Collective dynamics in crystalline polymorphs of ZnCl2_{2}: potential modelling and inelastic neutron scattering study

We report a phonon density of states measurement of $\alpha$-ZnCl$_{2}$ using the coherent inelastic neutron scattering technique and a lattice dynamical calculation in four crystalline phases of ZnCl$_{2}$ using a transferable interatomic potential. The model calculations agree reasonably well with the available experimental data on the structures, specific heat, Raman frequencies and their pressure variation in various crystalline phases. The calculated results have been able to provide a fair description of the vibrational as well as the thermodynamic properties of ZnCl$_{2}$ in all its four phases.Comment: Accepted in J. Phys.: Condens. Matte

The endocrine disruptor 17β-trenbolone alters the relationship between pre- and post-copulatory sexual traits in male mosquitofish (Gambusia holbrooki)

It is now well-established that reproduction in wildlife can be disrupted by anthropogenic environmental changes, such as chemical pollution. However, very little is known about how these pollutants might affect the interplay between pre- and post-copulatory mechanisms of sexual selection. Here, we investigated the impacts of 21-day exposure of male eastern mosquitofish (Gambusia holbrooki) to a field-realistic level (average measured concentration: 11 ng/L) of the endocrine-disrupting chemical 17β-trenbolone (17β-TB) on pre- and post-copulatory reproductive traits. We examined male reproductive behaviour by testing the time spent near a female behind a partition, as well as the number of copulation attempts made, and the time spent chasing a female in a free-swimming context. Sperm traits were also assayed for all males. We found that exposure of male fish to 17β-TB altered the relationship between key pre- and post-copulatory reproductive traits. Furthermore, 17β-TB-exposed males had, on average, a higher percentage of motile sperm, and performed fewer copulation attempts than unexposed males. However, there was no overall effect of 17β-TB exposure on either the time males spent associating with or chasing females. Taken together, our findings demonstrate the potential for chemical pollutants to affect both pre- and post-copulatory sexual traits, and the interplay between these mechanisms of sexual selection in contaminated wildlife

Sustained Klotho delivery reduces serum phosphate in a model of diabetic nephropathy

Diabetic nephropathy (DN) is a primary cause of end-stage renal disease and is becoming more prevalent because of the global rise in type 2 diabetes. A model of DN, the db/db uninephrectomized (db/db-uni) mouse, is characterized by obesity, as well as compromised renal function. This model also manifests defects in mineral metabolism common in DN, including hyperphosphatemia, which leads to severe endocrine disease. The FGF23 coreceptor, α-Klotho, circulates as a soluble, cleaved form (cKL) and may directly influence phosphate handling. Our study sought to test the effects of cKL on mineral metabolism in db/db-uni mice. Mice were placed into either mild or moderate disease groups on the basis of the albumin-to-creatinine ratio (ACR). Body weights of db/db-uni mice were significantly greater across the study compared with lean controls regardless of disease severity. Adeno-associated cKL administration was associated with increased serum Klotho, intact, bioactive FGF23 (iFGF23), and COOH-terminal fragments of FGF23 (P < 0.05). Blood urea nitrogen was improved after cKL administration, and cKL corrected hyperphosphatemia in the high- and low-ACR db/db-uni groups. Interestingly, 2 wk after cKL delivery, blood glucose levels were significantly reduced in db/db-uni mice with high ACR (P < 0.05). Interestingly, several genes associated with stabilizing active iFGF23 were also increased in the osteoblastic UMR-106 cell line with cKL treatment. In summary, delivery of cKL to a model of DN normalized blood phosphate levels regardless of disease severity, supporting the concept that targeting cKL-affected pathways could provide future therapeutic avenues in DN

Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble Klotho

αKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice. Stable delivery of adeno-associated virus (AAV) expressing cKL to diabetic endothelial nitric oxide synthase-deficient mice or αKL-null mice reduced serum phosphate levels. Acute injection of recombinant cKL downregulated the renal sodium-phosphate cotransporter Npt2a in αKL-null mice supporting direct actions of cKL in the absence of mKL. αKL-null mice with sustained AAV-cKL expression had a 74%-78% reduction in aorta mineral content and a 72%-77% reduction in mineral volume compared with control-treated counterparts (P<0.01). Treatment of UMR-106 osteoblastic cells with cKL + FGF23 increased the phosphorylation of extracellular signal-regulated kinase 1/2 and induced Fgf23 expression. CRISPR/Cas9-mediated deletion of fibroblast growth factor receptor 1 (FGFR1) or pretreatment with inhibitors of mitogen-activated kinase kinase 1 or FGFR ablated these responses. In summary, sustained cKL treatment reduced hyperphosphatemia in a mouse model of CKD-mineral bone disorder, and it reduced hyperphosphatemia and prevented VC in mice without endogenous αKL. Furthermore, cKL stimulated Fgf23 in an FGFR1-dependent manner in bone cells. Collectively, these findings indicate that cKL has mKL-independent activity and suggest the potential for enhancing cKL activity in diseases of hyperphosphatemia with associated VC

The contribution of predators and scavengers to human well-being

Predators and scavengers are frequently persecuted for their negative effects on property, livestock and human life. Research has shown that these species play important regulatory roles in intact ecosystems including regulating herbivore and mesopredator populations that in turn affect floral, soil and hydrological systems. Yet predators and scavengers receive surprisingly little recognition for their benefits to humans in the landscapes they share. We review these benefits, highlighting the most recent studies that have documented their positive effects across a range of environments. Indeed, the benefits of predators and scavengers can be far reaching, affecting human health and well-being through disease mitigation, agricultural production and waste-disposal services. As many predators and scavengers are in a state of rapid decline, we argue that researchers must work in concert with the media, managers and policymakers to highlight benefits of these species and the need to ensure their long-term conservation. Furthermore, instead of assessing the costs of predators and scavengers only in economic terms, it is critical to recognize their beneficial contributions to human health and well-being. Given the ever-expanding human footprint, it is essential that we construct conservation solutions that allow a wide variety of species to persist in shared landscapes. Identifying, evaluating and communicating the benefits provided by species that are often considered problem animals is an important step for establishing tolerance in these shared spaces

Competition between decay and dissociation of core-excited OCS studied by X-ray scattering

We show the first evidence of dissociation during resonant inelastic soft X-ray scattering. Carbon and oxygen K-shell and sulfur L-shell resonant and non-resonant X-ray emission spectra were measured using monochromatic synchrotron radiation for excitation and ionization. After sulfur, L2,3 -> {\pi}*, {\sigma}* excitation, atomic lines are observed in the emission spectra as a consequence of competition between de-excitation and dissociation. In contrast the carbon and oxygen spectra show weaker line shape variations and no atomic lines. The spectra are compared to results from ab initio calculations and the discussion of the dissociation paths is based on calculated potential energy surfaces and atomic transition energies.Comment: 12 pages, 6 pictures, 2 tables, http://link.aps.org/doi/10.1103/PhysRevA.59.428

Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours

The molecular mechanisms that underlie the development of squamous cell skin cancers (SSC) are poorly understood. We have used oligonucleotide microarrays to compare the differences in cellular gene expression between a series of keratinocyte cell that mimic disease progression with the aim of identifying genes that may potentially contribute towards squamous cell carcinoma (SCC) progression in vivo, and in particular to identify markers that may serve as potential therapeutic targets for SCC treatment. Gene expression differences were corroborated by polymerase chain reaction and Western blotting. We identified Axl, a receptor tyrosine kinase with transforming potential that has also been shown to have a role in cell survival, adhesion and chemotaxis, was upregulated in vitro in SCC-derived cells compared to premalignant cells. Extending the investigation to tumour biopsies showed that the Axl protein was overexpressed in vivo in a series of SCCs

Nitric oxide and cyclic nucleotides: Their roles in junction dynamics and spermatogenesis

Spermatogenesis is a highly complicated process in which functional spermatozoa (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n). This process involves the differentiation and transformation of several types of germ cells as spermatocytes and spermatids undergo meiosis and differentiation. Due to its sophistication and complexity, testis possesses intrinsic mechanisms to modulate and regulate different stages of germ cell development under the intimate and indirect cooperation with Sertoli and Leydig cells, respectively. Furthermore, developing germ cells must translocate from the basal to the apical (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction restructuring must occur to assist germ cell movement. Within the seminiferous tubules, three principal types of junctions are found namely anchoring junctions, tight junctions, and gap junctions. Other less studied junctions are desmosome-like junctions and hemidesmosome junctions. With these varieties of junction types, testes are using different regulators to monitor junction turnover. Among the uncountable junction modulators, nitric oxide (NO) is a prominent candidate due to its versatility and extensive downstream network. NO is synthesized by nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently shown to have putative junction regulation properties. More important, these two NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G signaling pathway to regulate the structural components at the tight junctions and adherens junctions in the testes. Apart from the involvement in junction regulation, NOS/NO also participates in controlling the levels of cytokines and hormones in the testes. On the other hand, NO is playing a unique role in modulating germ cell viability and development, and indirectly acting on some aspects of male infertility and testicular pathological conditions. Thus, NOS/NO bears an irreplaceable role in maintaining the homeostasis of the microenvironment in the seminiferous epithelium via its different downstream signaling pathways

A de novo paradigm for male infertility

Genetics of Male Infertility Initiative (GEMINI) consortium: Donald F. Conrad, Liina Nagirnaja, Kenneth I. Aston, Douglas T. Carrell, James M. Hotaling, Timothy G. Jenkins, Rob McLachlan, Moira K. O’Bryan, Peter N. Schlegel, Michael L. Eisenberg, Jay I. Sandlow, Emily S. Jungheim, Kenan R. Omurtag, Alexandra M. Lopes, Susana Seixas, Filipa Carvalho, Susana Fernandes, Alberto Barros, João Gonçalves, Iris Caetano, Graça Pinto, Sónia Correia, Maris Laan, Margus Punab, Ewa Rajpert-De Meyts, Niels Jørgensen, Kristian Almstrup, Csilla G. Krausz & Keith A. Jarvi.De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E.info:eu-repo/semantics/publishedVersio

Lessons from Australian water reforms: Indigenous and environmental values in market-based water regulation

The Australian model of water governance is considered one of the most effective, efficient and resilient approaches to designing and implementing water governance. In place since the early 1990s, the Australian approach is a hybrid governance system involving collaborative planning of water resources together with market mechanisms and statutory regulation. However, in implementing the model, successive reforms have yet to completely redress the historical exclusion of Aboriginal peoples from water law frameworks, and have struggled to account for the needs of a healthy and sustainable aquatic environment. In this chapter we examine the trajectory of water law and policy reform in Australia, including two of the most recent developments: the push to intensify water development in the northern Australian White Paper and the collaborative planning approach set in the Water for Victoria policy. Our study of the incremental and evolving Australian water law reforms highlights the difficulty of ensuring fairness in the operation of hybrid governance systems for water regulation, and reveals important lessons for international policy-makers embarking on and implementing water reforms in their own jurisdictions. From its inception, strategic planning for innovative water law reform must be supported by meaningful engagement with Indigenous peoples, and embed Indigenous and environmental values and rights in water planning and governance.Authors acknowledge assistance provided by CCIF grant 501319GL, The University of Melbourn