Path-integral Monte-Carlo simulations for electronic dynamics on molecular chains: I. Sequential hopping and super exchange

An improved real-time quantum Monte Carlo procedure is presented and applied to describe the electronic transfer dynamics along molecular chains. The model consists of discrete electronic sites coupled to a thermal environment which is integrated out exactly within the path integral formulation. The approach is numerically exact and its results reduce to known analytical findings (Marcus theory, golden rule) in proper limits. Special attention is paid to the role of superexchange and sequential hopping at lower temperatures in symmetric donor-bridge-acceptor systems. In contrast to previous approximate studies, superexchange turns out to play a significant role only for extremely high lying bridges where the transfer is basically frozen or for extremely low temperatures where for weaker dissipation a description in terms of rate constants is no longer feasible. For bridges with increasing length an algebraic decrease of the yield is found for short as well as for longer bridges. The approach can be extended to electronic systems with more complicated topologies including impurities and in presence of external time dependent forces.Comment: 14 pages, 9 figures submitted to the Journal of Chemical Physic

Years of life lost attributable to air pollution in Switzerland: dynamic exposure-response model

Background There is debate on how the effect of air pollution should be assessed. We propose an approach to estimate its impact on adult and infant mortality that integrates data from long-term epidemiological studies and studies of interventions to reduce pollution. We use the method to estimate the number of years of life lost (YLLs) attributable to air pollution during 1 year in Switzerland. Methods A dynamic exposure-response model was implemented, which uses an exponential function (exp−kt) to model the change in mortality after cessation of air pollution. The model was populated with relative risk estimates and estimates of time constant k from the literature. Air pollution exposure in Switzerland was modelled using data from emission inventories. YLLs attributable to air pollution were calculated by taking the difference between observed survival probabilities in Switzerland in 2000 and modified survival probabilities, assuming no air pollution during the year 2000. Results Meta-analyses of three studies of adult mortality and five studies of infant mortality gave relative risks of 1.059 (95% confidence interval (CI) 1.031-1.088) and 1.056 (95% CI 1.026-1.088) per 10 μg/m3 increase in PM10 concentration. Time constants k derived from two studies of the effects of the closing down of a steel mill in the Utah Valley and of the coal ban in Dublin were 0.88 and 0.11. Assuming a time constant k of 0.5 resulted in 42 400 (95% CI 22 600-63 600) YLLs, with 4.0% being ascribed to infant deaths. A total of 39% of the effect occurred in the same year and 80% within 5 years. The estimated number of YLLs was little affected by the choice of the time constant. Conclusions In contrast to traditional steady-state models the dynamic model allows changes in mortality following short-term increases or decreases in air pollution levels to be quantified. This type of information is of obvious interest to policy maker

Pcdh11x controls target specification of mossy fiber sprouting

Circuit formation is a defining characteristic of the developing brain. However, multiple lines of evidence suggest that circuit formation can also take place in adults, the mechanisms of which remain poorly understood. Here, we investigated the epilepsy-associated mossy fiber (MF) sprouting in the adult hippocampus and asked which cell surface molecules define its target specificity. Using single-cell RNAseq data, we found lack and expression of Pcdh11x in non-sprouting and sprouting neurons respectively. Subsequently, we used CRISPR/Cas9 genome editing to disrupt the Pcdh11x gene and characterized its consequences on sprouting. Although MF sprouting still developed, its target specificity was altered. New synapses were frequently formed on granule cell somata in addition to dendrites. Our findings shed light onto a key molecular determinant of target specificity in MF sprouting and contribute to understanding the molecular mechanism of adult brain rewiring

Editorial: Treatment of psychopathological and neurocognitive disorders in genetic syndromes: In need of multidisciplinary phenotyping and treatment design

Similar to the figures in a coloring book, which are set at the moment of printing, the framework for a new person is set the moment a human egg is fertilized. The genes that we are born with contribute to our vulnerability for a wide range of possible phenotypes, but which of these phenotypes will subsequently develop, is greatly influenced by contextual factors from the physical world and social environments we live in, and our lifestyles (e.g., nutrition and exercise). When looking at neurodevelopmental disorders with known genetic underpinnings, understanding the interaction between genes and context is vital for identification and support strategies. A fruitful way to achieve this would be through involvement of multiple disciplines, both in their additive capacities and in their ability to proceed from shared well-informed theoretical frameworks and clinical practice approaches. The inclusion of somatic, neuronal, cognitive and behavioral aspects, of rare genetic syndromes, and acquiring a more detailed understanding of altered brain development, new and fundamental insights can be gained, which can guide diagnosis and treatment decisions. In addition, a tailored approach to assessment and monitoring is necessary to understand how the contextual factors influence the (neuro)development of the individual patient under investigation. In the present Research Topic, nine studies have been brought together that illustrate ways to better assess the challenges that come with genetic neurodevelopmental disorders, to ameliorate symptoms, and in general to improve quality of life, not only of these individuals but also of their family members and other caregivers

Food insecurity increases energetic efficiency, not food consumption: an exploratory study in European starlings

