Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways

ABSTRACT Purpose/aim: Glutamate is one of the signaling molecules responsible for transmission in the central nervous system. Periodontal ligament (PDL) cells were recently reported to express metabotropic glutamate receptors (mGluRs). However, the functions of mGluR signaling in PDL cells or PDL-related cells remain largely unknown. The aim of this study was to investigate the expression and function of mGluRs in PDL-related cells. Materials and methods: OCCM-30 cells, immortalized murine cementoblasts, were stimulated with l-glutamate or mGluRs antagonists. The cells’ proliferative response was evaluated using a colorimetric assay and gene expression was assessed using real-time polymerase chain reaction. The nuclear translocation of cyclin D1 was evaluated by immunohistochemistry. Results: l-Glutamate promoted the proliferation of OCCM-30 cells, which expressed mGluR1, but not mGluR5. Dihydroxyphenylglycine (DHPG), an agonist of group I mGluRs (mGluR1 and mGluR5), also promoted cell proliferation, and this was inhibited by LY456236, an mGluR1 antagonist. DHPG increased the expression of cyclin D1, a key regulator of cell proliferation, and its nuclear translocation. DHPG also increased the expression of Bcl2A1, an antiapoptotic oncogene and simultaneously reduced the expression of Bax, a pro-apoptotic marker. Furthermore, the DHPG-induced proliferation of OCCM-30 cells was reduced by pretreatment with SB203580, SP600125, and PD98059, inhibitors of p38, JNK, and ERK1/2, respectively. Conclusions: These findings indicate that activation of mGluR1 expressed by OCCM-30 cells induces cell proliferation in a manner that is dependent on mitogen-activated protein kinase pathways and that cyclin D1 and Bcl2A1/Bax may be involved. Our results provide useful information for elucidating the mechanisms underlying cementum homeostasis and regeneration.
The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum

1. A single climbing fibre makes an extraordinarily extensive synaptic contact with the dendrites of a Purkinje cell. Investigation of this synaptic mechanism in the cerebellum of the cat has been based on the discovery by Szentagothai & Rajkovits (1959) that the climbing fibres have their cells of origin in the contralateral inferior olive.
SNP discovery performance of two second‐generation sequencing platforms in the NOD2 gene region

A potentially important application of second generation sequencing technologies is to identify disease‐associated variation. For comparison of the performance in SNP detection, the Crohn's disease (CD)‐associated NOD2 gene was subjected to targeted resequencing using two different second‐generation sequencing technologies. Eleven CD patients were selected based on their haplotype background at the NOD2 locus. The 40‐kb large NOD2 gene region was amplified using long‐range PCR (LR‐PCR), and sequenced with the Roche 454/FLX system, an Applied Biosystems SOLiD mate‐pair library (2×25 bp), and a SOLiD fragment (50 bp) library. The entire NOD2 region was also sequenced using conventional Sanger technology. Four‐hundred forty‐two single nucleotide polymorphisms (SNPs) were discovered with the SOLiD mate‐pair library, 454 with the fragment library, and 441 with the 454/FLX. For the homozygous SNPs, 98% were confirmed by Sanger for the mate‐pair library, 100% for the fragment library and 99% for the 454/FLX. Ninety‐six percent of the heterozygous SNPs detected with the SOLiD mate‐pair library, 91% with the fragment library and 96% with the 454/FLX were confirmed by Sanger. In a simulation, the SNP detection performance fell rapidly when the achieved coverage was below 40×. Due to uneven representation of the target region when using LR‐PCR, oversequencing of other regions is necessary. Hum Mutat 31:875–885, 2010. © 2010 Wiley‐Liss, Inc.
Investigational α-synuclein aggregation inhibitors: hope for Parkinson’s disease

