Abdominal obesity: prevalence, sociodemographic- and lifestyle-associated factors in adolescents

Objectives: The aim of this study was to determine the prevalence of abdominal obesity and its associated factors among adolescents, independent of confounders. Methods: A sample of 14–17-year-old individuals (n=1.231), who were students from Londrina/PR-Brazil public schools, was studied. A questionnaire about physical activity, sedentary behaviour and socioeconomic conditions was applied. Anthropometry was composed of body weight (kg), height (m), body mass index (BMI=kg/m²) and waist circumference (cm). The association of abdominal obesity and independent variables was assessed using the chi-square test and the magnitude of associations was verified using Binary Logistic Regression in an unadjusted model and adjusted for confounders (gender, age, socioeconomic status, physical activity and sedentary behaviour). The confidence interval and statistical significance were set at 95% and 5%, respectively, using SPSS v15.0. Results: The abdominal obesity prevalence was 17.5% (CI = 15.4%–19.6%), and was higher in boys than in girls. Adolescents with abdominal obesity had higher values of body weight, height, body mass index and sedentary behaviour compared to eutrophic individuals. Being male increased the risk of abdominal obesity by 36% in adolescents. This risk was two times higher in those with high levels of sedentary behaviour. Conclusion: Abdominal obesity was significantly associated with gender and high levels of sedentary behaviour, regardless of confounding factors. Lifestyle habits are important modifiable risk factors that can effectively contribute to the reduction of obesity from an early age

Biología reproductiva de Helianthemum apenninum (L.) Mill. y H. caput-felis Boiss. (Cistaceae) de Mallorca (Islas Baleares, España)

The study of reproductive biology of natural populations of Helianthemum apenninum and H. caput-felis from Majorca, has demonstrated them to be basically entomophilous, although they also produce many fruits by self-pollination. H. caput-felis flowers last for four days, while H. apenninum flowers last for one day, as ussualy occurs in other species of the genus. In the H. appeninum population, severe ungulate predation affects 50% of the plants. In germination tests, the optimum temperature was 16°C for H. apenninum and 23 °C for H. caput-felis. H. caput-felis shows high interannual germination variability. In the naturally occurring population of H. caput-felis, it has been observed atelechory, and related to this, the germination of the seeds covered by the fruit capsule.El estudio de la biología reproductiva de poblaciones naturales de Helianthemum apenninum y H. caput-felis en Mallorca ha demostrado que son básicamente entomófilos, aunque también producen numerosos frutos por auto-polinización. Las flores de H. caput-felis duran cuatro dias, mientras que las de H. apettninum duran uno, como suele ocurrir en otras especies del género. En la población de H. apenninum, la predación por ungulados afecta al 50% de los individuos. Los test de germinación mostraron una temperatura óptima de germinación de 16°C para H. apenninum y de 23°C para H. caput-felis. H. caput-felis muestra una importante variabilidad interanual en su comportamiento germinativo. En las poblaciones naturales de H. caput-felis, se ha observado atelecoria, y en relación con ésta, las semillas germinan dentro de la cápsula

Slab Driven Quaternary Rock‐Uplift and Topographic Evolution in the Northern‐Central Apennines From Linear Inversion of the Drainage System

Investigating rock-uplift variations in time and space provides insights into the processes driving mountain-belt evolution. The Apennine Mountains of Italy underwent substantial Quaternary rock uplift that shaped the present-day topography. Here, we present linear river-profile inversions for 28 catchments draining the eastern flank of the Northern-Central Apennines to reconstruct rock-uplift histories. We calibrated these results by estimating an erodibility coefficient (K) from incision rates and catchment-averaged erosion rates obtained from cosmogenic-nuclide data, and we tested whether a uniform or variable K produces a rock-uplift model that satisfactorily fits independent geochronological constraints. We employ a landscape-evolution model to demonstrate that our inversion results are reliable despite substantial seaward lengthening of the catchments during uplift. Our findings suggest that a rock-uplift pulse started around 3.0-2.5 Ma, coinciding with the onset of extension in the Apennines, and migrated southward at a rate of similar to 90 km/Myr. The highest reconstructed rock-uplift rates (>1 km/Myr) occur in the region encompassing the highest Apennine massifs. These results are consistent with numerical models and field evidence from other regions exhibiting rapid rock-uplift pulses and uplift migration related to slab break-off. Our results support the hypothesis of break-off of the Adria slab under the central Apennines and its southward propagation during the Quaternary. Moreover, the results suggest a renewed increase in rock-uplift rates after the Middle Pleistocene along the Adriatic coast, coeval with recent uplift acceleration along the eastern coast of southern Italy in the Apulian foreland

