Miracle-dz/UniFAR-FTUs huggingface dataset:
The cardiac-enriched microprotein mitolamban regulates mitochondrial respiratory complex assembly and function in mice

Significance Microproteins are a growing class of versatile small proteins previously overlooked by standard gene annotation methods due to their small size. Here we characterize mitolamban as a cardiac-enriched inner mitochondrial membrane–localized microprotein, which interacts with complex III of the electron transport chain and contributes to complex III assembly and function. Mitolamban gene deletion in mice leads to a reduction in complex III activity and metabolic perturbations in the heart that are consistent with complex III deficiency, as well as altered complex III assembly into respiratory supercomplexes. These findings define a functional role for mitolamban in the heart and highlight the importance of microproteins in regulating mitochondrial function and cardiomyocyte biology. Emerging evidence indicates that a subset of RNA molecules annotated as noncoding contain short open reading frames that code for small functional proteins called microproteins, which have largely been overlooked due to their small size. To search for cardiac-expressed microproteins, we used a comparative genomics approach and identified mitolamban (Mtlbn) as a highly conserved 47-amino acid transmembrane protein that is abundantly expressed in the heart. Mtlbn localizes specifically to the inner mitochondrial membrane where it interacts with subunits of complex III of the electron transport chain and with mitochondrial respiratory supercomplexes. Genetic deletion of Mtlbn in mice altered complex III assembly dynamics and reduced complex III activity. Unbiased metabolomic analysis of heart tissue from Mtlbn knockout mice further revealed an altered metabolite profile consistent with deficiencies in complex III activity. Cardiac-specific Mtlbn overexpression in transgenic (TG) mice induced cardiomyopathy with histological, biochemical, and ultrastructural pathologic features that contributed to premature death. Metabolomic analysis and biochemical studies indicated that hearts from Mtlbn TG mice exhibited increased oxidative stress and mitochondrial dysfunction. These findings reveal Mtlbn as a cardiac-expressed inner mitochondrial membrane microprotein that contributes to mitochondrial electron transport chain activity through direct association with complex III and the regulation of its assembly and function.
The influence of magnetostatic interactions on the magnetic properties of magnetite

The effect of magnetostatic interactions on the magnetisation structure and magnetic properties of magnetite grains for the size range 0.03 0.15 microns has been examined. The understanding of magnetostatic interactions is important because magnetite that occurs naturally by some precipitation process and in sedimentary rocks containing magnetosomes may form as magnetostatic interacting clumps of grains. This has implications in the way we perceive magnetic signals are recorded in rocks, bacterial magnetosomes found in sedimentary rocks, and also in magnetic recording media. The examination of magnetostatic interactions has been achieved by using a threedimensional micromagnetic model which considers arrays of 4x4x4 cubic magnetite grains with uniaxial shape anisotropy and arrays of 6x6 or 4x4 cubic grains, arranged analogous to arrays of particles that may be produced by a method of electron beam lithography. The grains have a maximum spacing of one grain width, when they are seen to be noninteracting; or a minimum where they are almost touching, when they are interacting. Using this method it is possible to see how grain interactions alter the magnetic domain structure of uniform and non-uniform grains. The effect of interactions on bulk properties, such as coercivity and remanence can be examined from simulated hysteresis cycles. Properties are examined when the grains are arranged within the arrays such that their easy axes of magnetocrystalline anisotropy are aligned parallel with every other grain in the array, and in the case where the axes are in a randomly differing orientation from every other grain within the array. Hysteresis parameters for non-interacting and interacting arrays of grains are calculated, and these theoretical values are compared with previous theoretical micromagnetic models and experimental work. The results from this study are in good agreement with previous work. The observed effect of magnetostatic interactions on domain structure is to make nonuniform grains more uniform, due to interactions aiding the alignment of individual grain's magnetisation directions with easy-axes. In addition, interactions will rotate magnetisation directions in such a way as to aid flux-closure of the entire ensemble When grains are aligned such that their axes of magnetocrystalline anisotropy are in randomly differing orientations from every other grain in the assemblage, it is found that interactions between grains will decrease the saturation remanence and the coercive force. However, when there is a large volume of interacting grains and they are arranged so each grain's easy axes are oriented in the same direction, the effect of inter-particle magnetostatic interactions is to increase the remanence and coercive force. In this case, the effect of interactions is to increase the recording ability of a grain, and the field required to switch it's magnetisation.
AASLD Practice Guidance: Palliative care and symptom‐based management in decompensated cirrhosis

by the American Association for the Study of Liver Diseases. M.V. was supported by aAQ19 Patient-Centered Outcomes Research Institute (PCORI) Award (PLC-1609-36714). S.R. ’s time was supported, in part, by K23DA048182. C.W. 's time was supported by R03 AG067992.
Association of prolonged nightly fasting with cardiovascular, renal, inflammation, and nutritional status biomarkers in community-dwelling older adults.