Food insecurity—defined as limited or unpredictable access to nutritionally adequate food—is associated with higher body mass in humans and birds. It is widely assumed that food insecurity-induced fattening is caused by increased food consumption, but there is little evidence supporting this in any species. We developed a novel technology for measuring foraging, food intake and body mass in small groups of aviary-housed European starlings (Sturnus vulgaris). Across four exploratory experiments, we demonstrate that birds responded to 1–2 weeks of food insecurity by increasing their body mass despite eating less. Food-insecure birds therefore increased their energetic efficiency, calculated as the body mass maintained per unit of food consumed. Mass gain was greater in birds that were lighter at baseline and in birds that faced greater competition for access to food. Whilst there was variation between experiments in mass gain and food consumption under food insecurity, energetic efficiency always increased. Bomb calorimetry of guano showed reduced energy density under food insecurity, suggesting that the energy assimilated from food increased. Behavioural observations of roosting showed inconsistent evidence for reduced physical activity under food insecurity. Increased energetic efficiency continued for 1–2 weeks after food security was reinstated, indicating an asymmetry in the speed of the response to food insecurity and the recovery from it. Future work to understand the mechanisms underlying food insecurity-induced mass gain should focus on the biological changes mediating increased energetic efficiency rather than increased energy consumption

Metabolic syndrome among treatment-naïve people living with and without HIV in Zambia and Zimbabwe: a cross-sectional analysis.

INTRODUCTION Chronic viral replication has been linked to an increased risk of cardiovascular and metabolic diseases in people living with HIV (PLWH), but few studies have evaluated this association in Southern Africa. We explored the determinants of metabolic syndrome (MetS) among treatment-naïve adults living with and without HIV in Southern Africa. METHODS Treatment-naïve PLWH and people living without HIV (PLWOH) ≥30 years were consecutively enrolled from primary care clinics in Zambia and Zimbabwe. PLWOH were seronegative partners or persons presenting for HIV testing. We defined MetS as the presence of central obesity plus any two of the following: raised blood pressure, impaired fasting glucose, reduced high-density lipoprotein cholesterol and raised triglycerides, as defined by the International Diabetes Federation. We used logistic regression to determine factors associated with MetS. RESULTS Between August 2019 and March 2022, we screened 1285 adults and enrolled 420 (47%) PLWH and 481 (53%) PLWOH. The median age was similar between PLWH and PLWOH (40 vs. 38 years, p < 0.24). In PLWH, the median CD4+ count was 228 cells/mm3 (IQR 108-412) and the viral load was 24,114 copies/ml (IQR 277-214,271). Central obesity was present in 365/523 (70%) females and 57/378 males (15%). MetS was diagnosed in 172/901 (19%, 95% confidence interval [CI] 17-22%), and prevalence was higher among females than males (27% vs. 9%). In multivariable analyses, HIV status was not associated with MetS (adjusted odds ratio [aOR] 1.05, 95% CI 0.74-1.51). Risk factors for MetS included age older than 50 years (aOR 2.31, 95% CI 1.49-3.59), female sex (aOR 3.47, 95% CI 2.15-5.60), highest income (aOR 2.19, 95% CI 1.39-3.44) and less than World Health Organization recommended weekly physical activity (aOR 3.35, 95% CI 1.41-7.96). CONCLUSIONS We report a high prevalence of MetS and central obesity among females in urban Zambia and Zimbabwe. Lifestyle factors and older age appear to be the strongest predictors of MetS in our population, with no evident difference in MetS prevalence between treatment-naïve PLWH and PLWOH

The physical oceanography of the transport of floating marine debris

Marine plastic debris floating on the ocean surface is a major environmental problem. However, its distribution in the ocean is poorly mapped, and most of the plastic waste estimated to have entered the ocean from land is unaccounted for. Better understanding of how plastic debris is transported from coastal and marine sources is crucial to quantify and close the global inventory of marine plastics, which in turn represents critical information for mitigation or policy strategies. At the same time, plastic is a unique tracer that provides an opportunity to learn more about the physics and dynamics of our ocean across multiple scales, from the Ekman convergence in basin-scale gyres to individual waves in the surfzone. In this review, we comprehensively discuss what is known about the different processes that govern the transport of floating marine plastic debris in both the open ocean and the coastal zones, based on the published literature and referring to insights from neighbouring fields such as oil spill dispersion, marine safety recovery, plankton connectivity, and others. We discuss how measurements of marine plastics (both in situ and in the laboratory), remote sensing, and numerical simulations can elucidate these processes and their interactions across spatio-temporal scales

A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?

Background: The minimal critical region in 2q23.1 deletion syndrome comprises one gene only, that is, the methyl-CpG-binding domain protein 5 (MBD5) gene. Since the phenotypes of patients with deletions, duplications or pathogenic variants of MBD5 show considerable overlap, the term MBD5-associated neurodevelopmental disorder (MAND) was proposed. These syndromes are characterized by intellectual disability, seizures of any kind and symptoms from the autism spectrum. In a very limited number of patients, MAND may be associated with regression starting either at early infancy or at midlife. Methods: The present paper describes a severely intellectually disabled autistic female with therapy resistant complex partial epilepsy starting at her 16the with gradual cognitive and behavioral regression towards her sixth decade. Results: Cognitive and behavioral regression occurred towards the patient's sixth decade. Exome sequencing disclosed a novel heterozygous pathogenic frameshift mutation of MBD5 that was considered to be causative for the combination of intellectual disability, treatment-resistant epilepsy and autism. Conclusion: The presented patient is the second with a pathogenic MBD5 mutation in whom the course of disease is suggestive of early onset dementia starting in her fifth decade. These findings stress the importance of exome sequencing, also in elderly intellectually disabled patients, particularly in those with autism

Tuberculosis in antiretroviral treatment programs in lower income countries: availability and use of diagnostics and screening.

In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries