A genome resequencing-based genetic map reveals the recombination landscape of an outbred parasitic nematode in the presence of polyploidy and polyandry

The parasitic nematode Haemonchus contortus is an economically and clinically important pathogen of small ruminants, and a model system for understanding the mechanisms and evolution of traits such as anthelmintic resistance. Anthelmintic resistance is widespread and is a major threat to the sustainability of livestock agriculture globally; however, little is known about the genome architecture and parameters such as recombination that will ultimately influence the rate at which resistance may evolve and spread. Here we performed a genetic cross between two divergent strains of H. contortus, and subsequently used whole-genome re-sequencing of a female worm and her brood to identify the distribution of genome-wide variation that characterises these strains. Using a novel bioinformatic approach to identify variants that segregate as expected in a pseudo-testcross, we characterised linkage groups and estimated genetic distances between markers to generate a chromosome-scale F1 genetic map. We exploited this map to reveal the recombination landscape, the first for any parasitic helminth species, demonstrating extensive variation in recombination rate within and between chromosomes. Analyses of these data also revealed the extent of polyandry, whereby at least eight males were found to have contributed to the genetic variation of the progeny analysed. Triploid offspring were also identified, which we hypothesise are the result of nondisjunction during female meiosis or polyspermy. These results expand our knowledge of the genetics of parasitic helminths and the unusual life-history of H. contortus, and enhance ongoing efforts to understand the genetic basis of resistance to the drugs used to control these worms and for related species that infect livestock and humans throughout the world. This study also demonstrates the feasibility of using whole-genome resequencing data to directly construct a genetic map in a single generation cross from a non-inbred non-model organism with a complex lifecycle

Ploidy variation in fungi: Polyploidy, aneuploidy, and genome evolution

The ability of an organism to replicate and segregate its genome with high fidelity is vital to its survival and for the production of future generations. Errors in either of these steps (replication or segregation) can lead to a change in ploidy or chromosome number. While these drastic genome changes can be detrimental to the organism, resulting in decreased fitness, they can also provide increased fitness during periods of stress. A change in ploidy or chromosome number can fundamentally change how a cell senses and responds to its environment. Here, we discuss current ideas in fungal biology that illuminate how eukaryotic genome size variation can impact the organism at a cellular and evolutionary level. One of the most fascinating observations from the past 2 decades of research is that some fungi have evolved the ability to tolerate large genome size changes and generate vast genomic heterogeneity without undergoing canonical meiosis

Acquisition of be by Cantonese ESL learners in Hong Kong and its pedagogical implications

The present study of the acquisition of be by Cantonese ESL learners in Hong Kong investigates the relationship between knowledge, input and perfonnance. Be is an . .exponent of two fundamental properties of sentence structure in English: tense and. subject verb agreement. Neither of these properties is realised overtly in Cantonese and therefore Cantonese ESL learners have to establish these properties from scratch. Past research has reported different kinds of p~oblems in the acquisition of English be by learners of different L1 backgrounds, including omission, overgeneralization and substitution of be for have, but few attempts have been made to provide a comprehensive account of these interlanguage features and how the topic can facilitate our understanding of the key issues in SLA. This study aims to fill this gap by examining the data obtained from an English test which consisted of three parts: a grammaticality judgment task, a production task and an acceptability judgment task completed by 243 Cantonese ESL learners in Hong Kong (of primary two and five, secondary one, four and six, and undergraduates of year 1 and 2) and a control group of 12 native English speakers. The results shed light both on a number of theoretical and pedagogical issues: the role of the L1 in the constructions involving be, whether any properties associated with be remain persistently problematic for Cantonese speakers; what the developmental stages are in the acquisition of be; what the relationship between morphology and syntax is (i.e. between knowledge and perfonnance), and finally suggesting how teachers can make use of the findings in selecting appropriate teaching approaches, equipping themselves, and being aware of what is 'teachable'.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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Motivational factors and structured input effects on the acquisition of English causative passive forms

This study investigated the possible effects of motivational factors on the positive effects generated by structured input on the acquisition of English causative passive forms. This investigation builds upon the work carried out within the structured input research framework with the intention to measure online effects utilising a self-paced reading test. The self-paced reading test is a reliable measurement of language processing. Fifty Chinese (L1) subjects participated in the current study. They were all learning English in a university in the United Kingdom. After receiving two motivation questionnaires three groups were formed: structured input low-motivated (n = 15); structured input high-motivated (n = 20); and a control group (n = 15). Pre-tests and post-tests (immediate and delayed) were administered before and after the instructional treatment period which lasted for 3 h over a two-day period. The main findings from this experimental study confirmed the positive effects of structured input in facilitating the correct processing of English causative passive forms (accuracy and response time). The structured input activities groups improved equally from pre-to post-tests and they both retained the positive instructional effects over a 3-week period. Motivation was not a factor influencing the positive results generated by structured input. The present study contributes to the current call in the field for more empirical research to investigate the role of instruction and individual differences and the use of online tests to measure in-depth language processing

Measuring Smoking Knowledge, Attitudes and Services (S-KAS) Among Clients in Addiction Treatment

