MacroH2A subtypes contribute antagonistically to the transcriptional regulation of the ribosomal cistron during seasonal acclimatization of the carp fish

<p>Abstract</p> <p>Background</p> <p>Incorporation of histone variants into chromatin is one of the epigenetic mechanisms used for regulation of gene expression. Macro (m)H2A is a histone variant that has two different subtypes in vertebrates: mH2A1 and mH2A2. It is known that mH2A is associated with gene silencing, but recent studies indicate that these mH2A subtypes could contribute more widely to transcriptional regulation. We have previously demonstrated that the gene-reprogramming response mediates adaptation of the carp fish to its environment, and that ribosomal gene transcription is seasonally regulated in carp. However, there have been few studies investigating how epigenetic mechanisms contribute to environmental adaptation and, in particular, to ribosomal cistron regulation.</p> <p>Results</p> <p>In this paper, we report the occurrence of differential incorporation of mH2A subtypes into chromatin during seasonal adaptation in the carp, an event that concurs with opposing transcriptional states. Moreover, we observed that enrichment of mH2A1 in the ribosomal cistron during winter, and conversely, enrichment of mH2A2 during summer. mH2A1 consistently colocalizes with a heterochromatin marker (H3K27me2; histone H3 trimethylated at lysine 27) and mH2A2 with a euchromatin marker (H3K4me3; histone H3 trimethylated at lysine 4). Similar results were found for the L41gene, with enrichment of mH2A in the promoter region.</p> <p>Conclusions</p> <p>We have characterized both mH2A subtypes from carp fish, and evaluated their participation in the regulation of the ribosomal cistron. Our findings indicate that differential incorporation of mH2A subtypes into the ribosome could regulate gene expression during the acclimatization process in carp. Our results reveal differential chromatin incorporation of the mH2A subtypes during the environmental adaptation process, correlating wtih antagonistic transcriptional states in the carp ribosomal cistron.</p

Topological Quantum Glassiness

Quantum tunneling often allows pathways to relaxation past energy barriers which are otherwise hard to overcome classically at low temperatures. However, this is not always the case. In this paper we provide simple exactly solvable examples where the barriers each system encounters on its approach to lower and lower energy states become increasingly large and eventually scale with the system size. If the environment couples locally to the physical degrees of freedom in the system, tunnelling under large barriers requires processes whose order in perturbation theory is proportional to the width of the barrier. This results in quantum relaxation rates that are exponentially suppressed in system size: For these quantum systems, no physical bath can provide a mechanism for relaxation that is not dynamically arrested at low temperatures. The examples discussed here are drawn from three dimensional generalizations of Kitaev's toric code, originally devised in the context of topological quantum computing. They are devoid of any local order parameters or symmetry breaking and are thus examples of topological quantum glasses. We construct systems that have slow dynamics similar to either strong or fragile glasses. The example with fragile-like relaxation is interesting in that the topological defects are neither open strings or regular open membranes, but fractal objects with dimension $d^* = ln 3/ ln 2$.Comment: (18 pages, 4 figures, v2: typos and updated figure); Philosophical Magazine (2011

Impacts of Co-Solvent Flushing on Microbial Populations Capable of Degrading Trichloroethylene

With increased application of co-solvent flushing technologies for removal of nonaqueous phase liquids from groundwater aquifers, concern over the effects of the solvent on native microorganisms and their ability to degrade residual contaminant has also arisen. This study assessed the impact of ethanol flushing on the numbers and activity potentials of trichloroethylene (TCE)-degrading microbial populations present in aquifer soils taken immediately after and 2 years after ethanol flushing of a former dry cleaners site. Polymerase chain reaction analysis revealed soluble methane monooxygenase genes in methanotrophic enrichments, and 16S rRNA analysis identified Methylocystis parvus with 98% similarity, further indicating the presence of a type II methanotroph. Dissimilatory sulfite reductase genes in sulfate-reducing enrichments prepared were also observed. Ethanol flushing was simulated in columns packed with uncontaminated soils from the dry cleaners site that were dosed with TCE at concentrations observed in the field; after flushing, the columns were subjected to a continuous flow of 500 pore volumes of groundwater per week. Total acridine orange direct cell counts of the flushed and nonflushed soils decreased over the 15-week testing period, but after 5 weeks, the flushed soils maintained higher cell counts than the nonflushed soils. Inhibition of methanogenesis by sulfate reduction was observed in all column soils, as was increasing removal of total methane by soils incubated under methanotrophic conditions. These results showed that impacts of ethanol were not as severe as anticipated and imply that ethanol may mitigate the toxicity of TCE to the microorganisms

The Lippmann–Schwinger Formula and One Dimensional Models with Dirac Delta Interactions

