Postcopulatory Sexual Selection Is Associated with Reduced Variation in Sperm Morphology

The evolutionary role of postcopulatory sexual selection in shaping male reproductive traits, including sperm morphology, is well documented in several taxa. However, previous studies have focused almost exclusively on the influence of sperm competition on variation among species. In this study we tested the hypothesis that intraspecific variation in sperm morphology is driven by the level of postcopulatory sexual selection in passerine birds.Using two proxy measures of sperm competition level, (i) relative testes size and (ii) extrapair paternity level, we found strong evidence that intermale variation in sperm morphology is negatively associated with the degree of postcopulatory sexual selection, independently of phylogeny.Our results show that the role of postcopulatory sexual selection in the evolution of sperm morphology extends to an intraspecific level, reducing the variation towards what might be a species-specific 'optimum' sperm phenotype. This finding suggests that while postcopulatory selection is generally directional (e.g., favouring longer sperm) across avian species, it also acts as a stabilising evolutionary force within species under intense selection, resulting in reduced variation in sperm morphology traits. We discuss some potential evolutionary mechanisms for this pattern

Phosphatase and tensin homologue: a therapeutic target for SMA

Spinal muscular atrophy (SMA) is one of the most common juvenile neurodegenerative diseases, which can be associated with child mortality. SMA is caused by a mutation of ubiquitously expressed gene, Survival Motor Neuron1 (SMN1), leading to reduced SMN protein and the motor neuron death. The disease is incurable and the only therapeutic strategy to follow is to improve the expression of SMN protein levels in motor neurons. Significant numbers of motor neurons in SMA mice and SMA cultures are caspase positive with condensed nuclei, suggesting that these cells are prone to a process of cell death called apoptosis. Searching for other potential molecules or signaling pathways that are neuroprotective for central nervous system (CNS) insults is essential for widening the scope of developmental medicine. PTEN, a Phosphatase and Tensin homologue, is a tumor suppressor, which is widely expressed in CNS. PTEN depletion activates anti-apoptotic factors and it is evident that the pathway plays an important protective role in many neurodegenerative disorders. It functions as a negative regulator of PIP3/AKT pathway and thereby modulates its downstream cellular functions through lipid phosphatase activity. Moreover, previous reports from our group demonstrated that, PTEN depletion using viral vector delivery system in SMN delta7 mice reduces disease pathology, with significant rescue on survival rate and the body weight of the SMA mice. Thus knockdown/depletion/mutation of PTEN and manipulation of PTEN medicated Akt/PKB signaling pathway may represent an important therapeutic strategy to promote motor neuron survival in SMA

A study of the Z production cross-section in pp collisions at √s = 7 using tau final states

A measurement of the inclusive Z → ττ cross-section in pp collisions at √s =7 is presented based on a dataset of 1.0 fb[superscript −1] collected by the LHCb detector. Candidates for Z → τ τ decays are identified through reconstructed final states with two muons, a muon and an electron, a muon and a hadron, or an electron and a hadron. The production cross-section for Z bosons, with invariant mass between 60 and 120 GeV/c[superscript 2], which decay to τ leptons with transverse momenta greater than 20 GeV/c and pseudorapidities between 2.0 and 4.5, is measured to be σ[subscript pp]→Z→ττ = 71.4 ± 3.5 ± 2.8 ± 2.5 pb; the first uncertainty is statistical, the second is systematic, and the third is due to the uncertainty on the integrated luminosity. The ratio of the cross-sections for Z → τ τ to Z → μμ is determined to be 0.93 ± 0.09, where the uncertainty is the combination of statistical, systematic, and luminosity uncertainties of the two measurements.National Science Foundation (U.S.

Coupling changes in cell shape to chromosome segregation

Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance

Precision measurement of the B0s-B¯0s oscillation frequency with the decay B0s → D−sπ+

A key ingredient to searches for physics beyond the Standard Model in B0s mixing phenomena is the measurement of the B0s– ${{\overline{ {\mathrm {B}}}{}}^0_{\mathrm { s}}}$ oscillation frequency, which is equivalent to the mass difference Δms of the B0s mass eigenstates. Using the world's largest B0s meson sample accumulated in a dataset, corresponding to an integrated luminosity of 1.0 fb−1, collected by the LHCb experiment at the CERN LHC in 2011, a measurement of Δms is presented. A total of about 34 000 B0s → D−sπ+ signal decays are reconstructed, with an average decay time resolution of 44 fs. The oscillation frequency is measured to be Δms = 17.768 ± 0.023 (stat) ± 0.006 (syst) ps−1, which is the most precise measurement to date

A canonical correlation analysis of the association between carcass and ham traits in pigs used to produce dry-cured ham