ABSTRACT Introduction: The therapeutic management of Parkinson’s disease (PD) is challenging and has not been fully resolved. The main challenges include motor fluctuations and levodopa-induced dyskinesia. Moreover, no disease-modifying or neuroprotective therapy is currently available. Areas covered: This review focuses on α-synuclein aggregation inhibitors and their therapeutic role in PD, with special attention to heat shock proteins, immunotherapy (active and passive), the potential of targeting the Ser129 phosphorylation site, and the antibiotic possibilities. Expert opinion: The induction of chaperones may provide beneficial strategy to target synucleinopathies, but further investigations are needed to find the best options. The promising preclinical results with immunotherapy suggest that it may be a valuable disease-modifying therapy in PD in the future. Clinical trials are currently in the initial phases, and future studies need to confirm the beneficial therapeutic effect in humans and clarify open questions as regards the exact mode of action and potential safety concerns. In case of covalent modifications, phosphorylation of α-synuclein is of outstanding importance; however, conflicting results and open questions exist which necessitate clarification. In vitro results suggest that several antibiotics may also influence α-synuclein aggregation, but these results are to be confirmed in the future.
Sorting Signals within the Saccharomyces cerevisiae Sporulation-Specific Dityrosine Transporter, Dtr1p, C Terminus Promote Golgi-to-Prospore Membrane Transport

ABSTRACT During sporulation in Saccharomyces cerevisiae, the dityrosine transporter Dtr1p, which is required for formation of the outermost layer of the spore wall, is specifically expressed and transported to the prospore membrane, a novel double-lipid-bilayer membrane. Dtr1p consists of 572 amino acids with predicted N- and C-terminal cytoplasmic extensions and 12 transmembrane domains. Dtr1p missing the largest internal cytoplasmic loop was trapped in the endoplasmic reticulum in both mitotically dividing cells and cells induced to sporulate. Deletion of the carboxyl 15 amino acids, but not the N-terminal extension of Dtr1p, resulted in a protein that failed to localize to the prospore membrane and was instead observed in cytoplasmic puncta. The puncta colocalized with a cis-Golgi marker, suggesting that Dtr1p missing the last 15 amino acids was trapped in an early Golgi compartment. Deletion of the C-terminal 10 amino acids resulted in a protein that localized to the prospore membrane with a delay and accumulated in cytoplasmic puncta that partially colocalized with a trans-Golgi marker. Both full-length Dtr1p and Dtr1p missing the last 10 amino acids expressed in vegetative cells localized to the plasma membrane and vacuoles, while Dtr1p deleted for the carboxyl-terminal 15 amino acids was observed only at vacuoles, suggesting that transport to the prospore membrane is mediated by distinct signals from those that specify plasma membrane localization. Transfer-of-function experiments revealed that both the carboxyl transmembrane domain and the C-terminal tail are important for Golgi complex-to-prospore membrane transport.
Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome.

Between September 1987 and December 1994, 80 patients with multiple myeloma (MM) received high-dose busulfan and cyclophosphamide without (n = 57) or with modified total body irradiation (n = 23) followed by marrow from allogeneic donors. At transplant, 71% of the patients had disease that was refractory to chemotherapy. Thirty-five patients died of transplant-related causes within 100 days and 11 deaths occurred later. The actuarial probabilities of survival and progression-free survival were . 24 +/- 0.17 and . 20 +/- 0.10 at 4.5 years. Complete remissions were obtained in 36% of patients who had actuarial probabilities of survival and event-free survival of . 50 +/- 0.21 and . 43 +/- 0.17 at 4.5 years. In a multivariate analysis, adverse risk factors for outcome endpoints included: transplantation greater than 1 year from diagnosis; beta-2 microglobulin > 2.5 at transplant; female patients transplanted from male donors; patients who had received greater than eight cycles of chemotherapy before transplant and Durie stage 3 disease at the time of transplant. These results indicate that allografting for patients with MM can result in long-term disease-free survival for a minority of patients. Efforts to reduce transplant-related mortality should focus on earlier transplantation, less toxic treatment regimens, better supportive care, and improved prevention and treatment of graft-versus-host disease (GVHD).
RNASeqMetaDB: a database and web server for navigating metadata of publicly available mouse RNA-Seq datasets

