Motor axonal sprouting and neuromuscular junction loss in an animal model of Charcot-Marie-Tooth disease

Muscle weakness in Charcot-Marie-Tooth Type 1A disease (CMT1A) caused by mutations in peripheral myelin protein 22 (PMP22) has been attributed to an axonopathy that results in denervation and muscle atrophy. The underlying pathophysiological mechanisms involved are not understood. We investigated motor performance, neuromuscular junctions (NMJs), physiological parameters, and muscle morphometry of PMP22 transgenic mice. Neuromuscular junctions were progressively lost in hindlimb muscles of PMP22 transgenic mice, but their motor performance did not completely deteriorate during the observation period. There was considerable variability, including in laterality, in deficits among the animals. Cross-sectional areas and mean fiber size measurements indicated variable myofiber atrophy in hindlimb muscles. There was substantial concomitant axonal sprouting, and loss of neuromuscular junctions was inversely correlated with the accumulated length of axonal branches. Synaptic transmission studied in isolated nerve/muscle preparations indicated variable partial muscle denervation. Acetylcholine sensitivity was higher in the mutant muscles, and maximum tetanic force evoked by direct or indirect stimulation, specific force, and wet weights were markedly reduced in some mutant muscles. In summary, there is partial muscle denervation, and axons may retain some regenerative capacity but fail to reinnervate muscles in PMP22 transgenic mice

Assessing Need and Access to LGBTQ+ Affirming and Affordable Behavioral Healthcare in Chicago

Overall LGBTQ+ individuals are 2.5 times more likely to experience depression, anxiety, and substance abuse compared to heterosexual individuals. Howard Brown Health worked in partnership with other community-based organizations (CBOs) that provide behavioral health services throughout Chicago to research and better understand barriers and facilitators to accessing affordable and LGBTQ+ affirming behavioral healthcare in the greater Chicago area. The research also illustrates unmet mental and behavioral healthcare needs and highlights existing gaps in LGBTQ+ affirming and affordable behavioral health services in Chicago

MENA Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer

Taxane therapy remains the standard of care for triple-negative breast cancer. However, high frequencies of recurrence and progression in treated patients indicate that metastatic breast cancer cells can acquire resistance to this drug. The actin regulatory protein MENA and particularly its invasive isoform, MENAINV , are established drivers of metastasis. MENAINV expression is significantly correlated with metastasis and poor outcome in human patients with breast cancer. We investigated whether MENA isoforms might play a role in driving resistance to chemotherapeutics. We find that both MENA and MENAINV confer resistance to the taxane paclitaxel, but not to the widely used DNA-damaging agents doxorubicin or cisplatin. Furthermore, paclitaxel treatment does not attenuate growth of MENAINV -driven metastatic lesions. Mechanistically, MENA isoform expression alters the ratio of dynamic and stable microtubule populations in paclitaxel-treated cells. MENA expression also increases MAPK signaling in response to paclitaxel treatment. Decreasing ERK phosphorylation by cotreatment with MEK inhibitor restored paclitaxel sensitivity by driving microtubule stabilization in MENA isoform-expressing cells. Our results reveal a novel mechanism of taxane resistance in highly metastatic breast cancer cells and identify a combination therapy to overcome such resistance

“Can It Read My Mind?” – What Do the Public and Experts Think of the Current (Mis)Uses of Neuroimaging?

Emerging applications of neuroimaging outside medicine and science have received intense public exposure through the media. Media misrepresentations can create a gulf between public and scientific understanding of the capabilities of neuroimaging and raise false expectations. To determine the extent of this effect and determine public opinions on acceptable uses and the need for regulation, we designed an electronic survey to obtain anonymous opinions from as wide a range of members of the public and neuroimaging experts as possible. The surveys ran from 1st June to 30 September 2010, asked 10 and 21 questions, respectively, about uses of neuroimaging outside traditional medical diagnosis, data storage, science communication and potential methods of regulation. We analysed the responses using descriptive statistics; 660 individuals responded to the public and 303 individuals responded to the expert survey. We found evidence of public skepticism about the use of neuroimaging for applications such as lie detection or to determine consumer preferences and considerable disquiet about use by employers or government and about how their data would be stored and used. While also somewhat skeptical about new applications of neuroimaging, experts grossly underestimated how often neuroimaging had been used as evidence in court. Although both the public and the experts rated highly the importance of a better informed public in limiting the inappropriate uses to which neuroimaging might be put, opinions differed on the need for, and mechanism of, actual regulation. Neuroscientists recognized the risks of inaccurate reporting of neuroimaging capabilities in the media but showed little motivation to engage with the public. The present study also emphasizes the need for better frameworks for scientific engagement with media and public education

Local Photorelease of Caged Thymosin β4 in Locomoting Keratocytes Causes Cell Turning

