It is important to separate socioeconomic factors affecting health care quality from confounders related to patients’ baseline status or disease biology when studying disparities in lymphoma survival.
TMEM18 is a hypothalamic gene that has recently been linked to obesity and BMI in genome wide association studies. However, the functional properties of TMEM18 are obscure.
The evolutionary history ...of TMEM18 was inferred using phylogenetic and bioinformatic methods. The gene's expression profile was investigated with real-time PCR in a panel of rat and mouse tissues and with immunohistochemistry in the mouse brain. Also, gene expression changes were analyzed in three feeding-related mouse models: food deprivation, reward and diet-induced increase in body weight. Finally, we genotyped 502 severely obese and 527 healthy Swedish children for two SNPs near TMEM18 (rs6548238 and rs756131).
TMEM18 was found to be remarkably conserved and present in species that diverged from the human lineage over 1500 million years ago. The TMEM18 gene was widely expressed and detected in the majority of cells in all major brain regions, but was more abundant in neurons than other cell types. We found no significant changes in the hypothalamic and brainstem expression in the feeding-related mouse models. There was a strong association for two SNPs (rs6548238 and rs756131) of the TMEM18 locus with an increased risk for obesity (p = 0.001 and p = 0.002).
We conclude that TMEM18 is involved in both adult and childhood obesity. It is one of the most conserved human obesity genes and it is found in the majority of all brain sites, including the hypothalamus and the brain stem, but it is not regulated in these regions in classical energy homeostatic models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Opioid use disorder (OUD) is a serious health problem that may lead to physical dependence, in addition to affective disorders. Preclinical models are essential for studying the neurobiology of and ...developing pharmacotherapies to treat these problems. Historically, chronic morphine injections have most often been used to produce opioid-dependent animals, and withdrawal signs indicative of dependence were precipitated by administering an opioid antagonist. In the present studies, we have developed and validated a model of dependence on oxycodone (a widely prescribed opioid) during spontaneous withdrawal in male and female C57BL/6J mice. Dependence was induced by chronically administering oxycodone through osmotic minipumps at different doses for 7 days. Somatic withdrawal signs were measured after 3, 6, 24, and 48 h following minipump removal. Additionally, sensitivity to mechanical, thermal, and cold stimuli, along with anxiety-like behavior, were also measured. Our results indicated that spontaneous withdrawal following discontinuation of oxycodone produced an increase in total withdrawal signs after 60 and 120 mg/kg/day regimens of oxycodone administration. These signs were reversed by the administration of clinically approved medications for OUD. In general, both female and male mice showed similar profiles of somatic signs of spontaneous withdrawal. Spontaneous withdrawal also resulted in mechanical and cold hypersensitivity lasting for 24 and 14 days, respectively, and produced anxiety-like behaviors after 2 and 3 weeks following oxycodone removal. These results help validate a new model of oxycodone dependence, including the temporally distinct emergence of somatic, hyperalgesic, and anxiety-like behaviors, potentially useful for mechanistic and translational studies of opioid dependence.
•Chronic oxycodone induces a dose-dependent spontaneous physical withdrawal following discontinuation of the drug.•Spontaneous oxycodone withdrawal resulted in enhanced long-lasting mechanical and cold hypersensitivity.•Spontaneous oxycodone withdrawal resulted in a protracted and long-lasting anxiety-like behaviors.
The richness (number of species) and evenness (uniformity of species abundances) of death assemblages can differ from corresponding living communities due to processes such as between-habitat ...transport, environmental condensation, and differential taphonomic destruction. Analysis of 132 single-census live-dead comparisons of benthic molluscs from a variety of soft-bottom marine settings indicates that on average evenness does not differ greatly between live and dead assemblages, regardless of the particular depositional setting or grain size of associated sediment. However, individual death assemblages can deviate quite substantially from their corresponding living assemblages, especially if processed using a fine mesh. In addition, death assemblages collected using sieves with 2 mm mesh or coarser showed consistently and significantly greater evenness than corresponding living assemblages. These results are encouraging for broad-scale assessments of evenness in the fossil record based on the comparison of average values (rather than for individual assemblages) and where trends in evenness are the aim of the study. Our live-dead comparisons of richness sample-size corrected by rarefaction revealed that death assemblages were on average ∼1.45 times richer than the corresponding living assemblages regardless of rarefied size. In 63.6% of death assemblages both dead richness and dead evenness were greater than live, suggesting sufficient time-averaging to catch significant random or directional changes in the living community and/or introduction of individuals from outside the sampled habitat. In 12.9% of collections both dead richness and dead evenness were less than live, suggesting either rapid loss of dead shells so that dead diversity is depressed below the local living community or selective loss of taphonomically vulnerable taxa. In 18.2% of data sets dead richness was elevated but dead evenness was depressed relative to live: these are interpreted to reflect the addition of low-evenness allochthonous material. The remaining 4.5% of data sets had elevated dead evenness but depressed dead richness, suggesting that live and dead in this case may not be closely related. In seven available time series, temporal volatility in living communities over 6–24 months was considerable but could not account for observed (mostly higher) evenness values in corresponding death assemblages, whose evenness and composition were quite stable in the few examined studies. A densely sampled spatial transect shows that changes in living-assemblage evenness along an environmental gradient were preserved in the corresponding death assemblages, although dead evenness at any location on the gradient was substantially higher than living evenness.