We show how a proper use of the Lippmann–Schwinger equation simplifies the calculations to obtain scattering states for one dimensional systems perturbed by N Dirac delta equations. Here, we consider two situations. In the former, attractive Dirac deltas perturbed the free one dimensional Schrödinger Hamiltonian. We obtain explicit expressions for scattering and Gamow states. For completeness, we show that the method to obtain bound states use comparable formulas, although not based on the Lippmann–Schwinger equation. Then, the attractive N deltas perturbed the one dimensional Salpeter equation. We also obtain explicit expressions for the scattering wave functions. Here, we need regularisation techniques that we implement via heat kernel regularisation

Disparities in access to and use of HIV-related health services in the Netherlands by migrant status and sexual orientation: a cross-sectional study among people recently diagnosed with HIV infection

Background Migrants often face barriers to accessing healthcare. We examined disparities in access to and use of HIV-related health services between migrant and non-migrant people recently diagnosed with HIV living in the Netherlands, taken into account sexual orientation. Also, we examined differences in experiences in living with HIV between these groups. Methods We used a questionnaire and clinical data collected between July 2013 and June 2015 among migrant and non-migrant participants of the European cross-sectional aMASE (Advancing Migrant Access to health Services in Europe) study in the Netherlands. Using univariable logistic regression analyses, we compared outcomes on between migrants and non-migrants, stratified by sexual orientation (with non-migrant men having sex with men [MSM] as the reference group). Results We included 77 migrant MSM, 115 non-migrant MSM, 21 migrant heterosexual men, 14 non-migrant heterosexual men and 20 migrant women. In univariable analyses, all heterosexual groups were less likely to ever have had an HIV-negative test before their diagnosis and were more likely to be diagnosed late than non-migrant MSM. All migrant groups were more likely to have experienced difficulties accessing general healthcare in the Netherlands and were less likely to have heard of post-exposure prophylaxis than non-migrant MSM. Migrants frequently reported uncertainty about their rights to healthcare and language barriers. Most (93%) participants visited a healthcare facility in the 2 years before HIV diagnosis but only in 41% an HIV test was discussed during that visit (no statistical difference between groups). Migrant heterosexuals were more likely to have missed appointments at their HIV clinic due to the travel costs than non-migrant MSM. Migrant MSM and women were more likely to have experienced HIV discrimination in the Netherlands than non-migrant MSM. Conclusion Disparities in access to and use of HIV-related health services and experiences exist by migrant status but also by sexual orientation. Our data suggests heterosexual men and women may particularly benefit from improved access to HIV testing (e.g., through provider-initiated testing), while migrant MSM may benefit from improved access to HIV prevention interventions (e.g., pre-exposure prophylaxis)

Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice.

Alpha-synuclein (α-Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that α-Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing α-Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used α-Syn small interfering RNA (siRNA) to reduce total and aggregated α-Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease α-Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation-mimic S129D α-Syn, which exhibits aggregation. In normal mice we detected significantly reduced α-Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded with siRNA to α-Syn. In S129D α-Syn transgenic mice we found a decreased α-Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse brain α-Syn pathological conditions

Ellipsoidal analysis of coordination polyhedra

The idea of the coordination polyhedron is essential to understanding chemical structure. Simple polyhedra in crystalline compounds are often deformed due to structural complexity or electronic instabilities so distortion analysis methods are useful. Here we demonstrate that analysis of the minimum bounding ellipsoid of a coordination polyhedron provides a general method for studying distortion, yielding parameters that are sensitive to various orders in metal oxide examples. Ellipsoidal analysis leads to discovery of a general switching of polyhedral distortions at symmetry-disallowed transitions in perovskites that may evidence underlying coordination bistability, and reveals a weak off-centre ‘d(5) effect' for Fe(3+) ions that could be exploited in multiferroics. Separating electronic distortions from intrinsic deformations within the low temperature superstructure of magnetite provides new insights into the charge and trimeron orders. Ellipsoidal analysis can be useful for exploring local structure in many materials such as coordination complexes and frameworks, organometallics and organic molecules

The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with Ssubstitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening

Successful Medical Management of Status Post-Roux-en-Y-Gastric-Bypass Hyperinsulinemic Hypoglycemia

Roux-en-Y gastric bypass (RYGBP) is the most commonly performed type of bariatric surgery, which is used in the treatment of obesity and type 2 diabetes. Recent case reports and case series have described a rare complication of RYGBP, status post-gastric-bypass hyperinsulinemic hypoglycemia, which was mainly managed successfully with pancreatectomy. In this letter, we describe the first successful management of status post-gastric-bypass hyperinsulinemic hypoglycemia with diazoxide