Restoring fertility in yeast hybrids: Breeding and quantitative genetics of beneficial traits.

Hybrids between species can harbor a combination of beneficial traits from each parent and may exhibit hybrid vigor, more readily adapting to new harsher environments. Interspecies hybrids are also sterile and therefore an evolutionary dead end unless fertility is restored, usually via auto-polyploidisation events. In the Saccharomyces genus, hybrids are readily found in nature and in industrial settings, where they have adapted to severe fermentative conditions. Due to their hybrid sterility, the development of new commercial yeast strains has so far been primarily conducted via selection methods rather than via further breeding. In this study, we overcame infertility by creating tetraploid intermediates of Saccharomyces interspecies hybrids to allow continuous multigenerational breeding. We incorporated nuclear and mitochondrial genetic diversity within each parental species, allowing for quantitative genetic analysis of traits exhibited by the hybrids and for nuclear-mitochondrial interactions to be assessed. Using pooled F12 generation segregants of different hybrids with extreme phenotype distributions, we identified quantitative trait loci (QTLs) for tolerance to high and low temperatures, high sugar concentration, high ethanol concentration, and acetic acid levels. We identified QTLs that are species specific, that are shared between species, as well as hybrid specific, in which the variants do not exhibit phenotypic differences in the original parental species. Moreover, we could distinguish between mitochondria-type-dependent and -independent traits. This study tackles the complexity of the genetic interactions and traits in hybrid species, bringing hybrids into the realm of full genetic analysis of diploid species, and paves the road for the biotechnological exploitation of yeast biodiversity.

The effectiveness of a short course to improve coaches' knowledge on considerations for female athletes.

This study aimed to assess the effectiveness of an online short course in improving the knowledge and confidence of coaching and support staff when working with female athletes. A mixed-methods survey design was used, where participants completed surveys pre-, post-, and 6 months following an 8-week online course. Qualitative responses were analysed inductively using thematic analysis based on two pre-identified themes. Of the 92 participants who completed both pre- and post-course surveys, 72% (n = 66) were female and 67% (n = 62) were from team sports. Perceived knowledge and confidence improved following the course (p < 0.001) and were above pre-course values 6-months post (p < 0.001). A-priori theme Course Expectations generated two sub-themes: 'Empowering [me] to empower and support [them]', and "Sharing knowledge and experiences". A-priori theme Changes in Practice had subthemes of "Relaxing into it" and "Embedding support structures". Participants indicated that they enjoyed learning from a variety of content experts as well as other participants in an online format. Future courses aimed at coaching/support staff should design and deliver accessible programs aligned with the learning preferences of these individuals. When delivering specific education regarding supporting female athletes, targeting and encouraging men to participate may be beneficial.

The Disease Loophole: Index Terms and Their Role in Disease Misclassification.

The definitions of disease proffered by philosophers and medical actors typically require that a state of ill health be linked to some known bodily dysfunction before it is classified as a disease. I argue that such definitions of disease are not fully implementable in current medical discourse and practice. Adhering to the definitions would require that medical actors keep close track of the current state of knowledge on the causes and mechanisms of particular illnesses. Yet, unaddressed problems in medical terminology can make this difficult to do. I show that unrecognized misuse of "heterogeneous," "biomarker," and other important health terms-which I call index terms-can misrepresent the current empirical evidence on illness pathophysiology, such that unvalidated illness constructs become mistaken for diseases. Thus, implementing common definitions of disease would require closing this "loophole" in medical discourse. I offer a simple rule that, if followed, could help do just that.

Weight as an indicator of enclosure suitability in Livingstone's fruit bats (Pteropus livingstonii).

Obesity is common in zoo animals, and both dietary management and the provision of adequate opportunities for exercise are needed to tackle it. We used 30 years of records from Jersey Zoo to compare the weight and forearm length of wild and captive-born Livingstone's fruit bats (Pteropus livingstonii), and to assess the impact on weight of enclosure space. The mean capture weight of wild-caught male Livingstone's bats was 657 g, significantly higher than that of females (544 g). In both wild and captive-born bats, males had significantly longer forearms than females, but there was no effect of birth location. Males weighed more in the mating season than at other times of year. Both sexes gained more weight during development if born in enclosures that restricted flight rather than a large aviary; this was particularly noticeable in females. After reaching maturity at 3 years, weights of bats born in restricted enclosures continued to increase, reached a peak of over 1000 g at 8-10 years, and then declined in both sexes. The weight of bats born in the aviary remained more stable after the age of three. Like wild bats, adult females born in the aviary weighed less than males. However, females born in restricted enclosures weighed more than males born in the same enclosures. Enclosure designs that maximize opportunities for flight can limit excessive weight gain in captive fruit bats and may therefore improve fitness and health, essential in planning for future reintroduction programs.

