Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression.

In this article, we briefly describe human neurodegenerative diseases (NDs) and the experimental models used to study them. The main focus is the yeast Saccharomyces cerevisiae as an experimental model used to study neurodegenerative processes. We review recent experimental data on the aggregation of human neurodegenerative disease-related proteins in yeast cells. In addition, we describe the results of studies that were designed to investigate the molecular mechanisms that underlie the aggregation of reporter proteins. The advantages and disadvantages of the experimental approaches that are currently used to study the formation of protein aggregates are described. Special attention is given to the similarity between aggregates that form as a result of protein misfolding and viral factories-special structural formations in which viral particles are formed inside virus-infected cells. A separate part of the review is devoted to our previously published study on the formation of aggregates upon expression of the insect densovirus capsid protein in yeast cells. Based on the reviewed results of studies on NDs and related protein aggregation, as well as viral protein aggregation, a new experimental model system for the study of human NDs is proposed. The core of the proposed system is a comparative transcriptomic analysis of changes in signaling pathways during the expression of viral capsid proteins in yeast cells.

Unsupervised machine learning and geometric morphometrics as tools for the identification of inter and intraspecific variations in the Anopheles Maculipennis complex.

Geometric morphometric analysis was combined with two different unsupervised machine learning algorithms, UMAP and HDBSCAN, to visualize morphological differences in wing shape among and within four Anopheles sibling species (An. atroparvus, An. melanoon, An. maculipennis s.s. and An. daciae sp. inq.) of the Maculipennis complex in Northern Italy. Specifically, we evaluated: (1) wing shape variation among and within species; (2) the consistencies between groups of An. maculipennis s.s. and An. daciae sp. inq. identified based on COI sequences and wing shape variability; and (3) the spatial and temporal distribution of different morphotypes. UMAP detected at least 13 main patterns of variation in wing shape among the four analyzed species and mapped intraspecific morphological variations. The relationship between the most abundant COI haplotypes of An. daciae sp. inq. and shape ordination/variation was not significant. However, morphological variation within haplotypes was reported. HDBSCAN also recognized different clusters of morphotypes within An. daciae sp. inq. (12) and An. maculipennis s.s. (4). All morphotypes shared a similar pattern of variation in the subcostal vein, in the anal vein and in the radio-medial cross-vein of the wing. On the contrary, the marginal part of the wings remained unchanged in all clusters of both species. Any spatial-temporal significant difference was observed in the frequency of the identified morphotypes.  Our study demonstrated that machine learning algorithms are a useful tool combined with geometric morphometrics and suggest to deepen the analysis of inter and intra specific shape variability to evaluate evolutionary constrains related to wing functionality.

Psychometric Properties of the Interpersonal Needs Questionnaire-15 in Spanish Adolescents.

Background: Thwarted Belongingness (TB) and Perceived Burdensomeness (PB) are considered risk factors of suicide behavior in the Interpersonal Theory of Suicide and constitute the main factors of the Interpersonal Needs Questionnaire-INQ. Aims: The present study analyzes the internal consistency, construct validity, and invariance across sex and age of the INQ-15, which comprises two subscales, in a sample of Spanish community adolescents. Methods: Participants were 1,536 adolescents from 12 to 19 years old. The INQ-15, the total number of non-suicidal self-injuries (NSSI), the Hopelessness Scale, and the Purpose in Life Test-Adolescents (PIL-A) were used. Results: The INQ-15 showed good internal consistency for TB ( ω ¯ = 0.88) and PB ( ω ¯ = 0.78) subscales and construct and concurrent/discriminant validity in the whole sample. Both the PB and TB subscales showed a good fit { S B χ 2 ( 9 ) = 6.448, p = 0.694, CFI = 1.000, RMSEA = 0.000 [90% CI (0.000, 0.022)] and S B χ 2 ( 27 ) = 248.973, p = 0.000, CFI = 0.922, RMSEA = 0.073 [90% CI (0.065, 0.082)]}, respectively. Regarding the invariance analyses, we found (1) non-invariance in the PB subscale across sex groups and metric, scalar, and stric invariance across age groups, and (2) that it was not possible to perform the invariance analysis for the TB subscale across both sex and age because the fit was not adequate for both boys and 12-15 years old groups. Positive and significant relationships were found between the INQ-15 subscales and hopelessness and NSSI frequency, and negative and significant correlations with meaning in life. Conclusions: The INQ-15 is a valid instrument for assessing TB and PB in Spanish adolescents. Future studies should analyze the invariance of this instrument in adolescents across sex and age.

The Association Among Maternal Index of Nutritional Quality, Dietary Antioxidant Index, and Odds of Miscarriage Incidence: Case-Control Study.

OBJECTIVE: Miscarriage is a pregnancy condition in which the fetus or embryo naturally dies before being able to survive independently. According to studies, diet and dietary factors are associated with the risk of miscarriage (pregnancies <20 weeks). A 168-item semi-quantitative feed frequency questionnaire was used to estimate the Dietary Antioxidant Index (DAI) and the Index of Nutritional Quality (INQ). We aimed to assess the relationship between INQ and DAI with odds of miscarriage. METHOD: In summary, 135 Iranian women with a history of three or more miscarriages were included. We calculated the INQ using the following formula: INQ = consumed amount of a nutrient per 1,000 kcal/Recommended Dietary Allowance of that nutrient per 1,000 kcal. We standardized each dietary vitamins/minerals by subtracting the global mean and dividing the result by the universal standard deviation to compute DAI. We computed the DAI by summing up the standardized intakes of these vitamins and minerals and equal weight. RESULTS: Regression models were used to extract the odds ratios (ORs) and 95% confidence intervals (CIs) in crude and multivariate adjustments. Controls significantly had higher INQ of vitamin B12, niacin, vitamin D, vitamin E, vitamin C, and zinc. Modeling INQs of vitamin D (OR: 0.004, 95% CI, 0.00-0.025) and B12 (OR: 0.04, 95% CI, 0.005-0.41) as a continuous variable showed a significant and protective effect in multivariate adjustment. Modeling DAI as a categorical variable showed a significant protective effect (ORDAI<0.054vs.DAI ≥0.054 = 0.43, 95% CI, 0.20-0.91). CONCLUSIONS: Recommending a diet rich in antioxidants such as vitamin E, C, zinc, and selenium and a quality diet containing vitamins B12 and D can be considered an effective strategy to reduce the odds of miscarriage in women with a history of recurrent miscarriage.

The role of dietary antioxidant index and index of nutritional quality in MS onset: finding from an Iranian population-based incident case-control study.

METHODS: This was a large population-based case-control study recruiting 547 incident cases and 1057 population controls between August 2013 and February 2015. DAI and INQ were calculated based on the adolescence dietary intake of the participants. Logistic regression was employed for estimating adjusted odds ratios (OR) and their 95% confidence interval in 2018. RESULTS: Participants with less than median DAI values had two-fold increased risk of MS onset (adjusted OR 2.05, 95% CI: 1.64-2.58, P < 0.001). A significant dose-response pattern for DAI (adjusted OR 1.35, 95% CI: 1.18-1.55, P for trend <0.001) was also detected. In the case of INQ, the strongest decreased risk were detected for vitamin D (OR = 0.09) and Zinc (OR = 0.34), followed by vitamin A (OR = 0.49), Calcium (OR = 0.49) and vitamin B6 (OR = 0.51) (All P-values < 0.05). CONCLUSION: Considering the inherent limitation of case-control designs, an appropriate intake of nutrient antioxidants may have a role in decreasing the likelihood of MS risk. Moreover, those with healthier diet assessed by index of nutritional quality were at decreased risk for MS.

Examining psychometric properties of the Interpersonal Needs Questionnaire among college students in India.

BACKGROUND: With the second-highest population in the world, suicide-related deaths in India are high, and adults under 30 are particularly at an increased risk. However, empirical examinations of factors contributing to suicide in India and assessments of reliability and validity of self-report measures assessing these constructs are rare. AIMS: The present study examined the psychometric properties of the Interpersonal Needs Questionnaire (INQ). MATERIALS & METHODS: Undergraduate students in India (N = 432) completed the INQ and questionnaires assessing suicidal ideation, depression, fearlessness about death, and pain tolerance. RESULTS: Confirmatory factor analyses of the 15-item INQ indicated that after removing three items assessing perceived burdensomeness, the two-factor structure of INQ demonstrated acceptable fit with good internal consistency for each of the subscales (α = .84-.90). In line with the interpersonal-psychological theory of suicidal behavior (IPTS), thwarted belongingness and perceived burdensomeness interacted to predict suicidal ideation. Additionally, these constructs were positively associated with suicidal ideation and depression, and weakly correlated with fearlessness about death and pain tolerance. DISCUSSION: Results support the relevance of the IPTS for understanding suicidal ideation among college students in India. CONCLUSION: The results suggest that modified INQ demonstrates strong internal consistency, as well as good construct, criterion, and discriminant validity among Indian college students.

Age-Specific Association Between Handgrip Strength and Nutritional Quality in Korean Men: A Nationwide Cross-Sectional Study.

This study aimed to determine the potential association between handgrip strength and nutritional quality in Korean men aged ≥20 years using data from the Korea National Health and Nutrition Examination Survey 2016 to 2018. This population-based cross-sectional study included 5,748 men aged ≥20 years. A dietary intake survey was performed using the 24-hr dietary recall method. Nutritional quality was examined using the Index of Nutritional Quality (INQ) score. A high INQ score reflected poor nutritional quality, with insufficient intake of many nutrients. Multivariate linear regression was used to determine the association between handgrip strength and INQ scores after adjusting for other covariates. The intake of carbohydrates, fiber, calcium, and vitamins B2 and C was significantly positively associated with a higher quartile for handgrip strength for those aged ≥65 years (all p < .01). A significant inverse association was found between the quartiles of handgrip strength and INQ scores among men aged ≥65 years after adjusting for all covariates (ß = -0.26, p < .01). This association was not found among those aged <65 years (p = .25). The age-specific association between handgrip strength and nutritional quality underscores the importance of public policies that promote sufficient and comprehensive nutrient intake among older adults. Handgrip strength may be useful in clinical practice as a simple and cost-effective tool for screening for nutritional quality in older adults.

Proteotoxicity: A Fatal Consequence of Environmental Pollutants-Induced Impairments in Protein Clearance Machinery.

A tightly regulated protein quality control (PQC) system maintains a healthy balance between correctly folded and misfolded protein species. This PQC system work with the help of a complex network comprised of molecular chaperones and proteostasis. Any intruder, especially environmental pollutants, disrupt the PQC network and lead to PQCs disruption, thus generating damaged and infectious protein. These misfolded/unfolded proteins are linked to several diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and cataracts. Numerous studies on proteins misfolding and disruption of PQCs by environmental pollutants highlight the necessity of detailed knowledge. This review represents the PQCs network and environmental pollutants' impact on the PQC network, especially through the protein clearance system.

Index of Nutritional Quality (INQ) and the Risk of Obesity in Male Adolescents: a Case-Control Study.

Dietary factors may play a key role in the etiology of obesity. The Index of Nutritional Quality (INQ) provides a comprehensive overview of the nutrients content of the diet. This study aimed to investigate the association between INQ and obesity in male adolescents. We hypothesize that receiving a high-quality diet reduces the risk of overweight or obese. This study was carried out on 214 obese/overweight as the case group and 321 normal-weight male adolescents as the control group. Dietary intakes of the participants were collected using a food frequency questionnaire (FFQ). The FFQ-derived dietary data were used to calculate the INQ scores. After adjustments for age and height, an inverse association was found between obesity and INQ of iron, vitamin B6, and magnesium, and a positive association was found between obesity and INQ of zinc (all P < 0.05). After further adjustments for nutritional knowledge and calorie intake, an inverse association was observed between obesity and INQ of vitamin C, iron, vitamin B6, pantothenic acid, selenium, and magnesium (all P < 0.05). The positive association of obesity and INQ of zinc remained significant after adjustments. A higher intake of vitamin C, iron, vitamin B6, pantothenic acid, selenium, and magnesium and a lower intake of zinc may be protective against adolescent obesity. More longitudinal studies are required to investigate the relationship between these nutrients and obesity.

Psychometric properties of the Italian version of the Interpersonal Needs Questionnaire-15 (INQ-15-I).

