Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila

During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Antennapedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental patterning in the developing CNS.     

Polysomnographic Characteristics of Sleep in Stroke: A Systematic Review and Meta-Analysis

BackgroundResearch on sleep after stroke has focused mainly on sleep disordered breathing. However, the extend to which sleep physiology is altered in stroke survivors, how these alterations compare to healthy volunteers, and how sleep changes might affect recovery as well as physical and mental health has yet to be fully researched. Motivated by the view that a deeper understanding of sleep in stroke is needed to account for its role in health and well-being as well as its relevance for recovery and rehabilitation, we conducted a systematic review and meta-analysis of polysomnographic studies comparing stroke to control populations.MethodMedline and PsycInfo databases were searched using "stroke" and words capturing polysomnographic parameters as search terms. This yielded 1692 abstracts for screening, with 15 meeting the criteria for systematic review and 9 for meta-analysis. Prisma best practice guidelines were followed for the systematic review; the Comprehensive Meta-Analysis software was used for random effects modelling.ResultsThe meta-analysis revealed that patients with stroke have poorer sleep than controls. Patients had lower sleep efficiency (mean 75% vs 84%), shorter total-sleep-time (309.4 vs 340.3 min) and more wake-after-sleep-onset (97.2 vs 53.8 min). Patients also spend more time in stage 1 (13% vs 10%) and less time in stage 2 sleep (36% vs 45%) and slow-wave-sleep (10% vs 12%). No group differences were identified for REM sleep. The systematic review revealed a strong bias towards studies in the early recovery phase of stroke, with no study reporting specifically on patients in the chronic state. Moreover, participants in the control groups included community samples as well as other patients groups.ConclusionsThese results indicate poorer sleep in patients with stroke than controls. While strongly suggestive in nature, the evidence base is limited and methodologically diverse, and hands a clear mandate for further research. A particular need regards polysomnographic studies in chronic community-dwelling patients compared to age-matched individuals.     

Strong sexual selection in males against a mutation load that reduces offspring production in seed beetles

Theory predicts that sexual reproduction can increase population viability relative to asexual reproduction by allowing sexual selection in males to remove deleterious mutations from the population without large demographic costs. This requires that selection acts more strongly in males than females and that mutations affecting male reproductive success have pleiotropic effects on population productivity, but empirical support for these assumptions is mixed. We used the seed beetle Callosobruchus maculatus to implement a three‐generation breeding design where we induced mutations via ionizing radiation (IR) in the F₀ generation and measured mutational effects (relative to nonirradiated controls) on an estimate of population productivity in the F₁ and effects on sex‐specific competitive lifetime reproductive success (LRS) in the F₂. Regardless of whether mutations were induced via F₀ males or females, they had strong negative effects on male LRS, but a nonsignificant influence on female LRS, suggesting that selection is more efficient in removing deleterious alleles in males. Moreover, mutations had seemingly shared effects on population productivity and competitive LRS in both sexes. Thus, our results lend support to the hypothesis that strong sexual selection on males can act to remove the mutation load on population viability, thereby offering a benefit to sexual reproduction.     

Synthesis,Characterization and in vitro Studies of a Cathepsin B‐Cleavable Prodrug of the VEGFR Inhibitor Sunitinib

Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small‐molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B‐cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non‐cathepsin B‐cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B‐expressing cell lines Caki‐1 and RU‐MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B‐cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.     

An environmental assessment of small hydropower in India: the real costs of dams’ construction under a life cycle perspective

The International Journal of Life Cycle Assessment - In the last years, India has taken a number of initiatives to boost small hydropower development based on the assumption of being a green energy...     

Development of Eco-factors for the European Union based on the Ecological Scarcity Method

The International Journal of Life Cycle Assessment - Weighting as an optional step in life cycle impact assessment (LCIA) has recently gained momentum through increased policy requirements in the...     

Does thermal plasticity align with local adaptation? An interspecific comparison of wing morphology in sepsid flies

Although genetic and plastic responses are sometimes considered as unrelated processes, their phenotypic effects may often align because genetic adaptation is expected to mirror phenotypic plasticity if adaptive, but run counter to it when maladaptive. Because the magnitude and direction of this alignment has further consequences for both the tempo and mode of adaptation, they are relevant for predicting an organisms’ reaction to environmental change. To better understand the interplay between phenotypic plasticity and genetic change in mediating adaptive phenotypic variation to climate variability, we here quantified genetic latitudinal variation and thermal plasticity in wing loading and wing shape in two closely related and widespread sepsid flies. Common garden rearing of 16 geographical populations reared across multiple temperatures revealed that wing loading decreases with latitude in both species. This pattern could be driven by selection for increased dispersal capacity in the cold. However, although allometry, sexual dimorphism, thermal plasticity and latitudinal differentiation in wing shape all show similar patterns in the two species, the relationship between the plastic and genetic responses differed between them. Although latitudinal differentiation (south to north) mirrored thermal plasticity (hot to cold) in Sepsis punctum, there was no relationship in Sepsis fulgens. While this suggests that thermal plasticity may have helped to mediate local adaptation in S. punctum, it also demonstrates that genetic wing shape differentiation and its relation to thermal plasticity may be complex and idiosyncratic, even among ecologically similar and closely related species. Hence, genetic responses can, but do not necessarily, align with phenotypic plasticity induced by changing environmental selection pressures.     

Integrated Phosphoproteome and Transcriptome Analysis Reveals Chlamydia-Induced Epithelial-to-Mesenchymal Transition in Host Cells

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The effect of ultraviolet-depleted light on the flavonol contents of the cactus species Opuntia wilcoxii and Opuntia violacea

An early investigation at the Biosphere-2 Laboratory, an artificial ecosystem in the Arizona desert, had shown that the flavonoid content of cacti grown in glass-filtered solar light was lower than of cacti grown in normal solar light. This was attributed to the absence of ultraviolet (UV) radiation, which is required for flavonoid biosynthesis. In this study, two species of Opuntia cacti were grown in solar and UV-depleted light, and their flavonol contents of different tissues were determined by HPLC. O. wilcoxii, previously raised in the absence of UV light, was exposed to normal solar light. The flavonol content of young O. wilcoxii pads was 28-fold higher when grown in solar light as compared to UV-depleted light. The flavonol contents of mature outer tissues were only slightly higher. O. violacea, previously raised in solar light, was also maintained in the same UV-depleted artificial ecosystem. The flavonol content after hydrolysis of outer tissues was similar, whether grown in solar light or UV-depleted light. We attribute these responses to different biosynthetic and metabolic rates of young vs. mature plant tissues; slow-growing mature tissues neither produce nor metabolize compounds as quickly as immature tissues. These findings indicate that artificial ecosystems can influence the production of natural products in cultivated plants.