Responses of common diving petrel chicks (Pelecanoides urinatrix) to burrow and colony specific odours in a simple wind tunnel

Researchers have previously assumed that common diving petrels (Pelecanoides urinatrix) have a limited sense of smell since they have relatively small olfactory bulbs. A recent study, however, showed that adult diving petrels prefer the scent of their own burrow compared to burrows of other diving petrels, implying that personal scents contribute to the burrow’s odour signature. Because diving petrels appear to be adapted to use olfaction in social contexts, they could be a useful model for investigating how chemically mediated social recognition develops in birds. A first step is to determine whether diving petrel chicks can detect familiar and unfamiliar odours. We compared behavioural responses of chicks to three natural stimuli in a wind tunnel: soil collected from their burrow or colony, and a blank control. During portions of the experiment, chicks turned the least and walked the shortest distances in response to odours from the nest, which is consistent with their sedentary behaviour within the burrow. By contrast, behaviours linked to olfactory search increased when chicks were exposed to blank controls. These results suggest that common diving petrel chicks can detect natural olfactory stimuli before fledging, and lay the foundation for future studies on the role of olfaction in social contexts for this species

Conflicting evidence for the role of JNK as a target in breast cancer cell proliferation: comparisons between pharmacological inhibition and selective shRNA knockdown approaches

As a target, the JNK pathway has been implicated in roles including cell death, proliferation, and inflammation in variety of contexts which span cardiovascular disease, neurodegenerative pathologies, and cancer. JNK1 and JNK2 have recently been demonstrated to function independently, highlighting a new parameter in the study of the JNK pathway. In order for JNK1 and JNK2-specific roles to be defined, better tools need to be employed. Previous studies have relied upon the broad spectrum JNK inhibitor, SP600125, to characterize the role of JNK signaling in a number of cell lines, including the breast cancer cell line MCF-7. In line with previous literature, our study has demonstrated that SP600125 treatment inhibited c-Jun and JNK phosphorylation and MCF-7 proliferation. However, in addition to targeting JNK1, JNK2, and JNK3, SP600125 has been previously demonstrated to suppress the activity of a number of other serine/threonine kinases, making SP600125 an inadequate tool for JNK isoform-specific roles to be determined. In this study, lentiviral shRNA was employed to selectively knockdown JNK1, JNK2, and JNK1/2 in MCF-7 cells. Using this approach, JNK phosphorylation was fully inhibited following stable knockdown of respective JNK isoforms. Interestingly, despite suppression of JNK phosphorylation, MCF-7 cell proliferation, cell cycle progression, or cell death remained unaffected. These findings raise the question of whether JNK phosphorylation really is pivotal in MCF-7 cell growth and death or if suppression of these events is a result of one of the many off-targets cited for SP600125

Induction of Myocarditis and Valvuluitis in Lewis Rats by Different Epitopes of Cardiac Myosin and its Implications in Rheumatic Carditis

Immune responses against cardiac myosin and group A streptococcal M protein have been implicated in the pathogenesis of rheumatic heart disease. Although cardiac myosin is known to produce myocarditis in susceptible animals, it has never been investigated for its role in production of valvular heart disease, the most serious sequelae of group A streptococcal infection in acute rheumatic fever. In our study, cardiac myosin induced valvulitis in the Lewis rat, and epitopes responsible for production of valvulitis were located in the rod region. Human and rat cardiac myosins induced severe myocarditis in the Lewis rats as expected. A purified S2 fragment (amino acid sequences 842 to 1295) produced the most severe myocarditis as well as valvulitis. Different regions of light meromyosin produced valvulitis (residues 1685 to 1936) or myocarditis (residues 1529 to 1611). Because streptococcal M proteins produced valvular heart disease in Lewis rats and have been linked to anti-cardiac myosin responses, we reacted myosin-sensitized lymphocytes isolated from the hearts of Lewis rats with peptides of streptococcal M5 protein in tritiated thymidine assays. Infiltrating lymphocytes responded most strongly to peptides within the B repeat region of streptococcal M protein. These data show direct evidence that immune responses against cardiac myosin lead to valvular heart disease and the infiltration of the heart by streptococcal M protein reactive T lymphocytes