The biopsychosocial model: Its use and abuse.

The biopsychosocial model (BPSM) is increasingly influential in medical research and practice. Several philosophers and scholars of health have criticized the BPSM for lacking meaningful scientific content. This article extends those critiques by showing how the BPSM's epistemic weaknesses have led to certain problems in medical discourse. Despite its lack of content, many researchers have mistaken the BPSM for a scientific model with explanatory power. This misapprehension has placed researchers in an implicit bind. There is an expectation that applications of the BPSM will deliver insights about disease; yet the model offers no tools for producing valid (or probabilistically true) knowledge claims. I argue that many researchers have, unwittingly, responded to this predicament by developing certain patterns of specious argumentation I call "wayward BPSM discourse." The arguments of wayward discourse share a common form: They appear to deliver insights about disease gleaned through applications of the BPSM; on closer inspection, however, we find that the putative conclusions presented are actually assertions resting on question-begging arguments, appeals to authority, and conceptual errors. Through several case studies of BPSM articles and literatures, this article describes wayward discourse and its effects. Wayward discourse has introduced into medicine forms of conceptual instability that threaten to undermine various lines of research. It has also created a potentially potent vector of medicalization. Fixing these problems will likely require reimposing conceptual rigor on BPSM discourse.

Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment.

BACKGROUND: Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline. METHODS: We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients. RESULTS: Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group. DISCUSSION: IL-6 may have some specificity to depression in early schizophrenia. TNF-α may be an indicator of immune dysfunction relevant to negative symptoms, and our longitudinal findings add to this evidence. However, minocycline continues to show very little promise as a treatment for any symptom dimension of early schizophrenia.

Connect through PLAY: a randomized-controlled trial in afterschool programs to increase adolescents' physical activity.

The current study is a randomized controlled trial to test a novel 10-week climate-based intervention within pre-existing afterschool programs, designed to increase moderate-to-vigorous physical activity (MVPA) in underserved (low-income, minority status) middle school youth by addressing youth social developmental needs. Participants (n = 167; 56% female; 62% Black; 50% overweight/obese) enrolled in 6 middle schools were randomized to either the Connect through PLAY intervention or a wait-list control. Process evaluation measures (i.e., observations of external evaluators; staff surveys) indicated that essential elements were implemented with fidelity, and staff endorsed implementation ease/feasibility and acceptability. Regression analysis demonstrated that participation in the intervention (vs. control) was associated with an increase of 8.17 min of daily accelerometry-measured MVPA (56 min of additional weekly MVPA) at post-intervention controlling for baseline MVPA, school, gender, and weight status. The results provide support for social-motivational climate-based interventions for increasing MVPA in underserved youth that can inform future school-based health initiatives.Trial Registration: NCT03850821: https://clinicaltrials.gov/ct2/show/study/NCT03850821?term=NCT03850821&rank=1.

A Brief Mindfulness-Based Intervention (bMBI) to Reduce Teacher Stress and Burnout.

Teacher stress and burnout contribute to attrition and stress-related health concerns. Despite some positive effects, previous mindfulness-based interventions (MBI) have failed to incorporate key elements of methodological rigor and have included large dosages despite research suggesting that such dosages are iatrogenic. The current study demonstrates the efficacy of a brief MBI (bMBI; four sessions, six total hours) to reduce self-reported stress, burnout, and depression, and suggests the bMBI can protect against deleterious impacts to physiological functioning. The study informs the design and implementation of future MBIs, including strategies for reducing intervention dosages, in order to improve effectiveness and maximize cost-effectiveness.

The Relation Between Early Adolescent Physical Activity and Internalizing Problems: Variations in Exercise Motivations as a Critical Moderator.