Composición en ácidos grasos de las margarinas de mayor consumo en España y su importancia nutricional

This study examines the fatty acid composition of margarines of major consumption in Spain in 2000. All the margarines contained at least 20% of linoleic acid, the average content of this fatty acid being 38%. Saturated fatty acids (lauric and miristic acids) did not exceed 4 % of the total fatty acid content. Most of the margarines analyzed contained less than 5% trans C18:1, although this content varied greatly among margarines (coefficient of variation: 112%) being median value 2.5%; polyunsaturated trans C18:2 and trans C18:3 did not represent more than 1 %. Nutritionally important ratios like saturated/unsaturated fatty acids, thrombogenicity and atherogenicity indexes were lower than 0.5. The findings suggest that Spanish margarines have moved to becoming products with a potentially healthier distribution of fatty acids. Even so, the great variability shown in fatty acid composition of margarines and poor labeling, highlight the importance of greater consumer information to avoid upsetting the traditional Mediterranean diet of SpainEste estudio examina la composición de ácidos grasos de las margarinas de mayor consumo en España en el año 2000, incluyendo ácidos grasos trans. Todas las margarinas contenían al menos 20% de linoleico, siendo el contenido medio del 38%. Los ácidos grasos saturados (laúrico y mirístico) no sobrepasaron el 4% del total de ácidos grasos. La mayoría de las margarinas contenían menos del 5 % de ácidos grasos trans C18:1, aunque la variabilidad era elevada entre las distintas marcas (coeficiente de variación:112 %), siendo la mediana del 2.5 %; los ácidos grasos trans poliinsaturados C18:2 y C18:3 no representaron más del 1 %. Índices nutricionalmente importantes como el cociente ácidos grasos saturados/insaturados, índices trombogénico y aterogénico, fueron menores de 0,5. Los resultados sugieren que las margarinas españolas muestran un cambio hacia una distribución de ácidos grasos más saludable, aunque debido a la gran variabilidad en su composición, la información del etiquetado debe mejorar para evitar perturbaciones en la tradicional dieta Mediterránea de España

Annexin A6 Is Critical to Maintain Glucose Homeostasis and Survival During Liver Regeneration in Mice

Background and Aims: Liver regeneration requires the organized and sequential activation of events that lead to restoration of hepatic mass. During this process, other vital liver functions need to be preserved, such as maintenance of blood glucose homeostasis, balancing the degradation of hepatic glycogen stores, and gluconeogenesis (GNG). Under metabolic stress, alanine is the main hepatic gluconeogenic substrate, and its availability is the rate‐limiting step in this pathway. Na+‐coupled neutral amino acid transporters (SNATs) 2 and 4 are believed to facilitate hepatic alanine uptake. In previous studies, we demonstrated that a member of the Ca2+‐dependent phospholipid binding annexins, Annexin A6 (AnxA6), regulates membrane trafficking along endo‐ and exocytic pathways. Yet, although AnxA6 is abundantly expressed in the liver, its function in hepatic physiology remains unknown. In this study, we investigated the potential contribution of AnxA6 in liver regeneration. Approach and Results: Utilizing AnxA6 knockout mice (AnxA6−/−), we challenged liver function after partial hepatectomy (PHx), inducing acute proliferative and metabolic stress. Biochemical and immunofluorescent approaches were used to dissect AnxA6−/− mice liver proliferation and energetic metabolism. Most strikingly, AnxA6−/− mice exhibited low survival after PHx. This was associated with an irreversible and progressive drop of blood glucose levels. Whereas exogenous glucose administration or restoration of hepatic AnxA6 expression rescued AnxA6−/− mice survival after PHx, the sustained hypoglycemia in partially hepatectomized AnxA6−/− mice was the consequence of an impaired alanine‐dependent GNG in AnxA6−/− hepatocytes. Mechanistically, cytoplasmic SNAT4 failed to recycle to the sinusoidal plasma membrane of AnxA6−/− hepatocytes 48 hours after PHx, impairing alanine uptake and, consequently, glucose production. Conclusions: We conclude that the lack of AnxA6 compromises alanine‐dependent GNG and liver regeneration in mice

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation

Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer

BACKGROUND: In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting a higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study, we assess the potential value of adding white blood cells (WBCs) to tumor tissue sequencing to enhance the accuracy of sequencing results. PATIENTS AND METHODS: A total of 148 patients diagnosed with localized CC were prospectively recruited at the Hospital Clínico Universitario in Valencia (Spain). Employing a custom 29-gene panel, sequencing was conducted on tumor tissue, plasma and corresponding WBCs. Droplet digital PCR and amplicon-based NGS were performed on plasma samples post-surgery to track MRD. Oncogenic somatic variants were identified by annotating with COSMIC, OncoKB and an internal repository of pathogenic mutations database. A variant prioritization analysis, mainly characterized by the match of oncogenic mutations with the evidence levels defined in OncoKB, was carried out to select specific targeted therapies. RESULTS: Utilizing paired tumor and WBCs sequencing, we identified somatic mutations in all patients (100%) within our cohort, compared to 89% using only tumor tissue. Consequently, the top 10 most frequently mutated genes for plasma monitoring were altered. The sequencing of WBCs identified 9% of patients with pathogenic mutations in the germline, with APC and TP53 being the most frequently mutated genes. Additionally, mutations in genes related to clonal hematopoiesis of indeterminate potential were detected in 27% of the cohort, with TP53, KRAS, and KMT2C being the most frequently altered genes. There were no observed differences in the sensitivity of monitoring MRD using ddPCR or amplicon-based NGS (p = 1). Ultimately, 41% of the patients harbored potentially targetable alterations at diagnosis. CONCLUSION: The germline testing method not only enhanced sequencing results and raised the proportion of patients eligible for plasma monitoring, but also uncovered the existence of pathogenic germline variations, thereby aiding in the identification of patients at a higher risk of hereditary cancer syndromes

Uncoupling the functions of CALM in VAMP sorting and clathrin-coated pit formation.

CALM (clathrin assembly lymphoid myeloid leukemia protein) is a cargo-selective adaptor for the post-Golgi R-SNAREs VAMPs 2, 3, and 8, and it also regulates the size of clathrin-coated pits and vesicles at the plasma membrane. The present study has two objectives: to determine whether CALM can sort additional VAMPs, and to investigate whether VAMP sorting contributes to CALM-dependent vesicle size regulation. Using a flow cytometry-based endocytosis efficiency assay, we demonstrate that CALM is also able to sort VAMPs 4 and 7, even though they have sorting signals for other clathrin adaptors. CALM homologues are present in nearly every eukaryote, suggesting that the CALM family may have evolved as adaptors for retrieving all post-Golgi VAMPs from the plasma membrane. Using a knockdown/rescue system, we show that wild-type CALM restores normal VAMP sorting in CALM-depleted cells, but that two non-VAMP-binding mutants do not. However, when we assayed the effect of CALM depletion on coated pit morphology, using a fluorescence microscopy-based assay, we found that the two mutants were as effective as wild-type CALM. Thus, we can uncouple the sorting function of CALM from its structural role

KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

Contains fulltext : 96042.pdf (publisher's version ) (Open Access)BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis

‘Fractional Recovery’ Analysis of a Presynaptic Synaptotagmin 1-Anchored Endocytic Protein Complex

BACKGROUND: The integral synaptic vesicle protein and putative calcium sensor, synaptotagmin 1 (STG), has also been implicated in synaptic vesicle (SV) recovery. However, proteins with which STG interacts during SV endocytosis remain poorly understood. We have isolated an STG-associated endocytic complex (SAE) from presynaptic nerve terminals and have used a novel fractional recovery (FR) assay based on electrostatic dissociation to identify SAE components and map the complex structure. The location of SAE in the presynaptic terminal was determined by high-resolution quantitative immunocytochemistry at the chick ciliary ganglion giant calyx-type synapse. METHODOLOGY/PRINCIPLE FINDINGS: The first step in FR analysis was to immunoprecipitate (IP) the complex with an antibody against one protein component (the IP-protein). The immobilized complex was then exposed to a high salt (1150 mM) stress-test that caused shedding of co-immunoprecipitated proteins (co-IP-proteins). A Fractional Recovery ratio (FR: recovery after high salt/recovery with control salt as assayed by Western blot) was calculated for each co-IP-protein. These FR values reflect complex structure since an easily dissociated protein, with a low FR value, cannot be intermediary between the IP-protein and a salt-resistant protein. The structure of the complex was mapped and a blueprint generated with a pair of FR analyses generated using two different IP-proteins. The blueprint of SAE contains an AP180/X/STG/stonin 2/intersectin/epsin core (X is unknown and epsin is hypothesized), and an AP2 adaptor, H-/L-clathrin coat and dynamin scission protein perimeter. Quantitative immunocytochemistry (ICA/ICQ method) at an isolated calyx-type presynaptic terminal indicates that this complex is associated with STG at the presynaptic transmitter release face but not with STG on intracellular synaptic vesicles. CONCLUSIONS/SIGNIFICANCE: We hypothesize that the SAE serves as a recognition site and also as a seed complex for clathrin-mediated synaptic vesicle recovery. The combination of FR analysis with quantitative immunocytochemistry provides a novel and effective strategy for the identification and characterization of biologically-relevant multi-molecular complexes