Radiative and isospin-violating decays of Ds mesons in the hadrogenesis conjecture

The masses and decays of the scalar D_{s0}^*(2317) and axial-vector D_{s1}^*(2460) charmed strange mesons are calculated consistently in the hadrogenesis conjecture. These mesons decay either strongly into the isospin-violating pi^0 D_s and pi^0 D_s^* channels or electromagnetically. They are generated by coupled-channel dynamics based on the leading order chiral Lagrangian. The effect of chiral corrections to chiral order Q_\chi^2 is investigated. We show that taking into account large-N_c relations to determine the strength of these correction terms implies a measurable signal for an exotic axial-vector state in the eta D* invariant mass distribution. The one-loop contribution to the electromagnetic decay amplitudes of scalar and axial-vector states is calculated. The Lagrangian describing electromagnetic interactions is obtained by gauging the chiral Lagrangian for hadronic interactions and adding gauge-invariant correction terms to chiral order Q_chi^2. In addition the role of light vector meson degrees of freedom is explored. We confront our results with measured branching ratios. Once the light vector mesons are included, a natural explanation of all radiative decay parameters is achieved.Comment: 102 pages, 7 figures, further improved presentatio

Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism

This work was supported by a Cancer Research UK Career Development Award (C28598/A9787), Biotechnology and Biological Sciences Research Council Project grant (BB/R01003X/1), and a Queen Mary University of London Laboratory startup grant to V.M. Draviam, a Universiti Brunei Darussalam PhD studentship to I. Zulkipli, a Queen Mary University of London PhD studentship to M. Hart, a London Interdisciplinary Biosciences Consortium Biotechnology and Biological Sciences Research Council–Doctoral Training Partnerships PhD studentship to D. Dang (cosupervised by V.M. Draviam and N. Sastry; BB/M009513/1), and an Islamic Development Bank PhD studentship to P. Gul

Povezanost između polimorfizama XRCC1 ARG399GLN i P53 ARG72PRO s rizikom od raka želuca i debeloga crijeva u turskoj populaciji

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall fi ve-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence. As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.Rak želuca najčešći je oblik karcinoma probavnoga sustava, a ukupno mu je preživljenje i dalje 15 % do 20 %, budući da se većinom dijagnosticira u poodmakloj fazi razvoja. S druge pak strane, premda rak debeloga crijeva ima prilično dobru prognozu, smrtnost je i dalje 50 %. Vjeruje se da je nastanak karcinoma povezan s reaktivnim radikalima koji uzrokuju stvaranje DNA-adukata, onemogućavaju popravak DNA te slabe supresiju tumora. Stoga bi bilo korisno razumjeti ulogu polimorfi zama gena za enzim XRCC1 koji sudjeluje u popravku isjecanjem nukleotida i tumor-supresorskoga gena p53 u nastanku raka želuca i debeloga crijeva. Naše je ispitivanje obuhvatilo 94 bolesnika s rakom želuca, 96 bolesnika s rakom debeloga crijeva te 108 kontrolnhih ispitanika (koji nisu oboljeli od bilo kojeg oblika raka) s ciljem da se utvrdi povezanost između polimorfi zama XRCC1 Arg399Gln i p53 Arg72Pro i sklonosti nastanku raka. DNA je dobiven iz stanica periferne krvi, a genotip utvrđen s pomoću metode lančane reakcije polimerazom - polimorfi zma restrikcijskih fragmenata na osnovi dužine (PCRRLFP). Polimorfi zam p53 Arg72Pro nije se pokazao povezanim s povećanim rizikom od raka želuca ili debeloga crijeva niti je XRCC1 Arg399Gln bio povezan s povećanim rizikom od raka debeloga crijeva, ali je zato rizik od raka želuca u homozigotnih nositelja ovoga polimorfi zma bio 2,54 puta veći

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

Background: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. Methods: SLC3A2 was assessed at the genomic level, using METABRIC data (n=1,980), and proteomic level, using immunohistochemistry on TMA sections constructed from a large well-characterised primary BC cohort (n=2,500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes, and patient outcome. Results: SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple negative (TN), HER2+, and ER+ high proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p<0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p<0.001)), but only in the ER+ high proliferation (p=0.01) and triple negative (p=0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter breast cancer specific survival (p<0.001). Conclusions: SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes

Symbiodinium Genotypic and Environmental Controls on Lipids in Reef Building Corals