Inconsistencies exist regarding the relation between physical activity (PA) and internalizing symptomology in early adolescence, and there is need for investigation of potential moderators that may account for these discrepancies. The current study utilized a Self-Determination Theory Framework to investigate the main effects of five key motivations to exercise and their moderating effects between PA and internalizing problems in an underserved sample of adolescents (n = 167; mean age = 12.19 years; 73% African American). Analyses showed that intrinsic motivations were negatively related to internalizing problems and extrinsic motivations were positively related. PA was only protective against internalizing problems when intrinsic motivations were high and had iatrogenic effects when these were low. Exploratory analyses further delineated the unique effects of motivational orientations. Clinical implications and future research directions are discussed.

Antimicrobial use in UK long-term care facilities: results of a point prevalence survey.

BACKGROUND: The majority of people in long-term care facilities (LTCFs) are aged 65 years and older, and most of their care needs are provided by the LTCF staff. Provision of healthcare services for residents in LTCFs is variable and can result in disjointed care between carers and NHS healthcare professionals. OBJECTIVES: Our aim was to understand the use of antibiotics in LTCFs across the UK and to identify potential gaps in knowledge and support for carers and residents when using antibiotics, in order to determine how community pharmacy teams can provide additional support. METHODS: A point prevalence survey (PPS) was conducted by community pharmacists (n = 57) when they carried out visits to LTCFs across the UK between 13 November and 12 December 2017. Anonymized data were recorded electronically by the individual pharmacists. RESULTS: Data were analysed for 17909 residents in 644 LTCFs across the UK. The mean proportion of residents on antibiotics on the day of the visit was as follows: 6.3% England (536 LTCFs), 7.6% Northern Ireland (35 LTCFs), 8.6% Wales (10 LTCFs) and 9.6% Scotland (63 LTCFs). The percentage of antibiotics prescribed for prophylactic use was 25.3%. Antibiotic-related training was reported as being available for staff in 6.8% of LTCFs and 7.1% of LTCFs reported use of a catheter passport scheme. Pharmacists conducting the PPS intervened during the survey for 9.5% of antibiotic prescription events; 53.4% of interventions were for clinical reasons and 32.2% were for administration reasons. CONCLUSIONS: This survey identified high prophylactic use of antibiotics. There are opportunities for community pharmacy teams to improve antimicrobial stewardship in LTCF settings, including workforce education.

A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA.

Mitophagy is a cellular mechanism for the recycling of mitochondrial fragments. This process is able to improve mitochondrial DNA (mtDNA) quality in heteroplasmic mtDNA disease, in which mutant mtDNA co-exists with normal mtDNA. In disorders where the load of mutant mtDNA determines disease severity it is likely to be an important determinant of disease progression. Measuring mitophagy is technically demanding. We used pharmacological modulators of autophagy to validate two techniques for quantifying mitophagy. First we used the IN Cell 1000 analyzer to quantify mitochondrial co-localisation with LC3-II positive autophagosomes. Unlike conventional fluorescence and electron microscopy, this high-throughput system is sufficiently sensitive to detect transient low frequency autophagosomes. Secondly, because mitophagy preferentially removes pathogenic heteroplasmic mtDNA mutants, we developed a heteroplasmy assay based on loss of m.3243A>G mtDNA, during culture conditions requiring oxidative metabolism ("energetic stress"). The effects of the pharmacological modulators on these two measures were consistent, confirming that the high throughput imaging output (autophagosomes co-localising with mitochondria) reflects mitochondrial quality control. To further validate these methods, we performed a more detailed study using metformin, the most commonly prescribed antidiabetic drug that is still sometimes used in Maternally Inherited Diabetes and Deafness (MIDD). This confirmed our initial findings and revealed that metformin inhibits mitophagy at clinically relevant concentrations, suggesting that it may have novel therapeutic uses.

Factor Structure of the Teacher Strengths and Difficulties Questionnaire in a Large Community-Based Sample: An Investigation of Alternative Measurement Models.

The Strengths and Difficulties Questionnaire (SDQ) is a screening measure commonly used to assess behavioral and emotional symptoms and strengths among children and adolescents. However, despite its frequent use, its underlying factor structure remains an important area of inquiry. Whereas the original five-factor structure has often been supported through exploratory factor analysis, results from confirmatory analyses continue to yield mixed results. We analyzed data from youth in Grades K through 12 from a large epidemiologic study in the Southeastern United States. Teacher-report SDQ data were used to test three confirmatory factor models by school level (i.e., elementary [Grades K-5] and secondary [Grades 6-12]): The original five-factor model, a three-factor model, and a bifactor model. Model fit indices and reliability measures supported the original five-factor model as the preferred model when using the teacher-reported SDQ with both elementary and secondary school children. Implications for using the SDQ in applied research and predictive modeling are discussed.

