287 research outputs found
Collective dynamics in crystalline polymorphs of ZnCl: potential modelling and inelastic neutron scattering study
We report a phonon density of states measurement of -ZnCl using
the coherent inelastic neutron scattering technique and a lattice dynamical
calculation in four crystalline phases of ZnCl 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 in all its four phases.Comment: Accepted in J. Phys.: Condens. Matte
Factors associated with HIV viral load âblipsâ and the relationship between self-reported adherence and efavirenz blood levels on blip occurrence: a caseâcontrol study
Yoongoorrookoo
Since the momentous release of the Montecristi Constitution of
Ecuador in 2008, which recognised Nature, or Pacha Mama, as a
subject of rights, the rights of Nature movement across the world
has gained exponential momentum, with numerous jurisdictions
worldwide now recognising some form of legal subjectivity vested
upon Nature. In particular, since 2017, river personhood has
dominated news headlines around the world as one of the most
recognisable forms of Natureâs novel subjectivity. The emergence
of legal personhood for nature, however, has been far from
uncontroversial, and numerous critiques have been advanced
against the use of such a legal category â traditionally applied to
humans and their abstract creations (such as States and
corporations) â to the natural world, resulting in numerous calls for
an alternative category of legal personhood (one that some rights
of Nature advocates have termed an âenvironmental personâ).
Against the backdrop of this emerging debate, this paper
acknowledges the work undertaken by the Martuwarra Fitzroy
River Council (Martuwarra Council), which was established in 2018
in the Kimberley region of Western Australia by six independent
Indigenous nations to preserve, promote and protect their
ancestral River from ongoing destructive âdevelopmentâ. The
Council believes it is time to recognise the pre-existing and
continuing legal authority of Indigenous law, or âFirst Lawâ, in
relation to the River, in order to preserve its integrity through a
process of legal decolonisation. First Law differs markedly from its
colonial counterpart, as its principles are not articulated in terms of
rules, policies and procedures, but rather through stories. This
paper, therefore, begins with a dialogical translation of one First
Law story relating to Yoongoorrookoo,1 the ancestral serpent being,2 to create a semantic bridge between two apparently distant
legal worldviews. A dialogical comparative analysis is then followed
to posit and explore the concept of an âancestral personâ as a novel
comparative tool that may be able not only to capture the idea of
Nature as a legal subject, but also complex Indigenous worldviews
that see Nature â in this case instantiated in the Martuwarra â as
an ancestral being enmeshed in a relationship of interdependence
and guardianship between the human and the nonhuman world.
To instantiate and embody such relationships, the paper directly,
and somewhat provocatively, acknowledges the River itself, the
Martuwarra RiverOfLife, as the primary participant in such dialogue,
an embodied non-human co-author who began a conversation
then left to human writers to continue
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
Preparation of TiO2-rich Ba-Ti-O thick films by laser chemical vapor deposition method
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
A monoclonal antibody raised against bacterially expressed MPV17 sequences shows peroxisomal, endosomal and lysosomal localisation in U2OS cells
Recessive mutations in the MPV17 gene cause mitochondrial DNA depletion syndrome, a fatal infantile genetic liver disease in humans. Loss of function in mice leads to glomerulosclerosis and sensineural deafness accompanied with mitochondrial DNA depletion. Mutations in the yeast homolog Sym1, and in the zebra fish homolog tra cause interesting, but not obviously related phenotypes, although the human gene can complement the yeast Sym1 mutation. The MPV17 protein is a hydrophobic membrane protein of 176 amino acids and unknown function. Initially localised in murine peroxisomes, it was later reported to be a mitochondrial inner membrane protein in humans and in yeast. To resolve this contradiction we tested two new mouse monoclonal antibodies directed against the human MPV17 protein in Western blots and immunohistochemistry on human U2OS cells. One of these monoclonal antibodies showed specific reactivity to a protein of 20 kD absent in MPV17 negative mouse cells. Immunofluorescence studies revealed colocalisation with peroxisomal, endosomal and lysosomal markers, but not with mitochondria. This data reveal a novel connection between a possible peroxisomal/endosomal/lysosomal function and mitochondrial DNA depletion
The Potential Link between Thermal Resistance and Virulence in Salmonella: A Review
In some animals, the typical body temperature can be higher than humans, for example, 42°C in poultry and 40°C in rabbits which can be a potential thermal stress challenge for pathogens. Even in animals with lower body temperatures, when infection occurs, the immune system may increase body temperature to reduce the chance of survival for pathogens. However, some pathogens can still easily overcome higher body temperatures and/or rise in body temperatures through expression of stress response mechanisms. Salmonella is the causative agent of one of the most prevalent foodborne illnesses, salmonellosis, and can readily survive over a wide range of temperatures due to the efficient expression of the heat (thermal) stress response. Therefore, thermal resistance mechanisms can provide cross protection against other stresses including the non-specific host defenses found within the human body thus increasing pathogenic potential. Understanding the molecular mechanisms associated with thermal responses in Salmonella is crucial in designing and developing more effective or new treatments for reducing and eliminating infection caused by Salmonella that have survived heat stress. In this review, Salmonella thermal resistance is assessed followed by an overview of the thermal stress responses with a focus on gene regulation by sigma factors, heat shock proteins, along with the corresponding thermosensors and their association with virulence expression including a focus on a potential link between heat resistance and potential for infection
The Relationship Between GPS Sampling Interval and Estimated Daily Travel Distances in Chacma Baboons (Papio ursinus)
Modern studies of animal movement use the Global Positioning System (GPS) to estimate animalsâ distance traveled. The temporal resolution of GPS fixes recorded should match those of the behavior of interest; otherwise estimates are likely to be inappropriate. Here, we investigate how different GPS sampling intervals affect estimated daily travel distances for wild chacma baboons (Papio ursinus). By subsampling GPS data collected at one fix per second for 143 daily travel distances (12 baboons over 11â12 days), we found that less frequent GPS fixes result in smaller estimated travel distances. Moving from a GPS frequency of one fix every second to one fix every 30 s resulted in a 33% reduction in estimated daily travel distance, while using hourly GPS fixes resulted in a 66% reduction. We then use the relationship we find between estimated travel distance and GPS sampling interval to recalculate published baboon daily travel distances and find that accounting for the predicted effect of sampling interval does not affect conclusions of previous comparative analyses. However, if short-interval or continuous GPS dataâwhich are becoming more common in studies of primate movement ecologyâare compared with historical (longer interval) GPS data in future work, controlling for sampling interval is necessary
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. OâBryan, 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, JoĂŁo Gonçalves, Iris Caetano, Graça Pinto, SĂłnia Correia, Maris Laan, Margus Punab, Ewa Rajpert-De Meyts, Niels JĂžrgensen, 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 Ă 10â5) 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 Ă 10â4) 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 âMale Germ Cellsâ (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
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