Mammalian Adaptation of an Avian Influenza A Virus Involves Stepwise Changes in NS1

Influenza A viruses (IAVs) are common pathogens of birds that occasionally establish endemic infections in mammals. The processes and mechanisms that result in IAV mammalian adaptation are poorly understood. The viral non-structural 1 (NS1) protein counteracts the interferon (IFN) response, a central component of the host-species barrier. We characterised the NS1 proteins of equine influenza virus (EIV), a mammalian IAV lineage of avian origin. We showed that evolutionary distinct NS1s counteract the IFN response using different and mutually exclusive mechanisms: while the NS1s of early EIVs block general gene expression by binding to the cellular polyadenylation specific factor 30 (CPSF30), NS1s from more evolved EIVs specifically block the induction of IFN-stimulated genes by interfering with the JAK/STAT pathway. These contrasting anti-IFN strategies are associated with two mutations that appeared sequentially and became rapidly selected during EIV evolution, highlighting the importance of evolutionary processes on immune evasion mechanisms during IAV adaptation

Are Neurotrophin Genes Involved in the Pathophysiology of Gambling Disorder?

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Periodogram Connectivity of EEG Signals for the Detection of Dyslexia

Electroencephalography (EEG) signals provide an important source of information of brain activity at different areas. This information can be used to diagnose brain disorders according to different activation patterns found in controls and patients. This acquisition technology can be also used to explore the neural basis of less evident learning disabilities such as Developmental Dyslexia (DD). DD is a specific difficulty in the acquisition of reading skills not related to mental age or inadequate schooling, whose prevalent is estimated between 5% and 12% of the population. In this paper we propose a method to extract discriminative features from EEG signals based on the relationship among the spectral density at each channel. This relationship is computed by means of different correlation measures, inferring connectivity-like markers that are eventually selected and classified by a linear support vector machine. The experiments performed shown AUC values up to 0.7, demonstrating the applicability of the proposed approach for objective DD diagnosis

Beyond paradigm : The ‘what’ and the ‘how’ of classroom research

This article reviews studies in second language classroom research from a cross-theoretic perspective, arguing that the classroom holds the potential for bringing together researchers from opposing theoretical orientations. It shows how generative and general cognitive approaches share a view of language that implicates both implicit and explicit knowledge, and that holds a bias towards implicit knowledge. Arguing that it is implicit knowledge that should be the object of research, it proposes that classroom research would benefit from incorporating insights from a generative understanding of language. Specifically, there is a need for a more nuanced view of the complexity of language in terms of linguistic domain, and the interaction between those domains. Generative second language acquisition research that shows developmental differences in terms of both linguistic domain and interface is reviewed. The core argument is a call for more attention to the ‘what’ of language development in classroom research and, by implication, teaching practice. As such, the language classroom is seen to offer potential for research that goes beyond paradigm to address both the ‘what’ and the ‘how’ of language development

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. We here present the pharmacokinetics, safety and efficacy of BKI-1553 in pregnant ewes and foetuses using a pregnant sheep model of N. caninum infection. BKI-1553 showed exposure in pregnant ewes with trough concentrations of approximately 4 µM, and of 1 µM in foetuses. Subcutaneous BKI-1553 administration increased rectal temperatures shortly after treatment, and resulted in dermal nodules triggering a slight monocytosis after repeated doses at short intervals. BKI-1553 treatment decreased fever in infected pregnant ewes already after two applications, resulted in a 37–50% reduction in foetal mortality, and modulated immune responses; IFN¿ levels were increased early after infection and IgG levels were reduced subsequently. N. caninum was abundantly found in placental tissues; however, parasite detection in foetal brain tissue decreased from 94% in the infected/untreated group to 69–71% in the treated groups. In summary, BKI-1553 confers partial protection against abortion in a ruminant experimental model of N. caninum infection during pregnancy. In addition, reduced parasite detection, parasite load and lesions in foetal brains were observed

Shifting from Seedling Mandarin Trees to Grafted Trees and Controlling Huanglongbing and Viroids: a Biotechnological Revolution in Nepal

Poverty in Nepal, largely a rural phenomenon, is widespread, with 30.8% of the population living below the poverty line. Agriculture is the main source of livelihood of the Nepalese people who are living below poverty. Citrus, the first cash crop, is grown in small to very small orchards producing less than 10 tons/ha. More than 90% of the trees are seedlings of a local mandarin and therefore they are essentially free of most graft-transmissible diseases. Huanglongbing (HLB) and the Asian psyllid vector, Diaphorina citri, were reported in Nepal in the mid-1960s and, in the absence of any control measures, have continued to spread ever since. Here we report the information available regarding the presence of HLB in several important citrus-growing areas (Armalakur, Bandipur, Dhankuta/Karmitar, Kathmandu, Lamjung, Paripatle, Pokhara, Sindulimadi and Syangja) and the identification of four citrus viroids (Citrus exocortis viroid, Hop stunt viroid, Citrus viroid-III, and Citrus viroid-V) in the experimental citrus station of Pokhara. Citrus rehabilitation, as part of a program to improve food security for the Nepalese population, was started in 2004, and is based on (I) producing disease-free citrus trees, grafted on adequate rootstocks, in covered, insect-proof nursery facilities, (II) demonstration orchards with grafted trees, (III) control of HLB by trunk applications of systemic insecticides and/or guava interplants, (IV) selection of viroid-free budwood sources, and (V) transfer of technology to the farmers

Characterization of Patients with Chronic Diseases and Complex Care Needs: A New High-Risk Emergent Population

Background: To analyze the prevalence and main epidemiological, clinical and outcome features of in-Patients with Complex Chronic conditions (PCC) in internal medicine areas, using a pragmatic working definition. Methods: Prospective study in 17 centers from Spain, with 97 in-hospital, monthly prevalence cuts. A PCC was considered when criteria of polypathological patient (two or more major chronic diseases) were met, or when a patient suffered one major chronic disease plus one or more of nine predefined complexity criteria like socio-familial risk, alcoholism or malnutrition among others (PCC without polypathology). A complete set of baseline features as well as 12-months survival were collected. Then, we compared clinical, outcome variables, and PROFUND index accuracy between polypathological patients and PCC without polypathology. Results: The global prevalence of PCC was 61% (40% of them were polypathological patients, and 21% PCC withouth polypathology) out of the 2178 evaluated patients. Their median age was 82 (59.5% men), suffered 2.3 ± 1.1 major diseases (heart diseases (70.5%), neurologic (41.5%), renal (36%), and lung diseases (26%)), 5.5 ± 2.5 other chronic conditions, met 2.5 ± 1.5 complexity criteria, and presented functional decline (Barthel index 55 (25-90)). Compared to polypathological patients, the subgroup of PCC without polypathology were younger, with a different pattern of major diseases and comorbidities, a better functional status, and lower 12-months mortality rates ((36.2% vs 46.8%; p = .003; OR 0.7(0.48-0.86). The PROFUND index obtained adequate calibration and discrimination power (AUC-ROC 0.67 (0.63-0.69)) in predicting 12-month mortality of PCC. Conclusion: Patients with complex chronic conditions are highly prevalent in internal medicine areas; their clinical pattern has changed in parallel to socio-epidemiological modifications, but their death-risk is still adequately predicted by PROFUND index