23 research outputs found

    The molecular chaperone Hsp90 is a component of the cap-binding complex and interacts with the translational repressor Cup during Drosophila oogenesis

    Get PDF
    In metazoa, the spatio-temporal translation of diverse mRNAs is essential to guarantee proper oocyte maturation and early embryogenesis. The eukaryotic translation initiation factor 4E (eIF4E), which binds the 5′ cap structure of eukaryotic mRNAs, associates with either stimulatory or inhibitory factors to modulate protein synthesis. In order to identify novel factors that might act at the translational level during Drosophila oogenesis, we have undertaken a functional proteomic approach and isolated the product of the Hsp83 gene, the evolutionarily conserved chaperone Hsp90, as a specific component of the cap-binding complex. Here we report that Hsp90 interacts in vitro with the translational repressor Cup. In addition, we show that Hsp83 and cup interact genetically, since lowering Hsp90 activity enhances the oogenesis alterations linked to diverse cup mutant alleles. Hsp90 and Cup co-localize in the cytoplasm of the developing germ-line cells within the germarium, thus suggesting a common function from the earliest stages of oogenesis. Taken together, our data start elucidating the role of Hsp90 during Drosophila female germ-line development and strengthen the idea that Cup has multiple essential functions during egg chamber development

    Genomic and physiological resilience in extreme environments are associated with a secure attachment style

    Get PDF
    Understanding individual capability to adjust to protracted confinement and isolation may inform adaptive plasticity and disease vulnerability/resilience, and may have long-term implications for operations requiring prolonged presence in distant and restricted environments. Individual coping depends on many different factors encompassing psychological dispositional traits, endocrine reactivity and their underlying molecular mechanisms (e.g. gene expression). A positive view of self and others (secure attachment style) has been proposed to promote individual resilience under extreme environmental conditions. Here, we tested this hypothesis and investigated the underlying molecular mechanisms in 13 healthy volunteers confined and isolated for 12 months in a research station located 1670 km away from the south geographic pole on the Antarctic Plateau at 3233 m above sea level. Study participants, stratified for attachment style, were characterised longitudinally (before, during and after confinement) for their psychological appraisal of the stressful nature of the expedition, diurnal fluctuations in endocrine stress reactivity, and gene expression profiling (transcriptomics). Predictably, a secure attachment style was associated with reduced psychological distress and endocrine vulnerability to stress. In addition, while prolonged confinement and isolation remarkably altered overall patterns of gene expression, such alteration was largely reduced in individuals characterised by a secure attachment style. Furthermore, increased resilience was associated with a reduced expression of genes involved in energy metabolism (mitochondrial function and oxidative phosphorylation). Ultimately, our data indicate that a secure attachment style may favour individual resilience in extreme environments and that such resilience can be mapped onto identifiable molecular substrates

    Reduced availability of a selective human milk oligosaccharide during lactation impairs post-weaning executive functions

