The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity

Tumors comprise functionally diverse subpopulations of cells with distinct proliferative potential. Here, we show that dynamic epigenetic states defined by the linker histone H1.0 determine which cells within a tumor can sustain the long-term cancer growth. Numerous cancer types exhibit high inter- and intratumor heterogeneity of H1.0, with H1.0 levels correlating with tumor differentiation status, patient survival, and, at the single-cell level, cancer stem cell markers. Silencing of H1.0 promotes maintenance of self-renewing cells by inducing derepression of megabase-sized gene domains harboring downstream effectors of oncogenic pathways. Self-renewing epigenetic states are not stable, and reexpression of H1.0 in subsets of tumor cells establishes transcriptional programs that restrict cancer cells’ long-term proliferative potential and drive their differentiation. Our results uncover epigenetic determinants of tumor-maintaining cells

Metabolomics reveals novel insight on dormancy of aquatic invertebrate encysted embryos

Numerous aquatic invertebrates survive harsh environments by displaying dormancy as encysted embryos. This study aimed at determining whether metabolomics could provide molecular insight to explain the “dormancy syndrome” by highlighting functional pathways and metabolites, hence offering a novel comprehensive molecular view of dormancy. We compared the metabolome of morphologically distinct dormant encysted embryos (resting eggs) and non-dormant embryos (amictic eggs) of a rotifer (Brachionus plicatilis). Metabolome profiling revealed ~5,000 features, 1,079 of which were annotated. Most of the features were represented at significantly higher levels in non-dormant than dormant embryos. A large number of features was assigned to putative functional pathways indicating novel differences between dormant and non-dormant states. These include features associated with glycolysis, the TCA and urea cycles, amino acid, purine and pyrimidine metabolism. Interestingly, ATP, nucleobases, cyclic nucleotides, thymidine and uracil, were not detected in dormant resting eggs, suggesting an impairment of response to environmental and internal cues, cessation of DNA synthesis, transcription and plausibly translation in the dormant embryos. The levels of trehalose or its analogues, with a role in survival under desiccation conditions, were higher in resting eggs. In conclusion, the current study highlights metabolomics as a major analytical tool to functionally compare dormancy across species.Animal science

Coliform pyosalpinx as a rare complication of appendicectomy: a case report and review of the literature on best practice

<p>Abstract</p> <p>Introduction</p> <p>Coliform pyosalpinx is a rare entity. We report a case that occurred three months after appendicectomy for gangrenous appendicitis. There follows a literature review on best practice for the treatment of pyosalpinx.</p> <p>Case presentation</p> <p>A seventeen year old girl presented with an acute abdomen three months after an appendicectomy for gangrenous appendicitis. Intraoperative findings were bilateral pyosalpinx treated by aspiration, saline and Betadine irrigation and intravenous antibiotics.</p> <p>Conclusion</p> <p>Microbiological analysis of the pus revealed <it>Escherichia coli </it>and anaerobes. Chlamydia and Candida were not isolated. This is the first known reported case of Coliform Pyosalpinx following appendicectomy. The best treatment does not necessarily involve salpingectomy especially in women of reproductive age where fertility may become compromised.</p

Fermion Electric Dipole Moments in Supersymmetric Models with R-parity Violation

We analyze the electron and neutron electric dipole moments induced by R-parity violating interactions in supersymmetric models. It is pointed out that dominant contributions can come from one-loop diagrams involving both the bilinear and trilinear R-parity odd couplings, leading to somewhat severe constraints on the products of those couplings.Comment: Revtex, 19pp, four figures in axodraw.st

REALISTIC MODELS WITH A LIGHT U(1) GAUGE BOSON COUPLED TO BARYON NUMBER

We recently showed that a new gauge boson $\gamma_B$ coupling only to baryon number is phenomenologically allowed, even if $m_B<m_Z$ and $\alpha_B \approx 0.2$. In our previous work we assumed that kinetic mixing between the baryon number and hypercharge gauge bosons (via an $F^{\mu\nu}_B F_{\mu\nu}^Y$ term) was small enough to evade constraints from precision electroweak measurements. In this paper we propose a class of models in which this term is naturally absent above the electroweak scale. We show that the generation of a mixing term through radiative corrections in the low-energy effective theory does not lead to conflict with precision electroweak measurements and may provide a leptonic signal for models of this type at an upgraded Tevatron.Comment: 21 pages, LaTeX, 4 figures in a uuencoded compressed postscript file

Optimal background pharmacological therapy for heart failure patients in clinical trials: JACC review topic of the week

With the current landscape of approved therapies for heart failure (HF), there is a need to determine the role of a standard background therapy against which novel therapies are studied. The Heart Failure Collaboratory convened a multistakeholder group of clinical investigators, clinicians, patients, government representatives including U.S. Food and Drug Administration and National Institutes of Health participants, payers, and industry in March 2021 to discuss whether standardization of background drug therapy is necessary in clinical trials in patients with HF. The current paper summarizes the discussion and provides potential conceptual approaches, with a focus on therapies indicated for HF with reduced ejection fraction