BACKGROUND: Addiction treatment programs are increasingly working to address prevalent and comorbid tobacco dependence in their service populations. However at present there are few published measurement tools, with known psychometric properties, that can be used to assess client-level constructs related to tobacco dependence in addiction treatment settings. Following on previous work that developed a staff-level survey instrument, this report describes the development and measurement characteristics of the smoking knowledge, attitudes and services (S-KAS) for use with clients in addiction treatment settings. METHOD: 250 clients enrolled in residential drug abuse treatment programs were surveyed. Summary statistics were used to characterize both the participants and their responses, and exploratory factor analysis (EFA) was used to examine the underlying factor structure. RESULTS: Examination of the rotated factor pattern indicated that the latent structure was formed by one knowledge factor, one attitude factor, and two service factors reflecting program services and clinician services related to tobacco dependence. Standardized Cronbach\u27s alpha coefficients for the four scales were, respectively, .57, .75, .82 and .82. CONCLUSIONS: The proposed scales have reasonably good psychometric characteristics, although the knowledge scale leaves room for improvement, and will allow researchers to quantify client knowledge, attitudes and services regarding tobacco dependence treatment. Researchers, program administrators, and clinicians may find the S-KAS useful in changing organizational culture and clinical practices related to tobacco addiction, help in program evaluation studies, and in tracking and improving client motivation

Identification and evaluation of the inhibitory effect of Prunella vulgaris extract on SARS-coronavirus 2 virus entry.

Until now, antiviral therapeutic agents are still urgently required for treatment or prevention of SARS-coronavirus 2 (SCoV-2) virus infection. In this study, we established a sensitive SCoV-2 Spike glycoprotein (SP), including an SP mutant D614G, pseudotyped HIV-1-based vector system and tested their ability to infect ACE2-expressing cells. Based on this system, we have demonstrated that an aqueous extract from the Natural herb Prunella vulgaris (NhPV) displayed potent inhibitory effects on SCoV-2 SP (including SPG614 mutant) pseudotyped virus (SCoV-2-SP-PVs) mediated infections. Moreover, we have compared NhPV with another compound, Suramin, for their anti-SARS-CoV-2 activities and the mode of their actions, and found that both NhPV and Suramin are able to directly interrupt SCoV-2-SP binding to its receptor ACE2 and block the viral entry step. Importantly, the inhibitory effects of NhPV and Suramin were confirmed by the wild type SARS-CoV-2 (hCoV-19/Canada/ON-VIDO-01/2020) virus infection in Vero cells. Furthermore, our results also demonstrated that the combination of NhPV/Suramin with an anti-SARS-CoV-2 neutralizing antibody mediated a more potent blocking effect against SCoV2-SP-PVs. Overall, by using SARS-CoV-2 SP-pseudotyped HIV-1-based entry system, we provide strong evidence that NhPV and Suramin have anti-SARS-CoV-2 activity and may be developed as a novel antiviral approach against SARS-CoV-2 infection

Generation and Characterization of a Mouse-Adapted Makona Variant of Ebola Virus

Ebola virus (EBOV) is a zoonotic pathogen that poses a significant threat to public health, causing sporadic yet devastating outbreaks that have the potential to spread worldwide, as demonstrated during the 2013–2016 West African outbreak. Mouse models of infection are important tools for the development of therapeutics and vaccines. Exposure of immunocompetent mice to clinical isolates of EBOV is nonlethal; consequently, EBOV requires prior adaptation in mice to cause lethal disease. Until now, the only immunocompetent EBOV mouse model was based on the Mayinga variant, which was isolated in 1976. Here, we generated a novel mouse-adapted (MA)-EBOV based on the 2014 Makona isolate by inserting EBOV/Mayinga-MA mutations into the EBOV/Makona genome, followed by serial passaging of the rescued virus in suckling mice. The resulting EBOV/Makona-MA causes lethal disease in adult immunocompetent mice within 6 to 9 days and has a lethal dose (LD50) of 0.004 plaque forming units (PFU). Two additional mutations emerged after mouse-adaptation in the viral nucleoprotein (NP) and membrane-associated protein VP24. Using reverse genetics, we found the VP24 mutation to be critical for EBOV/Makona-MA virulence. EBOV/Makona-MA infected mice that presented with viremia, high viral burden in organs, increased release of pro-inflammatory cytokines/chemokines, and lymphopenia. Our mouse model will help advance pre-clinical development of countermeasures against contemporary EBOV variants

Addressing Tobacco Through Organizational Change (ATTOC) in Residential Addiction Treatment Settings

BACKGROUND: Smoking prevalence among persons in addiction treatment is 3-4 times higher than in the general population. However, treatment programs often report organizational barriers to providing tobacco-related services. This study assessed the effectiveness of a six month organizational change intervention, Addressing Tobacco Through Organizational Change (ATTOC), to improve how programs address tobacco dependence. METHODS: The ATTOC intervention, implemented in three residential treatment programs, included consultation, staff training, policy development, leadership support and access to nicotine replacement therapy (NRT) medication. Program staff and clients were surveyed at pre- and post-intervention, and at 6 month follow-up. The staff survey measured knowledge of the hazards of smoking, attitudes about and barriers to treating smoking, counselor self-efficacy in providing such services, and practices used to address tobacco. The client survey measured knowledge, attitudes, and tobacco-related services received. NRT use was tracked. RESULTS: From pre- to post-intervention, staff beliefs became more favorable toward treating tobacco dependence (F(1, 163)=7.15, p=0.008), NRT use increased, and tobacco-related practices increased in a non-significant trend (F(1, 123)=3.66, p=0.058). Client attitudes toward treating tobacco dependence became more favorable (F(1, 235)=10.58, p=0.0013) and clients received more tobacco-related services from their program (F(1, 235)=92.86, p\u3c0.0001) and from their counselors (F(1, 235)=61.59, p\u3c0.0001). Most changes remained at follow-up. CONCLUSIONS: The ATTOC intervention can help shift the treatment system culture and increase tobacco services in addiction treatment programs