    No full text
    Maternal milk is considered the ideal source of early life nutrition. It contains nutritional, immunological and signalling factors that are essential for the correct development of the new-born, including development of cognitive capabilities, gastrointestinal tract, and immune functions. Thus, breast-feeding has been associated with improved cognitive capabilities and increased resistance to infection. Specifically, there is an association between duration of breast feeding and verbal IQ. Human milk oligosaccharides (HMOs) represent the third most abundant component of breast milk; many of them are composed by sialylated molecules that represent the principal source of sialic acid (Sia) for the infant. Sia is an essential component of glycolipids (gangliosides) and glycoproteins (polySia-NCAM), two highly represented molecules in the brain. Since endogenous synthesis of Sia is insufficient to meet the nutritional needs of the neonate, its dietary provision is fundamental. Among the components of the breast-milk, sialylated-HMOs have been indicated as possible mediators of its beneficial effects on neurodevelopment and brain function. This study investigated the effects of one specific HMO, sialyl(alpha2,3)lactose (3’SL), on cognitive development. Importantly, 3’SL is abundant in maternal milk, and absent in infant formula. We hypothesised that 3’SL during lactation has permanent effects on executive functions in adulthood and that variations in this HMO during lactation related to a differential development of learning, memory, attention and locomotion. Methods: To modulate the availability of 3’SL during lactation, we performed a cross-fostering study in which wild-type mice were reared to knock-out mice constitutively deficient of 3’SL. Specifically, the study involves C57BL/6J wild-type and C57BL/6-St3gal4tm1.1Jxm/J transgenic male mice. The deletion of the ST3GAL4 gene (B6-129 St3gal4-/-) resulted in an 80% decrease of 3’SL in milk. The cross-fostering design resulted in the following groups: WT mice reared to WT dams (WT to WT, N=11), WT mice reared to KO dams (WT to KO, N=12), KO mice reared to WT dams (KO to WT, N=12) and KO mice reared to KO dams (KO to KO, N=12). Adult subjects were tested for spatial memory (Barnes maze), recognition memory (Novel object recognition task), attention (Attentional set shifting task, ASST), impulsivity (T-maze), sensorimotor gating (Prepulse inhibition) and anxiety (Elevated plus maze). Data was analysed using a factorial ANOVA using 2 between subject factors (dams genotype and pups genotype). Results: compared to control subjects, all experimental groups exhibited a reduction of retention memory in the Barnes maze one day after training, but not in the novel object recognition task, indicating that early life presence of 3’SL may support spatial memory. When evaluating attentional capabilities, mice that received 3’SL deficient-milk exhibited poor performance in several stages of the ASST. Furthermore, the same experimental group showed increased impulsivity. The experimental groups did not differ in anxiety-like behaviour, evaluated through the elevated plus maze. Conclusion: reduced availability of 3’SL during lactation caused long-lasting deficits in cognitive abilities, thus confirming the importance of the presence of this breast-milk component during the crucial period of lactation. Since this study was the first to evaluate this deficiency, further studies will be needed to confirm these findings and deepen the mechanism underlying the effect of 3’SL

    Osteopathic Manipulative Treatment Limits Chronic Constipation in a Child with Pitt-Hopkins Syndrome

    No full text
    Pitt-Hopkins Syndrome (PTHS) is a rare genetic disorder caused by insufficient expression of the TCF4 gene. Children with PTHS typically present with gastrointestinal disorders and early severe chronic constipation is frequently found (75%). Here we describe the case of a PTHS male 10-year-old patient with chronic constipation in whom Osteopathic Manipulative Treatment (OMT) resulted in improved bowel functions, as assessed by the diary, the QPGS-Form A Section C questionnaire, and the Paediatric Bristol Stool Form Scale. The authors suggested that OMT may be a valid tool to improve the defecation frequency and reduce enema administration in PTHS patients

    Exposure to 3′Sialyllactose-Poor Milk during Lactation Impairs Cognitive Capabilities in Adulthood

    No full text
    Breast milk exerts pivotal regulatory functions early in development whereby it contributes to the maturation of brain and associated cognitive functions. However, the specific components of maternal milk mediating this process have remained elusive. Sialylated human milk oligosaccharides (HMOs) represent likely candidates since they constitute the principal neonatal dietary source of sialic acid, which is crucial for brain development and neuronal patterning. We hypothesize that the selective neonatal lactational deprivation of a specific sialylated HMOs, sialyl(alpha2,3)lactose (3′SL), may impair cognitive capabilities (attention, cognitive flexibility, and memory) in adulthood in a preclinical model. To operationalize this hypothesis, we cross-fostered wild-type (WT) mouse pups to B6.129-St3gal4tm1.1Jxm/J dams, knock-out (KO) for the gene synthesizing 3′SL, thereby providing milk with approximately 80% 3′SL content reduction. We thus exposed lactating WT pups to a selective reduction of 3′SL and investigated multiple cognitive domains (including memory and attention) in adulthood. Furthermore, to account for the underlying electrophysiological correlates, we investigated hippocampal long-term potentiation (LTP). Neonatal access to 3′SL-poor milk resulted in decreased attention, spatial and working memory, and altered LTP compared to the control group. These results support the hypothesis that early-life dietary sialylated HMOs exert a long-lasting role in the development of cognitive functions
    corecore