Directed growth of early cortical axons is influenced by a chemoattractant released from an intermediate target

Projection neurons throughout the mature mammalian neocortex extend efferent axons either through the ventrolaterally positioned internal capsule to subcortical targets or through the dorsally located midline corpus callosum to the contralateral cortex. In rats, the internal capsule is pioneered on E14, but the corpus callosum is not pioneered until E17, even though these two types of projection neurons are generated at the same time. Here we use axonal markers to demonstrate that early cortical axon growth is directed toward the nascent internal capsule, which could account for the timing difference in the development of the two efferent pathways, This directed axon growth may be due to a chemoattractant and/or a chemorepellent secreted by intermediate targets of corlical efferent axons, the nascent internal capsule, or the medial wall of the dorsal telencephalon (MDT), respectively, To test for these soluble activities, explants of E15 rat neocortex and intermediate targets were cocultured in collagen gels. Cortical axon outgrowth was directed toward the internal capsule, but outgrowth was nondirected and suppressed when cocultured with MDT, suggesting that the internal capsule releases a chemoattractant for cortical axons, whereas the MDT releases a chemosuppressant. Because the chemoattractant Netrin-1 is expressed in the internal capsule, we cocultured cortical explants with E13 rat floor plate, which expresses Netrin-1, or with Netrin-1-transfected or control-transfected 293T cells. Cortical axon growth was directed toward both floor plate and Netrin-1-transfected 293T cells, as it had been toward the internal capsule, but not toward control-transfected 293T cells. These findings suggest that early events in cortical axon pathfinding may be controlled by a soluble activity which attracts initial axon growth toward the internal capsule and that this activity may be due to Netrin-1

All You Can Eat: High Performance Capacity and Plasticity in the Common Big-Eared Bat, Micronycteris microtis (Chiroptera: Phyllostomidae)

Ecological specialization and resource partitioning are expected to be particularly high in the species-rich communities of tropical vertebrates, yet many species have broader ecological niches than expected. In Neotropical ecosystems, Neotropical leaf-nosed bats (Phyllostomidae) are one of the most ecologically and functionally diverse vertebrate clades. Resource partitioning in phyllostomids might be achieved through differences in the ability to find and process food. We selected Micronycteris microtis, a very small (5–7 g) animalivorous phyllostomid, to explore whether broad resource use is associated with specific morphological, behavioral and performance traits within the phyllostomid radiation. We documented processing of natural prey and measured bite force in free-ranging M. microtis and other sympatric phyllostomids. We found that M. microtis had a remarkably broad diet for prey size and hardness. For the first time, we also report the consumption of vertebrates (lizards), which makes M. microtis the smallest carnivorous bat reported to date. Compared to other phyllostomids, M. microtis had the highest bite force for its size and cranial shape and high performance plasticity. Bite force and cranial shape appear to have evolved rapidly in the M. microtis lineage. High performance capacity and high efficiency in finding motionless prey might be key traits that allow M. microtis, and perhaps other species, to successfully co-exist with other gleaning bats

Assessing the Impact of Defects on Lead-Free Perovskite-Inspired Photovoltaics via Photoinduced Current Transient Spectroscopy