The broad aim of this work was to explore the feasibility of using light-directed perturbation techniques to study cell locomotion. Specifically, a caged form of thymosin β4 (Tβ4) was photoactivated in a defined local region of locomoting fish scale keratocytes and the resulting perturbation of locomotion was studied. Purified Tβ4 was produced in an inactive form by “caging” with ([n-nitroveratryl]oxy)chlorocarbamate. In vitro spectrophotofluorometric assays indicated that caged Tβ4 did not change the normal actin polymerization kinetics, whereas photoactivated Tβ4 significantly inhibited actin polymerization. With an a priori knowledge of the cytoplasmic diffusion coefficient of Tβ4 as measured by fluorescence recovery after photobleaching experiments, the rapid sequestration of actin monomers by uncaged Tβ4 and the consequent reduction in the diffusional spread of the Tβ4–actin complex were predicted using Virtual Cell software (developed at the Center for Biomedical Imaging Technology, University of Connecticut Health Center). These simulations demonstrated that locally photoactivating Tβ4 in keratocytes could potentially elicit a regional locomotory response. Indeed, when caged Tβ4 was locally photoactivated at the wings of locomoting keratocytes, specific turning about the irradiated region was observed, whereas various controls were negative. Additionally, loading of exogenous Tβ4 into both keratocytes and fibroblasts caused very rapid disassembly of actin filaments and reduction of cellular contractility. Based on these results, a mechanical model is proposed for the turning behavior of keratocytes in response to photoreleased Tβ4

A new method for ecoacoustics? Toward the extraction and evaluation of ecologically-meaningful soundscape components using sparse coding methods

Passive acoustic monitoring is emerging as a promising non-invasive proxy for ecological complexity with potential as a tool for remote assessment and monitoring (Sueur and Farina, 2015). Rather than attempting to recognise species-specific calls, either manually or automatically, there is a growing interest in evaluating the global acoustic environment. Positioned within the conceptual framework of ecoacoustics, a growing number of indices have been proposed which aim to capture community-level dynamics by (e.g. Pieretti et al., 2011; Farina, 2014; Sueur et al., 2008b) by providing statistical summaries of the frequency or time domain signal. Although promising, the ecological relevance and efficacy as a monitoring tool of these indices is still unclear. In this paper we suggest that by virtue of operating in the time or frequency domain, existing indices are limited in their ability to access key structural information in the spectro-temporal domain. Alternative methods in which time-frequency dynamics are preserved are considered. Sparse-coding and source separation algorithms (specifically, shift-invariant probabilistic latent component analysis in 2D) are proposed as a means to access and summarise time- frequency dynamics which may be more ecologically-meaningful

A rare case of small bowel volvulus after jenjunoileal bariatric bypass requiring emergency surgery: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bariatric surgery is on the increase throughout the world. Jejunoileal bypass bariatric procedures have fallen out of favor in western surgical centers due to the high rate of associated complications. They are, however, performed routinely in other centers and as a consequence of health tourism, management of complications related to these procedures may still be encountered.</p> <p>Case presentation</p> <p>We describe a rare case of small bowel obstruction in a 45-year-old British Caucasian woman, secondary to a volvulus of the jejunoileal anastomosis following bariatric bypass surgery. The pre-operative diagnosis was confirmed by radiology. We describe a successful surgical technique for this rare complication.</p> <p>Conclusions</p> <p>Bariatric surgery may be complicated by bowel obstruction. Early imaging is vital for diagnosis and effective management. The use of our surgical technique provides a simple and effective approach for the successful management of this bariatric complication.</p

Tracing Personalized Health Curves during Infections

By concentrating on the relationship between health and microbe number over the course of infections, most pathogenic and mutualistic infections can be summarized by a small alphabet of curves, which has implications not only for basic research but for how we might treat patients

An international inter-laboratory study on Nosema spp. spore detection and quantification through microscopic examination of crushed honey bee abdomens

Nosemosis is a microsporidian disease causing mortality and weakening of honey bee colonies, especially in the event of co-exposure to other sources of stress. As a result, the disease is regulated in some countries. Reliable and harmonised diagnosis is crucial to ensure the quality of surveillance and research results. For this reason, the first European Interlaboratory Comparison (ILC) was organised in 2017 in order to assess both the methods and the results obtained by National Reference Laboratories (NRLs) in counting Nosema spp. spores by microscopy. Implementing their own routine conditions of analysis, the 23 participants were asked to perform an assay on & nbsp;a & nbsp;panel of ten positive and negative samples of crushed honey bee abdomens. They were asked to report results from a qualitative and quantitative standpoint. The assessment covered specificity, sensitivity, trueness and precision. Quantitative results were analysed in compliance with international standards NF ISO 13528 (2015) and NF ISO 5725-2 (1994). Three results showed a lack of precision and five a lack of trueness. However, overall results indicated a global specificity of 98% and a global sensitivity of 100%, thus demonstrating the advanced performance of the microscopic methods applied to Nosema spores by the NRLs. Therefore, the study concluded that using microscopy to detect and quantify spores of Nosema spp. was reliable and valid.panel of ten positive and negative samples of crushed honey bee abdomens. They were asked to report results from a qualitative and quantitative standpoint. The assessment covered specificity, sensitivity, trueness and precision. Quantitative results were analysed in compliance with international standards NF ISO 13528 (2015) and NF ISO 5725-2 (1994). Three results showed a lack of precision and five a lack of trueness. However, overall results indicated a global specificity of 98% and a global sensitivity of 100%, thus demonstrating the advanced performance of the microscopic methods applied to Nosema spores by the NRLs. Therefore, the study conclude