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Western honey bee (Apis mellifera L.) populations face declines commonly attributed to pesticide, pathogen, and parasite stress. One way beekeepers combat these stressors is by providing supplemental protein diets to honey bee colonies to ensure adequate colony nutrition. However Nosema spp., a microsporidian parasite of the honey bee, is thought to be associated closely with a colony's nutritional intake, thus possibly negating any benefit the bees otherwise would have received from a nutritional supplement. Through three objectives, we examined how adult bees' consumption of wildflower pollen or commercial pollen substitute diets affected Nosema levels in the bees' midguts. For our first objective, we investigated how method of inoculation with Nosema affects infection levels in inoculated bees. Bees were infected with spores of Nosema four days after emergence. On day 15, bees were collected from the cages and Nosema spores were quantified. We found that inoculation through the pollen diet resulted in the highest Nosema levels in inoculated bees. In our second and third objectives, we provided the test diets to caged, newly emerged bees for a period of 15 days. Bees consuming pollen and a sucrose solution had more Nosema in their midguts than did bees consuming the sucrose solution alone (control). The overall volume of diet consumed by the bees did not correlate with the level of Nosema in their midguts. The level of Nosema was higher in bees fed certain commercial pollen substitute diets than in bees fed wildflower pollen. Our study illustrates how providing nutritional supplements to adult honey bees can impact the intensity of Nosema in their midguts.

Cardiac contractility is enhanced by phosphorylation of myosin light chain 2 (MLC2) by cardiac-specific MLC kinase (cMLCK), located at the neck region of myosin heavy chain. In normal mouse and human hearts, the level of phosphorylation is maintained relatively constant, at around 30-40% of total MLC2, likely by well-balanced phosphorylation and phosphatase-dependent dephosphorylation. Overexpression of cMLCK promotes sarcomere organization, while the loss of cMLCK leads to cardiac atrophy in vitro and in vivo. In this study, we showed that cMLCK is predominantly expressed at the Z-disc with additional diffuse cytosolic expression in normal adult mouse and human hearts. cMLCK interacts with the Z-disc protein, α-actinin2, with a high-affinity kinetic value of 13.4 ± 0.1 nM through the N-terminus region of cMLCK unique to cardiac-isoform. cMLCK mutant deficient for interacting with α-actinin2 did not promote sarcomeric organization and reduced cardiomyocyte cell size. In contrast, a cMLCK kinase-deficient mutant showed effects similar to wild-type cMLCK on sarcomeric organization and cardiomyocyte cell size. Our results suggest that cMLCK plays a role in sarcomere organization, likely distinct from its role in phosphorylating MLC2, both of which will contribute to the enhancement of cardiac contractility.

: To evaluate the cost, safety, surgical outcome, and efficacy of modified Cutler-Beard eyelid reconstruction utilizing a novel silicone plate as a tarsal plate replacement in the repair of 60% to 100% eyelid defects following the excision of large malignant tumors. : A prospective, noncomparative, interventional study of 30 eyes was done over 3 years. Fourteen patients were female, and 16 patients were male. In all the cases, a silicone plate, the synthetic, artificial tarsal plate, was utilized for a total or subtotal replacement of the tarsal plate. The created defect was measured in mm (length and width) and later expressed in percentage. Pre- and postoperative action of levator palpebrae superioris (LPS) was measured. Pre- and postoperative measurements of the margin-to-margin reflex distance (MRD1) were noted. : Preoperative LPS action was 1.23 ± 1.35 mm, whereas postoperative LPS actions at the end of 1 week and 18 months were 11. 8 ± 0.88 mm and 13.53 ± 0. 73 mm, respectively. Preoperative MRD1 was - 3.0 ± 1.144 mm, whereas postoperative MRD1 values at the end of 1 week and 18 months were 2.18 ± 0.27 mm and 4.16 mm ± 0.35, respectively. The mean created defect after the removal of the tumor was 87.3% ±11.10. The mean length of the silicone plate implanted in this study was 27.53 ± 2.48 mm. The follow-up period for the study participants was 18 months. : The synthetic novel silicone plate was successful as a tarsal plate replacement. A second surgical site for ear cartilage harvesting is avoided. Cadaver transfer of Achilles tendon carries the risk of transmission of communicable diseases, for example, hepatitis B and HIV. Silicone is an inert, nonreacting, and tissue-tested material, thus eliminating the possibility of graft rejection. This material is readily available and cost-effective. The novel silicone plate is considered to be the most promising alternative material as a tarsal replacement in the future generation.