Funder: Collaborative Innovation Center of Suzhou Nano Science & TechnologyFunder: Priority Academic Program Development of Jiangsu Higher Education Institutions; Id: http://dx.doi.org/10.13039/501100012246Funder: 111 Project; Id: http://dx.doi.org/10.13039/501100013314Funder: Joint International Research Laboratory of Carbon‐Based Functional Materials and DevicesThe formidable rise of lead-halide perovskite photovoltaics has energized the search for lead-free perovskite-inspired materials (PIMs) with related optoelectronic properties but free from toxicity limitations. The photovoltaic performance of PIMs closely depends on their defect tolerance. However, a comprehensive experimental characterization of their defect-level parameters—concentration, energy depth, and capture cross-section—has not been pursued to date, hindering the rational development of defect-tolerant PIMs. While mainstream, capacitance-based techniques for defect-level characterization have sparked controversy in lead-halide perovskite research, their use on PIMs is also problematic due to their typical near-intrinsic character. This study demonstrates on four representative PIMs (Cs3Sb2I9, Rb3Sb2I9, BiOI, and AgBiI4) for which Photoinduced Current Transient Spectroscopy (PICTS) offers a facile, widely applicable route to the defect-level characterization of PIMs embedded within solar cells. Going beyond the ambiguities of the current discussion of defect tolerance, a methodology is also presented to quantitatively assess the defect tolerance of PIMs in photovoltaics based on their experimental defect-level parameters. Finally, PICTS applied to PIM photovoltaics is revealed to be ultimately sensitive to defect-level concentrations <1 ppb. Therefore, this study provides a versatile platform for the defect-level characterization of PIMs and related absorbers, which can catalyze the development of green, high-performance photovoltaics.Royal Academy of Engineerin

Radiofrequency-based treatment in therapy-related clinical practice – a narrative review. Part I : acute conditions

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Physical Therapy Reviews on 24 June 2015, available online at: https://www.tandfonline.com/doi/full/10.1179/1743288X15Y.0000000016Background: Radiofrequency electromagnetic field (RFEMF or simply RF)-based electrophysical agents (EPAs) have been employed in therapy-related clinical practice for several decades. They are used to reduce pain and inflammation and enhance tissue healing. Although these agents have generally become less popular in contemporary therapy practice, surveys have shown that some of these modalities are still reasonably widely used. Objective: To review the evidence for the use of non-invasive low frequency RFs (30 kHz–30 MHz) in therapy-related clinical practice. Major findings: All peer reviewed therapy-related clinical studies published in English and concerning low frequency RF were sought. Identified literature was divided into acute and chronic segments based on their clinical area and analysed to assess the volume and scope of current evidence. The studies on acute conditions were reviewed in detail for this paper. One hundred twenty clinical studies were identified, of which 30 related to acute conditions. The majority of studies employed Pulsed Shortwave Therapy (PSWT). Twenty-two studies out of 30 were related to conditions of pain and inflammation, seven to tissue healing and one to acute pneumothorax. No studies were identified on frequencies other than shortwave. Conclusions: Evidence for and against RF-based therapy is available. There is reasonable evidence in support of PSWT to alleviate postoperative pain and promote postoperative wound healing. Evidence for other acute conditions is sparse and conflicting. A general lack of research emphasis in the non-shortwave RF band is evident, with studies on acute conditions almost non-existent. Further and wider research in this area is warranted.Peer reviewe

RNA Gain-of-Function in Spinocerebellar Ataxia Type 8

Microsatellite expansions cause a number of dominantly-inherited neurological diseases. Expansions in coding-regions cause protein gain-of-function effects, while non-coding expansions produce toxic RNAs that alter RNA splicing activities of MBNL and CELF proteins. Bi-directional expression of the spinocerebellar ataxia type 8 (SCA8) CTG CAG expansion produces CUG expansion RNAs (CUGexp) from the ATXN8OS gene and a nearly pure polyglutamine expansion protein encoded by ATXN8 CAGexp transcripts expressed in the opposite direction. Here, we present three lines of evidence that RNA gain-of-function plays a significant role in SCA8: 1) CUGexp transcripts accumulate as ribonuclear inclusions that co-localize with MBNL1 in selected neurons in the brain; 2) loss of Mbnl1 enhances motor deficits in SCA8 mice; 3) SCA8 CUGexp transcripts trigger splicing changes and increased expression of the CUGBP1-MBNL1 regulated CNS target, GABA-A transporter 4 (GAT4/Gabt4). In vivo optical imaging studies in SCA8 mice confirm that Gabt4 upregulation is associated with the predicted loss of GABAergic inhibition within the granular cell layer. These data demonstrate that CUGexp transcripts dysregulate MBNL/CELF regulated pathways in the brain and provide mechanistic insight into the CNS effects of other CUGexp disorders. Moreover, our demonstration that relatively short CUGexp transcripts cause RNA gain-of-function effects and the growing number of antisense transcripts recently reported in mammalian genomes suggest unrecognized toxic RNAs contribute to the pathophysiology of polyglutamine CAG CTG disorders

