Lyhnemorris5547

The effectors of the Rab7 small GTPase play multiple roles in Rab7-dependent endosome-lysosome and autophagy-lysosome pathways. However, it is largely unknown how distinct Rab7 effectors coordinate to maintain the homeostasis of late endosomes and lysosomes to ensure appropriate endolysosomal and autolysosomal degradation. Here we report that WDR91, a Rab7 effector required for early-to-late endosome conversion, is essential for lysosome function and homeostasis. Mice lacking Wdr91 specifically in the central nervous system exhibited behavioral defects and marked neuronal loss in the cerebral and cerebellar cortices. At the cellular level, WDR91 deficiency causes PtdIns3P-independent enlargement and dysfunction of lysosomes, leading to accumulation of autophagic cargoes in mouse neurons. WDR91 competes with the VPS41 subunit of the HOPS complex, another Rab7 effector, for binding to Rab7, thereby facilitating Rab7-dependent lysosome fusion in a controlled manner. WDR91 thus maintains an appropriate level of lysosome fusion to guard the normal function and survival of neurons.

CircRNAs are covalently closed RNA molecules that are particularly abundant in the brain. While circRNA expression data from the human brain is rapidly accumulating, integration of large-scale datasets remains challenging and time-consuming, and consequently an integrative view of circRNA expression in the human brain is currently lacking.

NeuroCirc is a web-based resource that allows interactive exploration of multiple types of circRNA data from the human brain, including large-scale expression datasets, circQTL data and circRNA expression across neuronal differentiation and cellular maturation time-courses. NeuroCirc also allows users to upload their own circRNA expression data and explore it in the integrative platform, thereby supporting circRNA prioritization for experimental validation and functional studies. NeuroCirc is freely available at https//voineagulab.github.io/NeuroCirc/. The source code and user documentation are available at https//github.com/Voineagulab/NeuroCirc.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

Antiseizure medication (ASM) treatment duration for acute symptomatic neonatal seizures is variable. A randomized clinical trial of phenobarbital compared with placebo after resolution of acute symptomatic seizures closed early owing to low enrollment.

To assess whether ASM discontinuation after resolution of acute symptomatic neonatal seizures and before hospital discharge is associated with functional neurodevelopment or risk of epilepsy at age 24 months.

This comparative effectiveness study included 303 neonates with acute symptomatic seizures (282 with follow-up data and 270 with the primary outcome measure) from 9 US Neonatal Seizure Registry centers, born from July 2015 to March 2018. The centers all had level IV neonatal intensive care units and comprehensive pediatric epilepsy programs. Data were analyzed from June 2020 to February 2021.

The primary exposure was duration of ASM treatment dichotomized as ASM discontinued vs ASM maintained at the time of discharge from the neonatal seizure admisonal neurodevelopment or epilepsy at age 24 months among children whose ASM was discontinued vs maintained at hospital discharge after resolution of acute symptomatic neonatal seizures. These results support discontinuation of ASM prior to hospital discharge for most infants with acute symptomatic neonatal seizures.

Missed opportunities for human papillomavirus (HPV) vaccination during pediatric health care visits are common.

To evaluate the effect of online communication training for clinicians on missed opportunities for HPV vaccination rates overall and at well-child care (WCC) visits and visits for acute or chronic illness (hereafter referred to as acute or chronic visits) and on adolescent HPV vaccination rates.

From December 26, 2018, to July 30, 2019, a longitudinal cluster randomized clinical trial allocated practices to communication training vs standard of care in staggered 6-month periods. A total of 48 primary care pediatric practices in 19 states were recruited from the American Academy of Pediatrics Pediatric Research in Office Settings network. Participants were clinicians in intervention practices. Outcomes were evaluated for all 11- to 17-year-old adolescents attending 24 intervention practices (188 clinicians) and 24 control practices (177 clinicians). Analyses were as randomized and performed on 069 girls [50.3%]; mean [SD] age, 14.2 [2.0] years) made 17 910 WCC and 35 281 acute or chronic visits to control practices. Intervention practices reduced missed opportunities overall by 2.4 percentage points (-2.4%; 95% CI, -3.5% to -1.2%) more than controls. Intervention practices reduced missed opportunities for vaccine initiation during WCC visits by 6.8 percentage points (-6.8%; 95% CI, -9.7% to -3.9%) more than controls. The intervention had no effect on missed opportunities for subsequent doses of the HPV vaccine or at acute or chronic visits. Adolescents in intervention practices had a 3.4-percentage point (95% CI, 0.6%-6.2%) greater improvement in HPV vaccine initiation compared with adolescents in control practices.

This scalable, online communication training increased HPV vaccination, particularly HPV vaccine initiation at WCC visits. Results support dissemination of this intervention.

ClinicalTrials.gov Identifier NCT03599557.

ClinicalTrials.gov Identifier NCT03599557.

In delayed breast reconstruction, the thoraco-mammary cutaneous tissue often shows residual damage from radiotherapy. The fragility of this tissue is associated with a risk of skin necroses of about 8% when dissection is performed by reopening of the mastectomy scar.

The objective of our study was to adapt the technique of short-scar latissimus dorsi flap surgery with an abdominal advancement flap using a lateral approach only avoiding re-incision of the mastectomy scar.

In this retrospective study, we performed 150 reconstructions in 146 patients to assess the safety and effectiveness of the SSLD technique with lateral approach. The primary outcome was the occurrence of postoperative skin necrosis of the thoraco-mammary area.

