Mammalian Fused is essential for sperm head shaping and periaxonemal structure formation during spermatogenesis

During mammalian spermatogenesis, the diploid spermatogonia mature into haploid spermatozoa through a highly controlled process of mitosis, meiosis and post-meiotic morphological remodeling (spermiogenesis). Despite important progress made in this area, the molecular mechanisms underpinning this transformation are poorly understood. Our analysis of the expression and function of the putative serine–threonine kinase Fused (Fu) provides critical insight into key steps in spermatogenesis. In this report, we demonstrate that conditional inactivation of Fu in male germ cells results in infertility due to diminished sperm count, abnormal head shaping, decapitation and motility defects of the sperm. Interestingly, mutant flagellar axonemes are intact but exhibit altered periaxonemal structures that affect motility. These data suggest that Fu plays a central role in shaping the sperm head and controlling the organization of the periaxonemal structures in the flagellum. We show that Fu localizes to multiple tubulin-containing or microtubule-organizing structures, including the manchette and the acrosome–acroplaxome complex that are involved in spermatid head shaping. In addition, Fu interacts with the outer dense fiber protein Odf1, a major component of the periaxonemal structures in the sperm flagellum, and Kif27, which is detected in the manchette. We propose that disrupted Fu function in these structures underlies the head and flagellar defects in Fu-deficient sperm. Since a majority of human male infertility syndromes stem from reduced sperm motility and structural defects, uncovering Fu?s role in spermiogenesis provides new insight into the causes of sterility and the biology of reproduction.     

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype.     

Ammonium Metabolism Enzymes Aid Helicobacter pylori Acid Resistance

The gastric pathogen Helicobacter pylori possesses a highly active urease to support acid tolerance. Urea hydrolysis occurs inside the cytoplasm, resulting in the production of NH₃ that is immediately protonated to form NH₄⁺. This ammonium must be metabolized or effluxed because its presence within the cell is counterproductive to the goal of raising pH while maintaining a viable proton motive force (PMF). Two compatible hypotheses for mitigating intracellular ammonium toxicity include (i) the exit of protonated ammonium outward via the UreI permease, which was shown to facilitate diffusion of both urea and ammonium, and/or (ii) the assimilation of this ammonium, which is supported by evidence that H. pylori assimilates urea nitrogen into its amino acid pools. We investigated the second hypothesis by constructing strains with altered expression of the ammonium-assimilating enzymes glutamine synthetase (GS) and glutamate dehydrogenase (GDH) and the ammonium-evolving periplasmic enzymes glutaminase (Ggt) and asparaginase (AsnB). H. pylori strains expressing elevated levels of either GS or GDH are more acid tolerant than the wild type, exhibit enhanced ammonium production, and are able to alkalize the medium faster than the wild type. Strains lacking the genes for either Ggt or AsnB are acid sensitive, have 8-fold-lower urea-dependent ammonium production, and are more acid sensitive than the parent. Additionally, we found that purified H. pylori GS produces glutamine in the presence of Mg²⁺ at a rate similar to that of unadenylated Escherichia coli GS. These data reveal that all four enzymes contribute to whole-cell acid resistance in H. pylori and are likely important for assimilation and/or efflux of urea-derived ammonium.     

Crystal Structure of Marburg Virus VP24

The VP24 protein plays an essential, albeit poorly understood role in the filovirus life cycle. VP24 is only 30% identical between Marburg virus and the ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while that of Marburg virus is not. The crystal structure of Marburg virus VP24, presented here, reveals that although the core is similar between the viral genera, Marburg VP24 is distinguished by a projecting β-shelf and an alternate conformation of the N-terminal polypeptide.     

Crystal Structure of the Nipah Virus Phosphoprotein Tetramerization Domain

The Nipah virus phosphoprotein (P) is multimeric and tethers the viral polymerase to the nucleocapsid. We present the crystal structure of the multimerization domain of Nipah virus P: a long, parallel, tetrameric, coiled coil with a small, α-helical cap structure. Across the paramyxoviruses, these domains share little sequence identity yet are similar in length and structural organization, suggesting a common requirement for scaffolding or spatial organization of the functions of P in the virus life cycle.     

Remote sensing reveals long-term effects of caribou on tundra vegetation

Declining use and abandonment of traditional ranges by migratory caribou (Rangifer tarandus) have often been related to density-dependent depletion of summer forage. The Pen Islands caribou herd (R. t. caribou), Ontario and Manitoba, Canada, numbered in the thousands on its traditional summer tundra range during the 1980s, but then declined in that region. We postulated that increased caribou abundance over three decades negatively affected phytomass, given that under the exploitation ecosystem hypothesis (EEH), grazers limit the amount of primary production if few predators are present. We tested this prediction using the Normalized Difference Vegetation Index (NDVI), as a proxy for phytomass available to caribou. We lagged caribou abundance in the explanatory model by the number of years (4–7) between peak caribou abundance and minimum NDVI. NDVI was negatively related to caribou abundance lagged by 6 years, and growing degree days explained much of the annual variation in NDVI. Precipitation was not an important predictor in the model. Our study is the first to apply NDVI to support the EEH for caribou. We propose that this method could be used over broad scales to shed light on limiting factors for migratory caribou across the circumpolar North.     

Post-autotomy claw regrowth and functional recovery in the snapping shrimp Alpheus angulosus

The ability to regenerate lost tissues, organs or whole body parts is widespread across animal taxa; in some animals, regeneration includes transforming a remaining structure to replace the one that was lost. The transformation of one limb into another involves considerable plasticity in morphology, physiology and behavior, and snapping shrimp offer excellent opportunities for studying this process. We examined the changes required for the transformation of the small pincer to a mature snapping claw in Alpheus angulosus. First molt claws differ from mature claws in overall shape as well as in morphology related to snapping function; nonetheless, shrimp with first molt claws do produce snaps. While most shape variables of second molt claws do not differ significantly from mature claws, the plunger (structure required for snap production) does not reach mature size until the third molt for females, or later for males. Thus, the pincer claw can be transformed into a functional snapping claw in one molt, although both the underlying morphology and superficial shape are not fully regenerated at this stage. The rapid production of a functional snapping claw that we observe in this study suggests that this particular function is of significant importance to snapping shrimp behavior and survival.