The association between carcass and ham traits in a pig population used to produce dry-cured ham was studied using canonical correlation analysis. The carcass traits examined were hot carcass weight (HCW), backfat thickness (BT) and loin depth (LD), and the ham traits studied were gross ham weight (GHW), trimmed ham weight (THW), ham inner layer fat thickness (HIFT), ham outer layer fat thickness (HOFT), pH (pH) and the Göfo value. Carcass and ham traits are not independent. The canonical correlations (r) between the carcass and ham traits at 130 kg were 0.77, 0.24 and 0.20 for the first, second and third canonical pair, respectively, and were all significant (p < 0.01) by the Wilks test. The corresponding canonical correlations between the three canonical variate pairs for the carcass and ham traits at 160 kg were 0.88, 0.42 and 0.14, respectively (p < 0.05 for all, except the third). The correlations between the traits and their canonical variate showed an association among HCW, GHW and THW, and between BT and HOFT. These results indicate that carcass traits should be used to cull pigs that are not suitable for dry-cured ham production

Specialized Peptidoglycan Hydrolases Sculpt the Intra-bacterial Niche of Predatory Bdellovibrio and Increase Population Fitness

Bdellovibrio are predatory bacteria that have evolved to invade virtually all Gram-negative bacteria, including many prominent pathogens. Upon invasion, prey bacteria become rounded up into an osmotically stable niche for the Bdellovibrio, preventing further superinfection and allowing Bdellovibrio to replicate inside without competition, killing the prey bacterium and degrading its contents. Historically, prey rounding was hypothesized to be associated with peptidoglycan (PG) metabolism; we found two Bdellovibrio genes, bd0816 and bd3459, expressed at prey entry and encoding proteins with limited homologies to conventional dacB/PBP4 DD-endo/carboxypeptidases (responsible for peptidoglycan maintenance during growth and division). We tested possible links between Bd0816/3459 activity and predation. Bd3459, but not an active site serine mutant protein, bound β-lactam, exhibited DD-endo/carboxypeptidase activity against purified peptidoglycan and, importantly, rounded up E. coli cells upon periplasmic expression. A ΔBd0816 ΔBd3459 double mutant invaded prey more slowly than the wild type (with negligible prey cell rounding) and double invasions of single prey by more than one Bdellovibrio became more frequent. We solved the crystal structure of Bd3459 to 1.45 Å and this revealed predation-associated domain differences to conventional PBP4 housekeeping enzymes (loss of the regulatory domain III, alteration of domain II and a more exposed active site). The Bd3459 active site (and by similarity the Bd0816 active site) can thus accommodate and remodel the various bacterial PGs that Bdellovibrio may encounter across its diverse prey range, compared to the more closed active site that “regular” PBP4s have for self cell wall maintenance. Therefore, during evolution, Bdellovibrio peptidoglycan endopeptidases have adapted into secreted predation-specific proteins, preventing wasteful double invasion, and allowing activity upon the diverse prey peptidoglycan structures to sculpt the prey cell into a stable intracellular niche for replication

A Novel Tandem Mass Spectrometry Method for Rapid Confirmation of Medium- and Very Long-Chain acyl-CoA Dehydrogenase Deficiency in Newborns

BACKGROUND:Newborn screening for medium- and very long-chain acyl-CoA dehydrogenase (MCAD and VLCAD, respectively) deficiency, using acylcarnitine profiling with tandem mass spectrometry, has increased the number of patients with fatty acid oxidation disorders due to the identification of additional milder, and so far silent, phenotypes. However, especially for VLCADD, the acylcarnitine profile can not constitute the sole parameter in order to reliably confirm disease. Therefore, we developed a new liquid chromatography tandem mass spectrometry (LC-MS/MS) method to rapidly determine both MCAD- and/or VLCAD-activity in human lymphocytes in order to confirm diagnosis. METHODOLOGY:LC-MS/MS was used to measure MCAD- or VLCAD-catalyzed production of enoyl-CoA and hydroxyacyl-CoA, in human lymphocytes. PRINCIPAL FINDINGS:VLCAD activity in controls was 6.95+/-0.42 mU/mg (range 1.95 to 11.91 mU/mg). Residual VLCAD activity of 4 patients with confirmed VLCAD-deficiency was between 0.3 and 1.1%. Heterozygous ACADVL mutation carriers showed residual VLCAD activities of 23.7 to 54.2%. MCAD activity in controls was 2.38+/-0.18 mU/mg. In total, 28 patients with suspected MCAD-deficiency were assayed. Nearly all patients with residual MCAD activities below 2.5% were homozygous 985A>G carriers. MCAD-deficient patients with one other than the 985A>G mutation had higher MCAD residual activities, ranging from 5.7 to 13.9%. All patients with the 199T>C mutation had residual activities above 10%. CONCLUSIONS:Our newly developed LC-MS/MS method is able to provide ample sensitivity to correctly and rapidly determine MCAD and VLCAD residual activity in human lymphocytes. Importantly, based on measured MCAD residual activities in correlation with genotype, new insights were obtained on the expected clinical phenotype

Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy

BACKGROUND: Maturity onset diabetes of the young type 2 (or GCK MODY) is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK). METHODOLOGY/PRINCIPAL FINDINGS: We screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%); 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu) and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: approximately 59%) than in the large (4/12: 33%) domain or in the connection (1/12: 8%) region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD) OGTT = 7.8 mMol/L (1.8)] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04). CONCLUSIONS: The prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings) but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation

Pathogenic T cell responses against aquaporin 4

Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4