Assessment of neuroactive effects of chemicals in cell-based assays remains challenging as complex functional tissue is required for biologically relevant readouts. Recent in vitro models using rodent primary neural cultures grown on multielectrode arrays allow quantitative measurements of neural network activity suitable for neurotoxicity screening. However, robust systems for testing effects on network function in human neural models are still lacking. The increasing number of differentiation protocols for generating neurons from human-induced pluripotent stem cells (hiPSCs) holds great potential to overcome the unavailability of human primary tissue and expedite cell-based assays. Yet, the variability in neuronal activity, prolonged ontogeny and rather immature stage of most neuronal cells derived by standard differentiation techniques greatly limit their utility for screening neurotoxic effects on human neural networks. Here, we used excitatory and inhibitory neurons, separately generated by direct reprogramming from hiPSCs, together with primary human astrocytes to establish highly functional cultures with defined cell ratios. Such neuron/glia cocultures exhibited pronounced neuronal activity and robust formation of synchronized network activity on multielectrode arrays, albeit with noticeable delay compared with primary rat cortical cultures. We further investigated acute changes of network activity in human neuron/glia cocultures and rat primary cortical cultures in response to compounds with known adverse neuroactive effects, including gamma amino butyric acid receptor antagonists and multiple pesticides. Importantly, we observed largely corresponding concentration-dependent effects on multiple neural network activity metrics using both neural culture types. These results demonstrate the utility of directly converted neuronal cells from hiPSCs for functional neurotoxicity screening of environmental chemicals.
Socioeconomic status (SES) has been suggested as a risk factor for falls but the few prospective studies to test this have had mixed results. We evaluated the prospective association between SES and falls in the Concord Health and Ageing in Men Project (CHAMP).

CHAMP is a population-based prospective cohort study of men aged ≥70 years in Sydney, Australia. Incident falls were ascertained by triannual telephone calls for up to four years. SES was assessed with four indicators (education, occupation, source of income, home ownership) and cumulative SES score. We tested for interaction between SES indicators and country of birth and conducted stratified analyses.

We evaluated 1624 men (mean age 77.3±5.4 years). During a mean±SD follow-up of 42.6±8.7 months, 766 (47%) participants reported ≥1 incident falls. In non-stratified analyses, there were no associations between SES indicators and falls. In stratified analyses, falls rates were higher among Australian-born men with less formal education (IRR 1.66, 95% CI 1.16 to 2.37, compared with those with more education) and those with low occupational position (1.45; 1.09 to 1.93). https://www.selleckchem.com/products/tram-34.html However, among men born in non-main English-speaking countries the rate of falls was lower among those with low educational level and no associations was evident for occupational position.

Lower educational level and occupational position predicted a higher falls rate in Australian-born men; the opposite relationship was evident for educational level among migrants born in non-main English-speaking countries. Further studies should test these relationships in different populations and settings and evaluate targeted interventions.
Lower educational level and occupational position predicted a higher falls rate in Australian-born men; the opposite relationship was evident for educational level among migrants born in non-main English-speaking countries. Further studies should test these relationships in different populations and settings and evaluate targeted interventions.We used transcriptome analysis to research ovary development in Bactrocera dorsalis (Hendel). The ovary transcriptome of B. dorsalis yielded 66,463,710 clean reads that were assembled into 23,822 unigenes. After aligning to the Nr database in NCBI, 15,473 (64.95%) of the unigenes were matched to identified proteins. As determined by BLAST search, 11,043 (46.36%), 6,102 (25.61%), and 12,603 (52.90%) unigenes were each allocated to clusters via gene ontology, orthologous groups, and SwissProt, respectively. The Kyoto encyclopedia database of genes and genomes (KEGG) was further used to annotate these sequences, and 11,068 unigenes were mapped to 255 known pathways. Afterward, the genes that were possibly involved in oogenesis and ovary development were obtained from the transcriptome data and analyzed. Interestingly, seven ovary-specific genes were identified, including a Nanos gene that is involved in maintaining the primordial germ cells in many insects. Therefore, we further focused on the function of the BdNanos gene, and the gene was injected into B. dorsalis. As expected, the knocking down of Nanos gene expression led to significant inhibition of ovary development, suggesting an important role of this gene in the reproductive process of B. dorsalis. In summary, the present study provides an important reference for identifying the molecular mechanisms of oogenesis and ovary development in B. dorsalis. The BdNanos gene is crucial for ovary development in B. dorsalis and is therefore a potential new pest control target.
Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria.

In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019.

No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C.