βcyto-Actin and γcyto-actin are ubiquitous proteins thought to be essential building blocks of the cytoskeleton in all non-muscle cells. Despite this widely held supposition, we show that γcyto-actin ...null mice (Actg1⁻/⁻) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of βcyto-actin. The surprising viability and normal hearing of young Actg1⁻/⁻ mice means that βcyto-actin can likely build all essential non-muscle actin-based cytoskeletal structures including mechanosensory stereocilia of hair cells that are necessary for hearing. Although γcyto-actin-deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, γcyto-actin localizes along the length of stereocilia but re-distributes to sites of F-actin core disruptions resulting from animal exposure to damaging noise. In Actg1⁻/⁻ stereocilia similar disruptions are observed even without noise exposure. We conclude that γcyto-actin is required for reinforcement and long-term stability of F-actin-based structures but is not an essential building block of the developing cytoskeleton.
Enteric methane (CH4) production from cattle contributes to global greenhouse gas emissions. Measurement of enteric CH4 is complex, expensive, and impractical at large scales; therefore, models are ...commonly used to predict CH4 production. However, building robust prediction models requires extensive data from animals under different management systems worldwide. The objectives of this study were to (1) collate a global database of enteric CH4 production from individual lactating dairy cattle; (2) determine the availability of key variables for predicting enteric CH4 production (g/day per cow), yield g/kg dry matter intake (DMI), and intensity (g/kg energy corrected milk) and their respective relationships; (3) develop intercontinental and regional models and cross‐validate their performance; and (4) assess the trade‐off between availability of on‐farm inputs and CH4 prediction accuracy. The intercontinental database covered Europe (EU), the United States (US), and Australia (AU). A sequential approach was taken by incrementally adding key variables to develop models with increasing complexity. Methane emissions were predicted by fitting linear mixed models. Within model categories, an intercontinental model with the most available independent variables performed best with root mean square prediction error (RMSPE) as a percentage of mean observed value of 16.6%, 14.7%, and 19.8% for intercontinental, EU, and United States regions, respectively. Less complex models requiring only DMI had predictive ability comparable to complex models. Enteric CH4 production, yield, and intensity prediction models developed on an intercontinental basis had similar performance across regions, however, intercepts and slopes were different with implications for prediction. Revised CH4 emission conversion factors for specific regions are required to improve CH4 production estimates in national inventories. In conclusion, information on DMI is required for good prediction, and other factors such as dietary neutral detergent fiber (NDF) concentration, improve the prediction. For enteric CH4 yield and intensity prediction, information on milk yield and composition is required for better estimation.
Illustration of predicted vs. observed value plots based on global CH4 production (g/day per cow) prediction equations at different complexity levels from global (n = 2, 652) data. A total of 11 models were developed and their performance is shown above. The models were based on (a) gross energy intake, (b) dry matter intake (DMI), (c) neutral detergent fiber, (d) ether extract, (e) dietary variables, (f) dietary composition, (g) milk yield, (h) energy corrected milk, (i) milk performance, (j) animal related variables, and (k) animal related variables without DMI. The panel (l) shows performance of the Intergovernmental Panel on Climate Change (IPCC) Tier 2 (2006) model for lactating dairy cows. It is interesting to see that the IPCC model, which is currently used widely for national inventories did not perform well. Relatively simple models (panels a and b) that only require feed intake variable could be used instead of the current IPCC models globally.
•Evaluating implementation informs understanding of public health impact.•Adopters perceive that the self-management program improves mental health outcomes.•Adopters benefit from program champions, ...strong partnerships, and sustained funding.•Continued refinement of implementation support will extend public health impact.
Project UPLIFT is an evidence-based epilepsy self-management program shown to prevent and treat depression through an 8-session, group telehealth intervention. Since 2012, the program has been disseminated by training community-based providers to deliver UPLIFT to people with epilepsy (PWE). Limited research has described the adoption, implementation, and practice-based maintenance of self-management programs like UPLIFT. We sought to gain a better understanding of this process from trained program adopters.
A cross-sectional evaluation of adoption and implementation experiences was conducted. An online survey with closed- and open-ended questions was distributed to 120 UPLIFT program adopters to collect information about reasons for being trained and experiences implementing the program. Survey items were developed based on the RE-AIM model to assess program reach, effectiveness, adoption, implementation, and maintenance. For closed-ended responses, frequencies and cross-tabs were calculated. Open-ended responses were reviewed and grouped by theme.
41 respondents completed the survey (34% response rate). Respondents were from a variety of organizations including clinical (39%, n = 16), educational/research (17%, n = 7), and Epilepsy Foundation affiliates/chapters (12%, n = 5), among others. The most frequently endorsed reason for training in UPLIFT was an interest in supporting PWE (73%, n = 30). Most respondents rated delivering UPLIFT as very important (49%, n = 20) or important (32%, n = 13) to the organization. Sixty-one percent (n = 25) of respondents reported implementing (implementors) UPLIFT. Of those who had not yet implemented UPLIFT, 50% (n = 8) planned on implementing it at some point. Among program implementors, the most frequently reported implementation facilitators included participant interest (68%, n = 17), training (68%, n = 17), and organizational support (64%, n = 16). Program implementors indicated having program champions (80%, n = 20). The most frequently reported implementation challenge reported was recruitment (72%, n = 18). In open-ended responses, funding was a key theme that would facilitate continued implementation, but 48% (n = 12) responded that did not have access to resources and/or funding to help continue offering UPLIFT. Developing partnerships was recommended to improve the reach and maintenance of the program. Despite challenges, implementors agreed (44%, n = 11) or strongly agreed (36%, n = 9) that UPLIFT was effective in addressing mental health problems among program participants, and 76% (n = 19) plan on continuing to offer UPLIFT.
Implementation surveys increase understanding of program adoption and impact for dissemination trainees. Implementation benefits from program champions, strong partnerships, and sustained funding. Continued refinement of implementation support, such as developing a sustained referral system, maintaining relationships with trainees, supporting evaluation activities, and exploring opportunities for program updates to further enhance adoption, implementation, and maintenance.
The aim of this study was to examine the effect of plane of nutrition between 8 and 13 months of age on reproductive performance of heifers of early (EM; n = 154) or late (LM; n = 155) maturing beef ...breeds and with dairy (dairy-bred, n = 154) or beef (beef-bred, n = 155) dams. Heifers were fed to have an average daily gain (ADG) of 0.50 kg (MOD) or >1.00 kg (HI) for a 141- and 150-day indoor winter period. Subsequently, heifers grazed pasture, and a 12 week breeding programme was implemented. Compared to heifers fed the MOD intake diet, heifers fed the HI intake diet were younger (P < 0.001) and had greater bodyweights (P < 0.001) at puberty but did not have a greater 6- (P = 0.41) or 12- (P = 0.32) week pregnancy rate. Dairy-bred heifers were of a similar age (P = 0.55) but had a lesser bodyweight (P < 0.001) at puberty and had a greater 6- (P < 0.05) and 12- (P < 0.01) week pregnancy rate compared to beef-bred heifers. Compared to LM heifers, EM heifers were younger (P < 0.001), had a lesser bodyweight (P < 0.01) at puberty and had a greater 6-week (P < 0.01) but not 12-week (P = 0.96) pregnancy rate. Enhanced nutrition resulted in a younger age at puberty but had no effect on 12-week pregnancy rate. Dam but not sire breed affected 12-week pregnancy rate.
In extending work on early life antecedents of parenting, we investigate associations between childhood family history of disadvantage, adolescent socioemotional wellbeing, and age at first ...parenthood and subsequent parenting behaviour.
Parent-child interactions were recorded when participants in the longitudinal Dunedin Multidisciplinary Health and Development Study (New Zealand) had a three-year-old child. Data were available for 358 mothers and 321 fathers, aged between 17.7 and 41.5 at the time of their child's birth. Associations between parenting and antecedent data on socioeconomic disadvantage, adolescent wellbeing and mental health, as well as current adult mental health and age at parenting, were tested for using structural equation modelling.
Family disadvantage in childhood and lower adolescent wellbeing was associated with less positive future parenting, but only adult (not adolescent) anxiety/depression symptoms were directly associated with parenting behaviour. Childhood family disadvantage was associated with further disadvantage across the life course that included less positive parenting of the next generation. In contrast, socioemotional wellbeing during adolescence and later age of onset of parenting were associated with more positive parenting.
Reducing childhood disadvantage and improving socioemotional wellbeing during childhood and adolescence is likely to have intergenerational benefits through better parenting of the next generation.
Arcanobacterium haemolyticum is a Gram-positive, β-hemolytic emerging human pathogen that is classified into smooth or rough biotypes. This bacterial species is also a rare pathogen of animals. ...Smooth biotypes possess smooth colony edges, are moderate to strong in β-hemolysis, and predominately cause wound infections. In contrast, rough biotypes possess rough and irregular colony edges, have weak to no β-hemolytic activity, and predominately cause pharyngitis. Using horse erythrocytes we confirmed that smooth isolates are generally more hemolytic than rough isolates. A hemolysin from A. haemolyticum, arcanolysin (aln/ALN), was recently discovered and is a member of the cholesterol-dependent cytolysin (CDC) family. PCR amplification of aln from all 36 smooth A. haemolyticum isolates yielded the expected 2.0 kb product. While 21 rough isolates yielded the 2.0 kb product, 16 isolates had a 3.2 kb product. The extra 1.2 kb segment was 99% identical to IS911 (insertion sequence) from Corynebacterium diphtheriae. PCR amplification and sequence analysis of the upstream region of aln revealed ~40 nucleotide polymorphisms among 73 clinical isolates from Finland, Denmark, Germany and United States (Nebraska). Remarkably, multi-sequence alignments of the aln upstream region demonstrated that ~90% of the isolates phylogenetically clustered as either smooths or roughs. Differential restriction enzyme analysis of the aln upstream region also demonstrated that the aln upstream region of most (~75%) smooth isolates was cleaved with ClaI while this region in most (~86%) rough isolates was cleaved with XcmI. We conclude that the aln upstream region can be used to genetically distinguish between smooth and rough biotypes of this important emerging pathogen.
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency in AIF is known to result in defective oxidative ...phosphorylation (OXPHOS), via loss of complex I activity and assembly in other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that a decrease in AIF would result in chronic kidney disease (CKD). Here, we report that partial knockdown of Aif in mice recapitulates many features of CKD, in association with a compensatory increase in the mitochondrial ATP pool via a shift toward mitochondrial fusion, excess mitochondrial reactive oxygen species production, and Nox4 upregulation. However, despite a 50% lower AIF protein content in the kidney cortex, there was no loss of complex I activity or assembly. When diabetes was superimposed onto Aif knockdown, there were extensive changes in mitochondrial function and networking, which augmented the renal lesion. Studies in patients with diabetic nephropathy showed a decrease in AIF within the renal tubular compartment and lower AIFM1 renal cortical gene expression, which correlated with declining glomerular filtration rate. Lentiviral overexpression of Aif1m rescued glucose-induced disruption of mitochondrial respiration in human primary proximal tubule cells. These studies demonstrate that AIF deficiency is a risk factor for the development of diabetic kidney disease.
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