasive capacity and migrated into the hindgut in large numbers. Although sacral-derived cells normally contribute a relatively small number of precursors to the post-umbilical gut, many heterotopic vagal cells were found within the hindgut enteric plexuses at much earlier stages of development than normal. Heterotopic grafting of invasive vagal NCC into the sacral neuraxis may, therefore, be a means of rescuing an aganglionic hindgut phenotype.
Why Semiconducting Single‐Walled Carbon Nanotubes are Separated from their Metallic Counterparts (2007)

The separation of single-walled carbon nanotubes (SWNTs) according to their electronic structure has attracted much recent attention. In many cases, metallic SWNTs are separated from semiconducting SWNTs and enriched in the supernatant due to stronger interaction between metallic SWNTs and adsorbates. However, the inverse separation of semiconducting from metallic SWNTs is often observed. In this computational study, the underlying mechanism is elucidated by density functional theory. We show that the shape of an aromatic molecule, the degree of hybridization between a molecule and a SWNT, and the oxidative state of SWNTs can affect the type of enriched SWNTs. In principle, one can control the type of enriched SWNTs by selecting a structurally compatible aromatic molecule or changing the hole concentration of the SWNTs.
Rapid freezing of mouse embryos in ethylene glycol at different preimplantation stages. (1996)

The objectives of this study were to examine the effects of a rapid freezing protocol on the survival and in vitro development of mouse embryos cryopreserved in ethylene glycol (EG) at different preimplantation stages, and secondly, to investigate the effect of exposure to 3.0 M EG with 0.25 M sucrose on the survival and in vitro development of mouse embryos without freezing at different developmental stages. To perform the rapid freezing procedure, embryos were equilibrated in Dulbecco's phosphate buffered saline (DPBS) containing 3.0 M EG and 0.25 M sucrose (freeze medium) for 20 min and loaded into 250 microliters straws in a single column of freeze medium. The straws were held in liquid nitrogen (LN2) vapour for 2 min and immersed into LN2. Embryos were thawed in a 37 degrees C water bath for 20 sec and transferred to DPBS supplemented with 0.5 M sucrose (rehydration medium) for 10 min and cultured for 24 to 96 h in HTF (Human Tubal Fluid) plus 4 mg/ml BSA (Bovine Serum Albumin). Significant differences were found in the survival and development of mouse embryos at different developmental stages rapid frozen in EG and sucrose: two cell 43/84 (51%), 4-8 cell 44/94 (47%), morula and early blastocyst 56/70 (80%), expanding and expanded blastocysts 10/59 (17% (p < 0.05). These data indicate that the developmental stage in which mouse embryos are subjected to this quick freeze protocol affects survival and development in vitro and the majority (80%) of morula and early blastocyst stage embryos survive the procedure. No significant differences were observed in the in vitro developmental capacity of embryos at different developmental stages after treatment with high concentrations (3.0 M) of EG solution without freezing. Further investigations are underway to better understand the reasons for different survival rates of embryos frozen at different developmental stages using the present procedure.