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The relationship between perceived social support and continuous positive airway pressure remains understudied among individuals with obstructive sleep apnea. The aim of this prospective cohort study was to determine if baseline perceived social support and subtypes predict regular continuous positive airway pressure use after 1month of therapy.

The future of computing requires heterogeneous integration, including the recent adoption of chiplet methodology, where high-speed cross-chip interconnects and packaging are critical for the overall system performance. As an example of advanced packaging, a high-density interconnect (HDI) printed circuit board (PCB) has been widely used in complex electronics ranging from cell phones to computing servers. A modern HDI PCB may have over 20 layers, each with its unique material properties and geometrical dimensions, i.e., stack-up, to meet various design constraints and performance requirements. Stack-up design is usually done manually in the industry, where experienced designers may devote many hours adjusting the physical dimensions and materials in order to meet the desired specifications. This process, however, is time-consuming, tedious, and suboptimal, largely depending on the designer’s expertise. In this article, we propose to automate the stack-up design with a new framework, ISOP+, using machine learning (ML) for inverse stack-up optimization for advanced package design with adaptive weight adjustment and multilevel optimization. Given a target design specification, ISOP+ automatically searches for ideal stack-up design parameters while optimizing performance. A novel ML-assisted hyperparameter optimization method is developed to make the search efficient and reliable. Experimental results demonstrate that ISOP+ is better in figure-of-merit (FoM) than conventional simulated annealing and Bayesian optimization algorithms, with all our design targets met with a shorter runtime. We also compare our fully automated ISOP+ with expert designers in the industry and achieve very promising results, with orders of magnitude reduction of turn-around time.

En banc hearings and re-hearings of cases and issues in Florida's district courts of appeal are limited to two circumstances: 1) when the case or issue is of exceptional importance; [...]

Comorbid insomnia and sleep apnea (COMISA) is a highly prevalent and debilitating condition that is more difficult to treat compared with insomnia alone or sleep apnea alone. Approximately 30% to 50% of sleep clinic patients with sleep apnea report comorbid insomnia symptoms. Comorbid insomnia is associated with lower adherence to positive airway pressure therapy for obstructive sleep apnea. Management approaches that include targeted treatments for both insomnia and sleep apnea lead to the best treatment outcomes for patients with COMISA. Therefore, sleep clinics should incorporate insomnia and COMISA management pathways including access to cognitive behavioral therapy for insomnia.

Isotopic enrichment factors are key to using stable isotope signatures in biogeochemical studies. However, these are typically determined in laboratory experiments and their applicability to environmental conditions is difficult to test. Here, we analyzed nitrogen stable isotope changes associated with nitrification in a coastal basin using weekly time‐series measurements of δ15N in particulate nitrogen, ammonium, nitrite, and nitrate. Two year‐long time series were selected as contrasting natural experiments in the ammonium‐rich, aphotic bottom water of Bedford Basin, Nova Scotia, Canada. In 2014, ammonia oxidation (AO) was associated with Thaumarchaeotaand nitrite concentrations remained low (< 0.5 μmol kg−1). In contrast, transient nitrite accumulation (~ 8 μmol kg−1) and a more rapid δ15NNH4increase in the fall of 2017 were likely caused by ammonia‐oxidizing bacteria, associated with higher AO rates and, possibly, stronger nitrogen‐isotope enrichment (15εAO). Estimates of 15εAO(21.8 ± 2.2‰, 24.1 ± 1.1‰) were derived empirically using Rayleigh models applied to field data from restricted periods during which the bottom waters approximated a closed system and influence on 15εAOfrom other processes was demonstrably insignificant. Using a numerical reactive‐transport model, we found that the best fit for the δ15N data was obtained with 15εAOvalues (18.9‰, 25.1‰) close to those determined by the Rayleigh models. The time series also revealed substantial (~ 7‰) 15N‐enrichment of the particulate nitrogen due to light‐independent assimilation of partially nitrified ammonium. Consistent with previous studies, these field‐based nitrogen isotope fractionation experiments suggest that the range of 15εAOvalues relevant for marine systems may be narrower than determined in laboratory studies.