UNLABELLED Gene targeting is a protocol for introducing a mutation to a specific gene in an organism. Because of the importance of in vivo assessment of gene function and modeling of human diseases, this technique has been widely adopted to generate a large number of mutant mouse models. Due to the recent breakthroughs in high-throughput sequencing technologies, RNA-Seq experiments have been performed on many of these mouse models, leading to hundreds of publicly available datasets. To facilitate the reuse of these datasets, we collected the associated metadata and organized them in a database called RNASeqMetaDB. The metadata were manually curated to ensure annotation consistency. We developed a web server to allow easy database navigation and data querying. Users can search the database using multiple parameters like genes, diseases, tissue types, keywords and associated publications in order to find datasets that match their interests. Summary statistics of the metadata are also presented on the web server showing interesting global patterns of RNA-Seq studies. AVAILABILITY AND IMPLEMENTATION Freely available on the web at http://rnaseqmetadb.ece. tamu.edu.
Colonization and/or mitochondrial selective sweeps across the North Atlantic intertidal assemblage revealed by multi‐taxa approximate Bayesian computation

Intertidal and subtidal communities of the western and eastern coasts of the North Atlantic Ocean were greatly affected by Pleistocene glaciations, with some taxa persisting on both coasts, and others recolonizing after being extirpated on one coast during the Last Glacial Maximum. In the original spirit of comparative phylogeography, we conducted a comparative analysis using mtDNA sequence data and a hierarchical approximate Bayesian computation (ABC) approach for testing these two scenarios across 12 intertidal and subtidal coastal invertebrates spanning the North Atlantic to determine the temporal dynamics of species membership of these two ephemeral communities. Conditioning on a low gene‐flow model, our results suggested that a colonization or mitochondrial selective sweep history was predominant across all taxa, with only the bivalve mollusc Mytilus edulis showing a history of trans‐Atlantic persistence. Conditioning on a high gene‐flow model weakened the support for this assemblage‐level demographic history. The predominance of a colonization‐type history also highlights concerns about analyses based on single‐locus data where genetic hitchhiking may be incorrectly inferred as colonization. In conclusion, driving factors in shifting species range distributions and membership of ephemeral coastal communities could be species‐specific environmental tolerances, species interactions, and/or stochastic demographic extinction. Through a re‐examination of a long‐standing question of North Atlantic phylogeography, we highlight the flexibility and statistical honesty of using a model‐based ABC approach.
Multilevel Samplers as Microcosms to Assess Microbial Response to Biostimulation

Passive multilevel samplers (MLS) containing a solid matrix for microbial colonization were used as in situ microcosms in conjunction with a push‐pull biostimulation experiment designed to promote biological U(VI) and Tc(VII) reduction. MLS were deployed at 24 elevations in the injection well and two downgradient wells to investigate the spatial variability in microbial community composition and growth prior to and following biostimulation. The microbial community was characterized by real‐time quantitative polymerase chain reaction (Q‐PCR) quantification of bacteria, NO3−‐reducing bacteria (nirS and nirK), δ‐proteobacteria, Geobacter sp. , and methanogens (mcrA). Pretest cell densities were low overall but varied substantially with significantly greater bacterial populations detected at circumneutral pH (t‐test, α= 0.05), suggesting carbon substrate and low pH limitations of microbial activity. Although pretest cell densities were low, denitrifying bacteria were dominant members of the microbial community. Biostimulation with an ethanol‐amended ground water resulted in concurrent NO3− and Tc(VII) reduction, followed by U(VI) reduction. Q‐PCR analysis of MLS revealed significant (1 to 2 orders of magnitude, Mann–Whitney U‐test, α= 0.05) increases in cell densities of bacteria, denitrifiers, δ‐proteobacteria, Geobacter sp. , and methanogens in response to biostimulation. Traditionally, characterization of sediment samples has been used to investigate the microbial community response to biostimulation; however, collection of sediment samples is expensive and not conducive to deep aquifers or temporal studies. The results presented demonstrate that push‐pull tests with passive MLS provide an inexpensive approach to determine the effect of biostimulation on contaminant concentrations, geochemical conditions, and the microbial community composition and function.
Effect of Atmospheric CO2 Enrichment on Root Growth and Carbohydrate Allocation of Phaseolus spp.

A glasshouse experiment was conducted with plants of Phaseolus grown in liquid culture. Root growth parameters (biomass, diameter, length, growth rate, zone of cell division), root rheological components (wall extensibility, water potential yield threshold, water potential), shoot growth, carbon allocation, and abscisic acid (ABA) concentration were measured in Phaseolus acutifolius A. Gray at ambient (550 &mgr;mol mol−1) and elevated (700 &mgr;mol mol−1) atmospheric CO2 concentrations. For contrast, measurements of above‐ and belowground growth were conducted on Phaseolus vulgaris L. in the same treatments. Under nonlimiting conditions of water and nutrients, elevated CO2 increased root and shoot growth of P. acutifolius but not P. vulgaris. While root mass was increased by nearly 60% in P. acutifolius, there was no effect of atmospheric CO2 on any of the rheological components measured. In contrast, starch and ABA accumulated in roots of P. acutifolius. The concentration of starch in roots of P. acutifolius increased by 10‐fold, while root concentrations of ABA doubled. From the data it is concluded that CO2 enrichment is favorable for root growth in some species in that more carbon is allocated to belowground growth. In addition, ABA may play a role in growth responses and/or allocation of photosynthates at elevated CO2 in P. acutifolius.
Understanding Twin-Twin Transfusion Syndrome: Role of Doppler Ultrasound

The high risks of monochorionic (MC) twin gestations are largely related to the vascular anatomy of the shared placentae and the presence of intertwin vascular connections. These anastomoses are implicated in twin-twin transfusion syndrome and co-twin sequelae after intrauterine death of one twin. Twin-twin transfusion syndrome is the most common complication of MC twinning. Obstetrical sonography, with the use of Doppler techniques, can be used to assess these high-risk pregnancies and to interrogate the vascular connections in the shared placentae. The information obtained can improve our understanding of the pathophysiology of syndromes that complicate these pregnancies and may help inform obstetrical management.
Systolic Elastance and Resistance in the Regulation of Cardiac Pumping Function in Early Streptozotocin-Diabetic Rats

We determined the roles of maximal systolic elastance (Emax) and theoretical maximum flow (Qmax) in the regulation of cardiac pumping function in early streptozotocin (STZ)-diabetic fats. Physically, Emax can reflect the intrinsic contractility of the myocardium as an intact heart, and Qmax has an inverse relation to the systolic resistance of the left ventricle. Rats given STZ 65 mg/kg l.v. (n = 17) were divided into two groups, 1 week and 4 weeks after induction of diabetes, and compared with untreated age-matched controls (n = 15). Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate Emax and Qmax, using the elastance-resistance model. After 1 or 4 weeks, STZ-diabetic animals show an increase in effective LV end-diastolic volume (Veed), no significant change in peak iso-volumic pressure (Pisomax), and a decline in effective arterial volume elastance (Ea). The maximal systolic elastance Emax is reduced from 751.5 ± 23.1 mmHg/ml in controls to 514.1 ± 22.4 mmHg/ml in 1- and 538.4 ± 33.8 mmHg/ml in 4-week diabetic rats. Since Emax equals PisomaxVeed, an increase in Veed with unaltered Pisomax may primarily act to diminish Emax so that the intrinsic contractility of the diabetic heart is impaired. By contrast, STZ-diabetic rats have higher theoretical maximum flow Qmax (40.9 ± 2.8 ml/s in 1- and 44.5 ± 3.8 ml/s in 4-week diabetic rats) than do controls (30.7 ± 1.7 ml/s). There exists an inverse relation between Qmax and Ea when a linear regression of Qmax on Ea is performed over all animals studied (r= 0.65, p < 0.01). The enhanced Qmax is indicative of the decline in systolic resistance of the diabetic rat heart. The opposing effects of enhanced Qmax and reduced Emax may negate each other, and then the cardiac pumping function of the early STZ-diabetic rat heart could be preserved before cardiac failure occurs.
Lesch-Nyhan disease: from mechanism to model and back again