OBJECTIVE: The Interpersonal Needs Questionnaire (INQ-15) is a self-report measure of thwarted belongingness and perceived burdensomeness, two constructs associated with suicidal ideation. The objective of the current study was to translate the INQ-15 from English to Italian (INQ-15-I) and to test its factor structure, reliability, and validity in Italian samples. METHOD: We examined (a) whether the components of the hypothesized two-factor measurement model are invariant across a community sample (N = 510) and a clinical sample (N = 259); (b) the relations between the INQ-15-I factors and measures of depression (Beck Depression Inventory-II), hopelessness (Beck Hopelessness Scale), and suicidal ideation (Beck Scale for Suicide Ideation); (c) the reliability and psychometric properties of the INQ-15-I. RESULTS: Results from multigroup confirmatory factor analyses supported the adequacy of the two-factor model to represent thwarted belongingness and perceived burdensomeness. The model is invariant across community and clinical groups, showing excellent fit. The two INQ-15-I scales measure highly intercorrelated constructs. Both significantly correlate with depression, hopelessness, and suicidal ideation, and correlations are high in the clinical sample. CONCLUSION: The INQ-15-I is a valid and reliable measure of thwarted belongingness and perceived burdensomeness. Implications for research, assessment, and intervention in suicidal ideation are discussed.

Cdc48 regulates intranuclear quality control sequestration of the Hsh155 splicing factor in budding yeast.

Cdc48 (known as VCP in mammals) is a highly conserved ATPase chaperone that plays an essential role in the assembly and disassembly of protein-DNA complexes and in degradation of misfolded proteins. We find that in Saccharomyces cerevisiae budding yeast, Cdc48 accumulates during cellular stress at intranuclear protein quality control sites (INQ). We show that Cdc48 function is required to suppress INQ formation under non-stress conditions and to promote recovery following genotoxic stress. Cdc48 physically associates with the INQ substrate and splicing factor Hsh155, and regulates its assembly with partner proteins. Accordingly, cdc48 mutants have defects in splicing and show spontaneous distribution of Hsh155 to INQ aggregates, where it is stabilized. Overall, this study shows that Cdc48 regulates deposition of proteins at INQ and suggests a previously unknown role for Cdc48 in the regulation or stabilization of splicing subcomplexes.This article has an associated First Person interview with the first author of the paper.

Nutritional Quality's Key Role in the Odds of Overweight in Adults with rs9939609 Polymorphism of FTO Gene- the Role of Manganese and Vitamin D.

BACKGROUND: Obesity and overweight are the most prevailing problem in most countries. Overweight people are very susceptible to diseases such as diabetes, hypertension, cardiovascular disease, metabolic syndrome, and cancers. Adequate intake of micronutrients along with a quality diet that is varied and balanced plays an important role regarding health and the immune system. Numerous studies have investigated the relationship between the quality of diet and different diseases. Genetics is a risk factor of great importance regarding obesity and overweight. Yet, the role of nutrition in relationship with the underlying mechanisms remains unclear and no specific pathways have been identified for this relation. METHODS: A valid food frequency questionnaire was employed to assess dietary intake. We calculated the INQ (Index of Nutritional Quality) of each dietary item using the following formulae: INQ=consumed amount of a nutrient per 1,000 kcal/recommended dietary allowance or adequate intake of that nutrient per 1,000 kcal. In a retrospective chart review, we determined the genotypes of FTO rs9939609 polymorphism (TT/AT/AA) via amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: Models obtained from the resulting INQs of manganese as a continuous variable in relationship with waist circumference represented a significant association after multivariate adjustment of age, sex, height, fat free mass, weight, body mass index, marital status, TF, fasting blood sugar, low-density lipoproteins, high-density lipoproteins, total cholesterol, insulin resistance, and total energy intake (odds ratio = 0.24, CI = 0.07-0.79). CONCLUSIONS: Intake of vitamin D from sunlight and its nutritional sources and adequate intake of Mn from a wide range of vegetables, legumes, seeds, and grains might be solutions for some overweight cases with FTO rs9939609 polymorphism.

INQ-15 cut-off scores for suicidal ideation screening of women with chronic, invisible illnesses.

