Miracle-dz/UniFAR-FTUs huggingface dataset:
Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists

Background: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. Objective: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. Methods: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53 067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. Results: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. Conclusion: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
Retrograde signaling at central synapses

Transcellular retrograde signaling from the postsynaptic target cell to the presynaptic neuron plays critical roles in the formation, maturation, and plasticity of synaptic connections. We here review recent progress in our understanding of the retrograde signaling at developing central synapses. Three forms of potential retrograde signals—membrane-permeant factors, membrane-bound factors, and secreted factors—have been implicated at both developing and mature synapses. Although many of these signals may be active constitutively, retrograde factors produced in association with activity-dependent synaptic plasticity, e.g., long-term potentiation and long-term depression, are of particular interest, because they may induce modification of neuronal excitability and synaptic transmission, functions directly related to the processing and storage of information in the nervous system.
Effect of antiviral treatment on the shedding of HIV‐1 in semen

Objective:The potential role of antiretroviral treatment on the infectiousness of HIV-1-infected men was examined by studying the effect of antiviral treatment on the shedding of HIV-1 in semen. Methods:Forty-four patients enrolled in various treatment protocols were asked to donate a semen sample before they began a new antiviral treatment and at a follow-up visit after 6 to 15 weeks of treatment. Since most patients were on blinded protocols, patients were stratified by response of blood viral load. The effect of each patient's treatment was classified as good (n = 24), fair (n = 8) and marginal (n = 13) by measurement of the HIV RNA reduction in blood plasma (> 1.0 log10; 0.5–1.0 log10 and <0.5 log10 HIV RNA copies/ml reduction, respectively). The effect of treatment on shedding of HIV-1 in semen was documented by the reduction of HIV RNA concentration in seminal plasma and by quantitative HIV-1 seminal cell culture. Results:Overall, antiviral treatment resulted in a significant fall in the viral load in semen (RNA and culture) that paralleled the reduction of viral load in blood. More pronounced reductions of HIV RNA in semen were observed as the effectiveness of treatment on blood HIV RNA levels increased (median drop from baseline 0, 0.3 log10 and 0.8 log10 RNA copies/ml in patients with marginal, fair and good treatment effect, respectively). Thirteen patients lost detectable HIV RNA in blood on treatment and all of these had undetectable levels of HIV-1 in semen by culture and RNA analysis at follow-up. In 19 of the 31 patients (62%) who still had HIV RNA in their blood during treatment, semen HIV levels were below detection in semen at follow-up. Conclusions:Treatment-induced changes of HIV RNA concentration in blood are generally associated with a corresponding change in seminal HIV RNA. If confirmed in larger studies, potent antiretroviral therapy might reduce the spread of HIV-1.
Protective Immunogenicity of Group A Streptococcal M-Related Proteins

ABSTRACT Many previous studies have focused on the surface M proteins of group A streptococci (GAS) as virulence determinants and protective antigens. However, the majority of GAS isolates express M-related protein (Mrp) in addition to M protein, and both have been shown to be required for optimal virulence. In the current study, we evaluated the protective immunogenicity of Mrp to determine its potential as a vaccine component that may broaden the coverage of M protein-based vaccines. Sequence analyses of 33 mrp genes indicated that there are three families of structurally related Mrps (MrpI, MrpII, and MrpIII). N-terminal peptides of Mrps were cloned, expressed, and purified from M type 2 (M2) (MrpI), M4 (MrpII), and M49 (MrpIII) GAS. Rabbit antisera against the Mrps reacted at high titers with the homologous Mrp, as determined by enzyme-linked immunosorbent assay, and promoted bactericidal activity against GAS emm types expressing Mrps within the same family. Mice passively immunized with rabbit antisera against MrpII were protected against challenge infections with M28 GAS. Assays for Mrp antibodies in serum samples from 281 pediatric subjects aged 2 to 16 indicated that the Mrp immune response correlated with increasing age of the subjects. Affinity-purified human Mrp antibodies promoted bactericidal activity against a number of GAS representing different emm types that expressed an Mrp within the same family but showed no activity against emm types expressing an Mrp from a different family. Our results indicate that Mrps have semiconserved N-terminal sequences that contain bactericidal epitopes which are immunogenic in humans. These findings may have direct implications for the development of GAS vaccines.
Thiamine Biosynthesis in Saccharomyces cerevisiae Is Regulated by the NAD+-Dependent Histone Deacetylase Hst1