Lesch-Nyhan disease (LND) is a rare inherited disorder caused by mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by overproduction of uric acid, leading to gouty arthritis and nephrolithiasis. Affected patients also have characteristic neurological and behavioral anomalies. Multiple cell models have been developed to study the molecular and metabolic aspects of LND, and several animal models have been developed to elucidate the basis for the neurobehavioral syndrome. The models have different strengths and weaknesses rendering them suitable for studying different aspects of the disease. The extensive modeling efforts in LND have questioned the concept that an ‘ideal’ disease model is one that replicates all of its features because the pathogenesis of different elements of the disease involves different mechanisms. Instead, the modeling efforts have suggested a more fruitful approach that involves developing specific models, each tailored for addressing specific experimental questions.
Efficacy of intravenous lidocaine in prevention of post extubation laryngospasm in children undergoing cleft palate surgeries

A one-year randomized placebo-controlled trial was conducted to study the effectiveness of intravenous lidocaine in the prevention of post extubation laryngospasm in children, following cleft palate surgeries. Children of age three months to six years were randomly assigned into two groups. Group P placebo (saline) and Group L (Lidocaine), 1.5 mg/kg. A sample size of 74 with n = 37 in each group was selected. The anaesthetic procedure was standardized. At the end of the procedure, three minutes after reversal, the study drug, that is, intravenous lidocaine (1.5 mg/kg) or placebo (saline) was administered and two minutes later the child was extubated. Following extubation for 10 minutes, the haemodynamic parameters, that is, pulse, blood pressure, oxygen saturation, severity of coughing, and laryngospasm were noted. The total reduction of laryngospasm and coughing was 29.9% and 18.92% with IV lidocaine. Significant alterations in haemodynamics and oxygen saturation were noted for 10 minutes, following extubation. Hence, intravenous lidocaine 1.5 mg/kg was effective in the prevention of post extubation laryngospasm in children undergoing cleft palate surgeries.
Transfer of terbutaline across the human placenta in late pregnancy.

Placental transfer of terbutaline was studied in 22 women in late pregnancy who were delivered by elective Caesarian section. A single i.v. dose of terbutaline (0.25 or 0.5 mg) was given at various times (13-295 min) before delivery. Immediately after delivery, one blood sample was drawn from the placental side of the umbilical vein and one from the mother's antecubital vein. By use of gas chromatography plus mass spectrometry terbutaline was assayed in maternal plasma and in plasma and whole blood from the umbilical vein. Plasma concentrations in the mothers (Cmv) were initially 7 micrograms/L, while the highest umbilical venous level ( Cuv ) recorded was 3.5 micrograms/L. The ratio Cuv /Cmv increased continuously during the time interval studied and approached unity after 2-3 h. The blood:plasma concentration ratio in venous umbilical blood was initially low. It reached unity after about 60 min, but increased steadily to about 1.5 during the time of study. Thus there was a continuous uptake of terbutaline from plasma into the erythrocytes. The slow in vivo equilibration of terbutaline between plasma and erythrocytes is probably due to the low lipophilicity of the drug. However, the latter characteristic did not seem to impede its diffusion across the placenta to any great degree.