Hippocampal Neuroligin-2 Overexpression Leads to Reduced Aggression and Inhibited Novelty Reactivity in Rats

Disturbances of the excitation/inhibition (E/I) balance in the brain were recently suggested as potential factors underlying disorders like autism and schizophrenia resulting in associated behavioral alterations including changes in social and emotional behavior as well as abnormal aggression. Neuronal cell adhesion molecules (nCAMs) and mutations in these genes were found to be strongly implicated in the pathophysiology of these disorders. Neuroligin2 (nlgn2) is a postsynaptic cell adhesion molecule, which is predominantly expressed at inhibitory synapses and required for synapse specification and stabilization. Changes in the expression of nlgn2 were shown to result in alterations of social behavior as well as altered inhibitory synaptic transmission, hence modifying the E/I balance. In our study, we focused on the role of nlgn2 in the dorsal hippocampus in the regulation of emotional and social behaviors. To this purpose, we injected an AAV construct overexpressing nlgn2 in the hippocampus of rats and investigated the effects on behavior and on markers for the E/I ratio. We could show an increase in GAD65, a GABA-synthesizing protein in neuronal terminals, and furthermore, reduced exploration of novel stimuli and less offensive behavior. Our data suggest nlgn2 in the hippocampus to be strongly implicated in maintaining the E/I balance in the brain and thereby modulating social and emotional behavior.     

Nitrous oxide emissions during establishment of eight alternative cellulosic bioenergy cropping systems in the North Central United States

Greenhouse gas (GHG) emissions from soils are a key sustainability metric of cropping systems. During crop establishment, disruptive land‐use change is known to be a critical, but under reported period, for determining GHG emissions. We measured soil N₂O emissions and potential environmental drivers of these fluxes from a three‐year establishment‐phase bioenergy cropping systems experiment replicated in southcentral Wisconsin (ARL) and southwestern Michigan (KBS). Cropping systems treatments were annual monocultures (continuous corn, corn–soybean–canola rotation), perennial monocultures (switchgrass, miscanthus, and poplar), and perennial polycultures (native grass mixture, early successional community, and restored prairie) all grown using best management practices specific to the system. Cumulative three‐year N₂O emissions from annuals were 142% higher than from perennials, with fertilized perennials 190% higher than unfertilized perennials. Emissions ranged from 3.1 to 19.1 kg N₂O‐N ha^?1 yr^?1 for the annuals with continuous corn > corn–soybean–canola rotation and 1.1 to 6.3 kg N₂O‐N ha^?1 yr^?1 for perennials. Nitrous oxide peak fluxes typically were associated with precipitation events that closely followed fertilization. Bayesian modeling of N₂O fluxes based on measured environmental factors explained 33% of variability across all systems. Models trained on single systems performed well in most monocultures (e.g., R² = 0.52 for poplar) but notably worse in polycultures (e.g., R² = 0.17 for early successional, R² = 0.06 for restored prairie), indicating that simulation models that include N₂O emissions should be parameterized specific to particular plant communities. Our results indicate that perennial bioenergy crops in their establishment phase emit less N₂O than annual crops, especially when not fertilized. These findings should be considered further alongside yield and other metrics contributing to important ecosystem services.     

C1D family proteins in coordinating RNA processing,chromosome condensation and DNA damage response

Research on the involvement of C1D and its yeast homologues Rrp47 (S. cerevisiae) and Cti1 (S. pombe) in DNA damage repair and RNA processing has remained mutually exclusive, with most studies predominantly concentrating on Rrp47. This review will look to reconcile the functions of these proteins in their involvement with the RNA exosome, in the regulation of chromatin architecture, and in the repair of DNA double-strand breaks, focusing on non-homologous end joining and homologous recombination. We propose that C1D is situated in a central position to maintain genomic stability at highly transcribed gene loci by coordinating these processes through the timely recruitment of relevant regulatory factors. In the event that the damage is beyond repair, C1D induces apoptosis in a p53-dependent manner.     

The Incidence Patterns Model to Estimate the Distribution of New HIV Infections in Sub-Saharan Africa: Development and Validation of a Mathematical Model

BackgroundProgrammatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates.ConclusionsIt is possible to reliably predict the distribution of new HIV infections acquired using data routinely available in many countries in the sub-Saharan African region with a single relatively simple mathematical model. This tool would complement more specific analyses to guide resource allocation, data collection, and programme planning.     

Pharmacological removal of serum amyloid P component from intracerebral plaques and cerebrovascular Aβ amyloid deposits in vivo

Human amyloid deposits always contain the normal plasma protein serum amyloid P component (SAP), owing to its avid but reversible binding to all amyloid fibrils, including the amyloid β (Aβ) fibrils in the cerebral parenchyma plaques and cerebrovascular amyloid deposits of Alzheimer''s disease (AD) and cerebral amyloid angiopathy (CAA). SAP promotes amyloid fibril formation in vitro, contributes to persistence of amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore developed (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrospinal fluid (CSF), in patients with AD. Here we report that, after introduction of transgenic human SAP expression in the TASTPM double transgenic mouse model of AD, all the amyloid deposits contained human SAP. Depletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these amyloid deposits crucially validates the strategy of the forthcoming ‘Depletion of serum amyloid P component in Alzheimer''s disease (DESPIAD)’ clinical trial of CPHPC. The results also strongly support clinical testing of CPHPC in patients with CAA.     

There's no place like home: seedling mortality contributes to the habitat specialisation of tree species across Amazonia

Understanding the mechanisms generating species distributions remains a challenge, especially in hyperdiverse tropical forests. We evaluated the role of rainfall variation, soil gradients and herbivory on seedling mortality, and how variation in seedling performance along these gradients contributes to habitat specialisation. In a 4‐year experiment, replicated at the two extremes of the Amazon basin, we reciprocally transplanted 4638 tree seedlings of 41 habitat‐specialist species from seven phylogenetic lineages among the three most important forest habitats of lowland Amazonia. Rainfall variation, flooding and soil gradients strongly influenced seedling mortality, whereas herbivory had negligible impact. Seedling mortality varied strongly among habitats, consistent with predictions for habitat specialists in most lineages. This suggests that seedling performance is a primary determinant of the habitat associations of adult trees across Amazonia. It further suggests that tree diversity, currently mostly harboured in terra firme forests, may be strongly impacted by the predicted climate changes in Amazonia.     

Effect of light environment on intra-specific variation in herbivory in the carnivorous plant Pinguicula moranensis (Lentibulariaceae)

Identifying the factors that affect a plant’s probability of being found and damaged by herbivores has been a central topic in the study of herbivory. Although herbivory could have important negative consequences on carnivorous plants, their interaction with herbivores remains largely unexplored. We evaluated the effect of spatial variation in light environment (sunny, shade and full-shade sites) on the pattern of leaf herbivory and florivory of the carnivorous plant Pinguicula moranensis. Plants’ overall probability of leaf damage was high (74.24%). Mean herbivory was four times higher in the sunny and shade sites than the observed in the full-shade site. Nearly 8% of plants suffered damage to reproductive structures, although the probability of florivory was similar among sites. Discussion addressed the inter-site variation in mean herbivory considering the effect of light exposure and the impact that herbivory could have on fitness components of this carnivorous plant.     

Simultaneous Regulation of Cytokinetic Furrow and Nucleus Positions by Cortical Tension Contributes to Proper DNA Segregation during Late Mitosis

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