ABSTRACT Genes encoding thiamine biosynthesis enzymes in microorganisms are tightly regulated such that low environmental thiamine concentrations activate transcription and high concentrations are repressive. We have determined that multiple thiamine (THI) genes in Saccharomyces cerevisiae are also regulated by the intracellular NAD+ concentration via the NAD+-dependent histone deacetylase (HDAC) Hst1 and, to a lesser extent, Sir2. Both of these HDACs associate with a distal region of the affected THI gene promoters that does not overlap with a previously defined enhancer region bound by the thiamine-responsive Thi2/Thi3/Pdc2 transcriptional activators. The specificity of histone H3 and/or H4 deacetylation carried out by Hst1 and Sir2 at the distal promoter region depends on the THI gene being tested. Hst1/Sir2-mediated repression of the THI genes occurs at the level of basal expression, thus representing the first set of transcription factors shown to actively repress this gene class. Importantly, lowering the NAD+ concentration and inhibiting the Hst1/Sum1 HDAC complex elevated the intracellular thiamine concentration due to increased thiamine biosynthesis and transport, implicating NAD+ in the control of thiamine homeostasis.
Sacred groves: a traditional way of conserving plant diversity in West Midnapore District, West Bengal, India

Sacred groves are forest patches conserved by the local people interwined with their socio-cultural and religious practices. An extricable link between the past and present society in terms of religion, socio-culture, heritage and biodiversity exists in the sacred groves. It is distributed globally where ethnic indigenous communities live. Several animals and plants that are threatened in forests are still abundant and well conserved in such sacred groves. The taboos, religious belief and sacredness play a significant role in promoting sustainable utilization and conservation. In this regard, the study of a sacred grove in the district of West Midnapore in West Bengal highlighting the tradition may provide a powerful tool for ensuring biodiversity conservation through community participation.
Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder.

OBJECTIVE This study evaluated the efficacy and safety of fixed doses of once-daily extended-release (XR) venlafaxine in outpatients with generalized anxiety disorder without concomitant major depressive disorder. METHOD Adult outpatients with generalized anxiety disorder but not major depressive disorder with total scores of 18 or higher on the Hamilton Rating Scale for Anxiety and scores of 2 or higher on its anxious mood and tension factors were eligible. Patients were randomly assigned to receive placebo or venlafaxine XR (75, 150, or 225 mg/day) for 8 weeks. Primary efficacy variables were final total and psychic anxiety factor scores on the Hamilton anxiety scale and final severity and global improvement item scores on the Clinical Global Impression (CGI) scale. RESULTS Of the 377 patients entering the study, 370 were included in a safety analysis and 349 in an efficacy analysis. Adjusted mean scores at 8 weeks (last-observation-carried-forward analysis) were significantly lower for one or more of the venlafaxine XR groups in four of four primary and three of four secondary outcome measures than for the placebo group. These included a change of 1.7 (versus 1.3) from baseline on CGI severity item scores and a final score of 2.2 (versus 2.6) on the CGI global improvement item. All doses of venlafaxine XR were well tolerated. CONCLUSIONS Venlafaxine XR is an effective and well-tolerated option for the short-term treatment of generalized anxiety disorder in outpatients without major depressive disorder.
Physical and Psychosocial Functions of Adults with Lower Limb Congenital Deficiencies and Amputations in Childhood

Objectives. (1) To describe the epidemiological and medical features of a sample with LLA and LLD in childhood and (2) to explore their relationship with subsequent physical and psychosocial functions in adulthood. Methods. Cross-sectional survey. Demographics, medical data, Locomotor Capabilities Index (LCI), and Discomfort-Engagement in Everyday Activities Involving Revealing the Body Scale (D-EEARB) were collected from thirty-two adults who suffered from LLA in childhood or LLD. Results. Most of the sample (53.1% males) was working (84.4%), living independently (75%), and single (75%). Mean age was 33.16 (SD = 7.64, range 18–50). Leading causes for LLA were traumatic (40.6%) and oncologic (25%). LLD was present in 6 cases (18.8%). LCI scores revealed a high performance among males (t 17,464 = 2.976, p = .008). D-EEARB scores showed that 56.25% stated feeling “quite” or “totally comfortable” in situations which involved revealing their body, but 43.75% stated the contrary (“uncomfortable” or “very uncomfortable”). LLD and traumatic LLA show higher scores in D-EEARB than vascular and oncological LLA (χ 2 = 7.744, df = 3, p = .05). Conclusions. Adults suffering from LLDs and LLAs during childhood seem to perform well once they are adults. However, 43.75% of patients express considerable discomfort in situations that involve revealing the body.
Interspecific variation in sternohyoideus muscle morphology in clariid catfishes: Functional implications for suction feeding

Depression of the hyoid apparatus plays a crucial role in generating suction, especially in fishes with a dorso‐ventrally flattened head shape. It is generally assumed that shortening of the sternohyoideus muscle, which connects the hyoid to the pectoral girdle, contributes to hyoid depression. However, a recent study on the clariid catfish Clarias gariepinus has shown that this muscle does not shorten but elongates during this phase through retraction of the pectoral girdle. Here, we test whether this pattern is general among clariid catfish, or if variation in the morphology of the sternohyoideus may result in a different sternohyoideus behavior during hyoid depression. First, sternohyoideus mass, effective cross‐sectional area, fiber length and fiber diameter were measured and compared for four clariid species. Next, velocity and magnitude of hyoid depression during prey capture (from high‐speed videos), as well as patterns of sternohyoideus strain were analyzed (from high‐speed X‐ray videos) in these species. While morphology and hyoid depression performance varied considerably among these species, only the species with the most massive sternohyoideus, Gymnallabes typus, showed shortening of the sternohyoideus muscle during the initial part of the expansive phase. The data for Channallabes apus demonstrate that increasing the magnitude of hyoid depression does not necessarily require a shortening of the m. sternohyoideus, as it shows elongation of this muscle during hyoid depression. J. Morphol. , 2007. © 2007 Wiley‐Liss, Inc.
Lack of Evidence for the Participation of Tonin in the Pathogenesis of One‐Kidney, One‐Clip Renovascular Hypertension

It has been reported that immunization against tonin normalizes blood pressure, and that sialoadenectomy, during which the tonin-rich salivary glands are removed, decreases blood pressure in one-kidney, one-clip hypertension. To investigate the role of tonin on this form of hypertension further, we actively immunized one-kidney, one-clip hypertensive rabbits with tonin and measured both the blood pressure response and the titer of antibodies raised against tonin. In addition, because sialoadenectomy may alter food intake, we assessed the effect of sialoadenectomy on the blood pressure of one-kidney, one-clip hypertensive rats fed a liquid diet to facilitate eating. After immunization, all rabbits developed antitonin-antibody titers ranging from 1:300 to 1:56,000. However, in none of the rabbits did the blood pressure decrease significantly (114 ± 3 mm Hg before immunization; 129 ± 6 mm Hg at 16 weeks after immunization). In one-kidney, one-clip hypertensive rats, sialoadenectomy did not lower blood pressure (179 ± 5 mm Hg before sialoadenectomy; 202 ± 9 mm Hg 3 weeks after sialoadenectomy). Neither blood pressure nor body weight differed between sialoadenectomy and sham-sialoadenectomy one-kidney, one-clip hypertensive rats (n = 6). In conclusion, neither active immunization against tonin in one-kidney, one-clip hypertensive rabbits nor sialoadenectomy in one-kidney, one-clip hypertensive rats significantly reduced established hypertension. These results do not support the hypothesis that tonin is involved in the pathogenesis of one-kidney, one-clip hypertension in these animal models.
Nb1.30Cr0.70S5: a layered ternary mixed-metal sulfide

The new layered ternary sulfide, Nb1.30Cr0.70S5, niobium chromium pentasulfide, is isostructural with the solid solution Nb1+xV1−xS5 and belongs to the FeNb3Se10 structure type. Each layer is composed of two unique chains of face-sharing [NbS8] bicapped trigonal prisms (m symmetry) and edge-sharing [MS6] (M= Nb, Cr) octahedra (m symmetry). One of the two metal sites is occupied by statistically disordered Nb and Cr atoms, with 0.3 and 0.7 occupancy, respectively. The chains are connected along the c axis, forming two-dimensional layers, which then stack on top of each other to complete the three dimensional structure. As a result, an undulating van der Waals gap is found between the layers.
Absence of pressure antagonism of ethanol narcosis in C. elegans

BECAUSE hydrostatic pressure can antagonize the behavioral effects of anesthetics in many organisms, we examined whether ethanol-induced immobility of the nematode Caenorhabditis elegans was antagonized by 100 ATA pressure. Nematode mobility was examined at pressures ranging from 1 ATA to 132 ATA, with, and without increasing concentrations of ethanol (0–1 M). Pressure > 100 ATA alone inhibited movement of the nematode (EP50 = 111.5 ± 0.6 ATA), as did increasing concentrations of ethanol (EC50 = 487 ± 44 mM). Pressure, and ethanol appeared to be additive, and not antagonistic. Because of previous results implicating glycine receptor antagonism as a mechanism of pressure reversal, and our current inability to observe significant behavioral effects of strychnine or glycine inhibition of high affinity strychnine binding, we suggest that an absence of glycine receptors in these organisms is the basis for a lack of pressure antagonism of ethanol immobility.
Low-bit rate subband video coding

Video coding using a three-dimensional subband decomposition is described and results are shown for 64 kbps. The three-dimensional subband structure allows for adaptive bit allocation between temporal and spatial information. Conditional replenishment is implemented in the low-temporal frequency bands to take advantage of temporal correlations. The high-frequency information is efficiently encoded using geometric vector quantization (GVQ) which takes advantage of the sparse structured data typically found in the high frequency bands. Coding results at 64 kbps on head-and-shoulder sequences typical of video teleconferencing applications are compared with results obtained with the CCITT Recommendation H.261 coder. <<ETX>>
Enhancement of IEEE 802.16 WirelessMAN Ranging Performance with EIED Backoff Algorithm

