Notes

Microbe CRISPR: achievements and leads.
Fungal community and functional responses to fertilizer varied across the ambient N deposition gradient. Fungal biomass and richness increased with simulated N deposition at sites with low ambient deposition and decreased at sites with high ambient deposition. Fungal functional genes involved in hydrolysis of organic matter increased with ambient N deposition while genes involved in oxidation of organic matter decreased. One of four genes involved in generalized abiotic stress tolerance increased with ambient N deposition. In summary, we found that the divergent response to simulated N deposition depended on ambient N deposition levels. Fungal biomass, richness, and oxidative enzyme potential were reduced by N deposition where ambient N deposition was high suggesting fungal communities were pushed beyond an environmental stress threshold. Fungal community structure and function responses to N enrichment depended on ambient N deposition at a regional scale.
To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania.

Cross-sectional study conducted between 2015 and 2016 in the selected communities. In each community, we randomly selected a sample of adults from the general population and from three putative risk groups including the following (i) fishermen, (ii) fish processors and traders, and (iii) women working in the recreational facilities. Participants were interviewed to obtain information about potential risk factors, and venous blood was collected for detection of HIV, syphilis and schistosome infections. We used logistic regression models to quantify the associations between potential risk factors and HIV, and also between schistosome infection and HIV.

We enrolled 1128 people from selected fishing communities. The overall prevalence of HIV, syphilis and schistosome infection was 14.2%, 15.6% and 83.1%, respectively. Mycophenolic Female recreational facility workers had the highest prevalence of HIV (30.4%) and syphilis (24%). The odds of being HIV infected were generally higher in all age categories. Transactional sex was commonly reported and especially receiving gifts for sex was found to be strongly associated with HIV (adjusted OR=2.50; 95% CI 1.44-4.34, P=0.008). Confirmed serological syphilis was associated with increased odds of having HIV infection. HIV was not associated with schistosome infection in a combined dataset and when we examined this separately for men and women alone.

We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents.
We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents.Hydroquinone has pharmacological uses in disorders of pigmentation because of its ability to competitively inhibit the enzyme tyrosinase. Our contemporary review presents the strongest evidence supporting the use of hydroquinone with the most effective and tolerable formulations combining hydroquinone, retinoid and corticosteroid (modified Kligman formula or 'triple combination cream'). The risk of exogenous ochronosis is low if prescribed concentrations of ≤ 5 for a limited period with regular monitoring. Dermatologists should reassure patients that with controlled use, hydroquinone can be well-tolerated and safe for a range of hyperpigmentary conditions.The SH2 domain-containing protein of 76 kDa, SLP76, is an important adaptor protein that coordinates a complex protein network downstream of T-cell receptors (TCR), ultimately regulating the immune response. Upon phosphorylation on Ser376, SLP76 interacts with 14-3-3 adaptor proteins, which leads to its proteolytic degradation. This provides a negative feedback mechanism by which TCR signalling can be controlled. To gain insight into the 14-3-3/SLP76 protein-protein interaction (PPI), we have determined a high-resolution crystal structure of a SLP76 synthetic peptide containing Ser376 with 14-3-3σ. We then characterized its binding to 14-3-3 proteins biophysically by means of fluorescence polarization and isothermal titration calorimetry. Furthermore, we generated two recombinant SLP76 protein constructs and characterized their binding to 14-3-3. Our work lays the foundation for drug design efforts aimed at targeting the 14-3-3/SLP76 interaction and, thereby, TCR signalling.
During liver fibrosis, liver sinusoidal endothelial cells (LSECs) release angiocrine signals to recruit inflammatory cells into the liver. P300, a master regulator of gene transcription, is associated with pathological inflammatory response. Therefore, we examined how endothelial p300 regulates angiocrine signaling and inflammation related to portal hypertension and fibrogenesis.

Carbon tetrachloride (CCl
) or partial inferior vena cava ligation (pIVCL) were used to induce liver injury. Mice with LSEC-specific p300 deletion (p300
) or C-C motif chemokine ligand 2 (Ccl2) deficiency, NFκB-p50 knockout mice and BRD4 inhibitors in wild-type mice were used to investigate mechanisms of inflammation regulation. Leukocytes were analyzed by mass cytometry by time-of-flight. Epigenetic histone marks were modified by CRISPR-dCas9-KRAB-mediated epigenome-editing. Portal pressure and liver fibrosis were reduced in p300
mice compared to p300
mice following liver injury. Accumulation of macrophages was also redupression, leading to macrophage accumulation, portal hypertension and liver fibrosis. Inhibition of p300 and its binding partners might serve as novel therapies in the treatment of liver diseases.
To evaluate the reliability of obstetric handheld smartphone-based point-of-care ultrasound (POCUS) in a resource-limited high-volume setting.

A single-center prospective observational study among women requiring urgent diagnosis and admitted to a maternity referral hospital in Sierra Leone from March to April 2019. Pre-specified ultrasound findings were obtained with a handheld POCUS device; a comprehensive ultrasound examination was then performed by an experienced operator using conventional full-feature apparatus. Agreement was assessed by diagnostic accuracy and Cohen κ-statistics.

Overall, there were 307 participants. The mean aggregated diagnostic accuracy was 95.5% (κ-statistic, 0.90; 95% confidence interval [CI], 0.89-0.93; P<0.001). Highest accuracy was reported for detecting free fluid collection in the abdominal cavity (100%; κ-statistic, 1.00; 95% CI, 1.00-1.00; P<0.001). Ultrasound findings obtained with the handheld device for intrauterine pregnancy, fetal heartbeat, cephalic presentation, multifetal pregnancy, and assessment of gestational age based on bi-parietal diameter were highly reliable (agreement, >90%; κ-statistic, >0.
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