PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy

Mitochondrial fission is essential for the degradation of damaged mitochondria. It is currently unknown how the dynamin-related protein 1 (DRP1)-associated fission machinery is selectively targeted to segregate damaged mitochondria. We show that PTEN-induced putative kinase (PINK1) serves as a pro-fission signal, independently of Parkin. Normally, the scaffold protein AKAP1 recruits protein kinase A (PKA) to the outer mitochondrial membrane to phospho-inhibit DRP1. We reveal that after damage, PINK1 triggers PKA displacement from A-kinase anchoring protein 1. By ejecting PKA, PINK1 ensures the requisite fission of damaged mitochondria for organelle degradation. We propose that PINK1 functions as a master mitophagy regulator by activating Parkin and DRP1 in response to damage. We confirm that PINK1 mutations causing Parkinson disease interfere with the orchestration of selective fission and mitophagy by PINK1

A Moment in These Times

This poster presentation Collects short essays by fall 2020 Effective Composition students. The authors share small moments they have experienced during the pandemic. This collection serves as a time capsule so that, years from now, others can understand what everyday life was like during Covid-19

Predicting water allocation trade prices using a hybrid Artificial Neural Network-Bayesian modelling approach

This paper proposes an integrated (hybrid) Artificial Neural Network-Bayesian (ANN-B) modelling approach to improve the accuracy of predicting seasonal water allocation prices in Australia’s Murry Irrigation Area, which is part of one of the world’s largest interconnected water markets. Three models (basic, intermediate and full), accommodating different levels of data availability, were considered. Data were analyzed using both ANN and hybrid ANN-B approaches. Using the ANN-B modelling approach, which can simulate complex and non-linear processes, water allocation prices were predicted with a high degree of accuracy (RBASIC = 0.93, RINTER. = 0.96 and RFULL = 0.99); this was a higher level of accuracy than realized using ANN. This approach can potentially be integrated with online data systems to predict water allocation prices, enable better water allocation trade decisions, and improve the productivity and profitability of irrigated agriculture

Distribution of amantadine-resistant H5N1 avian influenza variants in Asia

We examined the distribution of genetic mutations associated with resistance to the M2 ion channel-blocking adamantane derivatives, amantadine and rimantadine, among H5N1 viruses isolated in Vietnam, Thailand, Cambodia, Indonesia, Hong Kong, and China. More than 95% of the viruses isolated in Vietnam and Thailand contained resistance mutations, but resistant mutants were less commonly isolated in Indonesia (6.3% of isolates) and China (8.9% of isolates), where human infection was recently reported. The dual mutation motif Leu26Ile-Ser31Asn (leucine→isoleucine at aa 26 and serine→asparagine at aa 31) was found almost exclusively in all resistant isolates from Vietnam, Thailand, and Cambodia, suggesting the biological selection of these mutations. © 2006 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Infection control and the prevalence, management and outcomes of SARS-CoV-2 infections in mental health wards in London, UK: lessons learned from wave 1 to wave 2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has high morbidity and mortality in older adults and people with dementia. Infection control and prevention measures potentially reduce transmission within hospitals. AIMS: We aimed to replicate our earlier study of London mental health in-patients to examine changes in clinical guidance and practice and associated COVID-19 prevalence and outcomes between COVID-19 waves 1 and 2 (1 March to 30 April 2020 and 14 December 2020 to 15 February 2021). METHOD: We collected the 2 month period prevalence of wave 2 of COVID-19 in older (≥65 years) in-patients and those with dementia, as well as patients' characteristics, management and outcomes, including vaccinations. We compared these results with those of our wave 1 study. RESULTS: Sites reported that routine testing and personal protective equipment were available, and routine patient isolation on admission occurred throughout wave 2. COVID-19 infection occurred in 91/358 (25%; 95% CI 21-30%) v. 131/344, (38%; 95% CI 33-43%) P < 0.001 in wave 1. Hospitals identified more asymptomatic carriers (26/91; 29% v. 16/130; 12%) and fewer deaths (12/91; 13% v. 19/131; 15%; odds ratio = 0.92; 0.37-1.81) compared with wave 1. The patient vaccination uptake rate was 49/58 (85%). CONCLUSIONS: Patients in psychiatric in-patient settings, mostly admitted without known SARS-CoV-2 infection, had a high risk of infection compared with people in the community but lower than that during wave 1. Availability of infection control measures in line with a policy of parity of esteem between mental and physical health appears to have lowered within-hospital COVID-19 infections and deaths. Cautious management of vulnerable patient groups including mental health patients may reduce the future impact of COVID-19

Phasic Phosphorylation of Caldesmon and ERK 1/2 during Contractions in Human Myometrium

