Hidden supersymmetries in supersymmetric quantum mechanics

We discuss the appearance of additional, hidden supersymmetries for simple 0+1 $Ad(G)$-invariant supersymmetric models and analyse some geometrical mechanisms that lead to them. It is shown that their existence depends crucially on the availability of odd order invariant skewsymmetric tensors on the (generic) compact Lie algebra $\cal G$, and hence on the cohomology properties of the Lie algebra considered.Comment: Misprints corrected, two refs. added. To appear in NP

Assessing daily energy intake in adult women:validity of a food-recognition mobile application compared to doubly labelled water

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland–Altman plots, paired difference tests, and Pearson’s correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = −329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = −543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p &lt; 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).</p

Assessing daily energy intake in adult women:validity of a food-recognition mobile application compared to doubly labelled water

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland–Altman plots, paired difference tests, and Pearson’s correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = −329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = −543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p &lt; 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).</p

Assessing daily energy intake in adult women:validity of a food-recognition mobile application compared to doubly labelled water

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland–Altman plots, paired difference tests, and Pearson’s correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = −329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = −543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p &lt; 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).</p

Assessing daily energy intake in adult women:validity of a food-recognition mobile application compared to doubly labelled water

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland–Altman plots, paired difference tests, and Pearson’s correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = −329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = −543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p &lt; 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).</p

Identification of an Allosteric Small-Molecule Inhibitor Selective for the Inducible Form of Heat Shock Protein 70

Inducible Hsp70 (Hsp70i) is overexpressed in a wide spectrum of human tumors and its expression correlates with metastasis, poor outcomes, and resistance to chemotherapy in patients. Identification of small molecule inhibitors selective for Hsp70i could provide new therapeutic tools for cancer treatment. In this work, we used fluorescence-linked enzyme chemoproteomic strategy (FLECS) to identify HS-72, an allosteric inhibitor selective for Hsp70i. HS-72 displays the hallmarks of Hsp70 inhibition in cells, promoting substrate protein degradation and growth inhibition. Importantly, HS-72 is selective for Hsp70i over the closely related constitutively active Hsc70. Studies with purified protein show HS-72 acts as an allosteric inhibitor, reducing ATP affinity. In vivo HS-72 is well-tolerated, showing bioavailability and efficacy, inhibiting tumor growth and promoting survival in a HER2+ model of breast cancer. The HS-72 scaffold is amenable to resynthesis and iteration, suggesting an ideal starting point for a new generation of anticancer therapeutics targeting Hsp70i

The free-energy self:A predictive coding account of self-recognition

Recognising and representing one's self as distinct from others is a fundamental component of self-awareness. However, current theories of self-recognition are not embedded within global theories of cortical function and therefore fail to provide a compelling explanation of how the self is processed. We present a theoretical account of the neural and computational basis of self-recognition that is embedded within the free-energy account of cortical function. In this account one's body is processed in a Bayesian manner as the most likely to be "me". Such probabilistic representation arises through the integration of information from hierarchically organised unimodal systems in higher-level multimodal areas. This information takes the form of bottom-up "surprise" signals from unimodal sensory systems that are explained away by top-down processes that minimise the level of surprise across the brain. We present evidence that this theoretical perspective may account for the findings of psychological and neuroimaging investigations into self-recognition and particularly evidence that representations of the self are malleable, rather than fixed as previous accounts of self-recognition might suggest

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg2/σP2= 25%, h2= 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10-5were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P&lt;10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P&lt;5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe