Late‐life time‐restricted feeding and exercise differentially alter healthspan in obesity

Aging and obesity increase multimorbidity and disability risk, and determining interventions for reversing healthspan decline is a critical public health priority. Exercise and time‐restricted feeding (TRF) benefit multiple health parameters when initiated in early life, but their efficacy and safety when initiated at older ages are uncertain. Here, we tested the effects of exercise versus TRF in diet‐induced obese, aged mice from 20 to 24 months of age. We characterized healthspan across key domains: body composition, physical, metabolic, and cardiovascular function, activity of daily living (ADL) behavior, and pathology. We demonstrate that both exercise and TRF improved aspects of body composition. Exercise uniquely benefited physical function, and TRF uniquely benefited metabolism, ADL behavior, and circulating indicators of liver pathology. No adverse outcomes were observed in exercised mice, but in contrast, lean mass and cardiovascular maladaptations were observed following TRF. Through a composite index of benefits and risks, we conclude the net healthspan benefits afforded by exercise are more favorable than those of TRF. Extrapolating to obese older adults, exercise is a safe and effective option for healthspan improvement, but additional comprehensive studies are warranted before recommending TRF.     

Tortulomyces thailandicus gen. et sp. nov. and Nitschkia siamensis sp. nov. (Coronophorales,Ascomycota) from northern Thailand

Two new species collected in northern Thailand are herein described and discussed. Tortulomyces thailandicus is the type of a new genus characterized by a combination of such features as a dense subiculum, non-ostiolate ascomata, two kinds of paraphyses (filiform and bead-like), and 1-septate, brown ascospores. Nitschkia siamensis has non-ostiolate, turbinate and stalked ascomata and hyaline, often slightly curved, 1-septate ascospores.     

Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same “fast-spiking” phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species.     

The antioxidant enzymes activity in leaves of inter-varietal substitution lines of wheat (Triticum aestivum L.) with different tolerance to soil water deficit

Understanding of the genetic basis of physiological properties, which are most relevant to water-deficit tolerance would be helpful for genomic-assisted improvement of bread wheat. A set of bread wheat inter-varietal single chromosome substitution lines (ISCSLs) of variety ‘Janetzkis Probat’ (JP) in the genetic background of ‘Saratovskaya’ 29 (S29) were used to reveal the critical chromosomes in wheat genome controlling tolerance to water deficit. The same lines were involved in the identification of chromosomes associated with the activity of antioxidant enzymes that are closely related to the detoxification of H₂O₂ [catalase (CAT), ascorbate peroxidase, dehydroascorbate reductase and glutathione reductase (GR)]. The recipient cultivar S29 was highly drought tolerant while the donor JP was sensitive. Using non-metric multidimensional scaling of yield components and indices of drought tolerance/susceptibility chromosomes 2A and 4D, substitution in the genetic background of S29 was found to lead to a critical decrease of water-deficit tolerance. The drop of tolerance correlated with a sharp decline of cumulative activity of the catalase and the enzymes of ascorbate–glutathione cycle in wheat leaves. Clear evidence was obtained for the involvement of genes present on the homoeologous group 2 chromosomes in the control of GR and CAT activity. Substitution of the chromosome 4D had a significant reducing impact on the CAT activity level.     

The cis-Regulatory Atlas of the Mouse Immune System

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Prediagnostic Serum Biomarkers as Early Detection Tools for Pancreatic Cancer in a Large Prospective Cohort Study

BackgroundThe clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.MethodsSixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).ResultsThe panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.ConclusionsMost biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.     

Morpho-functional features in adolescent males under iodine deficiency of the Saratov region

An auxological study of 538 adolescent males (from 12 to 17) from different settlements of the Saratov region with various degrees of industrialization and iodine deficiency was carried out. All subjects have undergone an ultra-sound screening of thyroid volume to reveal the frequency of endemic goiter in each group. The results obtained during investigation showed the existence of deviations in the physical development of boys with goiter in skinfold thickness, body circumferences (chest, shoulder, and forearm), biacromial and biiliocristal diameters, transversal and sagittal chest diameters, body height and weight, BMI, leg length, and corpus length, all of which are greater in healthy adolescents (SD = 1.0, p = 0.000). In 46 subjects with endemic goiter, characteristics of metabolic status were investigated by the method of registration of endogenous intoxication (Malakhova, 1995). In comparison to the control group, a 1.2 times lower LAMM level in erythrocytes (p < 0.05) and 1.1 in urine (p < 0.05), and an increase by 2.3 in the LAMM level in blood plasma (p < 0.01) were detected. The relative percentage of catabolic substances exceeded the control values by 3.2 (p < 0.001). The OP level in erythrocytes is reduced by 2.2 (p < 0.01), in urine (p < 0.01) by 8.4. The OP level is higher in plasma by 3.0 (p < 0.01). The adolescents with endemic goiter have a reallocation of protein matter between erythrocytes, plasma and urine. The spectrogram of erythrocytes shows lowering metabolites on membrane frames, which testifies to the destruction of the structurally functional properties of erythrocytes, and a lowering of absorption properties in glycocalix erythrocytes.