Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms underlying synapse‐specific clustering of GABAA receptors

A principle that arises from a body of previous work is that each presynaptic terminal recognises its postsynaptic partner and that each postsynaptic site recognises the origin of the synaptic bouton innervating it. In response, the presynaptic terminal sequesters the proteins whose interactions result in the dynamic transmitter release pattern and chemical modulation appropriate for that connection. In parallel, the postsynaptic site sequesters, inserts or captures the receptors and postsynaptic density proteins appropriate for that type of synapse. The focus of this review is the selective clustering of GABAA receptors (GABAAR) at synapses made by each class of inhibitory interneurone. This provides a system in which the mechanisms underlying transynaptic recognition can be explored. There are many synaptic proteins, often with several isoforms created by post‐translational modifications. Complex cascades of interactions between these proteins, on either side of the synaptic cleft, are essential for normal function, normal transmitter release and postsynaptic responsiveness. Interactions between presynaptic and postsynaptic proteins that have binding domains in the synaptic cleft are proposed here to result in a local cleft structure that captures and stabilises only the appropriate subtype of GABAARs, allowing others to drift away from that synapse, either to be captured by another synapse, or internalised.
PHO5 Upstream sequences confer phosphate control on the constitutive PHO3 gene

To identify the sequences involved in the regulation of the yeast acid phosphatase gene (PHO5) we constructed a series of hybrid promoters. Increasing lengths of 5′‐flanking sequences of the PHO5 gene were placed in front of the TATA‐box of constitutively expressed acid phosphatase gene (PHO3).
Dietary intake and microsatellite instability in colon tumors

Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. Other than relatively rare mutations in mismatch repair genes, the causes of MSI are not generally known. The purpose of this study was to determine if dietary intake of nutrients previously reported as being associated with colon cancer relate specifically to the MSI disease pathway. Data from a population‐based case‐control study of adenocarcinoma of the colon were used to evaluate associations between dietary intake and MSI. Participants were between 30 and 79 years of age at time of diagnosis and included both men and women. Dietary intake data were obtained from a computerized diet history questionnaire. MSI was evaluated in several ways: by a panel of 10 tetranucleotide repeats, and by 2 mononucleotide repeats, BAT‐26 and TGFβRII. A total of 1,510 cases had valid study data and tumor DNA on which we were able to obtain MSI status. Cases with and without MSI were compared with dietary data reported by 2,410 population‐based controls to determine dietary associations that may be different for these 2 subsets of cases. We compared dietary intake for cases with and without MSI to further determine associations that are specific to the MSI disease pathway. When comparing MSI+ to MSI− tumors we observed that long‐term alcohol consumption, especially intake of liquor, increased the probability of having a tumor with MSI [odds ratio (OR) for MSI+ vs. MSI− tumors for alcohol 1.6, 95% confidence interval (CI) 1.0–2.5; OR for liquor 1.6, 95% CI 1.1–2.4]. The likelihood of having MSI in the tumor from the combined effects of high alcohol consumption and smoking cigarettes showed a 70% excess in risk from the additive model. There were some suggestions that high intakes of refined grain might also be associated with MSI+ tumors, although associations were less consistent. Risk estimates for most other dietary factors did not differ substantially by MSI status. Data from this large population‐based case‐control study of colon cancer indicate that alcohol consumption, especially consumption of liquor, may increase the odds of an MSI+ tumor. Most other dietary factors do not appear operate exclusively in the MSI+ disease pathway. © 2001 Wiley‐Liss, Inc.
Modulation of Ca2+ and K+ permeabilities by oxotremorine‐m (Oxo‐m) in rodent pancreatic B‐cells

The effects of the muscarinic agonist oxotremorine‐m (Oxo‐m) on 45Ca and 86Rb fluxes, insulin secretion, cytoplasmic Ca2+ concentration ([Ca2+]i) and membrane potential in pancreatic B‐cells were studied. Oxo‐m (40–200 microM) increased the [Ca2+]i by about 250 nM, irrespective of the glucose concentration present in the medium (2.8–22 mM). This effect was reduced by 50% upon the addition of EGTA. Oxo‐m (50 microM) increased the 45Ca efflux from islets perifused in the absence or presence of [Ca2+]o, although under the former condition this efflux was transient. The difference between effluxes measured in the absence and presence of [Ca2+]o represents the sustained second component, which presumably reflects Ca2+ influx. In both the absence and presence of 11.2 mM glucose. Oxo‐m (50 microM) transiently increased 86Rb efflux. In the presence of glucose, Oxo‐m provoked a transient polarization of the B‐cell membrane associated with an increase in the K+ permeability values. K+ permeability returned to basal values (no Oxo‐m) after 1–2 min. These results indicate that the initial phase of Oxo‐m‐induced insulin secretion depends partially on intracellular Ca2+ release, and that the sustained enhancement of release depends on Ca2+ influx. The participation of a calcium release‐activated current (ICRAC) is proposed to explain the sustained small changes in membrane potential.
A 3-coil wireless power transfer system with fine tuned power amplifier for biomedical capsule

This paper presents an optimized 3-coil inductive wireless power transfer system with wearable power transmitting coil (PTC), miniaturized power receiving coil (PRC), and power amplifier. The PTC is made wearable to improve system's compactness and portability. The PRC and its circuitry are sufficiently miniaturized so that they can be embedded in the tiny capsule replacing the conventional onboard battery. In addition, the power amplifier is specially designed and optimized to enable convenient fine-tune for impedance matching. This minimizes unnecessary mismatch normally contributed by changes on impedance of the power transmitting coil because of the use of different size of PTC for different patient group, deformation of the PTC, etc. The experimental test shows our proposed system obtained the power transfer efficiency at least 7.53% when 708 mW of power is transferred.
Eosinophil Chemokines and Chemokine Receptors: Their Role in Eosinophil Accumulation and Activation in Asthma and Potential as Therapeutic Targets

Eosinophils comprise up to 5% of white blood cells in healthy, nonatopic individuals. They are a subpopulation of granulocytes that can be distinguished morphologically from neutrophils on the basis of their bilobed nucleus and characteristic secondary granules. In humans, eosinophils are found primarily in the gastrointestinal tract and are thought to play an important role in host defense against parasitic (particularly nematode) infections. Activated eosinophils degranulate, releasing the proteins stored within the secondary granules. These include major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP), and eosinophilderived neurotoxin (EDN). ECP and MBP are both directly toxic to many parasites, whereas EPO produces hypophalous acids (which are capable of killing parasites by oxidizing halides). Eosinophils can also generate membrane-derived lipid mediators (such as platelet activating factor and leukotriene C4) and reactive oxygen species (ROS) that may add to their proinflammatory effects. The ability of eosinophils to generate toxic products to fight parasitic infections may also contribute toward the inflammation associated with eosinophil accumulation at sites of allergic inflammation (1).
The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain

Porphyromonas gingivalis contains high concentrations of numerous cysteine proteinases with trypsin-like activity which have been implicated as important virulence factors in adult-onset periodontitis. We have analyzed the subfractions of six P. gingivalis strains for the presence of arginine-X- and lysine-X-specific proteinases (Arg-gingipain [RGP] and Lys-gingipain [KGP]) previously purified from P. gingivalis H66. Western blot (immunoblot) analysis using antibodies produced against RGP and the N-terminal peptides of RGP or the catalytic subunit of KGP indicated that these enzymes are synthesized by the strains studied and exist as multiple molecular mass species. The major forms of RGP were identified as 110-, 95-, 70- to 90-, and 50-kDa proteins, the first two being a complex of the 50-kDa catalytic subunit with hemagglutinins, with or without an added membrane anchorage peptide. The other forms are single-chain enzymes. While the 95- and 50-kDa RGP were found predominantly in culture medium, the 110- and 70- to 90-kDa forms associated with membranous fractions of the bacteria. The predominant form of KGP in all strains was a complex of the 60-kDa catalytic domain with hemagglutinins, and vesicle- and membrane-associated KGP was about 15 kDa larger than the 105-kDa enzyme present in culture media. These data explain the apparent complexity of P. gingivalis proteinases and indicate that in all strains tested there are two identical enzymes, one with arginine-X specificity and the other with lysine-X specificity, which, working in concert, are responsible for the trypsin-like activity associated with this bacterium.
Survival of Dicor glass-ceramic dental restorations over 20 years: Part IV. The effects of combinations of variables.

PURPOSE Previous studies have shown the relationship of individual clinical variables to the survival of Dicor (Corning Glass Works) restorations. The purpose of the present investigation was to examine the effect of combinations of these variables on the intraoral survival of Dicor restorations. MATERIALS AND METHODS Dicor glass-ceramic restorations (n=1,444) were placed in 417 adult patients. Failure was defined as a restoration that required remake because of material fracture. The survival of restorations with different combinations of variables that were each individually associated with survival was described using Kaplan-Meier survivor functions. The statistical significance of differences in survival between different combinations of specific predictor variables was examined using the proportional hazards model. RESULTS Kaplan-Meier survival analysis indicated that significantly worse survival rates were found for restorations that included combinations of molar teeth, a dentin core, and a glass-ionomer luting agent; molar teeth, a dentin core, and a resin luting agent; and single-rooted teeth, a dentin core, and a glass-ionomer luting agent than for any other combinations tested. The Cox proportional hazards model described a hazard ratio of 3.37 (95% confidence interval [CI]: 2.23 to 5.08) for molar teeth (versus single-rooted teeth), 2.65 (95% CI: 1.44 to 4.87) for dentin core (versus gold core), 2.35 (95% CI: 1.58 to 3.51) for men (versus women), and 1.72 (95% CI: 1.13 to 2.60) for glass-ionomer luting agent (versus resin) after adjusting for the other variables in the model. CONCLUSION Factors beyond individual restoration design impact the survival of Dicor glass-ceramic. These include sex, tooth position, and restorations luted to gold core foundation bases.
Multidrug-resistant typhoid fever: a review.

INTRODUCTION Multidrug-resistant typhoid fever (MDRTF) is defined as typhoid fever caused by Salmonella enterica serovar Typhi strains (S. Typhi), which are resistant to the first-line recommended drugs for treatment such as chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. Since the mid-1980s, MDRTF has caused outbreaks in several countries in the developing world, resulting in increased morbidity and mortality, especially in affected children below five years of age and those who are malnourished. METHODOLOGY Two methods were used to gather the information presented in this article. First PubMed was searched for English language references to published relevant articles. Secondly, chapters on typhoid fever in standard textbooks of paediatric infectious diseases and preventive and social medicine were reviewed. RESULTS Although there are no pathognomonic clinical features of MDRTF at the onset of the illness, high fever ( > 104°F), toxaemia, abdominal distension, abdominal tenderness, hepatomegaly and splenomegaly are often reported. The gold standard for the diagnosis of MDRTF is bacterial isolation of the organism in blood cultures. Ciprofloxacin and ceftriaxone are the drugs most commonly used for treatment of MDRTF and produce good clinical results. CONCLUSION MDRTF remains a major public health problem, particularly in developing countries. Mass immunization in endemic areas with either the oral live attenuated Typhi 21a or the injectable unconjugated Vi typhoid vaccine, rational use of antibiotics, improvement in public sanitation facilities, availability of clean drinking water, promotion of safe food handling practices and public health education are vital in the prevention of MDRTF.
A Conformational Restriction in the Influenza A Virus Neuraminidase Binding Site by R152 Results in a Combinational Effect of I222T and H274Y on Oseltamivir Resistance

ABSTRACT The I222K, I222R, and I222T substitutions in neuraminidase (NA) have been found in clinically derived 2009 pandemic influenza A/H1N1 viruses with altered susceptibilities to NA inhibitors (NAIs). The effects of these substitutions, together with the most frequently observed resistance-related substitution, H274Y, on viral fitness and resistance mechanisms were further investigated in this study. Reduced sensitivities to oseltamivir were observed in all three mutants (I222K, I222R, and I222T). Furthermore, the I222K and I222T substitutions had a combinational effect of further increasing resistance in the presence of H274Y, which might result from a conformational restriction in the NA binding site. Of note, by using molecular dynamics simulations, R152, the neighbor of T222, was observed to translate to a position closer to T222, resulting in the narrowing of the binding pocket, which otherwise only subtends the residue substitution of H274Y. Moreover, significantly attenuated NA function and viral growth abilities were found in the I222K+H274Y double mutant, while the I222T+H274Y double mutant exhibited slightly delayed growth but had a peak viral titer similar to that of the wild-type virus in MDCK cells. The relative growth advantage of the I222T mutant versus the I222K mutant and the higher frequency of I222T emerging in N1 subtype influenza viruses raise concerns necessitating close monitoring of the dual substitutions I222T and H274Y.
The Predictive Value of Preoperative Myelography in Lumbar Spinal Stenosis

Study Design Restrospective follow-up study on the significance of myelographic findings on the postoperative results of patients with lumbar canal stenosis is not well defined. Objectives The authors studied the predictive influence of preoperetive myelography on the outcome of patients with surgically treated lumbar spinal stenosis, defined by an uppar limit of anteroposterior diameter of the dural sac on the lateral myelogram film of equal la or less than 12 mm. Summary of Background Data Patients with prior lumbar surgery were excluded. There were 251 patients [women 44% and men 56%] with a mean age of 55 years and a mean follow-up time of 4.2 years. Methods Patients with complete block or subtotal block on myalography were included in the block stenosis group, patients with an anteroposterior diameter of less than 10 mm were included in the absolute stenosis group and patients with an anteroposterior diameter of 10–12 mm were included in the relative stenosis group. Results The proportion of good-to-excellent outcomes was 76% in block stenosis, 56% in absolute stenosis, and 61% in relative stenosis. In the multivariate analysis, the pre-preoperative variables that correlated with good outcome were block stenosis and male sex. Conclusions The severity of myelographic findings is significantly related to the outcome of patients who underwent surgeries for lumbar canal stenosis.
Genomic Analysis Reveals Variation between Mycobacterium tuberculosis H37Rv and the AttenuatedM. tuberculosis H37Ra Strain

ABSTRACT Mycobacterium tuberculosis H37Ra is an attenuated tubercle bacillus closely related to the virulent type strain M. tuberculosis H37Rv. Despite extensive study, the reason for the decreased virulence of M. tuberculosis H37Ra has not been determined. A genomic approach was therefore initiated to identify genetic differences between M. tuberculosis H37Rv andM. tuberculosis H37Ra as a means of pinpointing the attenuating mutation(s). Digestion with the rare-cutting restriction endonuclease DraI revealed two polymorphisms between the strains: a 480-kb fragment in M. tuberculosis H37Rv was replaced by two fragments of 220 and 260 kb in M. tuberculosis H37Ra, while there was a ∼7.9-kb DraI fragment in M. tuberculosis H37Ra that had no counterpart in M. tuberculosis H37Rv. As the M. tuberculosis insertion sequence IS6110 contains a single DraI restriction site, it was considered possible that these polymorphisms were the result of IS6110transposition events in M. tuberculosis H37Ra, events that may have inactivated virulence genes. The 7.9-kb polymorphism was found to be due to the presence of the previously described H37Rv RvD2 deletion in M. tuberculosis H37Ra, with sequence analysis suggesting an IS6110-mediated deletion mechanism for loss of RvD2. Three other IS6110-catalyzed deletions from theM. tuberculosis H37Rv chromosome (RvD3 to RvD5) were also identified, suggesting that this mechanism plays an important role in genome plasticity in the tubercle bacilli. Comparative mapping and sequencing revealed that the 480-kb polymorphism was due to an IS6110 insertion in M. tuberculosis H37Ra nearoriC. Complementation of M. tuberculosis H37Ra with a 2.9-kb restriction fragment from M. tuberculosisH37Rv that encompassed the IS6110 insertion did not increase the survival of recombinant M. tuberculosis H37Ra in mice. In conclusion, this study describes the presence and mechanisms of genomic variation between M. tuberculosisH37Ra and M. tuberculosis H37Rv, although the role that they play in the attenuation of M. tuberculosis H37Ra is unclear.
An invertebrate‐like phototransduction cascade mediates light detection in the chicken retinal ganglion cells

Prebilaterian animals perceived ambient light through nonvisual rhabdomeric photoreceptors (RPs), which evolved as support of the chordate visual system. In vertebrates, the identity of nonvisual photoreceptors and the phototransduction cascade involved in nonimage forming tasks remain uncertain. We investigated whether chicken retinal ganglion cells (RGCs) could be nonvisual photoreceptors and the nature of the photocascade involved. We found that primary cultures of chicken embryonic RGCs express such RP markers as transcription factors Pax6 and Brn3, photopigment melanopsin, and G‐protein q but not markers for ciliary photoreceptors (α‐transducin and Crx). To investigate the photoreceptive capability of RGCs, we assessed the direct effect of light on 3H‐melatonin synthesis in RGC cultures synchronized to 12:12 h light‐dark cycles. In constant dark, RGCs displayed a daily variation in 3H‐melatonin levels peaking at subjective day, which was significantly inhibited by light. This light effect was further increased by the chromophore all‐trans‐retinal and suppressed by specific inhibitors of the invertebrate photocascade involving phosphoinositide hydrolysis (100 μM neomycin; 5 μM U73122) and Ca2+ mobilization (10 mM BAPTA; 1 mM lanthanum). The results demonstrate that chicken RGCs are intrinsically photosensitive RPs operating via an invertebrate‐like phototransduction cascade, which may be responsible for early detection of light before vision occurs. —Contin, M. A. , Verra, D. M. , Guido, M. E. An invertebrate‐like phototransduction cascade mediates light detection in the chicken retinal ganglion cells FASEB J. 20, E2249–E2257 (2006)
Invariant chain influences post-translational processing of HLA-DR molecules.

HLA class II MHC molecule alpha- and beta-chains are normally synthesized in the presence of a third molecule, the invariant chain (Ii). Although Ii is not required for surface expression of HLA class II molecules, the influence of Ii on post-translational processing and maturation HLA class II molecules has not been thoroughly studied. In the present study, BALB/c 3T3 cells were transfected with HLA-DR alpha- and beta-chains with or without co-transfection with human Ii. Although Ii had no effect on the surface expression of DR, Ii did have a profound effect on the post-translational processing of both the alpha- and beta-chains. In the absence of Ii, the major species of alpha- and beta-chains were of lower m.w. than when expressed in the presence of Ii. The differences in m.w. were shown to be caused by differences in glycosylation with the majority of alpha- and beta-chains remaining unprocessed and endo H sensitive in the absence of Ii. The small proportion of alpha-chains that were processed in the absence of Ii showed an altered m.w. and altered sensitivity to treatment with endo H relative to alpha-chains processed in the presence of Ii. Pulse/chase studies demonstrated that although the majority of the alpha- and beta-chains remained unprocessed in the absence of Ii, the small amount that was processed was done so at a rate similar to that observed for alpha- and beta-chains processed in the presence of Ii. These studies demonstrate that Ii influences the post-translational processing of human class II molecules by affecting the proportion of alpha- and beta-chains that are processed and by determining the degree of processing of oligosaccharides on mature alpha-chains.