Feature Learning Networks for Floor Sensor-based Gait Recognition.

Deep learning (DL) has become a powerful tool in many image classification applications but often requires large training sets to achieve high accuracy. For applications where the available data are limited, this can become a severely limiting factor in model performance. To address this limitation, feature learning network approaches that integrate traditional feature extraction methods with DL frameworks have been proposed. In this study, the performances of traditional methods: discrete wavelet transform (DWT), discrete cosine transform (DCT), independent component analysis (ICA), and principal component analysis (PCA); and their corresponding feature networks based on a convolutional neural network (CNN) framework: ScatNet (wavelet scattering network), DCTNet, ICANet, and PCANet, were investigated for use in pressure-based footstep recognition when the limited sample size is available for person authentication. The results show that the feature learning networks (90.6% accuracy) achieved significantly better performance on average than the conventional feature extraction methods (79.7% accuracy) (p < 0.05). Among the different feature networks, PCANet provided the best verification performance, with an accuracy of 92.2%. Feature learning networks are simple and effective approaches that can be a promising solution for applications like floor-based gait recognition in a security access scenario (such as workspace environment and border control) when small amounts of data are available for training models to differentiate between a larger group of users.

Complications of Cardiopulmonary Bypass From an Anesthesia Perspective: A Clinical Review.

Description Cardiopulmonary bypass (CPB) is frequently used for open heart surgery and other procedures that utilize temporary substitution or support of heart and lung function. While it is widely accepted as the predominant method to carry out these procedures, it is not without possible complications. CPB can be seen as the ultimate "team sport" as it includes and is dependent on contributions from multiple professionals including anesthesiologists, cardiothoracic surgeons, and perfusion technicians. In this clinical review paper, we examine possible complications of CPB, primarily from the perspective of the anesthesiologist, and how to troubleshoot them if they arise, which often requires the involvement of other essential team members.

Simulating the impact of varying vegetation on West African monsoon surface fluxes using a regional convection-permitting model.

This study assessed the sensitivity of the West African climate to varying vegetation fractions. The assessment of a such relationship is critical in understanding the interactions between land surface and atmosphere. Two sets of convection-permitting simulations from the UK Met Office Unified Model at 12 km horizontal resolution covering the monsoon period May-September (MJJAS) were used, one with fixed vegetation fraction (MF-V) and the other with time-varying vegetation fraction (MV-V). Vegetation fractions are based on MODIS retrievals between May and September. We focused on three climatic zones over West Africa: Guinea Coast, Sudanian Sahel, and the Sahel while investigating heat fluxes, temperature, and evapotranspiration. Results reveal that latent heat fluxes are the most strongly affected by vegetation fraction over the Sahelian and Sudanian regions while sensible heat fluxes are more impacted over the Guinea Coast and Sudanian Sahel. Also, in MV-V simulation there is an increase in evapotranspiration mainly over the Sahel and some specific areas in Guinea Coast from June to September. Moreover, it is noticed that high near-surface temperature is associated with a weak vegetation fraction, especially during May and June. Finally, varying vegetation seems to improve the simulation of surface energy fluxes and in turn impact on climate parameters. This suggests that climate modelers should prioritize the use of varying vegetation options to improve the representation of the West African climate system.

Mouthparts of the bumblebee (Bombus terrestris) exhibit poor acuity for the detection of pesticides in nectar.

Bees are important pollinators of agricultural crops, but their populations are at risk when pesticides are used. One of the largest risks bees face is poisoning of floral nectar and pollen by insecticides. Studies of bee detection of neonicotinoids have reported contradictory evidence about whether bees can taste these pesticides in sucrose solutions and hence avoid them. Here, we use an assay for the detection of food aversion combined with single-sensillum electrophysiology to test whether the mouthparts of the buff-tailed bumblebee (Bombus terrestris) detect the presence of pesticides in a solution that mimicked the nectar of oilseed rape (Brassica napus). Bees did not avoid consuming solutions containing concentrations of imidacloprid, thiamethoxam, clothianidin, or sulfoxaflor spanning six orders of magnitude, even when these solutions contained lethal doses. Only extremely high concentrations of the pesticides altered spiking in gustatory neurons through a slight reduction in firing rate or change in the rate of adaptation. These data provide strong evidence that bumblebees cannot detect or avoid field-relevant concentrations of pesticides using information from their mouthparts. As bees rarely contact floral nectar with other body parts, we predict that they are at high risk of unwittingly consuming pesticides in the nectar of pesticide-treated crops.