We demonstrate a fast and easy-to-use three-dimensional printed microfluidic platform for mitochondria isolation from cell and tissue lysates based on inertial microfluidics. We present and quantify the quality of the isolated mitochondria by measuring the respiration rate under various conditions. We demonstrate that the technology produces vital mitochondria of equal quality to traditional, but more burdensome, differential centrifugation. We anticipate that the availability of improved tools for studies of bioenergetics to the broader biological community will enable these and other links to be explored in more meaningful ways, leading to further understanding of the links between energy, health, and disease.

Prenatal alcohol exposure (PAE) can produce deficits in a wide range of cognitive functions but is especially detrimental to behaviors requiring accurate spatial information processing. In open field environments, spatial behavior is organized such that animals establish “home bases” marked by long stops focused around one location. Progressions away from the home base are circuitous and slow, while progressions directed toward the home base are non‐circuitous and fast. The impact of PAE on the organization of open field behavior has not been experimentally investigated. In the present study, adult female and male rats with moderate PAE or saccharin exposure locomoted a circular high walled open field for 30 minutes under lighted conditions. The findings indicate that PAE and sex influence the organization of open field behavior. Consistent with previous literature, PAE rats exhibited greater locomotion in the open field. Novel findings from the current study indicate that PAE and sex also impact open field measures specific to spatial orientation. While all rats established a home base on the periphery of the open field, PAE rats, particularly males, exhibited significantly less clustered home base stopping with smaller changes in heading between stops. PAE also impaired progression measures specific to distance estimation, while sex alone impacted progression measures specific to direction estimation. These findings support the conclusion that adult male rats have an increased susceptibility to the effects of PAE on the organization of open field behavior. The current study is the first to examine the effects of moderate PAE on rat movement organization in the open field. Several measures of performance consistent with spatial disorientation were observed in the moderate PAE group. Additionally, adult male rats showed an increased susceptibility to the effects of moderate PAE. This behavioral analysis may provide a sensitive and reliable way to clinically detect FASD, allowing protective interventions to begin earlier in development.

Rats track self-, conspecific, and artificial odors to locate food. The orbital frontal cortex has been implicated in olfactory behavior, but whether it plays a role in a species-typical behavior, such as odor-guided navigation, has not been studied. Rats were trained to track 1 of 3 different odors deposited on a string. After rats were reliably tracking a scented string, they received a series of 2- and 3-odor discrimination tests. Next, all the rats received bilateral aspiration lesions of the orbital frontal cortex and experienced the same sequence of tasks. Rats learned to track and discriminate between different odors reliably. These results suggest that other areas of the brain mediate odor-guided navigation following damage to the orbital frontal cortex.

This article will examine Florida law concerning the recovery of attorneys' fees and costs from an estate for unsuccessfully offering a will for probate. The article will also offer practical [...]

Objective: Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder. Method: The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups). Results: The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or

Nonadherence with positive airway pressure (PAP) therapy impedes the effectiveness of treatment and increases risk of mortality. Disparities in PAP adherence as a function of socioeconomic status (SES) are not well understood. A literature search identified 16 original publications meeting inclusion criteria that described effects of SES factors on objective PAP adherence; 69% of these articles found evidence of lower adherence as a function of SES. This integrative review provides a structured summary of the findings, highlights factors that may contribute to disparities among adult PAP users, and identifies future directions to improve equity in the management of OSA.

Large-scale randomized trials of positive airway pressure (PAP) efficacy have been largely negative but PAP adherence was notably suboptimal across the trials. To address this limitation, evidence-based PAP adherence protocols embedded within the larger trial protocol are recommended. The complexity of such protocols depends on adequacy of resources, including funding and inclusion of behavioral scientist experts on the scientific team, and trial-specific considerations (eg, target population) and methods. Recommendations for optimizing PAP adherence in large-scale trials are set forth that address rigor and reproducibility.

Leber's hereditary optic neuropathy, a disease which often occurs in young men, causes bilateral loss of central vision. Visual deterioration is progressive, first in one eye, then the other, usually over a period of days to weeks. Recently it was shown that this condition is caused by a mutation of mitochondrial deoxyribonucleic acid (mtDNA). Mitochondria, small structures within the cytoplasm that function in cell metabolism, contain a source of DNA. MtDNA is inherited exclusively from the mother and represents a unique inheritance pattern. For visual loss to occur a substantial percent of mtDNA molecules must be mutant. Sporadic cases of Leber's hereditary optic neuropathy may occur in patients whose maternal ancestors have heteroplasmy (both mutant and normal molecules). It is difficult to explain why all people with predominantly mutant mtDNA molecules do not lose their vision. The importance of heteroplasmy in Leber's patients and the discovery that the proportion of normal and mutant cells can change rapidly underscore the need for mtDNA analysis in order to improve genetic counseling for these patients and their families. (Consumer Summary produced by Reliance Medical Information, Inc.)

Leber's hereditary optic neuropathy, which often occurs in young adults, causes bilateral loss of central vision. When this neuropathy occurs in families, it can be traced through the mother's line, which suggests that it is caused by mutation of mitochondrial deoxyribonucleic acid (mtDNA). Mitochondria, small structures within the cytoplasm that function in cell metabolism, contain a source of DNA. This mtDNA mutation has been confirmed in Leber's hereditary optic neuropathy, and provides a simple molecular diagnostic test for this disease. A substantial percent of molecules must be mutant for visual loss to occur. A patient demonstrating visual loss will have ancestors with heteroplasmy (both mutant and normal molecules). Since normal molecules reduce the impact of the mutant ones, identification and quantification of heteroplasmy is important. It was found that the proportion of normal and mutant cells varied greatly, not only between generations, but within different tissues from the same person. To determine the mitochondrial genotype (the particular gene configuration on the chromosome) of a patient or family, more than one family member must be tested and more than one type of tissue must be obtained from the individual being tested. (Consumer Summary produced by Reliance Medical Information, Inc.)

Variation in the mitochondrial DNA (mtDNA) sequence is common in certain tumours. Two classes of cancer mtDNA variants can be identified: de novo mutations that act as ‘inducers’ of carcinogenesis and functional variants that act as ‘adaptors’, permitting cancer cells to thrive in different environments. These mtDNA variants have three origins: inherited variants, which run in families, somatic mutations arising within each cell or individual, and variants that are also associated with ancient mtDNA lineages (haplogroups) and are thought to permit adaptation to changing tissue or geographic environments. In addition to mtDNA sequence variation, mtDNA copy number and perhaps transfer of mtDNA sequences into the nucleus can contribute to certain cancers. Strong functional relevance of mtDNA variation has been demonstrated in oncocytoma and prostate cancer, while mtDNA variation has been reported in multiple other cancer types. Alterations in nuclear DNA-encoded mitochondrial genes have confirmed the importance of mitochondrial metabolism in cancer, affecting mitochondrial reactive oxygen species production, redox state and mitochondrial intermediates that act as substrates for chromatin-modifying enzymes. Hence, subtle changes in the mitochondrial genotype can have profound effects on the nucleus, as well as carcinogenesis and cancer progression.

Clinical trial transparency is important for scientific research and for the good of the general public. Diversity of study samples by race/ethnicity, gender, and age is important to ensure that results are generalizable. Moreover, reporting results might also be necessary to engage racial/ethnic minorities in clinical research. The primary objective of this study was to describe the results of clinical studies conducted for obstructive sleep apnea (OSA) and insomnia, two of the most prevalent sleep disorders. The secondary objective was to identify which factors were associated with voluntarily reporting the results.

