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Here we introduce position restraints, or "anchors" as a feature in our alignment tool AlignMe, providing an aid to pairwise global sequence alignment of alpha-helical membrane proteins. Applying this approach to realistic scenarios involving distantly-related and low complexity sequences, we illustrate how the addition of anchors can be used to modify alignments, while still maintaining the reproducibility and rigor of the rest of the alignment. Anchored alignments can be generated using the online version of AlignMe available at www.bioinfo.mpg.de/AlignMe/.

Sepsis was induced by cotton smoke inhalation followed by intranasal administration of Pseudomonas aeruginosa in female (> 6 months) Balb/c and syndecan-1 knockout mice. Survival of mice, lung capillary endothelial glycocalyx integrity, lung water content, and vascular hyper-permeability were determined with or without HMW-SH treatment in these mice. Effects of HMW-SH on endothelial permeability and neutrophil migration were tested in in vitro setting.

In septic wildtype mice, we found a severely damaged pulmonary microvascular endothelial glycocalyx and elevated levels of shed syndecan-1 in the circulation. These changes were associated with significantly increased pulmonary vascular permeability. Lipofermata In septic syndecan-1 knockout mice, extravascular lung water content was higher, and early death was observed. The administration of HMW-SH significantly reduced mortality and lung water content in septic syndecan-1 knockout mice, but not in septic wildtype mice. In in vitro setting, HMW-SH inhibited neutrophil migration and reduced cultured endothelial cell permeability increases. However, these effects were reversed by the addition of recombinant syndecan-1 ectodomain.

HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.

HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration. Highest concentrations of these toxicity markers were found during the induction phase of the therapy. Moreover, CSF concentrations of Tau and pTau during treatment were influenced by the children's particular MTHFR1298 genotype. CSF Tau (but not pTau) levels significantly dropped after folinic acid supplementation. At adult age (on average 13.1 years since the end of their treatment), their particular MTHFR1298 genotype (AA, AC or CC) influenced the changes in PIQ and cortical connectivity that we found to be related to their childhood exposure to chemotherapeutics. In summary, we suggest that homozygous MTHFR1298CC individuals are more vulnerable to the adult sequelae of antifolate chemotherapy.

The public health impact of Chikungunya virus (CHIKV) is often underestimated. Usually considered a mild condition of short duration, recent outbreaks have reported greater incidence of severe illness, fatality, and longer-term disability. In 2018/19, Eastern Sudan experienced the largest epidemic of CHIKV in Africa to date, affecting an estimated 487,600 people. Known locally as Kankasha, this study examines clinical characteristics, risk factors, and phylogenetics of the epidemic in Kassala City.

A prospective cohort of 102 adults and 40 children presenting with chikungunya-like illness were enrolled at Kassala Teaching Hospital in October 2018. Clinical information, socio-demographic data, and sera samples were analysed to confirm diagnosis, characterise illness, and identify viral strain. CHIKV infection was confirmed by real-time reverse transcription-PCR in 84.5% (120/142) of participants. Nine (7.5%) CHIKV-positive participants had concurrent Dengue virus (DENV) infection; 34/118 participants (28.8hods. This study highlights the importance of increasing awareness of the severity and impact of CHIKV outbreaks, and the need for urgent actions to reduce transmission risk in households.

Vulnerability to CHIKV remains in Kassala and elsewhere in Sudan due to widespread Aedes aegypti presence and mosquito-fostering household water storage methods. This study highlights the importance of increasing awareness of the severity and impact of CHIKV outbreaks, and the need for urgent actions to reduce transmission risk in households.Acesta excavata (Fabricius, 1779) is a slow growing bivalve from the Limidae family and is often found associated with cold-water coral reefs along the European continental margin. Here we present the compositional variability of frequently used proxy elemental ratios (Mg/Ca, Sr/Ca, Na/Ca) measured by laser-ablation mass spectrometry (LA-ICP-MS) and compare it to in-situ recorded instrumental seawater parameters such as temperature and salinity. Shell Mg/Ca measured in the fibrous calcitic shell section was overall not correlated with seawater temperature or salinity; however, some samples show significant correlations with temperature with a sensitivity that was found to be unusually high in comparison to other marine organisms. Mg/Ca and Sr/Ca measured in the fibrous calcitic shell section display significant negative correlations with the linear extension rate of the shell, which indicates strong vital effects in these bivalves. Multiple linear regression analysis indicates that up to 79% of elemental variability is explicable with temperature and salinity as independent predictor values.

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