In the interpersonal theory of suicide, perceived burdensomeness (PB) and thwarted belongingness (TB) are proximal triggers of suicidal ideation. Using the 15-item version of the Interpersonal Needs Questionnaire (INQ-15), suicidal ideation in psychiatric inpatients was predicted by the PB and TB scales, and cut-off scores were recommended. In this study, women (N = 942) who reported one or more chronic, invisible illnesses completed an online survey including the INQ-15 and the Suicide Behaviours Questionnaire-Revised (SBQ-R). PB and TB correlated significantly with SBQ-R total scores (r = 0.575 and 0.437, respectively; p < 0.01). In a Receiver Operating Characteristic analysis, scores of 17 for PB and 37 for TB maximized the correct classification of high-risk and low-risk participants, with slightly higher classification accuracy for PB than TB (AUCs = 0.781 and 0.701, respectively). These results support the INQ-15 scales in screening for suicidal ideation among chronically ill women.

Applying the food multimix concept for sustainable and nutritious diets.

Despite a rich and diverse ecosystem, and biodiversity, worldwide, more than 2 billion people suffer from micronutrient malnutrition or hidden hunger. Of major concern are a degradation of our ecosystems and agricultural systems which are thought to be unsustainable thereby posing a challenge for the future food and nutrition security. Despite these challenges, nutrition security and ensuring well balanced diets depend on sound knowledge and appropriate food choices in a complex world of plenty and want. We have previously reported on how the food multimix (FMM) concept, a food-based and dietary diversification approach can be applied to meet energy and micronutrient needs of vulnerable groups through an empirical process. Our objective in this paper is to examine how the concept can be applied to improve nutrition in a sustainable way in otherwise poor and hard-to-reach communities. We have reviewed over 100 FMM food recipes formulated from combinations of commonly consumed traditional candidate food ingredients; on average five per recipe, and packaged as per 100 g powders from different countries including Ghana, Kenya, Botswana, Zimbabawe and Southern Africa, India, Mexico, Malaysia and the UK; and for different age groups and conditions such as older infants and young children, pregnant women, HIV patients, diabetes and for nutrition rehabilitation. Candidate foods were examined for their nutrient strengths and nutrient content and nutrient density of recipes per 100 g were compared with reference nutrient intakes for the different population groups. We report on the nutrient profiles from our analysis of the pooled and age-matched data as well as sensory analysis and conclude that locally produced FMM foods can complement local diets and contribute significantly to meet nutrient needs among vulnerable groups in food-insecure environments.

Three Ca2+ channel inhibitors in combination limit chronic secondary degeneration following neurotrauma.

Following neurotrauma, cells beyond the initial trauma site undergo secondary degeneration, with excess Ca2+ a likely trigger for loss of neurons, compact myelin and function. Treatment using inhibitors of specific Ca2+ channels has shown promise in preclinical studies, but clinical trials have been disappointing and combinatorial approaches are needed. We assessed efficacy of multiple combinations of three Ca2+ channel inhibitors at reducing secondary degeneration following partial optic nerve transection in rat. We used lomerizine to inhibit voltage gated Ca2+ channels; oxidised adenosine-triphosphate (oxATP) to inhibit purinergic P2X7 receptors and/or 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-1,2,3,4-tetrahydro quinoxalin-1-yl]acetic acid (INQ) to inhibit Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Only the three Ca2+ channel inhibitors delivered in combination significantly preserved visual function, as assessed using the optokinetic nystagmus visual reflex, at 3 months after injury. Preservation of retinal ganglion cells was partial and is unlikely to have accounted for differential effects on function. A range of the Ca2+ channel inhibitor combinations prevented swelling of optic nerve vulnerable to secondary degeneration. Each of the treatments involving lomerizine significantly increased the proportion of axons with normal compact myelin. Nevertheless, limiting decompaction of myelin was not sufficient for preservation of function in our model. Multiple combinations of Ca2+ channel inhibitors reduced formation of atypical node/paranode complexes; outcomes were not associated with preservation of visual function. However, prevention of lengthening of the paranodal gap that was only achieved by treatment with the three Ca2+ channel inhibitors in combination was an important additional effect that likely contributed to the associated preservation of the optokinetic reflex using this combinatorial treatment strategy.