Mitochondrial homeostasis depends on mitophagy, the programmed degradation of mitochondria. Only a few proteins are known to participate in mitophagy. Here we develop a multidimensional CRISPR–Cas9 genetic screen, using multiple mitophagy reporter systems and pro-mitophagy triggers, and identify numerous components of parkin-dependent mitophagy1. Unexpectedly, we find that the adenine nucleotide translocator (ANT) complex is required for mitophagy in several cell types. Whereas pharmacological inhibition of ANT-mediated ADP/ATP exchange promotes mitophagy, genetic ablation of ANT paradoxically suppresses mitophagy. Notably, ANT promotes mitophagy independently of its nucleotide translocase catalytic activity. Instead, the ANT complex is required for inhibition of the presequence translocase TIM23, which leads to stabilization of PINK1, in response to bioenergetic collapse. ANT modulates TIM23 indirectly via interaction with TIM44, which regulates peptide import through TIM232. Mice that lack ANT1 show blunted mitophagy and consequent profound accumulation of aberrant mitochondria. Disease-causing human mutations in ANT1 abrogate binding to TIM44 and TIM23 and inhibit mitophagy. Together, our findings show that ANT is an essential and fundamental mediator of mitophagy in health and disease.

Mitochondria have emerged as a central factor in the pathogenesis and progression of heart failure, and other cardiovascular diseases, as well, but no therapies are available to treat mitochondrial dysfunction. The National Heart, Lung, and Blood Institute convened a group of leading experts in heart failure, cardiovascular diseases, and mitochondria research in August 2018. These experts reviewed the current state of science and identified key gaps and opportunities in basic, translational, and clinical research focusing on the potential of mitochondria-based therapeutic strategies in heart failure. The workshop provided short- and long-term recommendations for moving the field toward clinical strategies for the prevention and treatment of heart failure and cardiovascular diseases by using mitochondria-based approaches.

Fjords are representative marine ecosystems that play an important role in regulating coastal carbon cycling. As fingerprints of the dissolved organic matter (DOM) pool, fluorescent DOM (FDOM) is widely used to study the ocean carbon cycle. Here, we report on 1‐year of weekly observations of FDOM (from May 2018 to May 2019) in the Bedford Basin, a well‐studied northwestern Atlantic fjord. Results showed that differences in FDOM indices (biological index, fluorescence index, and humification indices) between the euphotic and aphotic layers changed during the investigation period, suggesting that classical definitions of these indices may not apply consistently. Spearman rank correlations showed that the surface FDOM was affected by physical and biological factors, while water mass renewal was the major control for the deeper layer. Humic‐like FDOM (FDOMH) changed following the Atlantic deep‐water intrusion, indicating that FDOMHmay be used to trace water mass movements in this region. FDOMHshows a significantly positive linear correlation with apparent oxygen utilization (AOU). Their slopes were higher than those from the open ocean, suggesting that the Bedford Basin is a hotspot of RDOM production. Hence, we proposed a possible carbon sequestration mechanism that fjords play as “RDOM producing hot spots” and that the produced RDOM is then transported to the open ocean via water mass movement and finally stored in the ocean for extended periods of time. The proposed biogeochemical processes may also occur, more generally, in the global coastal ocean. Fjords are representative marine systems and play an important role in regulating coastal carbon cycling; however, few high‐frequency long‐term time series observations of dissolved organic matter (DOM) have been reported to date. This study reports a 1‐year weekly observation of fluorescent DOM (FDOM) in the Bedford Basin, a 70‐m deep fjord located in Nova Scotia, Canada. The results suggested that FDOM indices are not reliable indicators as proposed originally, and the control factors of FDOM behaviors were different in the surface and bottom water, as well that humic‐like FDOM (FDOMH) have the potential to trace water mass movements. Significant positive linear relationships between apparent oxygen utilization and FDOMHwere observed in the aphotic zone, and their slopes were higher than those from the open ocean, suggesting that the Bedford Basin is a hotspot of RDOM production. Similar results are widely observed in dark marginal seas. Therefore, we propose a possible coastal carbon sequestration mechanism in which fjord systems (even coastal oceans) act as RDOM‐producing factories, and the produced RDOM is then transported to the open ocean via water mass movement and finally stored in the ocean at longer timescales. Weekly time series observations of fluorescent dissolved organic matter (FDOM) in the Bedford Basin are presentedFDOM signals trace deep seawater intrusionsFjords are potential hot spots of refractory dissolved organic matter (RDOM) production and serve as RDOM producing factories Weekly time series observations of fluorescent dissolved organic matter (FDOM) in the Bedford Basin are presented FDOM signals trace deep seawater intrusions Fjords are potential hot spots of refractory dissolved organic matter (RDOM) production and serve as RDOM producing factories

The mitochondrial ADP/ATP carrier (AAC) is a major transport protein of the inner mitochondrial membrane. It exchanges mitochondrial ATP for cytosolic ADP and controls cellular production of ATP. In addition, it has been proposed that AAC mediates mitochondrial uncoupling, but it has proven difficult to demonstrate this function or to elucidate its mechanisms. Here we record AAC currents directly from inner mitochondrial membranes from various mouse tissues and identify two distinct transport modes: ADP/ATP exchange and H+transport. The AAC-mediated H+current requires free fatty acids and resembles the H+leak via the thermogenic uncoupling protein 1 found in brown fat. The ADP/ATP exchange via AAC negatively regulates the H+leak, but does not completely inhibit it. This suggests that the H+leak and mitochondrial uncoupling could be dynamically controlled by cellular ATP demand and the rate of ADP/ATP exchange. By mediating two distinct transport modes, ADP/ATP exchange and H+leak, AAC connects coupled (ATP production) and uncoupled (thermogenesis) energy conversion in mitochondria. The mitochondrial ADP/ATP carrier mediates the proton leak in mitochondria from all tissues that lack UCP1, thereby linking coupled (ATP production) and uncoupled (thermogenesis) energy conversion.

Inherited mitochondrial DNA (mtDNA) diseases were discovered 30 years ago, and their characterization has provided a new perspective on the etiology of the common metabolic and degenerative diseases, cancer, and aging. The maternally inherited mtDNA contains 37 critical bioenergetic genes that are present in hundreds of copies per cell, but the ‘mitochondrial genome’ encompasses an additional 1,000–2,000 nuclear DNA (nDNA) mitochondrial genes. The interaction between these two mitochondrial genetic systems provides explanations for phenomena such as the non-Mendelian transmission of the common ‘complex’ diseases, age-related disease risk and progression, variable penetrance and expressivity, and gene–environment interactions. Thus, mtDNA genetics contributes to the quantitative and environmental components of human genetics that cannot be explained by Mendelian genetics. Because mtDNA is maternally inherited and cytoplasmic, it has fostered the first germline gene therapy, nuclear transplantation. However, effective interventions are still lacking for existing patients with mitochondrial dysfunction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)–encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.

The northwest Atlantic Ocean is an important sink for carbon dioxide produced by anthropogenic activities. However the strong seasonal variability in the surface waters paired with the sparse and summer biased observations of ocean carbon makes it difficult to capture a full picture of its temporal variations throughout the water column. We aim to improve the estimation of temporal trends of dissolved inorganic carbon (DIC) due to anthropogenic sources using a new statistical approach: a time series generalization of the extended multiple linear regression (eMLR) method. Anthropogenic increase of northwest Atlantic DIC in the surface waters is hard to quantify due to the strong, natural seasonal variations of DIC. We address this by separating DIC into its seasonal, natural and anthropogenic components. Ocean carbon data is often collected in the summer, creating a summer bias, however using monthly averaged data made our results less susceptible to the strong summer bias in the available data. Variations in waters below 1000m have usually been analyzed on decadal time scales, but our monthly analysis showed the anthropogenic carbon component had a sudden change in 2000 from stationary to an increasing trend at the same rate as the waters above. All depths layers had similar rates of anthropogenic increase of ∼0.57µmol kg−1year−1, and our uncertainty levels are smaller than with eMLR results. Integration throughout the water column (0–3,500 m) gives an anthropogenic carbon storage rate of 1.37 ± 0.57 mol m−2year−1, which is consistent with other published estimates. We need to measure the ocean sink for the CO2emitted by industrialized societies, and it is particularly important for the northwest Atlantic Ocean. The rate of carbon increase is often overshadowed by natural and seasonal variability. We introduce new statistical approaches to better estimate the rate of anthropogenic carbon that has accumulated due to human activities. Ocean carbon data is often collected in the summer, creating a summer bias, however using monthly averaged data made our results less susceptible to the strong summer bias in the available data. From 1993 to 2015 in the northwest Atlantic Ocean, anthropogenic carbon increased at ∼0.57 μmol kg−1year−1within all depth‐layers. Integration of results throughout the water column (0–3,500 m) gives an anthropogenic carbon storage rate of 1.37 ± 0.57 mol m−2year−1. A time series generalization of the extended multiple linear regression (eMLR) method is developed to produce monthly estimates with uncertainties of anthropogenic ocean carbonThe rate of anthropogenic carbon increase in northwest Atlantic is roughly the same for all depth layers, at 0.57 µmol/kg/yearOur method produces estimates of anthropogenic carbon increase that are comparable to those from eMLR, but with smaller uncertainties A time series generalization of the extended multiple linear regression (eMLR) method is developed to produce monthly estimates with uncertainties of anthropogenic ocean carbon The rate of anthropogenic carbon increase in northwest Atlantic is roughly the same for all depth layers, at 0.57 µmol/kg/year Our method produces estimates of anthropogenic carbon increase that are comparable to those from eMLR, but with smaller uncertainties

The aim of this study was to evaluate the association between actigraphy-based measures of sleep and prevalent hypertension in a sample of US Latinos.

Measurements of near‐surface oxygen (O2) concentrations and mixed layer depth from the K1 mooring in the central Labrador Sea are used to calculate the change in column‐integrated (0–1700 m) O2content over the deep convection winter 2014/2015. During the mixed layer deepening period, November 2014 to April 2015, the oxygen content increased by 24.3 ± 3.4 mol m−2, 40% higher than previous results from winters with weaker convection. By estimating the contribution of respiration and lateral transport on the oxygen budget, the cumulative air‐sea gas exchange is derived. The O2uptake of 29.1 ± 3.8 mol m−2, driven by persistent undersaturation (≥5%) and strong atmospheric forcing, is substantially higher than predicted by standard (nonbubble) gas exchange parameterizations, whereas most bubble‐resolving parameterizations predict higher uptake, comparable to our results. Generally large but varying mixed layer depths and strong heat and momentum fluxes make the Labrador Sea an ideal test bed for process studies aimed at improving gas exchange parameterizations. Substantial uptake of oxygen is observed in the Labrador Sea during the 2014–2015 winterStronger oxygen sink compared to previous studies is linked to North Atlantic OscillationMany commonly used gas exchange parameterizations underestimate the observed flux dramatically

Although racial and ethnic differences in CPAP adherence for OSA are widely established, no studies have examined the influence of perceived racial discrimination on CPAP usage, to our knowledge.

We present super-resolution microscopy of isolated functional mitochondria, enabling real-time studies of structure and function (voltages) in response to pharmacological manipulation. Changes in mitochondrial membrane potential as a function of time and position can be imaged in different metabolic states (not possible in whole cells), created by the addition of substrates and inhibitors of the electron transport chain, enabled by the isolation of vital mitochondria. By careful analysis of structure dyes and voltage dyes (lipophilic cations), we demonstrate that most of the fluorescent signal seen from voltage dyes is due to membrane bound dyes, and develop a model for the membrane potential dependence of the fluorescence contrast for the case of super-resolution imaging, and how it relates to membrane potential. This permits direct analysis of mitochondrial structure and function (voltage) of isolated, individual mitochondria as well as submitochondrial structures in the functional, intact state, a major advance in super-resolution studies of living organelles.