BACKGROUND Prolonged fasting, as a dietary strategy, has been linked to metabolic benefits; however, data corresponded to very small samples of young participants in controlled environments, a few cardiovascular risk markers, and for short periods of time. OBJECTIVES To assess the association of habitual prolonged nightly fasting with a wide array of cardiovascular, renal, inflammation, and nutritional status biomarkers among community-dwelling older adults. METHODS Cross-sectional analysis of data from 1047 adults ≥ 65 years from the Seniors Study on Nutrition and Cardiovascular Risk in Spain 2 (Seniors-ENRICA-2) cohort. Habitual diet was assessed through a validated diet history. Fasting time was classified into the following categories: <10, 10 to < 12, and ≥ 12 hours/day, the latter being considered prolonged nightly fasting. Adjusted geometric means of biomarkers concentrations in blood and serum were estimated using linear regression models, by categories of fasting time. Main confounders included overall diet quality, defined as adherence to a Mediterranean diet score, and body mass index. RESULTS Longer fasting time was associated with: lower concentration of high-density lipoprotein cholesterol (HDL-c) (difference between the longest and shortest fasting category: -2.94 mg/dL; 95% confidence interval: -4.80, -1.09; p-trend: 0.01); higher potassium levels (0.11 mEq/L; 0.03, 0.19; p-trend: 0.01); and lower concentration of chloride (-0.50 mEq/L; -0.91, -0.09; p-trend: 0.03). These results were slightly attenuated after additional adjustment for body mass index. CONCLUSIONS Habitual prolonged nightly fasting did not show beneficial associations with the examined biomarkers. By contrast, some modest detrimental associations were found suggesting that extended periods of time between meals may not be beneficial for older adults. Clinical Trial Registry: ClinicalTrials.gov NCT03541135.
Engineering Labour: Technical Workers in Comparative Perspective

Is the social status of an engineer the same in Britain as in the US or Japan? Engineers, often perceived as central agents of industrial capitalism, occupying roughly the same social status and performing similar functions in the capitalist enterprise. What the essays in this volume reveal, however, is that engineers are trained and organized quite distinctly in different national contexts. The book includes case studies of engineers in six major industrial economies: Japan, France, Germany, Sweden, Britain and the United States. The authors develop an approach to national differences which both retains the place of historical diversity in the experience of capitalism, and accommodates the forces of convergence from increasing globalization and economic integration. There are additional contributions by: Boel Berner, Stephen Crawford, Kees Gispen, Kevin McCormick and Peter Whalley.
The impact of storage on extracellular vesicles: A systematic study

Abstract Mounting evidence suggests that storage has an impact on extracellular vesicles (EVs) properties. While −80°C storage is a widespread approach, some authors proposed improved storage strategies with conflicting results. Here, we designed a systematic study to assess the impact of −80°C storage and freeze‐thaw cycles on EVs. We tested the differences among eight storage strategies and investigated the possible fusion phenomena occurring during storage. EVs were collected from human plasma and murine microglia culture by size exclusion chromatography and ultracentrifugation, respectively. The analysis included: concentration, size and zeta potential (tunable resistive pulse sensing), contaminant protein assessment; flow cytometry for the analysis of two single fluorescent‐tagged EVs populations (GFP and mCherry), mixed before preservation. We found that −80°C storage reduces EVs concentration and sample purity in a time‐dependent manner. Furthermore, it increases the particle size and size variability and modifies EVs zeta potential, with a shift of EVs in size‐charge plots. None of the tested conditions prevented the observed effects. Freeze‐thaw cycles lead to an EVs reduction after the first cycle and to a cycle‐dependent increase in particle size. With flow cytometry, after storage, we observed a significant population of double‐positive EVs (GFP+‐mCherry+). This observation may suggest the occurrence of fusion phenomena during storage. Our findings show a significant impact of storage on EVs samples in terms of particle loss, purity reduction and fusion phenomena leading to artefactual particles. Depending on downstream analyses and experimental settings, EVs should probably be processed from fresh, non‐archival, samples in majority of cases.
Does the domain of technology impact user trust? Investigating trust in automation across different consumer-oriented domains in young adults, military, and older adults

