Dynamic interactions of a conserved enterotoxigenic Escherichia coli adhesin with intestinal mucins govern epithelium engagement and toxin delivery

At present, there is no vaccine for enterotoxigenic Escherichia coli (ETEC), an important cause of diarrheal illness. Nevertheless, recent microbial pathogenesis studies have identified a number of molecules produced by ETEC that contribute to its virulence and are novel antigenic targets to complement canonical vaccine approaches. EtpA is a secreted two-partner adhesin that is conserved within the ETEC pathovar. EtpA interacts with the tips of ETEC flagella to promote bacterial adhesion, toxin delivery, and intestinal colonization by forming molecular bridges between the bacteria and the epithelial surface. However, the nature of EtpA interactions with the intestinal epithelium remains poorly defined. Here, we demonstrate that EtpA interacts with glycans presented by transmembrane and secreted intestinal mucins at epithelial surfaces to facilitate pathogen-host interactions that culminate in toxin delivery. Moreover, we found that a major effector molecule of ETEC, the heat-labile enterotoxin (LT), may enhance these interactions by stimulating the production of the gel-forming mucin MUC2. Our studies suggest, however, that EtpA participates in complex and dynamic interactions between ETEC and the gastrointestinal mucosae in which host glycoproteins promote bacterial attachment while simultaneously limiting the epithelial engagement required for effective toxin delivery. Collectively, these data provide additional insight into the intricate nature of ETEC interactions with the intestinal epithelium that have potential implications for rational approaches to vaccine design

Gendered perceptions of climate change and agricultural adaptation practices: A systematic review

The present systematic review was undertaken to obtain a detailed understanding of how climate change perceptions and adaptation differ globally by gender and different intersections among the farmers. Findings from 41 studies selected following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, mostly from Africa and Asia, suggest that climate change perceptions and adaptation are highly contextual and considerably varied by gender and different intersections. Existing gender role, farmers’ age, education, knowledge, marital status, intra-household power structure, religion, social status and ethnicity were intersecting with gender and climate change perception and adaptation. Apart from gender and intersectionality, access to resources, social network and local institutions are found to be important correlates of adaptation strategies by farmers. While agriculture being feminized, mere technological changes are not conclusive to climate change adaptation rather socio-cultural, structural and political changes in inevitable. Female farmers were tend to be more concerned and fatalistic about climate change which reminds us the urgency of culturally appropriate climate change communication to obtain informed decision regarding climate change. Future climate change research could be more gender transformative by exploring the existing inequalities lying in different intersections of gender rather than highlighting binary gender differences only

Semiclassical Tunneling of Wavepackets with Real Trajectories

Semiclassical approximations for tunneling processes usually involve complex trajectories or complex times. In this paper we use a previously derived approximation involving only real trajectories propagating in real time to describe the scattering of a Gaussian wavepacket by a finite square potential barrier. We show that the approximation describes both tunneling and interferences very accurately in the limit of small Plank's constant. We use these results to estimate the tunneling time of the wavepacket and find that, for high energies, the barrier slows down the wavepacket but that it speeds it up at energies comparable to the barrier height.Comment: 23 pages, 7 figures Revised text and figure

An analysis of the masking of speech by competing speech using self-report data (L)

Many of the items in the "Speech, Spatial, and Qualities of Hearing" scale questionnaire [S. Gatehouse and W. Noble, Int. J. Audiol. 43, 85–99 (2004)] are concerned with speech understanding in a variety of backgrounds, both speech and nonspeech. To study if this self-report data reflected informational masking, previously collected data on 414 people were analyzed. The lowest scores (greatest difficulties) were found for the two items in which there were two speech targets, with successively higher scores for competing speech (six items), energetic masking (one item), and no masking (three items). The results suggest significant masking by competing speech in everyday listening situations

Kinase-targeted cancer therapies: Progress, challenges and future directions

© 2018 The Author(s). The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies

A Review of Von Hippel-Lindau Syndrome

Von Hippel-Lindau syndrome (VHL) is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.</p

Relationships between farmer psychological profiles and farm business performance amongst smallholder beef and poultry farmers in South Africa