Of the 150 delayed breast reconstruction procedures performed, none showed skin necrosis of the thoraco-mammary area, and a positive effect on skin trophicity of this area was observed. click here The resulting patient and surgical team satisfaction were very favorable.

In our practice, this technique changed our paradigm because of good skin safety and effectiveness. It allows reconstruction without a patch-effect in patients with very poor skin quality in whom the thoraco-mammary skin would have been replaced in the past by a skin paddle. Reconstruction would have even be contraindicated. It could also be an alternative to many other more complex and longer techniques of autologous reconstruction.

In our practice, this technique changed our paradigm because of good skin safety and effectiveness. It allows reconstruction without a patch-effect in patients with very poor skin quality in whom the thoraco-mammary skin would have been replaced in the past by a skin paddle. Reconstruction would have even be contraindicated. It could also be an alternative to many other more complex and longer techniques of autologous reconstruction.Motivated by recent nanofluidics experiments, we use Brownian dynamics and Monte Carlo simulations to study the conformation, organization and dynamics of two polymer chains confined to a single box-like cavity. The polymers are modeled as flexible bead-spring chains, and the box has a square cross-section of side length L and a height that is small enough to compress the polymers in that dimension. For sufficiently large L, the system behaviour approaches that of an isolated polymer in a slit. However, the combined effects of crowding and confinement on the polymer organization, conformation and equilibrium dynamics become significant when where is the transverse radius of gyration for a slit geometry. In this regime, the centre-of-mass probability distribution in the transverse plane exhibits a depletion zone near the centre of the cavity (except at very small L) and a 4-fold symmetry with quasi-discrete positions. Reduction in polymer size with decreasing L arises principally from confinement rather than inter-polymer crowding. By contrast, polymer diffusion and internal motion are strongly affected by inter-polymer crowding. The two polymers tend to occupy opposite positions relative to the box centre, about which they diffuse relatively freely. Qualitatively, this static and dynamical behaviour differs significantly from that previously observed for confinement of two polymers to a narrow channel. The simulation results for a suitably chosen box width are qualitatively consistent with results from a recent experimental study of two λ-DNA chains confined to a nanofluidic cavity.We developed a novel Pd-catalysed enantioselective synthesis of C-N bonds using the chiral scaffold of DNA. The non-covalently linked [Pd(phen)(OAc)2] with st-DNA catalysed the Markonicov hydroamination of β-nitrostyrene with methoxyamine for the first time with >75% enantiomeric excess (ee) in an aqueous buffer (pH 7.4) at room temperature.Bi-C catalysts with the three-phase interfaces of CO2 (gas), electrolyte (liquid) and catalyst (solid) exhibit a remarkable electrocatalytic CO2 reduction (ECR) to formate selectivity (above 95% faradaic efficiency) with a high current (100 mA cm-2) in a broad potential range.The synthesis of di- and tritopic gold(i) metallaligands of the type [(Au4-py)2(μ2-diphosphane)] (diphosphane = bis(diphenylphosphanyl)isopropane or dppip (1), 1,2-bis(diphenylphosphanyl)ethane or dppe (2), 1,3-bis(diphenylphosphanyl)propane or dppp (3) and 1,4-bis(diphenylphosphanyl)butane or dppb (4)) and [(Au4-py)3(μ3-triphosphane)] (triphosphane = 1,1,1-tris(diphenylphosphanylmethyl)ethane or triphos (5) and 1,3,5-tris(diphenylphosphanyl)benzene or triphosph (6)) from [(AuCl)2(μ2-diphosphane)] or [(AuCl)3(μ3-triphosphane)] and 4-pyridylboronic acid in the presence of Cs2CO3 has been conducted. Interestingly, when [(AuCl)2(μ2-dppm)] (dppm = bis(diphenylphosphanyl)methane) was used as a starting material, the cyclic tetranuclear gold(i) compound [(Au4-py)2(CH)2μ2-Au(PPh2)22] (I) was obtained instead. All the products have been characterized by IR and multinuclear NMR spectroscopy, mass spectrometry and elemental analysis and in the case of 1, 3, 5 and I by X-ray crystallography, which showed the presence of aurophilic interactions in all of them. The obtained metallaligands have been used as building blocks in self-assembly reactions with cis-blocked palladium or platinum acceptor moieties producing [2 + 2] metallamacrocycles or trigonal bipyramidal (TBP) [2 + 3] metallacages in good yields. The photophysical properties of both the metallaligands and the corresponding assemblies have been investigated.The aim of this study was to investigate the effects and potential signaling pathway of selenium-enriched Bacillus subtilis (SEBS) on beta defensin 1 (BD1) expression in chicken intestine. Chinese Huainan Partridge chickens (500 individuals) were randomly allocated into five groups, including control, inorganic Se, B. subtilis, SEBS, and a mixture of Se and B. subtilis (Se-BS). After 56 d of feeding, chicken ileal mucous membranes were harvested to detect differences in expression of BD1. The results indicated that BD1 was produced in intestinal crypt cells and secreted into the lumen through the villi brush border. BD1 was up-regulated in distal ileum segments colonized by SEBS and B. subtilis. Chicken primary intestinal crypt cells were cultured and grouped into control, inorganic Se, B. subtilis, SEBS, and Se-BS treatments to identify the receptor of B. subtilis. Results indicated that B. subtilis and SEBS were recognized by toll-like receptor 2 (TLR2), stimulating the NF-κB1 signaling pathway to increase expression of BD-1, which was further enhanced when combined with Se.