Rapid, learning-induced inhibitory synaptogenesis in murine barrel field

The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse. Here, we show using quantitative transmission electron microscopy that a simple form of learning involving mystacial vibrissae results in approximately 70% increase in the density of inhibitory synapses on spines of neurons located in layer IV barrels that represent the stimulated vibrissae. The spines contain one asymmetrical (excitatory) and one symmetrical (inhibitory) synapse (double-synapse spines), and their density increases threefold as a result of learning with no apparent change in the density of asymmetrical synapses. This effect seems to be specific for learning because pseudoconditioning (in which the conditioned and unconditioned stimuli are delivered at random) does not lead to the enhancement of symmetrical synapses but instead results in an upregulation of asymmetrical synapses on spines. Symmetrical synapses of cells located in barrels receiving the conditioned stimulus also show a greater concentration of GABA in their presynaptic terminals. These results indicate that the immediate effect of classical conditioning in the "conditioned" barrels is rapid, pronounced, and inhibitory

Influence of Threat and Serotonin Transporter Genotype on Interference Effects

Emotion-cognition interactions are critical in goal-directed behavior and may be disrupted in psychopathology. Growing evidence also suggests that emotion-cognition interactions are modulated by genetic variation, including genetic variation in the serotonin system. The goal of the current study was to examine the impact of threat-related distracters and serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) on cognitive task performance in healthy females. Using a novel threat-distracter version of the Multi-Source Interference Task specifically designed to probe emotion-cognition interactions, we demonstrate a robust and temporally dynamic modulation of cognitive interference effects by threat-related distracters relative to other distracter types and relative to no-distracter condition. We further show that threat-related distracters have dissociable and opposite effects on cognitive task performance in easy and difficult task conditions, operationalized as the level of response interference that has to be surmounted to produce a correct response. Finally, we present evidence that the 5-HTTLPR/rs25531 genotype in females modulates susceptibility to cognitive interference in a global fashion, across all distracter conditions, and irrespective of the emotional salience of distracters, rather than specifically in the presence of threat-related distracters. Taken together, these results add to our understanding of the processes through which threat-related distracters affect cognitive processing, and have implications for our understanding of disorders in which threat signals have a detrimental effect on cognition, including depression and anxiety disorders

In-Reactor Polypropylene Functionalization-The Influence of Catalyst Structures and Reaction Conditions on the Catalytic Performance

To unravel the relationship between silylene-bridged metallocene catalyst structures and polymerization conditions and their effect on the performance in in-reactor functionalization of polypropylene, the behaviors of rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2/MMAO, rac-Me2Si(Ind)2ZrCl2, rac-Me2Si(2-Me-4-Ph-Ind)2HfCl2, and rac-Me2Si(Ind)2HfCl2 in propylene/aluminum alkyl-passivated 10-undecen-1-ol copolymerization were compared. Kinetic analysis revealed higher catalytic activities for zirconocenes compared to analogous hafnocenes. Both the zirconocene and hafnocene with substituted indenyl ligands afforded a higher molecular weight capability, improved stereo-selectivity, and enhanced ability to incorporate functionalized comonomers compared to their non-substituted congeners. An in-depth study of polypropylene functionalization using the best performing catalyst system, rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2/MMAO, at temperatures ranging from 40 to 100 °C, revealed a linear inversely proportional correlation of polymerization temperature with functionalized comonomer reactivity (↑Tp → ↓ r1), copolymer molecular weight (↑Tp → ↓Mn), and melting temperature (↑Tp → ↓Tm). While performing well under standard laboratory polymerization conditions, rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2/MMAO showed limited molecular weight and stereo-selectivity capabilities under high-temperature (130-150 °C) solution process conditions. Although immobilization of rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2 onto silica, allowing it to be used under industrially relevant slurry and gas-phase conditions, led to an active catalyst, it failed to incorporate any functionalized comonomer

Urgent vitrectomy with vancomycin infusion, silicone oil endotamponade, and general antibiotic treatment in multiple cases of endophthalmitis from a single day of intravitreal injections—case series

The aim of this study was to report on the anatomical and functional results of surgical management of seven cases of endophthalmitis related to a single day of intravitreal aflibercept injections. Patients with signs of endophthalmitis who underwent aflibercept injections (seven eyes) performed on the same day were retrospectively evaluated. The data of visual acuity and optical coherence tomography (OCT) within nine months of the follow-up and the treatment and results of microbiological cultures are reported. Four of the total seven cases had a positive bacterial culture outcome (Streptococcus mitis). All patients underwent vitrectomy combined with phacoemulsification when the eyes were not pseudophakic, vancomycin infusion, and silicone oil tamponade within 24 h; additionally, systemic antibiotics were administered intravenously. The final best-corrected visual acuity (BCVA) after the treatment was finger counting or light perception in all cases, and all eyes were saved with disruption of the inner retinal layers and stabilization of the retina in regard to changes related to the wet age-related macular degeneration (AMD). Although the retinal anatomy was mostly preserved, most of the patients affected by Streptococcus mitis-induced endophthalmitis did not regain baseline vision after the therapy

Tailoring the mechanical and degradation performance of Mg-2.0Zn-0.5Ca-0.4Mn alloy through microstructure design

A novel Mg-2.0Zn-0.5Ca-0.4Mn alloy has been formulated and processed through melt spinning and hot extrusion to enhance its mechanical and degradation properties. Microstructural characterization of rapidly solidified alloy ribbons consolidated by extrusion revealed a fine and fully recrystallized microstructure with average size of 4 µm. The conventionally extruded alloy consisted of several course second-phase strips as coarse as 100 µm, while the extrusion-consolidated ribbons were devoid of any second phases larger than 100 nm. Rapid solidification followed by extrusion processing resulted in significantly randomized texture where the majority of the basal planes were tilted toward transverse and extrusion directions. Such a weak texture resulted in higher activity of basal planes and thereby considerably improved the fracture elongation from 4% to 19%, while retaining relatively high tensile strength of 294 MPa. In addition to high strength and ductility due to the reduced activity of deformation twining during compression, the extrusion-consolidated alloy ribbons showed lower yielding asymmetric ratio than that measured for the conventionally extruded alloy (1.25 versus 1.61). Electrochemical measurements and immersion tests indicated that application of rapid solidification followed by extrusion remarkably reduced the corrosion rate from 2.49 mm/year to 0.37 mm/year due to recrystallization completion and suppression of coarse second-phase formation

Obesity and obesogenic growth are both highly heritable and modified by diet in a nonhuman primate model, the African green monkey (Chlorocebus aethiops sabaeus)

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity. STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a longitudinal clustering algorithm to detect obesogenic growth, and logistic growth curves implemented in nonlinear mixed effects models to estimate three growth parameters. We used maximum likelihood variance decomposition methods to estimate the genetic contributions to obesity-related traits and growth parameters, including a test for the effects of a calorie-restricted dietary intervention. We used multipoint linkage analysis to map implicated genomic regions. RESULTS: All measurements were significantly influenced by sex, and with the exception of WC, also influenced by maternal and post-natal diet. Chronic obesity outcomes were significantly associated with a pattern of extended growth duration with slow growth rates for BW. After accounting for environmental influences, all measurements were found to have a significant genetic component to variability. Linkage analysis revealed several regions suggested to be linked to obesity-related traits that are also implicated in human obesity and metabolic disorders. CONCLUSIONS: As in humans, growth patterns in vervets have a significant impact on adult obesity and are largely under genetic control with some evidence for maternal and dietary programming. These results largely mirror findings from human research, but reflect shorter developmental periods, suggesting that the vervet offers a strong genetic model for elucidating the ontogeny of human obesity

Improved gastrointestinal profile with diroximel fumarate is associated with a positive impact on quality of life compared with dimethyl fumarate: Results from the randomized, double-blind, phase III EVOLVE-MS-2 study

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate approved for relapsing forms of multiple sclerosis (MS). DRF demonstrated significantly improved gastrointestinal (GI) tolerability METHODS: A RESULTS: In total, 504 patients (DRF, CONCLUSIONS: The improved GI tolerability with DRF translated into clinically meaningful benefits to QoL, as patients experienced less impact on daily life and work and required less concomitant symptomatic medication use. TRIAL REGISTRATION: [ClinicalTrials.gov identifier: NCT03093324]

Genetic variation and gene expression across multiple tissues and developmental stages in a non-human primate

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders

Towards revealing key factors in mechanical instability of bioabsorbable Zn-based alloys for intended vascular stenting

Zn-based alloys are recognized as promising bioabsorbable materials for cardiovascular stents, due to their biocompatibility and favorable degradability as compared to Mg. However, both low strength and intrinsic mechanical instability arising from a strong strain rate sensitivity and strain softening behavior make development of Zn alloys challenging for stent applications. In this study, we developed binary Zn-4.0Ag and ternary Zn-4.0Ag-xMn (where x = 0.2–0.6wt%) alloys. An experimental methodology was designed by cold working followed by a thermal treatment on extruded alloys, through which the effects of the grain size and precipitates could be thoroughly investigated. Microstructural observations revealed a significant grain refinement during wire drawing, leading to an ultrafine-grained (UFG) structure with a size of 700 nm and 200 nm for the Zn-4.0Ag and Zn-4.0Ag-0.6Mn, respectively. Mn showed a powerful grain refining effect, as it promoted the dynamic recrystallization. Furthermore, cold working resulted in dynamic precipitation of AgZn3 particles, distributing throughout the Zn matrix. Such precipitates triggered mechanical degradation through an activation of Zn/AgZn3 boundary sliding, reducing the tensile strength by 74% and 57% for Zn-4.0Ag and Zn-4.0Ag-0.6Mn, respectively. The observed precipitation softening caused a strong strain rate sensitivity in cold drawn alloys. Short-time annealing significantly mitigated the mechanical instability by reducing the AgZn3 fraction. The ternary alloy wire showed superior microstructural stability relative to its Mn-free counterpart due to the pinning effect of Mn-rich particles on the grain boundaries. Eventually, a shift of the corrosion regime from localized to more uniform was observed after the heat treatment, mainly due to the dissolution of AgZn3 precipitates. Statement of Significance Owing to its promising biodegradability, zinc has been recognized as a potential biodegradable material for stenting applications. However, Zn's poor strength alongside intrinsic mechanical instability have propelled researchers to search for Zn alloys with improved mechanical properties. Although extensive researches have been conducted to satisfy the mentioned concerns, no Zn-based alloys with stabilized mechanical properties have yet been reported. In this work, the mechanical properties and stability of the Zn-Ag-based alloys were systematically evaluated as a function of microstructural features. We found that the microstructure design in Zn alloys can be used to find an effective strategy to not only improve the strength and suppress the mechanical instability but also to minimize any damage by augmenting the corrosion uniformity