BACKGROUND: Lipids in reef building corals can be divided into two classes; non-polar storage lipids, e.g. wax esters and triglycerides, and polar structural lipids, e.g. phospholipids and cholesterol. Differences among algal endosymbiont types are known to have important influences on processes including growth and the photobiology of scleractinian corals yet very little is known about the role of symbiont types on lipid energy reserves. METHODOLOGY/PRINCIPAL FINDINGS: The ratio of storage lipid and structural lipid fractions of Scott Reef corals were determined by thin layer chromatography. The lipid fraction ratio varied with depth and depended on symbiont type harboured by two corals (Seriatopora hystrix and Pachyseris speciosa). S. hystrix colonies associated with Symbiodinium C1 or C1/C# at deep depths (>23 m) had lower lipid fraction ratios (i.e. approximately equal parts of storage and structural lipids) than those with Symbiodinium D1 in shallow depths (<23 m), which had higher lipid fraction ratios (i.e. approximately double amounts of storage relative to structural lipid). Further, there was a non-linear relationship between the lipid fraction ratio and depth for S. hystrix with a modal peak at ∼23 m coinciding with the same depth as the shift from clade D to C types. In contrast, the proportional relationship between the lipid fraction ratio and depth for P. speciosa, which exhibited high specificity for Symbiodinium C3 like across the depth gradient, was indicative of greater amounts of storage lipids contained in the deep colonies. CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that Symbiodinium exert significant controls over the quality of coral energy reserves over a large-scale depth gradient. We conclude that the competitive advantages and metabolic costs that arise from flexible associations with divergent symbiont types are offset by energetic trade-offs for the coral host

Selective Detection of Misfolded Tau From Postmortem Alzheimer’s Disease Brains

Tau aggregates are present in multiple neurodegenerative diseases known as “tauopathies,” including Alzheimer’s disease, Pick’s disease, progressive supranuclear palsy, and corticobasal degeneration. Such misfolded tau aggregates are therefore potential sources for selective detection and biomarker discovery. Six human tau isoforms present in brain tissues and both 3R and 4R isoforms have been observed in the neuronal inclusions. To develop selective markers for AD and related rare tauopathies, we first used an engineered tau protein fragment 4RCF as the substrate for ultrasensitive real-time quaking-induced conversion analyses (RT-QuIC). We showed that misfolded tau from diseased AD and other tauopathy brains were able to seed recombinant 4RCF substrate. We further expanded to use six individual recombinant tau isoforms as substrates to amplify misfolded tau seeds from AD brains. We demonstrated, for the first time to our knowledge, that misfolded tau from the postmortem AD brain tissues was able to specifically seed all six full-length human tau isoforms. Our results demonstrated that RT-QuIC analysis can discriminate AD and other tauopathies from non-AD normal controls. We further uncovered that 3R-tau isoforms displayed significantly faster aggregation kinetics than their 4R-tau counterparts under conditions of both no seeding and seeding with AD brain homogenates. In summary, our work offers potential new avenues of misfolded tau detection as potential biomarkers for diagnosis of AD and related tauopathies and provides new insights into isoform-specific human tau aggregation

Nuclear Progesterone Receptors Are Up-Regulated by Estrogens in Neurons and Radial Glial Progenitors in the Brain of Zebrafish

In rodents, there is increasing evidence that nuclear progesterone receptors are transiently expressed in many regions of the developing brain, notably outside the hypothalamus. This suggests that progesterone and/or its metabolites could be involved in functions not related to reproduction, particularly in neurodevelopment. In this context, the adult fish brain is of particular interest, as it exhibits constant growth and high neurogenic activity that is supported by radial glia progenitors. However, although synthesis of neuroprogestagens has been documented recently in the brain of zebrafish, information on the presence of progesterone receptors is very limited. In zebrafish, a single nuclear progesterone receptor (pgr) has been cloned and characterized. Here, we demonstrate that this pgr is widely distributed in all regions of the zebrafish brain. Interestingly, we show that Pgr is strongly expressed in radial glial cells and more weakly in neurons. Finally, we present evidence, based on quantitative PCR and immunohistochemistry, that nuclear progesterone receptor mRNA and proteins are upregulated by estrogens in the brain of adult zebrafish. These data document for the first time the finding that radial glial cells are preferential targets for peripheral progestagens and/or neuroprogestagens. Given the crucial roles of radial glial cells in adult neurogenesis, the potential effects of progestagens on their activity and the fate of daughter cells require thorough investigation

Orbital Observations of Dust Lofted by Daytime Convective Turbulence

Over the past several decades, orbital observations of lofted dust have revealed the importance of mineral aerosols as a climate forcing mechanism on both Earth and Mars. Increasingly detailed and diverse data sets have provided an ever-improving understanding of dust sources, transport pathways, and sinks on both planets, but the role of dust in modulating atmospheric processes is complex and not always well understood. We present a review of orbital observations of entrained dust on Earth and Mars, particularly that produced by the dust-laden structures produced by daytime convective turbulence called “dust devils”. On Earth, dust devils are thought to contribute only a small fraction of the atmospheric dust budget; accordingly, there are not yet any published accounts of their occurrence from orbit. In contrast, dust devils on Mars are thought to account for several tens of percent of the planet’s atmospheric dust budget; the literature regarding martian dust devils is quite rich. Because terrestrial dust devils may temporarily contribute significantly to local dust loading and lowered air quality, we suggest that martian dust devil studies may inform future studies of convectively-lofted dust on Earth

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18