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

BACKGROUND & AIMS Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. METHODS SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. RESULTS The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. CONCLUSIONS Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. LAY SUMMARY Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Virologic failure; Hepatitis CFracaso virológico; Hepatitis CFracàs virològic; Hepatitis CBackground & Aims Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.The initial SHARED development was funded in part by Merck and a User Partnership Program grant from Genome British Columbia to P.R.H and A.Y.M.H (UPP029). The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian (or any other) Government. C.R. and J.G. are supported by an NHMRC Investigator Grant (nos. 1173666, 1176131). An NHMRC Program Grant supported RAS testing and data collection by M.W.D. (1053206) and small grants from the Australian Centre for HIV and Hepatitis Virology Research, The University of Sydney, Western Sydney Local Health District Research Education Network, and the Robert W. Storr bequest to the Sydney Medical Foundation (University of Sydney). S.P. received personal fees from Gilead Sciences. Regarding the Italian data, the work was supported in part by the Italian Ministry of Instruction, University and Research (MIUR) (Bandiera InterOmics Protocollo PB05 1°), by the Italian Ministry of Health (RF-2016-02362422), and by Aviralia and Vironet C Foundations

Temporal Trends in Florida Panther Food Habits

Once on the brink of extinction, the Florida panther (Puma concolor coryi) has reoccupied parts of its extirpated range in southern Florida, USA over the past 20 years, which has largely been attributed to genetic restoration efforts initiated in 1995 to combat inbreeding depression and subsequent deleterious traits. Concurrent to the resurgence, an increase in documented livestock depredation events has heightened concern over human– panther conflicts. We examined 312 stomach content, scat, and feces (large intestine contents) samples collected 1989 to 2014 across the endemic range in southern Florida. We compared frequency of occurrence of prey items in samples by temporal (pre- and post-genetic restoration), geographic (north and south of 26° 10.017′ latitude), and demographic (age and sex) categories. We observed an apparent temporal shift in prey item occurrence in scats, where raccoon (Procyon lotor) occurrence increased while wild hog (Sus scrofa) occurrence decreased, whereas white-tailed deer (Odocoileus virginianus) occurrence appeared constant. Post-genetic restoration, we observed a geographic difference in panther prey, where white-tailed deer and raccoons were consumed more commonly in the southern part of the study area (characterized by lower soil quality and higher hydrological fluctuations), while wild hogs were consumed more frequently in the northern part of the study area. Neither sex nor age appeared to affect frequency of prey occurrence. Pets and livestock were not frequently found in the samples we examined. Overall, our results show shifts in panther diets both temporally and geographically; however, no notable changes in frequency of livestock found in panther diets were observed

Cytotoxic mAb from Rheumatic Carditis Recognizes Heart Valves and Laminin

Anti-streptococcal antibodies cross-reactive with N-acetyl-bD-glucosamine (GlcNAc) and myosin are present in the sera of patients with rheumatic fever (RF). However, their role in tissue injury is not clear. In this study, we show that anti-GlcNAc/anti-myosin mAb 3.B6 from a rheumatic carditis patient was cytotoxic for human endothelial cell lines and reacted with human valvular endothelium and underlying basement membrane. Reactivity of mAb 3.B6 with the valve was inhibited by human cardiac myosin \u3e laminin \u3e GlcNAc. The mAb 3.B6 epitopes were localized in fragments of human cardiac myosin, including heavy meromyosin (HMM), the S1 subfragment, and two light meromyosin (LMM) peptides containing amino acid sequences KEALISSLTRGKLTYTQQ (LMM 1) and SERVQLLHSQNTSLINQK (LMM 33). A novel feature of mAb 3.B6 was its reactivity with the extracellular matrix protein laminin, which may explain its reactivity with the valve surface. A laminin A-chain peptide (HTQNT) that includes homology to LMM33 inhibited the reactivity of mAb 3.B6 with human valve. These data support the hypothesis that cross-reactive antibodies in rheumatic carditis cause injury at the endothelium and underlying matrix of the valve

Abordaxe fisioterápico no asma infantil

[Resumen] Objetivo: analizar qué intervenciones se están llevando a cabo por parte de la fisioterapia en la patología del asma. Material y métodos: revisión de artículos en los cuales se lleven a cabo intervenciones de fisioterapia en niños asmáticos. La búsqueda se efectuó en las bases de datos Pubmed, PEDro, Web of Science y Scopus, seleccionando artículos publicados entre 2013 y 2017 en lengua inglesa, portuguesa y española. Resultados: se seleccionaron 6 artículos, la mayoría de calidad intermedia, con variabilidad en el número de sujetos en cada estudio. La población que se seleccionó comprende desde el nacimiento hasta los 18 años. Las terapias fisioterápicas empleadas son variables. Se realiza en todos los casos un tratamiento enfocado al abordaje de las capacidades físicas por medio de diferentes programas de entrenamiento que cada estudio enfocó de forma diferente. Los aspectos más evaluados han sido la función pulmonar, la calidad de vida y la disnea, medidos a través de diferentes test y pruebas funcionales. Se obtienen resultados positivos en el manejo del asma con cada uno de estos programas de entrenamiento físico. Conclusiones: existen múltiples programas de intervención fisioterápica sobre el asma. Se llevan a cabo programas de entrenamiento de la musculatura inspiratoria, entrenamiento aeróbico, anaeróbico, de fuerza y equilibrio por parte de la fisioterapia en el abordaje de esta patología y todos presentan beneficio sobre ella. Asimismo, se objetivó que el programa de tratamiento que engloba un entrenamiento basado en ejercicio aeróbico y ejercicios respiratorios presenta una mayor eficacia.[Abstract] Objective: to analyze what interventions are being carried out by physiotherapy in the pathology of asthma. Material and methods: review of articles in which physiotherapy interventions are carried out in asthmatic children. The search was carried out in the Pubmed, PEDro, Web of Science and Scopus databases, selecting articles published between 2013 and 2017 in English, Portuguese and Spanish. Results: Six articles were selected, most of intermediate quality, with variability in the number of subjects in each study. The population that was selected comprises from birth to 18 years. The physiotherapeutic therapies used are variable. In all cases, a treatment focused on addressing physical abilities is carried out through different training programs that each study focused on differently. The most evaluated aspects have been pulmonary function, quality of life and dyspnea, measured through different tests and functional tests. Positive results are obtained in the management of asthma with each of these physical training programs. Conclusions: There are multiple programs of physiotherapy intervention on asthma. Training programs for inspiratory musculature, aerobic, anaerobic, strength and balance training are carried out by physiotherapy in the approach to this pathology and all have benefit over it. Likewise, it was found that the treatment program that includes a training based on aerobic exercise and breathing exercises is more effective.[Resumo] Obxectivo: analizar que intervencións se están a facer por parte da fisioterapia na patoloxía da asma. Material e metodoloxía: revisión de artículos nos que se fagan intervencións de fisioterapia en nenos asmáticos. A búsqueda efectuouse nas bases de datos Pubmed, PEDro, Web of Science y Scopus, seleccionando artículos publicados entre 2013 y 2017 en lingua inglesa, portuguesa e española. Resultados: seleccionáronse 6 artigos, a maioría de calidade intermedia, con variabilidade no número de suxeitos en cada estudo. A poboación que se seleccionou comprende dende o nacemento ata os 18 anos. As terapias fisioterápicas empregadas son variables. Realizouse en todos os casos un tratamento enfocado á abordaxe das capacidades físicas por medio de diferentes programas de entrenamento que cada estudo enfocou de forma diferente. Os aspectos máis avaliados foron a función pulmonar, a calidade da vida e a disnea, medidos a través de diferentes test e probas funcionais. Obtéñense resultados positivos no manexo do asma con cada un destes programas de entrenamento físico. Conclusións: existen múltiples programas de intervención fisioterápica sobre a asma infantil. Lévanse a cabo programas de entrenamento da musculatura inspiratoria, entrenamiento aeróbico, anaeróbico, de forza e equilibrio por parte da fisioterapia no abordaxe desta patoloxía e todos presentan beneficio sobre ela. Así mesmo obxectivouse que o programa de tratamento que engloba un entrenamento baseado no exercicio aeróbico e exercicios respiratorios presenta unha maior eficacia.Traballo fin de grao (UDC.FCS). Fisioterapia. Curso 2017/201

Distribution of \u3ci\u3eBaylisascaris procyonis\u3c/i\u3e in Raccoons (\u3ci\u3eProcyon lotor\u3c/i\u3e) in Florida, USA

Baylisascaris procyonis, or raccoon roundworm, is an intestinal nematode parasite of raccoons (Procyon lotor) that is important to public and wildlife health. Historically, the parasite was uncommon in the southeastern US; however, the range of B. procyonis has expanded to include Florida, US. From 2010 to 2016, we opportunistically sampled 1,030 raccoons statewide. The overall prevalence was 3.7% (95% confidence interval=2.5–4.8%) of sampled individuals, and infection intensity ranged from 1 to 48 (mean±standard deviation 9.9±4.0). We found raccoon roundworm in 9/56 (16%) counties sampled, and the percent positive ranged from 1.1% to 13.3% of specimens collected per county. Including previously published data, B. procyonis was detected in 11 Florida counties. We used logistic regression to estimate the contribution of raccoon demographic variables and the presence of the endoparasite Macracanthorhynchus ingens to B. procyonis detection in Florida. Following the model selection process we found housing density, M. ingens presence, and urbanicity to be predictive of raccoon roundworm presence. We also found substantial among-county variation. Raccoon sex and age were not useful predictors. Public health officials, wildlife rehabilitators, wildlife managers, and others should consider any Florida raccoon to be potentially infected with B. procyonis, particularly in areas where housing density is high