In patients with thyroid-associated ophthalmopathy, responses to treatment are rare and usually minor. Teprotumumab, an antibody to the insulin-like growth factor I receptor, led to significant responses in 69% of patients and to decreased proptosis. Medical therapies for moderate-to-severe thyroid-associated ophthalmopathy (Graves’ orbitopathy) that have proved to be effective and safe in adequately powered, prospective, placebo-controlled trials are lacking. This unmet need is due to the incompletely understood pathogenesis of the disease. 1 Current treatments are inconsistently beneficial and often associated with side effects, and their modification of the ultimate disease outcome is uncertain. 1 – 3 Previous clinical trials, which were rarely placebo-controlled, suggest that high-dose glucocorticoids, alone 3 – 5 or with radiotherapy, 6 , 7 can reduce inflammation-related signs and symptoms in patients with active ophthalmopathy. However, glucocorticoids and orbital radiotherapy minimally affect proptosis and can cause dose-limiting adverse . . .

In mammalian cells, DNA double-strand breaks (DSBs) cause rapid phosphorylation of the H2AX core histone variant (to form γ-H2AX) in megabase chromatin domains flanking sites of DNA damage. To investigate the role of H2AX in mammalian cells, we generated H2AX-deficient (H2AXΔ/Δ) mouse embryonic stem (ES) cells. H2AXΔ/ΔES cells are viable. However, they are highly sensitive to ionizing radiation (IR) and exhibit elevated levels of spontaneous and IR-induced genomic instability. Notably, H2AX is not required for NHEJ per se because H2AXΔ/ΔES cells support normal levels and fidelity of V(D)J recombination in transient assays and also support lymphocyte development in vivo. However, H2AXΔ/ΔES cells exhibit altered IR-induced BRCA1 focus formation. Our findings indicate that H2AX function is essential for mammalian DNA repair and genomic stability.

In a good example of translational research, investigators who had initially demonstrated a role for insulin-like growth factor I in the pathogenesis of thyroid eye disease showed that an antibody to the receptor (teprotumumab) produced a meaningful improvement in 83% of patients.

The Mre11 complex (in Saccharomyces cerevisiae: Mre11, Rad50 and Xrs2) influences multiple facets of chromosome break metabolism. A conserved feature of the Mre11 complex is a zinc-coordinating motif in Rad50 called the Rad50 hook. We established a diploid yeast strain, rad50(hook), in which Rad50 is encoded in halves, one from each of the two RAD50 alleles, with the residues constituting the hook deleted. In all respects, rad50(hook) phenocopies complete Rad50 deficiency. Replacing the hook domain with a ligand-inducible FKBP dimerization cassette partially mitigated all phenotypes in a ligand-dependent manner. The data indicate that the Rad50 hook is critical for Mre11 complex-dependent DNA repair, telomere maintenance and meiotic double-strand break formation. Sister chromatid cohesion was unaffected by Rad50 deficiency, suggesting that molecular bridging required for recombinational DNA repair is qualitatively distinct from cohesin-mediated sister chromatid cohesion.

The article reports on a study to evaluate the safety and efficacy of teprotunumab as a form of treatment for patients with thyroid-associated ophthalmopathy. The results indicate that among these patients teprotunumab was found to be quite effective.

Western honey bee (Apis mellifera L.) populations face declines commonly attributed to pesticide, pathogen, and parasite stress. One way beekeepers combat these stressors is by providing supplemental protein diets to honey bee colonies to ensure adequate colony nutrition. However Nosema spp., a microsporidian parasite of the honey bee, is thought to be associated closely with a colony's nutritional intake, thus possibly negating any benefit the bees otherwise would have received from a nutritional supplement. Through three objectives, we examined how adult bees' consumption of wildflower pollen or commercial pollen substitute diets affected Nosema levels in the bees' midguts. For our first objective, we investigated how method of inoculation with Nosema affects infection levels in inoculated bees. Bees were infected with spores of Nosema four days after emergence. On day 15, bees were collected from the cages and Nosema spores were quantified. We found that inoculation through the pollen diet resulted in the highest Nosema levels in inoculated bees. In our second and third objectives, we provided the test diets to caged, newly emerged bees for a period of 15 days. Bees consuming pollen and a sucrose solution had more Nosema in their midguts than did bees consuming the sucrose solution alone (control). The overall volume of diet consumed by the bees did not correlate with the level of Nosema in their midguts. The level of Nosema was higher in bees fed certain commercial pollen substitute diets than in bees fed wildflower pollen. Our study illustrates how providing nutritional supplements to adult honey bees can impact the intensity of Nosema in their midguts.