EIED backoff algorithm was proposed in Song et al., (2003) to enhance the performance of the IEEE 802.11 DCF. EIED provides significant performance improvement without additional complexity. In this paper, we applied EIED to the periodic ranging process of IEEE 802.16, where BEB was originally used. As a performance metric, the average number of tries per periodic ranging attempt was used. The performance was shown analytically, which was verified by computer simulation. The performance results of EIED in the periodic ranging process of IEEE 802.16 are compared to those of BEB. The performance results show that EIED provides a significant performance gain over BEB. Using EIED, we can achieve comparable performance as BEB with significantly smaller set of ranging CDMA codes.
Human Cancer Biology Targeting Galectin-1 in Carcinoma-Associated Fibroblasts Inhibits Oral Squamous Cell Carcinoma Metastasis by Downregulating MCP-1 / CCL 2 Expression

Purpose: Carcinoma-associated fibroblasts (CAFs) in tumor stroma play an important role in tumor progression and have been associated with a poor prognosis in oral squamous cell carcinoma (OSCC). However, how CAFs influence OSCC malignancy and whether normalizing CAFs inhibits cancer progression remain unclear. Experimental Design: The relationship between the expression of Galectin-1 (Gal-1) and alpha-smooth muscle actin (a-SMA, a CAFmarker) inOSCC patient samples and primary cultured CAFs was examined by quantitative real-time PCR, Western blotting, and immunofluorescence. To examine the effect of Gal-1 on CAF activation and CAF-mediated tumor invasion and migration in vitro, Gal-1 expression was knocked down by small hairpin RNA. Finally, cancer cells and CAFs were coimplanted into SCID mice to evaluate the effect of Gal-1 on CAF-modulated tumor progression in vivo. Results: Gal-1 expression is positively associated with a-SMA in the stroma of OSCC specimens. Gal-1 knockdown decreases activated CAF characteristics, resulting in a decrease in a-SMA expression and extracellular matrix protein production. Notably, blocking Gal-1 expression significantly inhibits CAFconditioned medium-induced tumor cell migration and invasion, possibly by reducing the production of monocyte chemotactic protein-1 (MCP-1/CCL2). MCP-1 induces the migration of OSCC cells by binding to the receptor CCR2; adding anMCP-1 antibody to CAF-conditionedmedium that inhibits the interaction between MCP-1 and CCR2 abolishes migration. Finally, we found that Gal-1 knockdown in CAFs significantly reduces CAF-augmented tumor growth and metastasis in vivo. Conclusions: Our findings demonstrate that Gal-1 regulates CAF activation and indicate that targeting Gal-1 in CAFs inhibits OSCC metastasis by modulating MCP-1 expression. Clin Cancer Res; 17(6); 1306–
Temporal SILAC‐based quantitative proteomics identifies host factors involved in chikungunya virus replication

Chikungunya virus (CHIKV) is an arthropod‐borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12‐kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC‐MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified and per time point 2800–3500 proteins could be quantified in both biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut‐off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo‐like kinase 1 (Plk1), and ubiquitin‐conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection‐induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (http://proteomecentral.proteomexchange.org/dataset/PXD001330).
The Function of the MEF2 Family of Transcription Factors in Cardiac Development, Cardiogenomics, and Direct Reprogramming

Proper formation of the mammalian heart requires precise spatiotemporal transcriptional regulation of gene programs in cardiomyocytes. Sophisticated regulatory networks have evolved to not only integrate the activities of distinct transcription factors to control tissue-specific gene programs but also, in many instances, to incorporate multiple members within these transcription factor families to ensure accuracy and specificity in the system. Unsurprisingly, perturbations in this elaborate transcriptional circuitry can lead to severe cardiac abnormalities. Myocyte enhancer factor–2 (MEF2) transcription factor belongs to the evolutionarily conserved cardiac gene regulatory network. Given its central role in muscle gene regulation and its evolutionary conservation, MEF2 is considered one of only a few core cardiac transcription factors. In addition to its firmly established role as a differentiation factor, MEF2 regulates wide variety of, sometimes antagonistic, cellular processes such as cell survival and death. Vertebrate genomes encode multiple MEF2 family members thereby expanding the transcriptional potential of this core transcription factor in the heart. This review highlights the requirement of the MEF2 family and their orthologs in cardiac development in diverse animal model systems. Furthermore, we describe the recently characterized role of MEF2 in direct reprogramming and genome-wide cardiomyocyte gene regulation. A thorough understanding of the regulatory functions of the MEF2 family in cardiac development and cardiogenomics is required in order to develop effective therapeutic strategies to repair the diseased heart.