Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.     

Saucerization: A Modified Uncapitonnage Method of Surgery for Pulmonary Hydatidosis

Background

There are contrary opinions regarding the surgical treatment of pulmonary hydatid cysts. We report our experience performing a modified version of uncapitonnage surgery, called “saucerization,” for treating pulmonary hydatid cysts.

Methods

A total of 78 patients with pulmonary hydatid cysts were studied regarding their surgery outcome and the complication rate. The procedure used for cyst evacuation depended on whether the cyst had ruptured. If ruptured, cystotomy was done; otherwise, enucleation was preferred. To deal with the residual cavity in an uncapitonnage manner, we removed the thin margins of the pericyst and closed the bronchial openings at the cavity floor. All patients were followed up at least for 6 months.

Results

The intensive care unit stay ranged from 1 to 9 days. Incomplete lung expansion (six patients) was the main postoperative complication followed by wound infection (four patients) and persistent air leak (≥7 days) (one patient). There was one death. Dependence on mechanical ventilation and subsequent septic shock were also observed. The other patients exhibited no complications during the follow-up period.

Conclusions

Our experience demonstrated a low complication rate associated with removing the thin margins of the residual cavity and changing the shape of it into a “saucer.” The results were satisfactory and comparable to the results of other studies on pulmonary hydatid cysts.     

The effect of systemic erythropoietin and oral prednisolone on recent-onset non-arteritic anterior ischemic optic neuropathy: a randomized clinical trial

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent-onset non-arteritic...     

Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist

Histamine H3 receptors regulate the release of a variety of central neurotransmitters involved in cognitive processes. A-349821 ((4'-(3-((R,R)2,5-dimethyl-pyrrolidin-1-yl)-propoxy)-biphenyl-4-yl)-morpholin-4-yl-methanone) is a novel, non-imidazole H3 receptor ligand, displaying high affinity for recombinant rat and human H3 receptors, with pKi values of 9.4 and 8.8, respectively, and high selectivity for the H3 receptor versus H1, H2, and H4 histamine receptors. A-349821 is a potent H3 receptor antagonist in a variety of models using recombinant human and rat receptors, reversing agonist induced changes in cyclic AMP formation (pKb= 8.2 and pKb= 8.1, respectively), [35S]-GTPgammaS binding (pKb= 9.3 and pKb= 8.6, respectively) and calcium levels (human pKb= 8.3). In native systems, A-349821 competitively reversed agonist induced inhibition of electric field stimulated guinea-pig ileum (pA2= 9.5) and histamine-mediated inhibition of [3H]-histamine release from rat brain cortical synaptosomes (pKb= 9.2). Additionally, A-349821 inhibited constitutive GTPgammaS binding at both rat and human H3 receptors with respective pEC50 values of 9.1 and 8.6, demonstrating potent inverse agonist properties. In behavioral studies, A-349821 (0.4 mg/kg-4 mg/kg) potently blocked (R)-alpha-methylhistamine-induced dipsogenia in mice. The compound also enhanced cognitive activity in a five-trial inhibitory avoidance model in spontaneously hypertensive rat (SHR) pups at doses of 1-10mg/kg, with the 1mg/kg dose showing comparable efficacy to a fully efficacious dose of ciproxifan (3mg/kg). These doses of A-349821 were without effect on spontaneous locomotor activity. Thus, A-349821 is a novel, selective non-imidazole H3 antagonist/inverse agonist with balanced high potency across species and favorable cognition enhancing effects in rats.     

Association between diabetic retinopathy and polymorphisms of cytokine genes: a systematic review and meta-analysis

International Ophthalmology - Diabetic retinopathy (DR) is a medical condition caused by damage to the blood vessels of retina tissue due to diabetes mellitus. DR leads to injury in neural and...     

Achievement of behavioral efficacy and improved potency in new heterocyclic analogs of benzofuran H3 antagonists

Inflammation Research - .     

Identification of novel H3 receptor (H3R) antagonists with cognition enhancing properties in rats

Inflammation Research -