Mitochondrial dysfunction has been increasingly linked to neurodevelopmental disorders such as intellectual disability, childhood epilepsy, and autism spectrum disorder, conditions also associated with cortical GABAergic interneuron dysfunction. Although interneurons have some of the highest metabolic demands in the postnatal brain, the importance of mitochondria during interneuron development is unknown. We find that interneuron migration from the basal forebrain to the neocortex is highly sensitive to perturbations in oxidative phosphorylation. Both pharmacologic and genetic inhibition of adenine nucleotide transferase 1 (Ant1) disrupts the non-radial migration of interneurons, but not the radial migration of cortical projection neurons. The selective dependence of cortical interneuron migration on oxidative phosphorylation may be a mechanistic pathway upon which multiple developmental and metabolic pathologies converge.

Model organism (MO) research provides a basic understanding of biology and disease due to the evolutionary conservation of the molecular and cellular language of life. MOs have been used to identify and understand the function of orthologous genes, proteins, cells and tissues involved in biological processes, to develop and evaluate techniques and methods, and to perform whole-organism-based chemical screens to test drug efficacy and toxicity. However, a growing richness of datasets and the rising power of computation raise an important question: How do we maximize the value of MOs? In-depth discussions in over 50 virtual presentations organized by the National Institutes of Health across more than 10 weeks yielded important suggestions for improving the rigor, validation, reproducibility and translatability of MO research. The effort clarified challenges and opportunities for developing and integrating tools and resources. Maintenance of critical existing infrastructure and the implementation of suggested improvements will play important roles in maintaining productivity and facilitating the validation of animal models of human biology and disease.

In order to investigate production pathways of methyl iodide and controls on emissions from the surface ocean, a set of repeated in vitro incubation experiments were performed over an annual cycle in the context of a time series of in situ measurements in Kiel Fjord (54.3°N, 10.1°E). The incubation experiments revealed a diurnal variation of methyl iodide in samples exposed to natural light, with maxima during day time and losses during night hours. The amplitude of the daily accumulation varied seasonally and was not affected by filtration (0.2 µm), consistent with a photochemical pathway for CH3I production. The methyl iodide loss rate at nighttime correlates with the concentration accumulated during daytime suggesting a first‐order loss mechanism (R2= 0.29, p<< 0.01). Daily (24 h) net production (Pnet) was similar in magnitude between in vitro and in situ mass balances. However, the estimated gross production (Pgross) of methyl iodide ranged from −0.07 to 2.24 pmol L−1d−1and was up to 5 times higher in summer than Pnetcalculated from the in situ study. The large excess of Pgrossover Pnetin summer revealed by the incubation experiments is a consequence of large losses of CH3I by as‐yet uncharacterized processes (e.g., biological degradation or chemical pathways other than Cl−substitution). A diurnal variation of CH3I in sunlit samples with maxima in day timeDaily accumulation was not affected by filtrationA consequence of large losses of CH3I by as‐yet uncharacterized processes

Sexuality is a major quality-of-life issue, even into advanced age. Although relatively few studies have addressed sexuality, most studies have emphasized the decline in both sexual performance and satisfaction with aging. In an effort to assess possible positive modifiers of the decline, we included questions concerning sexuality in a multipurpose 90-item questionnaire submitted to members of the Fifty Plus Fitness Association based in Stanford, California. This group is unique in its commitment to a very active lifestyle and has served as a cohort for many prior studies related to fitness and medical outcomes. Sixty-seven percent of the membership returned the mail questionnaire, and 59% of these respondents replied to the sexually relevant items. The results indicated a high level of sexual activity and satisfaction in both older men and women of the Fifty Plus Fitness Association members. Further, sexual satisfaction seemed to correlate with the degree of fitness. We conclude that physical fitness and high levels of sexual activity are mutually supportive elements of successful aging. (Bortz WM II, Wallace DH. Physical fitness, aging, and sexuality. West J Med 1999; 170:167-169), Everyone wants to live longer if the latter years are replete with the vitality, virtues, and values of young life. A long life of high functional capacity until the moment [...]

To West Virginia, international trade is not about eating French toast, English muffins, and Canadian bacon for breakfast. Rather, it's about bringing home the bread. This was made clear May [...]