Beef cattle and poultry are critically important livestock for improving household food security and alleviating poverty amongst smallholder farmers in South Africa. In this paper, our goal is to examine the relationships between farmer psychological profiles and farm business performance of commercially oriented beef cattle and poultry smallholder farmers in South Africa. We employ a multipronged interdisciplinary approach to test the theory of planned behaviour and its relationship to farm business performance. First, a behavioural science-informed survey instrument was employed to collect data from randomly selected farmer participants in two major beef and poultry projects undertaken by the authors. Second, a latent profile analysis was used to identify the psychological profiles of those farmers. Third, traditional and estimated indicators of farm business performance were obtained using descriptive and econometric-based approaches, including logistic regression and stochastic frontier analyses. The estimated farm business performance indicators were correlated with the psychological profiles of farmers. Results from the latent profile analysis showed three distinct profiles of beef and poultry farmers clearly differentiated by their ability to control and succeed in their farm business enterprises; criteria included attitude, openness to ideas, personality, perceived capabilities, self-efficacy, time orientation, and farm- and personal-related concerns. Profile 1 (‘Fatalists’) scored themselves negatively on their ability to control and succeed in their business enterprises. The majority of farmers were generally neutral about their ability to control and succeed in their businesses (Profile 2, ‘Traditionalists’), while a relatively small group of farmers were confident of their ability to succeed (Profile 3, ‘Entrepreneurs’). We found evidence of significant differences in farm business performance amongst the different profiles of farmers. As far as we can determine, this is the only study to have assessed farm business performance based on a differentiation of farmers’ psychological profiles. Our results provide a framework to further investigate whether particular types of on-farm interventions and training methods can be customised for different segments of farmers based on their preferred learning styles

Can organic agriculture contribute to sustainable development in the tropics?

Agricultural intensification over last decades has resulted in a great increase of crop yields, but it also had a detrimental impact on biodiversity. The dramatic decline of arable weed diversity is a matter of great concern because weeds have an important ecological function as a key component of the food web of agroecosystems. Weeds are suitable indicators of management effects on wildlife diversity in arable crops because they have high sensitivity to cultivation measures and have a strong relation to other organism groups. Nevertheless, the effect of farming management on weed abundance and diversity will be more reliable on weed seed bank rather than on aboveground weed community because it is the result of processes that have occurred in the past and consequently, it could better reflect the effect of the agricultural practices over the years

Soil Biological Activity Contributing to Phosphorus Availability in Vertisols under Long-Term Organic and Conventional Agricultural Management

Mobilization of unavailable phosphorus (P) to plant available P is a prerequisite to sustain crop productivity. Although most of the agricultural soils have sufficient amounts of phosphorus, low availability of native soil P remains a key limiting factor to increasing crop productivity. Solubilization and mineralization of applied and native P to plant available form is mediated through a number of biological and biochemical processes that are strongly influenced by soil carbon/organic matter, besides other biotic and abiotic factors. Soils rich in organic matter are expected to have higher P availability potentially due to higher biological activity. In conventional agricultural systems mineral fertilizers are used to supply P for plant growth, whereas organic systems largely rely on inputs of organic origin. The soils under organic management are supposed to be biologically more active and thus possess a higher capability to mobilize native or applied P. In this study we compared biological activity in soil of a long-term farming systems comparison field trial in vertisols under a subtropical (semi-arid) environment. Soil samples were collected from plots under 7 years of organic and conventional management at five different time points in soybean (Glycine max) -wheat (Triticum aestivum) crop sequence including the crop growth stages of reproductive significance. Upon analysis of various soil biological properties such as dehydrogenase, β-glucosidase, acid and alkaline phosphatase activities, microbial respiration, substrate induced respiration, soil microbial biomass carbon, organically managed soils were found to be biologically more active particularly at R2 stage in soybean and panicle initiation stage in wheat. We also determined the synergies between these biological parameters by using the methodology of principle component analysis. At all sampling points, P availability in organic and conventional systems was comparable. Our findings clearly indicate that owing to higher biological activity, organic systems possess equal capabilities of supplying P for crop growth as are conventional systems with inputs of mineral P fertilizers