Metacarpal trabecular bone varies with distinct hand-positions used in hominid locomotion

Trabecular bone remodels during life in response to loading and thus should, at least in part, reflect potential variation in the magnitude, frequency and direction of joint loading across different hominid species. Here we analyse the trabecular structure across all non-pollical metacarpal distal heads (Mc2-5) in extant great apes, expanding on previous volume of interest and whole-epiphysis analyses that have largely focussed on only the first or third metacarpal. Specifically, we employ both a univariate statistical mapping and a multivariate approach to test for both inter-ray and interspecific differences in relative trabecular bone volume fraction (RBV/TV) and degree of anisotropy (DA) in Mc2-5 subchondral trabecular bone. Results demonstrate that while DA values only separate Pongo from African apes (Pan troglodytes, Pan paniscus, Gorilla gorilla), RBV/TV distribution varies with the predicted loading of the metacarpophalangeal (McP) joints during locomotor behaviours in each species. Gorilla exhibits a relatively dorsal distribution of RBV/TV consistent with habitual hyper-extension of the McP joints during knuckle-walking, whereas Pongo has a palmar distribution consistent with flexed McP joints used to grasp arboreal substrates. Both Pan species possess a disto-dorsal distribution of RBV/TV, compatible with multiple hand postures associated with a more varied locomotor regime. Further inter-ray comparisons reveal RBV/TV patterns consistent with varied knuckle-walking postures in Pan species in contrast to higher RBV/TV values toward the midline of the hand in Mc2 and Mc5 of Gorilla, consistent with habitual palm-back knuckle-walking. These patterns of trabecular bone distribution and structure reflect different behavioural signals that could be useful for determining the behaviours of fossil hominins

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

South American Spider Mites: New Hosts and Localities

In order to contribute to taxonomic information on Tetranychid mites (Acari: Tetranychidae) in South America, surveys were conducted in Brazil (15 States and the Federal District) and Uruguay (one Department); 550 samples of 120 plant species were collected. Tetranychid mite infestations were confirmed in 204 samples, and 22 species belonging to seven genera of the Bryobiinae and Tetranychinae subfamilies were identified on 58 different host plants. Thirty-six new plant hosts were found in Brazil, South America, and worldwide for the following species: Eutetranychus banksi (McGregor); Mononychellus tanajoa (Bondar); Oligonychus anonae Paschoal; O. mangiferus (Rahman and Sapra); Tetranychus bastosi Tuttle, Baker and Sales; T. desertorum Banks, 1900, T. evansi Baker and Pritchard; T. ludeni Zacher; T. mexicanus (McGregor); T. neocaledonicus André; and T. urticae Koch. Four new localities in Brazil were reported for Eotetranychus tremae De Leon; O. anonae; Panonychus ulmi (Koch); and T. gloveri Baker and Pritchard

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of ¹⁸F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C_H2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC_H2), radiolabeled with iodine-124 (¹²⁴I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC_H2 was radiolabeled with ¹²⁴I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of ¹²⁴I-HuCC49deltaC_H2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of ¹⁸F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, ¹²⁴I-HuCC49deltaC_H2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, ¹⁸F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, ¹²⁴I-HuCC49deltaC_H2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while ¹⁸F-FDG failed to demonstrate this. The antigen-directed and cancer-specific ¹²⁴I-radiolabled anti-TAG-72 monoclonal antibody conjugate, ¹²⁴I-HuCC49deltaC_H2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p