ABSTRACT Trust has been shown to be a determinant of automation usage and reliance. Thus, understanding the factors that affect trust in automation has been a focus of much research. Despite the increased appearance of automation in consumer-oriented domains, the majority of research examining human-automation trust has occurred in highly specialised domains (e.g. flight management, military) and with specific user groups. We investigated trust in technology across three different groups (young adults, military, and older adults), four domains (consumer electronics, banking, transportation, and health), two stages of automation (information and decision automation), and two levels of automation reliability (low and high). Our findings suggest that trust varies on an interaction of domain of technology, reliability, stage, and user group.
Childhood cancer risk in offspring of parents occupationally exposed to dusts: A register‐based nested case‐control study from Sweden of 5 decades

Some largely inconsistent associations between parental occupational dust exposure and childhood cancer have been reported, with maternal exposures inadequately studied. The authors examined whether maternal or paternal occupational exposure to animal, wood, textile, or paper dust around a child's birth was associated with an increased risk of childhood cancer, both overall and by type (leukemias, lymphomas, central nervous system tumors, and other cancers).
Some Insect Species are Good Quality Protein Sources for Children and Adults: Digestible Indispensable Amino Acid Score (DIAAS) Determined in Growing Pigs.

BACKGROUND Insect species are suitable for farming as 'mini livestock' for human and animal consumption. It is important to assess the protein quality of relevant species to understand the potential of these novel protein sources in future sustainable food systems. OBJECTIVES To determine the protein quality of five insect species: lesser mealworm (LMW), yellow mealworm (YMW), house cricket (HC), banded cricket (BC) and black soldier fly (BSF) using the digestible indispensable amino acid score (DIAAS) in a pig model. DESIGN Five diets were formulated to contain 10% insect crude protein (CP). A nitrogen (N)-free diet was included to estimate endogenous losses. In a 6 × 6 Latin square design, 6 ileal cannulated crossbred (Duroc × [Danish Landrace × Yorkshire]) male pigs with an initial body weight of 35 ± 2 kg were fed the 6 diets. Each diet was fed for 1 wk over 6 wk. Ileal digesta was collected for 8 h on days 5 and 7 each wk. Analyzed CP, amino acid (AA) contents and calculated values of standardized ileal digestibility (SID) for CP and AAs of each insect were used to assess the DIAAS. RESULTS The DIAAS for young children aged 6 mo to 3 y and for older children, adolescents and adults identified Sulphur AAs (SAAs, cysteine + methionine) as the first limiting AA in all four species of cricket and mealworm. For young children, both cricket species had DIAAS above 75 and for older children, adolescents and adults both cricket species and LMW had DIAAS above 75. CONCLUSIONS Both cricket species (HC and BC) are classified as good quality protein sources for young children aged 6 mo to 3 y and for older children, adolescents and adults. One mealworm species, LMW, is a good quality protein source for older children, adolescents and adults.
The Historical Significance of Titicut Follies in Psychiatric Treatment: An Anti-Censorship Perspective

Works of art and information judged as obscene can be censored or banned. This brief review evaluates the costs and benefits of censorship and the banning of artwork and information. In the history of psychology, Frederick Wiseman’s film Titicut Follies epitomizes the disadvantages of concealing art content. Despite protecting the privacy of patients, the ban of Titicut Follies delayed the reform of psychiatric treatment practices and hospitals. The decision to censor or ban artistic and scientific information can result in the loss of knowledge and potential improvements to social, political, and economic institution practices.
Long‐term effectiveness of HPV vaccination against HPV infection in young Japanese women: Real‐world data

In Japan, public funding for HPV vaccination began in 2010 for girls aged 13–16 years (birth cohort years 1994–1997) and women born in 1994 who turned 25 in 2019. We aimed to verify the long‐term effectiveness of the bivalent HPV vaccine in women aged 25 years. Subjects were women aged 25–26 years who underwent cervical cancer screening and HPV testing in Niigata from 2019 to 2020 (birth cohort years 1993–1994). Information on vaccination status and sexual behavior was obtained from a questionnaire and municipal records. We compared the HPV infection rates of the vaccinated and unvaccinated groups. Of the 429 registrants, 150 (35.0%) and 279 (65.0%) were vaccinated and unvaccinated, respectively. The average period from HPV vaccination to HPV testing was 102.7 months (8.6 years), with a median of 103 months (range 92–109 months). The HPV high‐risk infection rate was 21.3% (32/150) in the vaccinated group and 23.7% (66/279) in the unvaccinated group (P = 0.63). The HPV16/18 infection rate was 0% (0/150) in the vaccinated group and 5.4% (15/279) in the unvaccinated group, showing a significant difference (P = 0.0018), and the vaccine effectiveness was 100%. The cross‐protective type HPV31/45/52 infection rate in the vaccinated group was significantly lower than that in the unvaccinated group (3.3% vs. 10.0%, P = 0.013). There was no significant difference in the mean age at sexual debut and the number of previous sexual partners between the two groups. We have demonstrated the long‐term 9‐year effectiveness of the bivalent vaccine against HPV infection for the first time in Japan.
Assessment of the size selectivity of peritoneal permeability by the restriction coefficient to protein transport

Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include β2-microglobulin, albumin, immunoglobulin G and α2-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation.
Associations of Evolutionary-Concordance Diet and Lifestyle Pattern Scores with Incident, Sporadic Colorectal Adenoma in a Pooled Case-Control Study

Abstract Differences in diet and lifestyle relative to those of our Paleolithic-era ancestors may explain current high incidences of chronic diseases, including colorectal cancer (CRC), in Westernized countries. Previously reported evolutionary-concordance diet and lifestyle pattern scores, reflecting closeness of diet and lifestyle patterns to those of Paleolithic-era humans, were associated with lower CRC incidence. Separate and joint associations of the scores with colorectal adenoma among men and women are unknown. To address this, we pooled data from three case-control studies of incident, sporadic colorectal adenomas (n = 771 cases, 1,990 controls), used participants’ responses to food frequency and lifestyle questionnaires to calculate evolutionary-concordance diet and lifestyle pattern scores, and estimated the scores’ associations with adenomas using multivariable unconditional logistic regression. The multivariable-adjusted odds ratios comparing those in the highest relative to the lowest diet and lifestyle score quintiles were 0.84 (95% confidence interval [CI] 0.62, 1.12; Ptrend :0.03) and 0.41 (95% CI 0.29, 0.59; Ptrend :<0.0001), respectively. The inverse associations were stronger for high-risk adenomas, and among those with both high relative to those with both low diet and lifestyle scores. These results suggest that more evolutionary-concordant diet and lifestyle patterns, separately and jointly, may be associated with lower risk for incident, sporadic colorectal adenoma. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021. 2002919 .
USP5 promotes breast cancer cell proliferation and metastasis by stabilizing HIF2α

Hypoxia‐inducible factor 2α (HIF2α) plays a pivotal role in breast tumor growth and metastasis. However, the regulatory mechanisms of HIF2α protein stability remain poorly understood. The precise role of the deubiquitinase (DUB) ubiquitin‐specific peptidase 5 (USP5) in breast cancer and the underlying mechanism remains largely unknown. Here, we identified USP5 as a novel DUB for HIF2α. Physically, USP5 interacts with HIF2α and protects HIF2α from ubiquitin‐proteasome degradation, thereby promoting the transcription of HIF2α target genes, such as SLC2A1, PLOD2, P4HA1, and VEGFA. USP5 ablation impairs breast cancer cells proliferation, colony formation, migration, and invasion. Moreover, USP5 is highly expressed in breast cancer, and the protein levels of USP5 are positively correlated with HIF2α protein levels in human breast cancer tissues. Importantly, high levels of USP5 leads to poor clinical outcome in patients with breast cancer. Collectively, USP5 stabilizes HIF2α through its DUB activity and provides a potential therapeutic target for breast cancer.
Heritability and Clinical Characteristics of Neuropsychological Profiles in Youth With and Without Elevated ADHD Symptoms

Objective: In the last decade, there has been an increase in research that aims to parse heterogeneity in attention deficit hyperactivity disorder (ADHD). The current study tests heritability of latent class neuropsychological subtypes. Method: Latent class analysis was used to derive subtypes in a sample of school-age twins (N = 2,564) enriched for elevated ADHD symptoms. Results: Five neuropsychological profiles replicated across twin 1 and twin 2 datasets. Latent class membership was heritable overall, but heritability varied by profile and was lower than heritability of ADHD status. Variability in neuropsychological performance across domains was the strongest predictor of elevated ADHD symptoms. Neuropsychological profiles showed distinct associations with age, psychiatric symptoms and reading ability. Conclusion: Neuropsychological profiles are associated with unique neurocognitive presentations, but are not strong candidate endophenotypes for ADHD diagnosis.