Vitamin D status and determinants of deficiency in non-supplemented athletes during the winter months in Tunisia

Recent reports suggest that hypovitaminosis D in athletes is as common as in the general population. This study was devised to examine vitamin D status and determinants of deficiency in athletes living in a sunny country (Tunisia). One hundred and fifty national elite athletes, training outdoors (n = 83) or indoors (n = 67), were enrolled from January to February 2012. Plasma 25-hydroxyvitamin D was measured by radioimmunoassay. Concentrations were between 50 and 75 nmol · l^-1 in 21.3% of participants, between 25 and 50 nmol · l^-1 in 55.3% of participants and <25 nmol · l^-1 in 14.7% of participants. The concentrations were significantly lower in indoor athletes than outdoor athletes (36.2±19.0 nmol · l^-1 vs. 49.1±19.2 nmol · l^-1; p < 0.001). In multivariate analysis, vitamin D deficiency (25-hydroxyvitamin D <50 nmol · l^-1) was associated with indoor sports [multi-adjusted odds ratio (95% confidence interval), 5.03 (1.64-15.4); p = 0.005], female gender [3.72 (1.44-9.65); p = 0.007] and age < 18 years [2.40 (1.01-5.85); p = 0.05]. Athletes living in sun-rich environments are exposed to a high risk of vitamin D inadequacy. Given the importance of vitamin D in health and athletic ability, targeting sufficient levels of plasma 25-hydroxyvitamin D in athletes is well justified.     

The Proximate Basis of the Oak Dispersal Syndrome: Detection of Seed Dormancy by Rodents

Previously we have shown how a range of physical and chemicalcharacteristics of acorns influences the behavioral decisionsof food-hoarding rodents which in turn affects the dispersal,establishment and spatial arrangement of oaks. One such behaviorinvolves the selective caching of acorns of red oaks (subgenus:Erythrobalanus) over those of white oaks (Quercus) because ofreduced perishability that results from delayed germinationof acorns in the red oak group. In this study, we sought toidentify the specific proximate cues (visual and olfactory)that eastern gray squirrels (Sciurus carolinensis) use whenmaking these decisions. In two series of field experiments,we presented individual, free-ranging animals with pairs ofexperimentally altered acorns (that differed with respect toa single chemical or visual characteristic) and recorded theirfeeding and caching responses. Squirrels cached artificial acornswith pericarps (shells) of red oak acorns and ate those withshells of white oak regardless of the internal chemical compositionof either type of acorn. Only when the shells of artificialacorns were first soaked in acetone (to remove potential chemicalodors) did animals eat artificial acorns made with the shellsof red oak acorns. Squirrels also ate one-year old red oak acornsthat had broken dormancy, even when they exhibited no signsof germination. We argue that a chemical cue in the shell ofacorns is important in the detection of seed dormancy and thedecision to cache acorns, and that such a cue might ultimatelycontribute to the differential dispersal of red and white oaksby rodents.     

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis>, <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> and <Emphasis Type="Italic">Neisseria meningitidis</Emphasis>

Background  

Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients.     

The role of collagen structure in mitogen stimulation of ERK,cyclin D1 expression,and G1-S progression in rat hepatocytes

Adhesion to type 1 collagen can elicit different cellular responses dependent upon whether the collagen is in a fibrillar form (gel) or monomeric form (film). Hepatocytes adherent to collagen film spread extensively, express cyclin D1, and increase DNA synthesis in response to epidermal growth factor, whereas hepatocytes adherent to collagen gel have increased differentiated function, but lower DNA synthesis. The signaling mechanisms by which different forms of type I collagen modulate cell cycle progression are unknown. When ERK MAP kinase activation was analyzed in hepatocytes attached to collagen film, two peaks of ERK activity were demonstrated. Only the second peak, which correlated with an increase of cyclin D1, was required for G1-S progression. Notably, this second peak of ERK activity was absent in cells adherent to collagen gel, but not required in the presence of exogenous cyclin D1. Expression of activated mutants of the Ras/Raf/MEK signaling pathway in cells adherent to collagen gel restored ERK phosphorylation and DNA synthesis, but differentially affected cell shape. Although Ras, Raf, and MEK all increased expression of cyclin D1 on collagen film, only Ras and Raf significantly up-regulated cyclin D1 levels on collagen gel. These results demonstrate that adhesion to polymerized collagen induces growth arrest by inhibiting the Ras/ERK-signaling pathway to cyclin D1 required in late G1.     