Bees and other pollinators often encounter pesticides while collecting nectar and pollen from agricultural crops. Widely used to protect crops, pesticides are toxic to insects and have contributed to population declines in all bee species. One way that bees might be able to avoid pesticides is using their incredibly good sense of taste, which can detect subtle differences between sugary solutions. Therefore, if pesticides taste bitter to them, bumblebees may be able to avoid feeding treated crops. However, it was not clear if bees can taste pesticides. Previous studies investigating whether they can taste a group of pesticides called "neonicotinoids" gave contradictory results. Furthermore, explicit behavioural tests of their ability to taste pesticides had not been performed. To shed light on this, Parkinson et al. compared the responses of neurons within structures used for detecting taste in bumblees eating a pure sugar solution with those eating a solution containing pesticides. Experiments with a group of pesticides known as 'cholinergic' showed that neuron responses were the same whether the sugar solution contained pesticides or not. Secondly, by looking at bumblebee feeding behaviour, Parkinson et al. found that bees offered both pure and pesticide-laced sugar solutions would still drink the pesticide solution, even when it was toxic enough to make them very ill or kill them. This was the case regardless of which pesticide was used. The experiments showed that bumblebees cannot use their sense of taste to avoid drinking pesticide-laced nectar, which is an important finding for policymakers making decisions about the use of pesticides on agricultural crops. It is possible that bees simply have a poor sense of bitter taste. However, in the future, these methods could be used to identify a compound that tastes bad to bees. Including such a compound in pesticides, could deter bees from feeding on pesticide-treated crops that do not require pollination, and help to restore their declining populations.

Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial.

Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed.

Complications of TAVR From an Anesthesia Perspective.

Description Transcatheter aortic valve replacement (TAVR) has become the predominant technique for aortic valve replacement in the United States. Initially approved for high surgical risk patients, TAVR is now approved for most patients requiring valve therapy, including younger, lower-risk patients. The procedure is ideally performed in a hybrid operating room equipped with fluoroscopic equipment and transesophageal echocardiogram (TEE) imaging that can be viewed simultaneously by the operating team. The operating room should also be equipped to allow initiation of cardiopulmonary bypass, if necessary. Cardiac anesthesia teams are often involved with the management of these patients. This mini-review is designed to summarize potential complications that anesthesiologists may contend with during TAVR.

Watchman Device Dislodgement Creating a Left Ventricular Outflow Tract Obstruction Requiring Emergency Cardiopulmonary Bypass.

Left atrial appendage (LAA) occlusion device implantation is becoming a more common alternative for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF) who are not able to tolerate long-term anticoagulation. Studies suggest the procedure has a 98.5% successful deployment rate (Boersma et al., 2016). We present a case where a rare but known complication involving dislodgement and migration of an implanted Watchman LAA occlusion device led to functional stenosis of the aortic valve creating a left ventricular outflow tract (LVOT) obstruction necessitating emergency cardiopulmonary bypass in the electrophysiology lab to safely retrieve the device.

The Factor Structure and Gender Invariance of ADHD Symptoms in College Students.

Previous studies examining the factor structure of attention-deficit/hyperactivity disorder (ADHD) symptoms in adults using self-report measures have shown mixed results, supporting two-, three-, and bifactor solutions. The current study further investigated the structure of ADHD symptoms in adults using the Current Symptoms Scale and rigorous model evaluation in a sample of 892 college students. Confirmatory factor analysis was used to analyze and compare five-factor structures; a single-factor model, a two-factor model, a three-factor model, and two bifactor models. A single-factor model with correlated residuals best fit the data. Factor correlations with nearly all related constructs (i.e., symptoms of oppositional defiant disorder, depression, impairment, previous ADHD diagnosis, grades, and substance use) were significant in the expected directions and the model was invariant across gender. These findings contribute to a growing body of work suggesting a unidimensional factor may best represent ADHD symptoms in adults. Implications are discussed.