Human myometrium develops phasic contractions during labor. Phosphorylation of caldesmon (h-CaD) and extracellular signal-regulated kinase 1/2 (ERK 1/2) has been implicated in development of these contractions, however the phospho-regulation of these proteins is yet to be examined during periods of both contraction and relaxation. We hypothesized that protein phosphorylation events are implicated in the phasic nature of myometrial contractions, and aimed to examine h-CaD and ERK 1/2 phosphorylation in myometrium snap frozen at specific stages, including; (1) prior to onset of contractions, (2) at peak contraction and (3) during relaxation. We aimed to compare h-CaD and ERK 1/2 phosphorylation in vitro against results from in vivo studies that compared not-in-labor (NIL) and laboring (L) myometrium. Comparison of NIL (n = 8) and L (n = 8) myometrium revealed a 2-fold increase in h-CaD phosphorylation (ser-789; P = 0.012) during onset of labor in vivo, and was associated with significantly up-regulated ERK2 expression (P = 0.022), however no change in ERK2 phosphorylation was observed (P = 0.475). During in vitro studies (n = 5), transition from non-contracting tissue to tissue at peak contraction was associated with increased phosphorylation of both h-CaD and ERK 1/2. Furthermore, tissue preserved at relaxation phase exhibited diminished levels of h-CaD and ERK 1/2 phosphorylation compared to tissue preserved at peak contraction, thereby producing a phasic phosphorylation profile for h-CaD and ERK 1/2. h-CaD and ERK 1/2 are phosphorylated during myometrial contractions, however their phospho-regulation is dynamic, in that h-CaD and ERK 1/2 are phosphorylated and dephosphorylated in phase with contraction and relaxation respectively. Comparisons of NIL and L tissue are at risk of failing to detect these changes, as L samples are not necessarily preserved in the midst of an active contraction

Gender-Related Differences in the Prevalence of Cardiovascular Disease Risk Factors and their Correlates in Urban Tanzania.

\ud Urban areas in Africa suffer a serious problem with dual burden of infectious diseases and emerging chronic diseases such as cardiovascular diseases (CVD) and diabetes which pose a serious threat to population health and health care resources. However in East Africa, there is limited literature in this research area. The objective of this study was to examine the prevalence of cardiovascular disease risk factors and their correlates among adults in Temeke, Dar es Salaam, Tanzania. Results of this study will help inform future research and potential preventive and therapeutic interventions against such chronic diseases. The study design was a cross sectional epidemiological study. A total of 209 participants aged between 44 and 66 years were included in the study. A structured questionnaire was used to evaluate socioeconomic and lifestyle characteristics. Blood samples were collected and analyzed to measure lipid profile and fasting glucose levels. Cardiovascular risk factors were defined using World Health Organization criteria. The age-adjusted prevalence of obesity (BMI > or = 30) was 13% and 35%, among men and women (p = 0.0003), respectively. The prevalence of abdominal obesity was 11% and 58% (p < 0.0001), and high WHR (men: >0.9, women: >0.85) was 51% and 73% (p = 0.002) for men and women respectively. Women had 4.3 times greater odds of obesity (95% CI: 1.9-10.1), 14.2-fold increased odds for abdominal adiposity (95% CI: 5.8-34.6), and 2.8 times greater odds of high waist-hip-ratio (95% CI: 1.4-5.7), compared to men. Women had more than three-fold greater odds of having metabolic syndrome (p = 0.001) compared to male counterparts, including abdominal obesity, low HDL-cholesterol, and high fasting blood glucose components. In contrast, female participants had 50% lower odds of having hypertension, compared to men (95%CI: 0.3-1.0). Among men, BMI and waist circumference were significantly correlated with blood pressure, triglycerides, total, LDL-, and HDL-cholesterol (BMI only), and fasting glucose; in contrast, only blood pressure was positively associated with BMI and waist circumference in women. The prevalence of CVD risk factors was high in this population, particularly among women. Health promotion, primary prevention, and health screening strategies are needed to reduce the burden of cardiovascular disease in Tanzania.\u

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

Dietary species richness as a measure of food biodiversity and nutritional quality of diets

Biodiversity is key for human and environmental health. Available dietary and ecological indicators are not designed to assess the intricate relationship between food biodiversity and diet quality. We applied biodiversity indicators to dietary intake data from and assessed associations with diet quality of women and young children. Data from 24-hour diet recalls (55% in the wet season) of n = 6,226 participants (34% women) in rural areas from seven lowand middle-income countries were analyzed. Mean adequacies of vitamin A, vitamin C, folate, calcium, iron, and zinc and diet diversity score (DDS) were used to assess diet quality. Associations of biodiversity indicators with nutrient adequacy were quantified using multilevel models, receiver operating characteristic curves, and test sensitivity and specificity. A total of 234 different species were consumed, of which < 30% were consumed in more than one country. Nine specieswere consumed in all countries and provided, on average, 61% of total energy intake and a significant contribution of micronutrients in the wet season. Compared with Simpson's index of diversity and functional diversity, species richness (SR) showed stronger associations and better diagnostic properties with micronutrient adequacy. For every additional species consumed, dietary nutrient adequacy increased by 0.03 (P < 0.001). Diets with higher nutrient adequacy were mostly obtained when both SR and DDS were maximal. Adding SR to the minimum cutoff for minimum diet diversity improved the ability to detect diets with higher micronutrient adequacy in women but not in children. Dietary SR is recommended as the most appropriate measure of food biodiversity in diets