A simulation comparison of phylogeny algorithms under equal and unequal evolutionary rates [published erratum appears in Mol Biol Evol 1995 May;12(3):525]

Using simulated data, we compared five methods of phylogenetic tree estimation: parsimony, compatibility, maximum likelihood, Fitch- Margoliash, and neighbor joining. For each combination of substitution rates and sequence length, 100 data sets were generated for each of 50 trees, for a total of 5,000 replications per condition. Accuracy was measured by two measures of the distance between the true tree and the estimate of the tree, one measure sensitive to accuracy of branch lengths and the other not. The distance-matrix methods (Fitch- Margoliash and neighbor joining) performed best when they were constrained from estimating negative branch lengths; all comparisons with other methods used this constraint. Parsimony and compatibility had similar results, with compatibility generally inferior; Fitch- Margoliash and neighbor joining had similar results, with neighbor joining generally slightly inferior. Maximum likelihood was the most successful method overall, although for short sequences Fitch- Margoliash and neighbor joining were sometimes better. Bias of the estimates was inferred by measuring whether the independent estimates of a tree for different data sets were closer to the true tree than to each other. Parsimony and compatibility had particular difficulty with inaccuracy and bias when substitution rates varied among different branches. When rates of evolution varied among different sites, all methods showed signs of inaccuracy and bias.      

Short term cyclin D1 overexpression induces centrosome amplification, mitotic spindle abnormalities, and aneuploidy

In normal cells, cyclin D1 is induced by growth factors and promotes progression through the G(1) phase of the cell cycle. Cyclin D1 is also an oncogene that is thought to act primarily by bypassing the requirement for mitogens during the G(1) phase. Studies of clinical tumors have found that cyclin D1 overexpression is associated with chromosome abnormalities, although a causal effect has not been established in experimental systems. In this study, we found that transient expression of cyclin D1 in normal hepatocytes in vivo triggered dysplastic mitoses, accumulation of supernumerary centrosomes, abnormalities of the mitotic spindle, and marked chromosome changes within several days. This was associated with up-regulation of checkpoint genes p53 and p21 as well as hepatocyte apoptosis in the liver. Transient transfection of cyclin D1 also induced centrosome and mitotic spindle abnormalities in breast epithelial cells, suggesting that this may be a generalized effect. These results indicate that cyclin D1 can induce deregulation of the mitotic apparatus and aneuploidy, effects that could contribute to the role of this oncogene in malignancy.     

Possible role of eclosion rhythm in mediating the effects of light-dark environments on pre-adult development in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Background  

In insects, circadian clocks have been implicated in affecting life history traits such as pre-adult development time and adult lifespan. Studies on the period (per) mutants of Drosophila melanogaster, and laboratory-selected lines of Bactrocera cucurbitae suggested a close link between circadian clocks and development time. There is a possibility of clock genes having pleiotropic effects on clock period and pre-adult development time. In order to avoid such pleiotropic effects we have used wild type flies of same genotype under environments of different periodicities, which phenotypically either speeded up or slowed down the eclosion clock of D. melanogaster.     

Ecdysteroids: A novel class of anabolic agents?

Increasing numbers of dietary supplements with ecdysteroids are marketed as “natural anabolic agents”. Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class “S1.2 Other Anabolic Agents” of the list of prohibited substances of the World Anti-Doping Agency.     

In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum

Background

Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation.

Results

The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving XPA gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation (c.654del A) in exon 5 of XPA gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 (p.Lys218AsnfsX5). In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. In silico analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system.

Conclusions

Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain.