Long-term impacts of prenatal synthetic glucocorticoids exposure on functional brain correlates of cognitive monitoring in adolescence

The fetus is highly responsive to the level of glucocorticoids in the gestational environment. Perturbing glucocorticoids during fetal development could yield long-term consequences. Extending prior research about effects of prenatally exposed synthetic glucocorticoids (sGC) on brain structural development during childhood, we investigated functional brain correlates of cognitive conflict monitoring in term-born adolescents, who were prenatally exposed to sGC. Relative to the comparison group, behavioral response consistency (indexed by lower reaction time variability) and a brain correlate of conflict monitoring (the N2 event-related potential) were reduced in the sGC exposed group. Relatedly, source localization analyses showed that activations in the fronto-parietal network, most notably in the cingulate cortex and precuneus, were also attenuated in these adolescents. These regions are known to subserve conflict detection and response inhibition as well as top-down regulation of stress responses. Moreover, source activation in the anterior cingulate cortex correlated negatively with reaction time variability, whereas activation in the precuneus correlated positively with salivary cortisol reactivity to social stress in the sGC exposed group. Taken together, findings of this study indicate that prenatal exposure to sGC yields lasting impacts on the development of fronto-parietal brain functions during adolescence, affecting multiple facets of adaptive cognitive and behavioral control

Parps: Rapidly Evolving Weapons in the War against Viral Infection

Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic 'arms races' with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in 'housekeeping' functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts

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Not AvailableThe research efforts in microbiology over last two decades have focussed on assessing the microbial diversity in various soiltypes and cropping systems in all agro-eco-regions, including extreme environments resulting in creation of a vast repositoryof microorganisms, free living and endophytes. A marked departure from the past is their identification by both conventionaland molecular methods, resulting in discovery of many novel species. The effects of various soil and agronomic managementpractices were assessed on soil microbial diversity and soil health by both classical and metagenomic approach. Thebeneficial effects of organic and integrated farming, and adverse effects of chemical intensification have been assessed,leading to the identification of actinobacteria as important players in maintaining soil health. A major impact has been thefirm attention received from policy makers on the urgent need to conserve soil biodiversity and improve soil health.Identification of rapid methods of soil biological health assessment, improved rhizobial inoculants, microbial technologyfor rapid in situ and ex situ residue and waste breakdown, and mitigating climate change effects are the current priorities.Future priorities include assessment of the structure and function of the vast reservoir of unculturable microbes;deleterious microorganisms, assessment of soil-plant-microbe continuum and plant immunity modulation by microbes;rhizosphere engineering, role of archaea in maintaining soil health, microbial methods to improve soil organic matterformation; assessment and quantification of ecosystem services rendered by agriculturally important microorganisms; andimproved microbial technology for biofertilizers and delivery systems. The tremendous advances in agricultural microbiologyin last two decades in India are a cause for optimism that solutions will be forged for the above challenges using bothclassical and modern approaches, thereby ushering in the process more sustainable agricultural systems.Not Availabl

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NEDDylation negatively regulates ERRβ expression to promote breast cancer tumorigenesis and progression

Estrogen related receptor beta (ERRβ) is down-regulated in breast cancer cells and its over expression in breast cancer patients is positively correlated with an improved prognosis and prolonged relapse-free survival. Here, we unravelled a molecular mechanism for ERRβ down-regulation in breast cancer. We found that ERRβ is a key substrate of the SCF complex and that NEDDylation can activate the Cullin sub units of the SCF complex to target ERRβfor degradation in breast cancer. Consistently, using in vitro and in vivo models, we demonstrated that MLN4924, a specific small molecule inhibitor of NEDDylation, can restore ERRβ expressionand culminate in a reduction in cell proliferation and migration of breast cancer cells.We also showed that increased ERRβ expression promotes the up-regulation of its 34target genes, including the tumour suppressors p21Cip1/Waf1and E-cadherin,involved in cell proliferation and migration arrest at the gene promoter level. Interestingly, this tumour suppressive role of ERRβ does not depend on the expression of ERain breast cancer. Moreover, our data revealed that the ERRβ recruits the transcription co-activator p300 to its targeted gene promoters to up regulate their expression. Collectively,our work revealed that restoration of ERRβ expression using the NEDDylation inhibitor MLN4924 can be a novel and effective strategy for breast cancer treatmen

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