The basis for persistence of leukemic stem cells in the bone marrow microenvironment remains poorly understood. We present evidence that signaling cross-talk between α4 integrin and Abelson ...interactor-1 (Abi-1) is involved in the acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl-positive leukemia cells. Comparison of Abi-1 (ABI-1) and α4 integrin (ITGA4) gene expression in relapsing Bcr-Abl-positive CD34+progenitor cells demonstrated a reduction in Abi-1 and an increase in α4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi-1 and α4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate -resistant leukemic cells. These results indicate that the α4-Abi-1 signaling pathway may mediate acquisition of the drug-resistant phenotype of leukemic cells.
A
bstract
A search for squarks and gluinos in final states containing high-
p
T
jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS ...experiment in
s
=
8
TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20
.
3 fb
−1
. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that
R
-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan
β
= 30,
A
0
= −2
m
0
and
μ >
0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.
A search is presented for the pair production of heavy vectorlike quarks, TT¯ or BB¯, that decay into final states with jets and no reconstructed leptons. Jets in the final state are classified using ...a deep neural network as arising from hadronically decaying W/Z bosons, Higgs bosons, top quarks, or background. The analysis uses data from the ATLAS experiment corresponding to 36.1 fb−1 of proton-proton collisions with a center-of-mass energy of s=13 TeV delivered by the Large Hadron Collider in 2015 and 2016. No significant deviation from the Standard Model expectation is observed. Results are interpreted assuming the vectorlike quarks decay into a Standard Model boson and a third-generation-quark, T→Wb,Ht,Zt or B→Wt,Hb,Zb, for a variety of branching ratios. At 95% confidence level, the observed (expected) lower limit on the vectorlike B-quark mass for a weak-isospin doublet (B, Y) is 950 (890) GeV, and the lower limits on the masses for the pure decays B→Hb and T→Ht, where these results are strongest, are 1010 (970) GeV and 1010 (1010) GeV, respectively.
Spatial thinking permeates much of our lives and is an asset when solving problems involving well-structured visual information or imagining solutions in physical or digital space. However, an ...estimated three million US school children have spatial talents that go unrecognized because of the tools commonly used for identification of academic talent. For decades, educational and psychological research has explored the range of spatial thinking skills that are demanded by many career fields, including science, engineering, and mathematics. Spatial thinking has been found to be particularly important to early mathematical thinking. In this article, we explore what spatial thinking entails, where it is important in the curriculum, and how we can begin to develop spatial literacy and identify spatial talents in our K-12 classrooms.
In a three-year field experiment the assessment of leaves and ears photosynthesis rate in spring wheat was made using a LI-COR 6400 portable photosynthesis system. The photosynthetic rate of spring ...wheat was affected by cultivars, nitrogen fertilization and weather conditions. We generally found a negative correlation between the yield of spring wheat and the rate of photosynthesis in flag leaves in phases 39-55 BBCH (the strength of this effect depended on the level of nitrogen fertilization). Strong negative correlation occurred for cv. Bryza in phases: 39-51 BBCH in treatment fertilized with lower dose of nitrogen and in phase 39-41 BBCH for dose 120 kg/ha. There was a significant negative correlation for cv. Tybald only in phase 39-41 BBCH for higher dose of nitrogen and 52-55 BBCH for lower dose. Our studies show that the photosynthetic activity of flag leaves decreased from the booting (39-41 BBCH) to heading stage (52-55 BBCH), and their function was taken over by ears. Contrary to flag leaf, in wheat ears the intensity of photosynthesis correlated positively with grain yield for most of the studied period (52-65 BBCH, with highly significant correlation at 56-57 BBCH and - only for high nitrogen treatments - at 59-61 BBCH; a negative correlation was generally observed at a later phase, i.e. at 65-69 BBCH). Contrary to flag leaf photosynthesis, the intensity of this process in wheat ears (at the heading and flowering stages) seems highly relevant for grain yield. High positive correlation was noted in 56-57 BBCH and 61-65 BBCH. However, the study was done in field conditions and for definitive conclusions observations over a longer period would be desirable.
A search is made for potential cccover ¯cover ¯ tetraquarks decaying into a pair of charmonium states in the four muon final state using proton-proton collision data at sqrts=13 TeV, corresponding ...to an integrated luminosity of 140 fb^{-1} recorded by the ATLAS experiment at LHC. Two decay channels, J/ψ+J/ψ→4μ and J/ψ+ψ(2S)→4μ, are studied. Backgrounds are estimated based on a hybrid approach involving Monte Carlo simulations and data-driven methods. Statistically significant excesses with respect to backgrounds dominated by the single parton scattering are seen in the di-J/ψ channel consistent with a narrow resonance at 6.9 GeV and a broader structure at lower mass. A statistically significant excess is also seen in the J/ψ+ψ(2S) channel. The fitted masses and decay widths of the structures are reported.
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