TNF-α-induced E3 ligase, TRIM15 inhibits TNF-α-regulated NF-κB pathway by promoting turnover of K63 linked ubiquitination of TAK1

Ubiquitin E3-ligases are recruited at different steps of TNF-α-induced NF-κB activation; however, their role in temporal regulation of the pathway remains elusive. The study systematically identified TRIMs as potential feedback regulators of the TNF-α-induced NF-κB pathway. We further observed that TRIM15 is “late” response TNF-α-induced gene and inhibits the TNF-α-induced NF-κB pathway in several human cell lines. TRIM15 promotes turnover of K63-linked ubiquitin chains in a PRY/SPRY domain-dependent manner. TRIM15 interacts with TAK1 and inhibits its K63-linked ubiquitination, thus NF-κB activity. Further, TRIM15 interacts with TRIM8 and inhibits cytosolic translocation to antagonize TRIM8 modualted NF-κB. TRIM8 and TRIM15 also show functionally inverse correlation in psoriasis condition. In conclusion, TRIM15 is TNF-α-induced late response gene and inhibits TNF-α induced NF-κB pathway hence a feedback modulator to keep the proinflammatory NF-κB pathway under control

Long-Time Tails and Anomalous Slowing Down in the Relaxation of Spatially Inhomogeneous Excitations in Quantum Spin Chains

Exact analytic calculations in spin-1/2 XY chains, show the presence of long-time tails in the asymptotic dynamics of spatially inhomogeneous excitations. The decay of inhomogeneities, for $t\to \infty$, is given in the form of a power law $$(t/\tau_{Q}) ^{-\nu_{Q}}$$ where the relaxation time $\tau_{Q}$ and the exponent $\nu_{Q}$ depend on the wave vector $Q$, characterizing the spatial modulation of the initial excitation. We consider several variants of the XY model (dimerized, with staggered magnetic field, with bond alternation, and with isotropic and uniform interactions), that are grouped into two families, whether the energy spectrum has a gap or not. Once the initial condition is given, the non-equilibrium problem for the magnetization is solved in closed form, without any other assumption. The long-time behavior for $t\to \infty$ can be obtained systematically in a form of an asymptotic series through the stationary phase method. We found that gapped models show critical behavior with respect to $Q$, in the sense that there exist critical values $Q_{c}$, where the relaxation time $\tau_{Q}$ diverges and the exponent $\nu_{Q}$ changes discontinuously. At those points, a slowing down of the relaxation process is induced, similarly to phenomena occurring near phase transitions. Long-lived excitations are identified as incommensurate spin density waves that emerge in systems undergoing the Peierls transition. In contrast, gapless models do not present the above anomalies as a function of the wave vector $Q$.Comment: 25 pages, 2 postscript figures. Manuscript submitted to Physical Review

Pathogenic and genetic characterization of six Indian populations of Colletotrichum sublineolum, the causal agent of sorghum anthracnose

The pathogenic and genetic characterization of populations of C. sublineolum, the causal agent of anthracnose of sorghum, was investigated in isolates from 6 locations in India. Multi-location field evaluation and greenhouse tests were done on 16 sorghum lines that comprised the International Sorghum Anthracnose Virulence Nursery (ISAVN). The lines were tested in a field trial for 4-5 years (1992-96) at 6 locations: Indore, Surat, Patancheru, Dharwad, Udaipur and Pantnagar. Plants were scored for disease reaction (R/MR/S) and for disease severity (on a 1-9 scale where 1 is no lesions and 9 is >75% leaf area covered with lesions) at the soft-dough stage in the field and at the seedling stage in the greenhouse. Significant (P<0.001) differences were observed for virulence (disease reaction) and aggressiveness (disease severity) across locations (isolates) and sorghum lines both in field and greenhouse tests. In both tests, isolate x sorghum line interactions were highly significant (P<0.001) suggesting that populations of C. sublineolum at these 6 locations were different. A random amplified polymorphic DNA (RAPD) analysis exhibited genetic dissimilarities among the isolates and these were classified into 6 groups

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

&lt;b&gt;BACKGROUND:&lt;/b&gt; The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

Psychological impact of anti-VEGF treatments for wet macular degeneration-a review.

To review the current literature on the psychological impact of anti-VEGF treatments for wet age-related macular degeneration (wAMD), in terms of patients' experiences of receiving these treatments, and the impact of these treatments for patients' mental health and quality of life.We critically analyzed current literature evaluating psychological impact of anti-VEGF treatments for wAMD. Primary searches of PubMed, Science Direct, and Web of Science were conducted in July and August of 2015. We reviewed all papers on the topic published until August 5, 2015.Our literature search found 14 papers addressing the psychological impact of anti-VEGF treatments for wAMD. Results highlighted potential anxieties and experiences of pain caused by receiving regular intravitreal injections. A positive visual outcome of anti-VEGF therapy is associated with positive vision-related QOL outcomes, although such association seems to be dependent on improvements on visual acuity. In the literature reviewed, patients receiving anti-VEGF treatments showed a prevalence rate of depression between 20 and 26 %.Although anti-VEGF treatments can cause some anxiety and being experienced as a stressful event, especially in the beginning of the treatment, preliminary findings suggest a potential benefit for long-term vision-related quality of life. Further longitudinal and qualitative research should bring more evidence on the positive and negative effects of these treatments on patients' long-term mental health

No association of xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan

<p>Abstract</p> <p>Background</p> <p>The involvement of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer (PC) and chronic fatigue syndrome (CFS) is disputed as its reported prevalence ranges from 0% to 25% in PC cases and from 0% to more than 80% in CFS cases. To evaluate the risk of XMRV infection during blood transfusion in Japan, we screened three populations--healthy donors (<it>n </it>= 500), patients with PC (<it>n </it>= 67), and patients with CFS (<it>n </it>= 100)--for antibodies against XMRV proteins in freshly collected blood samples. We also examined blood samples of viral antibody-positive patients with PC and all (both antibody-positive and antibody-negative) patients with CFS for XMRV DNA.</p> <p>Results</p> <p>Antibody screening by immunoblot analysis showed that a fraction of the cases (1.6-3.0%) possessed anti-Gag antibodies regardless of their gender or disease condition. Most of these antibodies were highly specific to XMRV Gag capsid protein, but none of the individuals in the three tested populations retained strong antibody responses to multiple XMRV proteins. In the viral antibody-positive PC patients, we occasionally detected XMRV genes in plasma and peripheral blood mononuclear cells but failed to isolate an infectious or full-length XMRV. Further, all CFS patients tested negative for XMRV DNA in peripheral blood mononuclear cells.</p> <p>Conclusion</p> <p>Our data show no solid evidence of XMRV infection in any of the three populations tested, implying that there is no association between the onset of PC or CFS and XMRV infection in Japan. However, the lack of adequate human specimens as a positive control in Ab screening and the limited sample size do not allow us to draw a firm conclusion.</p

LPS Regulates SOCS2 Transcription in a Type I Interferon Dependent Autocrine-Paracrine Loop

Recent studies suggest that SOCS2 is involved in the regulation of TLR signaling. In this study, we found that the expression of SOCS2 is regulated in human monocyte-derived DC by ligands stimulating TLR2, 3, 4, 5, 8 and 9 signaling. SOCS2 induction by LPS was dependent on the type I IFN regulated transcription factors IRF1 and IRF3 as shown by using silencing RNAs for IRFs. Blocking endogenous type I IFN signaling, by neutralizing antibodies to the receptor IFNAR2, abolished SOCS2 mRNA expression after TLR4 stimulation. Transcription factors STAT3, 5 and 6 displayed putative binding sites in the promoter regions of the human SOCS2 gene. Subsequent silencing experiments further supported that STAT3 and STAT5 are involved in LPS induced SOCS2 regulation. In mice we show that SOCS2 mRNA induction is 45% lower in bone marrow derived macrophages derived from MyD88−/− mice, and do not increase in BMMs from IRF3−/− mice after BCG infection. In conclusion, our results suggest that TLR4 signaling indirectly increases SOCS2 in late phase mainly via the production of endogenous type I IFN, and that subsequent IFN receptor signaling activates SOCS2 via STAT3 and STAT5

Unconscious biases in neural populations coding multiple stimuli

Throughout the nervous system information is commonly coded in activity distributed over populations of neurons. In idealized situations where a single, continuous stimulus is encoded in a homogeneous population code, the value of the encoded stimulus can be read out without bias. However in many situations multiple stimuli are simultaneously present, for example, multiple motion patterns might overlap. Here we find that when multiple stimuli that overlap in their neural representation are simultaneously encoded in the population, biases in the read-out emerge. Although the bias disappears in the absence of noise, the bias is remarkably persistent at low noise levels. The bias can be reduced by competitive encoding schemes or by employing complex decoders. To study the origin of the bias, we develop a novel general framework based on Gaussian processes that allows for an accurate calculation of the estimate distributions of maximum likelihood decoders, and reveals that the distribution of estimates is bimodal for overlapping stimuli. The results have implications for neural coding and behavioural experiments on, for instance, overlapping motion patterns