Snapshot of the Atlantic Forest canopy: surveying arboreal mammals in a biodiversity hotspot

The Atlantic Forest of South America supports a rich terrestrial biodiversity but has been reduced to only a small extent of its original forest cover. It hosts a large number of endemic mammalian species but our knowledge of arboreal mammal ecology and conservation has been limited because of the challenges of observing arboreal species from ground level. Camera trapping has proven to be an effective tool in terrestrial mammal monitoring but the technique has rarely been used for arboreal species. For the first time in the Atlantic Forest, we obtained data on the arboreal mammal community using arboreal camera trapping, focusing on Caparaó National Park, Brazil. We placed 24 infrared camera traps in the forest canopy in seven areas within the Park, operating them continuously during January 2017–June 2019. During this period the camera traps accumulated 4,736 camera-days of footage and generated a total of 2,256 photographs and 30-s videos of vertebrates. The arboreal camera traps were able to detect arboreal mammals of a range of body sizes. The mammal assemblage comprised 15 identifiable species, including the Critically Endangered northern muriqui Brachyteles hypoxanthus and buffy-headed marmoset Callithrix flaviceps as well as other rare, nocturnal and inconspicuous species. We confirmed for the first time the occurrence of the thin-spined porcupine Chaetomys subspinosus in the Park. Species richness varied across survey areas and forest types. Our findings demonstrate the potential of arboreal camera trapping to inform conservation strategies

Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization

BACKGROUND: Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. METHODOLOGY AND PRINCIPAL FINDINGS: Actinium-225 ((225)Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225)Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225)Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225)Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225)Ac-E4G10 therapy. CONCLUSIONS: The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy

Deconvoluting hepatic processing of carbon nanotubes

Single-wall carbon nanotubes present unique opportunities for drug delivery, but have not advanced into the clinic. Differential nanotube accretion and clearance from critical organs have been observed, but the mechanism not fully elucidated. The liver has a complex cellular composition that regulates a range of metabolic functions and coincidently accumulates most particulate drugs. Here we provide the unexpected details of hepatic processing of covalently functionalized nanotubes including receptor-mediated endocytosis, cellular trafficking and biliary elimination. Ammonium-functionalized fibrillar nanocarbon is found to preferentially localize in the fenestrated sinusoidal endothelium of the liver but not resident macrophages. Stabilin receptors mediate the endocytic clearance of nanotubes. Biocompatibility is evidenced by the absence of cell death and no immune cell infiltration. Towards clinical application of this platform, nanotubes were evaluated for the first time in non-human primates. The pharmacologic profile in cynomolgus monkeys is equivalent to what was reported in mice and suggests that nanotubes should behave similarly in humans

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.<p></p> Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.<p></p> Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.<p></p> Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.<p></p> Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.<p></p&gt

Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation

Smyd3 is a lysine methyltransferase implicated in chromatin and cancer regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5 (H4K5me). This novel histone methylation mark is detected in diverse cell types and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3-driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via H4K5 methylation, provides a potential new link between chromatin dynamics and neoplastic disease

Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research

Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care

Decline of Leach’s Storm Petrels Hydrobates leucorhous at the largest colonies in the northeast Atlantic

Leach’s Storm Petrel Hydrobates leucorhous has undergone substantial population declines at North Atlantic colonies over recent decades, but censusing the species is challenging because it nests in burrows and is only active at colonies at night. Acoustic playback surveys allow birds present in nest sites to be detected when they respond to recordings of vocalisations. However, not all birds respond to playback on every occasion, response rate is likely to decline with increasing distance between the bird and the playback location, and the observer may not detect all responses. As a result, various analysis methods have been developed to measure and correct for these imperfect response and detection probabilities. We applied two classes of methods (calibration plot and hierarchical distance sampling) to acoustic survey data from the two largest colonies of breeding Leach’s Storm Petrels in the northeast Atlantic: the St Kilda archipelago off the coast of northwest Scotland, and the island of Elliðaey in the Vestmannaeyjar archipelago off the southwest of Iceland. Our results indicate an overall decline of 68% for the St Kilda archipelago between 2000 and 2019, with a current best estimate of ~8,900 (95% CI: 7,800–10,100) pairs. The population on Elliðaey appears to have declined by 40 –49% between 1991 and 2018, with a current best estimate of ~5,400 (95% CI: 4,300–6,700) pairs. We also discuss the relative efficiency and precision of the two survey methods