Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS

published_or_final_versio

Monosaccharide composition of polysaccharides of borojo from tropical rain forest

2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Population seroprevalence of antibody to influenza A(H7N9) virus, Guangzhou, China

BACKGROUND: Since the identification in early 2013 of severe disease caused by influenza A(H7N9) virus infection, there have been few attempts to characterize the full severity profile of human infections. Our objective was to estimate the number and severity of H7N9 infections in Guangzhou, using a serological study. METHODS: We collected residual sera from patients of all ages admitted to a hospital in the city of Guangzhou in southern China in 2013 and 2014. We screened the sera using a haemagglutination inhibition assay against a pseudovirus containing the H7 and N9 of A/Anhui/1/2013(H7N9), and samples with a screening titer ≥10 were further tested by standard hemagglutination-inhibition and virus neutralization assays for influenza A(H7N9). We used a statistical model to interpret the information on antibody titers in the residual sera, assuming that the residual sera provided a representative picture of A(H7N9) infections in the general population, accounting for potential cross-reactions. RESULTS: We collected a total of 5360 residual sera from December 2013 to April 2014 and from October 2014 to December 2014, and found two specimens that tested positive for H7N9 antibody at haemagglutination inhibition titer ≥40 and a neutralization titer ≥40. Based on this, we estimated that 64,000 (95 % credibility interval: 7300, 190,000) human infections with influenza A(H7N9) virus occurred in Guangzhou in early 2014, with an infection-fatality risk of 3.6 deaths (95 % credibility interval: 0.47, 15) per 10,000 infections. CONCLUSIONS: Our study suggested that the number of influenza A(H7N9) virus infections in Guangzhou substantially exceeded the number of laboratory-confirmed cases there, albeit with considerable imprecision. Our study was limited by the small number of positive specimens identified, and larger serologic studies would be valuable. Our analytic framework would be useful if larger serologic studies are done.published_or_final_versio

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

The impact of telehealth remote patient monitoring on glycemic control in type 2 diabetes: a systematic review and meta-analysis of systematic reviews of randomised controlled trials

Background There is a growing body of evidence to support the use of telehealth in monitoring HbA1c levels in people living with type 2 diabetes. However, the overall magnitude of effect is yet unclear due to variable results reported in existing systematic reviews. The objective of this study is to conduct a systematic review and meta-analysis of systematic reviews of randomised controlled trials to create an evidence-base for the effectiveness of telehealth interventions on glycemic control in adults with type 2 diabetes. Methods Electronic databases including The Cochrane Library, MEDLINE, EMBASE, HMIC, and PsychINFO were searched to identify relevant systematic reviews published between 1990 and April 2016, supplemented by references search from the relevant reviews. Two independent reviewers selected and reviewed the eligible studies. Of the 3279 references retrieved, 4 systematic reviews reporting in total 29 unique studies relevant to our review were included. Both conventional pairwise meta-analyses and network meta-analyses were performed. Results Evidence from pooling four systematic reviews found that telehealth interventions produced a small but significant improvement in HbA1c levels compared with usual care (MD: -0.55, 95% CI: -0.73 to − 0.36). The greatest effect was seen in telephone-delivered interventions, followed by Internet blood glucose monitoring system interventions and lastly interventions involving automatic transmission of SMBG using a mobile phone or a telehealth unit. Conclusion Current evidence suggests that telehealth is effective in controlling HbA1c levels in people living with type 2 diabetes. However there is need for better quality primary studies as well as systematic reviews of RCTs in order to confidently conclude on the impact of telehealth on glycemic control in type 2 diabetes

Regionalização para o cultivo do feijão no Rio Grande do Sul com base na interação genótipo x ambiente¹.

bitstream/item/59171/1/Iraja-V59N002P19810.pd

Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells

<p>Abstract</p> <p>Background</p> <p>Cancer stem cells (CSCs) play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs) and glioma stem cells (GSCs) in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated.</p> <p>Methods</p> <p>We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using γ-secretase inhibitors (GSI) and assessed the potential functions of Notch signaling in human GSCs.</p> <p>Results</p> <p>Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h.</p> <p>Conclusions</p> <p>These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle.</p

Comparative Expression Profiling of the Chlamydia trachomatis pmp Gene Family for Clinical and Reference Strains

Chlamydia trachomatis, an obligate intracellular pathogen, is a leading worldwide cause of ocular and urogenital diseases. Advances have been made in our understanding of the nine-member polymorphic membrane protein (Pmp) gene (pmp) family of C. trachomatis. However, there is only limited information on their biologic role, especially for biological variants (biovar) and clinical strains.We evaluated expression for pmps throughout development for reference strains E/Bour and L2/434, representing different biovars, and for clinical E and L2 strains. Immunoreactivity of patient sera to recombinant (r)Pmps was also determined. All pmps were expressed at two hours. pmpA had the lowest expression but was up-regulated at 12 h for all strains, indicating involvement in reticulate body development. For pmpD, expression peaked at 36 h. Additionally, 57.7% of sera from infected and 0% from uninfected adolescents were reactive to rPmpD (p = 0.001), suggesting a role in immunogenicity. pmpF had the highest expression levels for all clinical strains and L2/434 with differential expression of the pmpFE operon for the same strains. Sera were nonreactive to rPmpF despite immunoreactivity to rMOMP and rPmpD, suggesting that PmpF is not associated with humoral immune responses. pmpFE sequences for clinical strains were identical to those of the respective reference strains. We identified the putative pmpFE promoter, which was, surprisingly, 100% conserved for all strains. Analyses of ribosomal binding sites, RNase E, and hairpin structures suggested complex regulatory mechanism(s) for this >6 Kb operon.The dissimilar expression of the same pmp for different C. trachomatis strains may explain different strain-specific needs and phenotypic distinctions. This is further supported by the differential immunoreactivity to rPmpD and rPmpF of sera from patients infected with different strains. Furthermore, clinical E strains did not correlate with the E reference strain at the gene expression level, reinforcing the need for expansive studies of clinical strains

Secured Communication over Frequency-Selective Fading Channels: a practical Vandermonde precoding

In this paper, we study the frequency-selective broadcast channel with confidential messages (BCC) in which the transmitter sends a confidential message to receiver 1 and a common message to receivers 1 and 2. In the case of a block transmission of N symbols followed by a guard interval of L symbols, the frequency-selective channel can be modeled as a N * (N+L) Toeplitz matrix. For this special type of multiple-input multiple-output (MIMO) channels, we propose a practical Vandermonde precoding that consists of projecting the confidential messages in the null space of the channel seen by receiver 2 while superposing the common message. For this scheme, we provide the achievable rate region, i.e. the rate-tuple of the common and confidential messages, and characterize the optimal covariance inputs for some special cases of interest. It is proved that the proposed scheme achieves the optimal degree of freedom (d.o.f) region. More specifically, it enables to send l <= L confidential messages and N-l common messages simultaneously over a block of N+L symbols. Interestingly, the proposed scheme can be applied to secured multiuser scenarios such as the K+1-user frequency-selective BCC with K confidential messages and the two-user frequency-selective BCC with two confidential messages. For each scenario, we provide the achievable secrecy degree of freedom (s.d.o.f.) region of the corresponding frequency-selective BCC and prove the optimality of the Vandermonde precoding. One of the appealing features of the proposed scheme is that it does not require any specific secrecy encoding technique but can be applied on top of any existing powerful encoding schemes.Comment: To appear in EURASIP journal on Wireless Communications and Networking, special issue on Wireless Physical Security, 200