Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative genomics reveals divergent thermal selection in warm‐ and cold‐tolerant marine mussels

Investigating the history of natural selection among closely related species can elucidate how genomes diverge in response to disparate environmental pressures. Molecular evolutionary approaches can be integrated with knowledge of gene functions to examine how evolutionary divergence may affect ecologically relevant traits such as temperature tolerance and species distribution limits. Here, we integrate transcriptome‐wide analyses of molecular evolution with knowledge from physiological studies to develop hypotheses regarding the functional classes of genes under positive selection in one of the world's most widespread invasive species, the warm‐tolerant marine mussel Mytilus galloprovincialis. Based on existing physiological information, we test the hypothesis that genomic functions previously linked to divergent temperature adaptation at the whole‐organism level show accelerated molecular divergence between warm‐adapted M. galloprovincialis and cold‐adapted congeners. Combined results from codon model tests and analyses of polymorphism and divergence reveal that divergent selection has affected genomic functions previously associated with species‐specific expression responses to heat stress, namely oxidative stress defence and cytoskeletal stabilization. Examining specific loci implicated in thermal tolerance among Mytilus species (based on interspecific biochemical or expression patterns), we find close functional similarities between known thermotolerance candidate genes under positive selection and positively selected loci under predicted genomic functions (those associated with divergent expression responses). Taken together, our findings suggest a contribution of temperature‐dependent selection in the molecular divergence between warm‐ and cold‐adapted Mytilus species that is largely consistent with results from physiological studies. More broadly, this study provides an example of how independent experimental evidence from ecophysiological investigations can inform evolutionary hypotheses about molecular adaptation in closely related nonmodel species.
Maternal anemia and offspring failure to thrive – results from a large population-based cohort

Abstract Objective To evaluate whether an association exists between maternal anemia and offspring failure to thrive (FTT) during childhood. Methods A population-based cohort analysis was performed, comparing the risk for FTT among children (up to 18 years old) based on maternal hemoglobin (Hb) levels, upon postpartum discharge. Maternal Hb levels were categorized into 3 levels: <9.0 (moderate–severe anemia), 9.0–11.0 (mild anemia), and ≥11.0 g/dL (no anemia). FTT diagnosis was based on hospital records. All singletons born between 1991 and 2014 and discharged alive without congenital malformations were included. A survival curve was constructed to compare the cumulative FTT incidence, and a Weibull parametric survival analysis to assess the independent association between maternal anemia and offspring FTT while controlling for confounders. Results Of the 214,305 included deliveries, 22,071 parturients (10.3%) were discharged with Hb <9.00; 83,932 (39.2%) with Hb between 9.0–11.0; and 108,302 (50.5%) with Hb ≥11.0 g/dL. FTT rates were 1.3% (n = 287), 1.2% (n = 967), and 1.1% (n = 1141) in the same groups, respectively (p = .003). The survival curve demonstrated a significantly higher cumulative incidence of FTT diagnosis in the moderate–severe maternal anemia group (p < .001). In the Weibull analysis, constructed for newborns with appropriate birthweight, both groups of maternal anemia were found to be independently associated with FTT related hospitalizations (mild anemia aHR, 1.1; 95%CI 1.002–1.219; p = .045, moderate-severe anemia aHR, 1.321; 95%CI, 1.141–1.529; p < .001). Conclusion Maternal anemia is independently associated with long-term FTT in offspring, with increasing FTT rates proportional to anemia severity.
Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

Background: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. Methods: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. Results: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. Conclusion: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.
Impact of oxidative stress on male and female germ cells; implications for fertility.

Male and female germ lines are vulnerable to oxidative stress. In spermatozoa, such stress triggers a lipid peroxidation cascade that culminates in the generation of electrophilic lipid aldehydes that bind to DNA and a raft of proteins involved in the delivery of functionally competent cells. One set of targets for these aldehydes are the proteins of the mitochondrial electron transport chain. When this interaction occurs, mitochondrial ROS generation is enhanced leading to the sustained generation of oxidative damage in a self-perpetuating cycle. Such damage affects all aspects of sperm function including motility, sperm-egg recognition, acrosomal exocytosis and sperm-oocyte fusion. Oxidative stress in the male also attacks the integrity of sperm DNA with potential impacts on the developmental capacity of embryos and the health and wellbeing of the offspring. Potential pathways of reactive oxygen species (ROS) generation in male germ cells could involve enhanced lipoxygenase activity, activation of NADPH oxidase and/or electron leakage from mitochondria. Similarly, in the female germ line, both the induction of oocyte senescence following ovulation and the deterioration of oocyte quality with maternal age, appear to involve the generation of oxidative damage. In this case, the mitochondria appear to be a particularly important source of ROS compromising the viability and fertilizability of the oocyte and interfering with the normal segregation of chromosomes during meiosis. In light of these considerations, antioxidants should have some role to play in the preservation of reproductive function in both men and women; however, we still await appropriate trials to test this hypothesis.
Effects of the carbon source and the interaction between carbon sources on the physiology of the industrial Saccharomyces cerevisiae CAT-1

Abstract During industrial fermentation, wild isolates are able to persist and even predominate in the bioreactors. Saccharomyces cerevisiae CAT-1 was one of these isolates and now is one of the yeasts mostly used in industrial ethanol processes in Brazil due to its efficient fermentation capacity. Despite it, the strain’s physiology has been marginally studied so far. Since strains of the same species may have different responses to a specific cultivation condition, this work aimed to evaluate the physiology of S. cerevisiae CAT-1 in batch cultures using different carbon sources (glucose, fructose, sucrose, maltose, and galactose) as a sole carbon source and in binary mixtures, at 30 and 37 °C. The results showed that the fructose, sucrose, and maltose were the sugars that presented the highest ethanol yields on the substrate (0.40 gethanol gsubstrate−1) at both temperatures. Galactose was the sugar that the yeast had the lowest affinity given the lowest maximum specific growth rate (0.28 h−1). Despite the influence of a variety of mechanisms for sugar transport, the cells consume first substrates with fewer metabolic steps to catabolism and are susceptible to adaptive evolution depending on the availability of substrate.
Mitochondrial DNA damage in the hair bulb: can it be used as a noninvasive biomarker of local exposure to low LET ionizing radiation?

Abstract Purpose: Our aim was to evaluate whether mitochondrial DNA (mtDNA) damage in hair bulbs could be a suitable biomarker for the detection of local exposure to ionizing radiation. Materials and methods: Mouse hair was collected 4 and 24 hours, 3 and 10 days after single whole-body exposure to 0, 0.1, and 2 Gy radiation. Pubic hair (treated area) and scalp hair (control area) were collected from 13 prostate cancer patients before and after fractioned radiotherapy with an average total dose of 2.7 Gy to follicles after five fractions. Unspecified lesion frequency of mtDNA was analyzed with long PCR, large mtDNA deletion levels were tested with real-time PCR. Results: Unspecified lesion frequency of mtDNA significantly increased in mouse hair 24 hours after irradiation with 2 Gy, but variance among samples was high. No increase in lesion frequency could be detected after 0.1 Gy irradiation. In prostate cancer patients, there was no significant change in either the unspecified lesion frequency or in the proportion of 4934-bp deleted mtDNA in pubic hair after radiotherapy. The proportions of murine 3860-bp common deletion, human 4977-bp common deletion and 7455-bp deleted mtDNA were too low to be analyzed reliably. Conclusions: Our results suggest that the unspecified lesion frequency and proportion of large deletions of mtDNA in hair bulbs are not suitable biomarkers of exposure to ionizing radiation.
Design and usability evaluation of COOK, an assistive technology for meal preparation for persons with severe TBI

Abstract Aim In Canada, 100,000 people suffer a traumatic brain injury (TBI) every year. The prevalence of moderate to severe TBI is highest for young men, who will live an average of 50 years with this chronic condition associated with physical, emotional and cognitive deficits. Meal preparation, a complex activity with high safety risks, is one of the most significant activities impacted by TBI. Technology shows great promise to support their overall functioning, but no context-aware technology is available to support meal preparation for this population. The main goal of this study was to design and test a technology to support meal preparation with and for persons with severe TBI living in a supported-living residence. Methodology As part of a transdisciplinary technology project linking rehabilitation and informatics, COOK (Cognitive Orthosis for coOKing) was designed with and for future users and stakeholders with a user-centred design methodology. COOK was implemented in three participants’ apartments, and its usability was evaluated at 1, 3 and 6 months post-implementation. Results COOK is a context-aware assistive technology consisting of two main systems: security and cognitive support system. After implementation of COOK, participants were able to resume safe preparation of meals independently. Usability testing showed good effectiveness and an acceptable level of satisfaction. Conclusion COOK appears promising for rehabilitating clients with cognitive disabilities, improving safety in a home environment, and diminishing the need for human supervision. Future studies will need to explore how COOK can be adapted to a broader TBI population, other environments, and other clienteles. Implications for rehabilitation This paper presents a promising context-aware assistive technology for cognition designed with and for clients with severe brain injury to support their independence in meal preparation; COOK, (Cognitive Orthesis for coOKing) is the first cooking assistant in which evidence-based cognitive rehabilitation interventions have been translated into smart technological assistance, to support cognition and ensure safety in a real-life context; Its context-aware characteristic ensures that users receive the assistance they need at the right time and at the right moment. The long-term perspective regarding the use of COOK in clinical practice is promising as this technology has the potential of becoming an additional means of supporting the rehabilitation of people with cognitive impairments and becoming part of a comprehensive solution to help them live at home more independently.
Prediction of Suicide and Nonfatal Self-harm After Bariatric Surgery: A Risk Score Based on Sociodemographic Factors, Lifestyle Behavior, and Mental Health

Supplemental Digital Content is available in the text Objective: To identify preoperative sociodemographic and health-related factors that predict higher risk of nonfatal self-harm and suicide after bariatric surgery. Background: Evidence is emerging that bariatric surgery is related to an increased risk of suicide and self-harm, but knowledge on whether certain preoperative characteristics further enhance the excess risk is scarce. Methods: The nonrandomized, prospective, controlled Swedish Obese Subjects study was linked to 2 Nationwide Swedish registers. The bariatric surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual care. Participants were recruited from 1987 to 2001, and information on the outcome (a death by suicide or nonfatal self-harm event) was retrieved until the end of 2016. Subhazard ratios (sub-HR) were calculated using competing risk regression analysis. Results: The risk for self-harm/suicide was almost twice as high in surgical patients compared to control patients both before and after adjusting for various baseline factors [adjusted sub-HR = 1.98, 95% confidence interval (CI) = 1.34–2.93]. Male sex, previous healthcare visits for self-harm or mental disorders, psychiatric drug use, and sleep difficulties predicted higher risk of self-harm/suicide in the multivariate models conducted in the surgery group. Interaction tests further indicated that the excess risk for self-harm/suicide related to bariatric surgery was stronger in men (sub-HR = 3.31, 95% CI = 1.73–6.31) than in women (sub-HR = 1.54, 95% CI = 1.02–2.32) (P = 0.007 for adjusted interaction). A simple-to-use score was developed to identify those at highest risk of these events in the surgery group. Conclusions: Our findings suggest that male sex, psychiatric disorder history, and sleep difficulties are important predictors for nonfatal self-harm and suicide in postbariatric patients. High-risk patients who undergo surgery might require regular postoperative psychosocial monitoring to reduce the risk for future self-harm behaviors.
Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.
The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier

The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec61 complex, a heterotrimeric channel that comprises the Sec61p/Sec61α, Sss1p/Sec61γ, and Sbh1p/Sec61β subunits. In addition to forming a protein-conducting channel, the Sec61 complex also functions to maintain the ER permeability barrier, preventing the mass free flow of essential ER-enriched molecules and ions. Loss in Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61γ C terminus is juxtaposed to the key gating module of Sec61p/Sec61α, and we hypothesize it is important for gating the ER translocon. The ER stress response was found to be constitutively induced in two temperature-sensitive sss1 mutants (sss1ts) that are still proficient to conduct ER translocation. A screen to identify intergenic mutations that allow for sss1ts cells to grow at 37 °C suggests the ER permeability barrier to be compromised in these mutants. We propose the extreme C terminus of Sss1p/Sec61γ is an essential component of the gating module of the ER translocase and is required to maintain the ER permeability barrier.
Controlling, Confounding, and Construct Clarity: Responding to Criticisms of “Revisiting the Marshmallow Test” by Doebel, Michaelson, and Munakata (2020) and Falk, Kosse, and Pinger (2020)

Many researchers of human development use correlations to gauge the extent to which early life phenomena predict later life outcomes, while at the same time warning that their correlations should not be accorded a causation interpretation. However, discussions of results from predictive models often cross the line if they are used to infer latent causal processes and to draw implications for policy and practice (e.g., Reinhart, Haring, Levin, Patall, & Robinson, 2013). In developmental psychology, the temptation to assign causal interpretations grows stronger when longitudinal data provide temporal ordering and when researchers believe that an observed “effect” might be caused by a malleable early life factor. These kinds of interpretation issues were at the heart of our recent article, “Revisiting the Marshmallow Test: A Conceptual Replication Investigating Links Between Early Delay of Gratification and Later Outcomes,” in which we reexamined well-known longitudinal correlations between early gratification delay and later indicators of cognitive and behavioral functioning (Watts, Duncan, & Quan, 2018). Our study had two primary goals: (a) to estimate the correlations reported by Shoda, Mischel, and Peake (1990) using a larger and more diverse sample of children and (b) to explore possible interpretations of the links between gratification delay and later outcomes by estimating regressionbased models not previously considered by Shoda et al. In pursuit of our first goal, we estimated bivariate correlations between performance on the marshmallow test and later measures of adolescent functioning. Correlations with adolescent academic achievement were smaller in magnitude than what was reported by Shoda et al. (1990) but were still positive and statistically significant, indicating at least partial replication of their achievement correlations. In contrast to Shoda et al., however, we found null correlations with behavioral outcomes. We titled our article a “conceptual replication” because of the measurement and sample-composition differences between our work and that of Shoda et al. (1990). But our main goal was to probe possible interpretations of the original findings with a novel set of multivariate regression models. The Commentaries of Doebel, Michaelson, and Munakata (2020) and Falk, Kosse, and Pinger (2020) criticize our regression models for overcontrolling for variables inextricably tied to a child’s ability to delay gratification and thereby obscuring the predictive association of interest. In this Reply, we motivate our modeling approach and argue that it illuminates possible interpretations of the correlation between gratification delay and later outcomes. In the final section, we comment briefly on the measurement concerns raised by Falk et al.
Cold Adapted Nitrosospira sp.: A Potential Crucial Contributor of Ammonia Oxidation in Cryosols of Permafrost-Affected Landscapes in Northeast Siberia

Permafrost-affected landscape soils are rich in organic matter and contain a high fraction of organic nitrogen, but much of this organic matter remains inaccessible due to nitrogen limitation. Microbial nitrification is a key process in the nitrogen cycle, controlling the availability of dissolved inorganic nitrogen (DIN) such as ammonium and nitrate. In this study, we investigate the microbial diversity of canonical nitrifiers and their potential nitrifying activity in the active layer of different Arctic cryosols in the Lena River Delta in North-East Siberia. These cryosols are located on Samoylov Island, which has two geomorphological landscapes with mineral soils in the modern floodplain and organic-rich soils in the low-centered polygonal tundra of the Holocene river terrace. Microcosm incubations show that the highest potential ammonia oxidation rates are found in low organic soils, and the rates depend on organic matter content and quality, vegetation cover, and water content. As shown by 16S rRNA amplicon sequencing, nitrifiers represented 0.6% to 6.2% of the total microbial community. More than 50% of the nitrifiers belonged to the genus Nitrosospira. Based on PCR amoA analysis, ammonia-oxidizing bacteria (AOB) were found in nearly all soil types, whereas ammonia-oxidizing archaea (AOA) were only detected in low-organic soils. In cultivation-based approaches, mainly Nitrosospira-like AOB were enriched and characterized as psychrotolerant, with temperature optima slightly above 20 °C. This study suggests a ubiquitous distribution of ammonia-oxidizing microorganisms (bacteria and archaea) in permafrost-affected landscapes of Siberia with cold-adapted AOB, especially of the genus Nitrosospira, as potentially crucial ammonia oxidizers in the cryosols.