Karyotype and C-banding analyses of haploid male chromosomes of Apis florea F.

Chromosomes, with detailed karyotype information (number, shape, total length, relative length, arm ratio and centromeric index) and C-banding patterns in the somatic division of haploid male of Apis florae in Iran are described. Samples were obtained from the colonies in south of Iran. Prior to the swarming season, drone-brood cells were added adjoining to the lower rows of the worker-brood cells. Testes from young larvae were removed, fixed in acetic acid methanol (1:3), and stored at -20°C. The slides pretreatment were made by usual air dry method. C-banding and staining was carried out by barium hydroxide and Giemsa solution. Sixteen chromosomes of this species were observed and divided into two groups, 4 metacentric (no.1, 4, 7, 11), 12 sub metacentric and sub telocentric

Genetic variation among pelt sheep population using microsatellite markers

Genetic variation in three Iranian pelt sheep breeds namely: Gray Shiraz, Zandi and Karakul were investigated using fifteen microsatellite loci. Genomic DNA was extracted from 360 blood samples by extraction kits and salting-out procedure with some modifications. The total number of alleles ranged from 6 to12 in loci. The fifteen tested loci were all polymorphic in the three breeds. The average direct count of heterozygosity overall loci in each tested breed was more than the expected heterozygosity. Tests of genotype frequencies for deviation from the Hardy-Weinberg equilibrium (HWE) were performed at each locus of overall breeds and revealed significant departure from HWE (P < 0.001) due to heterozygote excess. Polymorphism information content value in Gray Shiraz, Zandi and Karakul were 0.815, 0.808 and 0.808, respectively. Rate of inbreeding within the three breeds was not noticeable (global Fis = - 0.19). Low genetic differentiation was detected by estimation of Fst index between all pairs of breeds. Results showed that high level of genetic diversity was observed in pelt sheep. The phylogenetic tree based on Nei distances were drown using the neighbor-joining (NJ) and unweighted pair-group method using an arithmetic average (UPGMA). With both methods, Gray Shiraz and Karakul sheep populations were located together at one cluster and Zandi sheep population at another. The results can be useful in the development of breeding strategy for genetic improvement of pelt sheep in Iran. © 2010 Academic Journals

Muscle and tendon adaptations to moderate load eccentric vs. concentric resistance exercise in young and older males.

Resistance exercise training (RET) is well-known to counteract negative age-related changes in both muscle and tendon tissue. Traditional RET consists of both concentric (CON) and eccentric (ECC) contractions; nevertheless, isolated ECC contractions are metabolically less demanding and, thus, may be more suitable for older populations. However, whether submaximal (60% 1RM) CON or ECC contractions differ in their effectiveness is relatively unknown. Further, whether the time course of muscle and tendon adaptations differs to the above is also unknown. Therefore, this study aimed to establish the time course of muscle and tendon adaptations to submaximal CON and ECC RET. Twenty healthy young (24.5 ± 5.1 years) and 17 older males (68.1 ± 2.4 years) were randomly allocated to either isolated CON or ECC RET which took place 3/week for 8 weeks. Tendon biomechanical properties, muscle architecture and maximal voluntary contraction were assessed every 2 weeks and quadriceps muscle volume every 4 weeks. Positive changes in tendon Young's modulus were observed after 4 weeks in all groups after which adaptations in young males plateaued but continued to increase in older males, suggesting a dampened rate of adaptation with age. However, both CON and ECC resulted in similar overall changes in tendon Young's modulus, in all groups. Muscle hypertrophy and strength increases were similar between CON and ECC in all groups. However, pennation angle increases were greater in CON, and fascicle length changes were greater in ECC. Notably, muscle and tendon adaptations appeared to occur in synergy, presumably to maintain the efficacy of the muscle-tendon unit

Short-term, equipment-free high intensity interval training elicits significant improvements in the cardiorespiratory fitness of young adults irrespective of supervision

Introduction:Serious health implications from having low levels of cardiorespiratory fitness (CRF) and/or being overweight in young adulthood are carried forward into later life. High-intensity interval training (HIIT) is a time-effective, potent stimulus for improving CRF and indices of cardiometabolic health. To date, few studies have investigated the use of equipment-free HIIT or the impact of supervision for improving CRF via HIIT.Methods:Thirty healthy young adults (18-30 y) were randomised to 4 weeks equipment-free supervised HIIT (L-HIIT), unsupervised HIIT (H-HIIT) or no-intervention (CON). Measurements of CRF (anaerobic threshold (AT) and VO2peak (VO2)), blood pressure (BP), body mass index (BMI), blood glucose, plasma insulin and muscle architecture were performed at baseline and after the intervention.Results:Both HIIT protocols improved CRF (AT: L-HIIT mean difference (MD) +2.1 (95% CI: 0.34 to 4.03) ml/kg/min; p=0.02; H-HIIT MD +3.01 (1.17 to 4.85) ml/kg/min; p=0.002), VO2: L-HIIT MD +2.94 (0.64 to 5.25) ml/kg/min; p=0.01; H-HIIT MD +2.55 (0.34 to 4.76) ml/kg/min; p=0.03), BMI (L-HIIT MD 0.18 (-0.35 to 0.5) kg/m2; p=0.04; H-HIIT: MD 0.19 (-0.25 to 0.63) kg/m2; p=0.03) and m. vastus lateralis pennation angle (L-HIIT MD 0.2 (0.13 to 0.27)º; p[less than]0.001; H-HIIT MD 0.17 (0.09 to 0.24)º; p[less than]0.001). There was no significant change in BP, glucose or insulin in any of the groups.Conclusions:Four weeks’ time-efficient, equipment-free, bodyweight-based HIIT ais able to elicit improvements in CRF irrespective of supervision status. Unsupervised HIIT may be a useful tool for counteracting the rise of sedentary behaviours and consequent cardiometabolic disorders in young adults

Spaceflight Induces Strength Decline in Caenorhabditis elegans

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Raw RNA sequencing data are deposited in the NCBI Sequence Read Archive with links to BioProject ID PRJNA1026503 (https://www.ncbi.nlm.nih.gov/bioproject/).Background: Understanding and countering the well-established negative health consequences of spaceflight remains a primary challenge preventing safe deep space exploration. Targeted/personalized therapeutics are at the forefront of space medicine strategies, and cross-species molecular signatures now define the 'typical' spaceflight response. However, a lack of direct genotype-phenotype associations currently limits the robustness and, therefore, the therapeutic utility of putative mechanisms underpinning pathological changes in flight. Methods: We employed the worm Caenorhabditis elegans as a validated model of space biology, combined with 'NemaFlex-S' microfluidic devices for assessing animal strength production as one of the most reproducible physiological responses to spaceflight. Wild-type and dys-1 (BZ33) strains (a Duchenne muscular dystrophy (DMD) model for comparing predisposed muscle weak animals) were cultured on the International Space Station in chemically defined media before loading second-generation gravid adults into NemaFlex-S devices to assess individual animal strength. These same cultures were then frozen on orbit before returning to Earth for next-generation sequencing transcriptomic analysis. Results: Neuromuscular strength was lower in flight versus ground controls (16.6% decline, p < 0.05), with dys-1 significantly more (23% less strength, p < 0.01) affected than wild types. The transcriptional gene ontology signatures characterizing both strains of weaker animals in flight strongly corroborate previous results across species, enriched for upregulated stress response pathways and downregulated mitochondrial and cytoskeletal processes. Functional gene cluster analysis extended this to implicate decreased neuronal function, including abnormal calcium handling and acetylcholine signaling, in space-induced strength declines under the predicted control of UNC-89 and DAF-19 transcription factors. Finally, gene modules specifically altered in dys-1 animals in flight again cluster to neuronal/neuromuscular pathways, suggesting strength loss in DMD comprises a strong neuronal component that predisposes these animals to exacerbated strength loss in space. Conclusions: Highly reproducible gene signatures are strongly associated with space-induced neuromuscular strength loss across species and neuronal changes in calcium/acetylcholine signaling require further study. These results promote targeted medical efforts towards and provide an in vivo model for safely sending animals and people into deep space in the near future.NASABiotechnology and Biological Sciences Research Council (BBSRC)Engineering and Physical Sciences Research Council (EPSRC)Osteopathic Heritage Foundatio

Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men

Higher plasma leucine, isoleucine and valine (BCAA) concentrations are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. Fasting plasma BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m2; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m2; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m2; 46 ± 8 y) then underwent 6-weeks of VLCD (600–800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, p < 0.001). Despite significant weight loss (baseline 103.9 ± 12.3 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m2), no changes were observed in BCAAs after 6-weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19 ± 0.62 to 0.51 ± 0.21 post-VLCD; p < 0.001), Pearson’s r revealed no relationships between BCAA and HOMA-IR, either before (leucine R2: 2.49e−005, p = 0.98; isoleucine R2: 1.211−e006, p = 0.9; valine R2: 0.004, p = 0.85) or after VLCD (leucine R2: 0.003, p = 0.86; isoleucine R2: 0.006, p = 0.82; valine R2: 0.002, p = 0.65). Plasma BCAA are higher in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight

Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery

BACKGROUND: Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer. METHODS: Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m 2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m 2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling. RESULTS: OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day −1 , p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160 Thr642 (p = 0.046) post-HIIT. CONCLUSIONS: A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass)

Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans

This is the final version. Available on open access from the National Academy of Sciences via the DOI in this recordData, Materials, and Software Availability: All study data are included in the article and/or supporting information. The raw RNA sequencing data can be found within the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under the Sequence Read Archive (SRA) accession PRJNA996496 (93).Living longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H2S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2S (NaGYY4137, 100 µM and 100 nM) and mtH2S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2S donor-mediated health span. Developmentally administered mtH2S (100 nM) improved life/health span vs. equivalent untargeted H2S doses. mtH2S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2S metabolism enzymes and FoxO/daf-16 prevented the positive health span effects of mtH2S, whereas DCAF11/wdr-23 - Nrf2/skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2S treatments. Adult mtH2S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6/elt-3 transcription factor circuit. H2S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2S is a potential healthy aging therapeutic.US Army Research OfficeUnited Mitochondrial Disease FoundationUniversity of ExeterUK Space AgencyBiotechnology and Biological Sciences Research Council (BBSRC)NASAOsteopathic Heritage Foundatio

Differences in Immunoglobulin Light Chain Species Found in Urinary Exosomes in Light Chain Amyloidosis (AL)

Renal involvement is a frequent consequence of plasma cell dyscrasias. The most common entities are light chain amyloidosis, monoclonal immunoglobulin deposition disease and myeloma cast nephropathy. Despite a common origin, each condition has its own unique histologic and pathophysiologic characteristic which requires a renal biopsy to distinguish. Recent studies have shown urinary exosomes containing kidney-derived membrane and cytosolic proteins that can be used to probe the proteomics of the entire urinary system from the glomerulus to the bladder. In this study, we analyzed urine exosomes to determine the differences between exosomes from patients with light chain amyloidosis, multiple myeloma, monoclonal gammopathy of undetermined significance, and non-paraproteinemia related kidney disease controls. In patients with light chain amyloidosis, multiple myeloma and monoclonal gammopathy of undetermined significance, immunoreactive proteins corresponding to monomeric light chains were found in exosomes by western blot. In all of the amyloidosis samples with active disease, high molecular weight immunoreactive species corresponding to a decamer were found which were not found in exosomes from the other diseases or in amyloidosis exosomes from patients in remission. Few or no light chains monomeric bands were found in non-paraproteinemia related kidney disease controls. Our results showed that urinary exosomes may have tremendous potential in furthering our understanding of the pathophysiology and diagnosis of plasma cell dyscrasia related kidney diseases

Efficient Nuclear Transport of Structurally Disturbed Cargo: Mutations in a Cargo Protein Switch Its Cognate Karyopherin

The Karyopherin (Kap) family of nuclear transport receptors enables trafficking of proteins to and from the nucleus in a precise, regulated manner. Individual members function in overlapping pathways, while simultaneously being very specific for their main cargoes. The details of this apparent contradiction and rules governing pathway preference remain to be further elucidated. S. cerevisiae Lhp1 is an abundant protein that functions as an RNA chaperone in a variety of biologically important processes. It localizes almost exclusively to the nucleus and is imported by Kap108. We show that mutation of 3 of the 275 residues in Lhp1 alters its import pathway to a Kap121-dependent process. This mutant does not retain wild-type function and is bound by several chaperones. We propose that Kap121 also acts as a chaperone, one that can act as a genetic buffer by transporting mutated proteins to the nucleus