Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics

Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs) harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs) within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

Anticoagulant rodenticide uptake in resistant rat populations

The use of potent anticogulant rodenticide ‘resistance-breakers’ is avoided due to their higher toxicity and potential to be more hazardous in the environment [6]. However, in areas where practitioners seek to control resistant rodent infestations, their use may pose less of a risk than applications of ineffective baits. Compounds to which rodents are resistant to, do not provide effective control and create a long-term source of AR in the environment. The higher quantities of anticoagulant rodenticide used show that using ineffective compounds may extend both the period and severity of exposure to non-target animals to anticoagulant rodenticides. Conversely the effective use of resistance-breakers to control anticoagulant rodenticide-resistant rat populations results in lower environmental exposure of anticoagulant rodenticides for non-targets. Of course, the relative toxicity of the different anticoagulant rodenticides will also play an important part in overall risk assessments. However, this can be outweighed by the relative exposure to different anticoagulant rodenticides in such situations.

Human gut microbiota and its relationship to health and disease

Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics.

Activation of p21-activated protein kinase alpha (alpha PAK) by hyperosmotic shock in neonatal ventricular myocytes.

The p21-activated protein kinases (PAKs) may participate in signalling from Cdc42/Rac1 to the stress-regulated MAPKs (SAPKs/JNKs and p38-/HOG-1-related-MAPKs). We characterized the expression and regulation of alpha PAK in cultured ventricular myocytes. alpha PAK was specifically immunoprecipitated from myocyte extracts. High basal alpha PAK activity was detected in unstimulated myocytes. Its activity was increased rapidly (<30 s) by hyperosmotic shock in the presence of okadaic acid, and was maximal by 3 min (187 +/- 7% relative to unstimulated cells). Endothelin-1 and interleukin-1beta, which also activate SAPKs/JNKs, did not increase alpha PAK activity and presumably act through different PAK isoforms or other mechanisms.

Sibling influence on the human capital of the left-behind

While a growing literature has analyzed the effects of parental migration on the educational outcomes of children left behind, this study is the first to highlight the importance of sibling interactions in such a context. Using panel data from the RUMiC Survey, we find that sibling influence on school performance is stronger among left- behind children. Hence, parental migration seems to trigger changes in familial roles and sibling effects among children. However, it is primarily older sisters who exhibit a positive influence on their younger siblings. We corroborate our results by performing a series of tests to mitigate endogeneity issues. The results from the analysis suggest that sibling effects in migrant households might be a mechanism shaping children’s outcomes and success and that adjustments within the family left behind have the potential to generate benefits – or reduce hardships – in response to parental migration.

Where were the monsoon regions and arid zones in Asia prior to the Tibetan Plateau uplift?

The impact of the Tibetan Plateau uplift on the Asian monsoons and inland arid climates is an important but also controversial question in studies of paleoenvironmental change during the Cenozoic. In order to achieve a good understanding of the background for the formation of the Asian monsoons and arid environments, it is necessary to know the characteristics of the distribution of monsoon regions and arid zones in Asia before the plateau uplift. In this study, we discuss in detail the patterns of distribution of the Asian monsoon and arid regions before the plateau uplift on the basis of modeling results without topography from a global coupled atmosphere–ocean general circulation model, compare our results with previous simulation studies and available biogeological data, and review the uncertainties in the current knowledge. Based on what we know at the moment, tropical monsoon climates existed south of 20°N in South and Southeast Asia before the plateau uplift, while the East Asian monsoon was entirely absent in the extratropics. These tropical monsoons mainly resulted from the seasonal shifts of the Inter-Tropical Convergence Zone. There may have been a quasi-monsoon region in central-southern Siberia. Most of the arid regions in the Asian continent were limited to the latitudes of 20–40°N, corresponding to the range of the subtropical high pressure year-around. In the meantime, the present-day arid regions located in the relatively high latitudes in Central Asia were most likely absent before the plateau uplift. The main results from the above modeling analyses are qualitatively consistent with the available biogeological data. These results highlight the importance of the uplift of the Tibetan Plateau in the Cenozoic evolution of the Asian climate pattern of dry–wet conditions. Future studies should be focused on effects of the changes in land–sea distribution and atmospheric CO2 concentrations before and after the plateau uplift, and also on cross-comparisons between numerical simulations and geological evidence, so that a comprehensive understanding of the evolution of the Cenozoic paleoenvironments in Asia can be achieved.

Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility

Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry. A decline in BMPR1B density occurred at the time of dominant follicle selection and during the terminal stage of folliculogenesis in the 23-30 y good ovarian reserve patients. The 40+ y poor ovarian reserve patients experienced a reversal of this pattern. The results demonstrate an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density at the two critical time points of dominant follicle selection and pre-ovulatory follicle maturation. Dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients.