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Abstract Reciprocal differences persist in nature because of the unequal contribution of cytoplasmic determinants from male and female gametes to the zygote. The inheritance of genetic differences is an important factor that influences various traits, including somatic embryogenesis and regeneration in vitro. In this report, we estimate the cytoplasmic and maternal effects in pearl millet and their adequacy in describing the observed reciprocal differences based on an in depth study of the parents, F2s and reciprocal backcross progenies needed for fitting genetical models. Our study revealed that of the two characters examined, embryogenic callus quantity and regeneration frequency, the former showed a greater proportion of cytoplasmic nuclear interaction whereas the latter showed a greater role of nuclear factors. Additive-maternal effects influenced total callus quantity and dominance-maternal effects influenced total callus quantity, embryogenic callus quantity and regeneration frequency. Dwarfing was associated with the production of large quantities of embryogenic callus that had visually recognizable characteristics. The phenotypic nature of dwarf parents (green dwarf with long narrow leaves) with a genetic basis for a given character controlled by nuclear and cytoplasmic determinants can be exploited for other breeding programs.

Background: Pulsed field ablation (PFA) induces cell death through electroporation using ultrarapid electrical pulses. We sought to compare the procedural efficiency characteristics, safety, and efficacy of ablation of atrial fibrillation (AF) using PFA compared with thermal energy ablation., Methods: We performed an extensive literature search and systematic review of studies that compared ablation of AF with PFA versus thermal energy sources. Risk ratio (RR) 95% confidence intervals (CI) were measured for dichotomous variables and mean difference (MD) 95% CI were measured for continuous variables, where RR < 1 and MD < 0 favor the PFA group., Results: We included 6 comparative studies for a total of 1012 patients who underwent ablation of AF: 43.6% with PFA (n = 441) and 56.4% (n = 571) with thermal energy sources. There were significantly shorter procedures times with PFA despite a protocolized 20-min dwell time (MD - 21.95, 95% CI - 33.77, - 10.14, p = 0.0003), but with significantly longer fluroscopy time (MD 5.71, 95% CI 1.13, 10.30, p = 0.01). There were no statistically significant differences in periprocedural complications (RR 1.20, 95% CI 0.59-2.44) or recurrence of atrial tachyarrhythmias (RR 0.64, 95% CI 0.31, 1.34) between the PFA and thermal ablation cohorts., Conclusions: Based on the results of this meta-analysis, PFA was associated with shorter procedural times and longer fluoroscopy times, but no difference in periprocedural complications or rates of recurrent AF when compared to ablation with thermal energy sources. However, larger randomized control trials are needed., (© 2023. The Author(s).)

Background: Pulsed field ablation (PFA) has emerged as a novel energy source for the ablation of atrial fibrillation (AF) using ultrarapid electrical pulses to induce cell death via electroporation., Objective: The purpose of this study was to compare the safety and acute efficacy of ablation for AF with PFA vs thermal energy sources., Methods: We performed an extensive literature search and systematic review of studies that evaluated the safety and efficacy of ablation for AF with PFA and compared them to landmark clinical trials for ablation of AF with thermal energy sources. Freeman-Tukey double arcsine transformation was used to establish variance of raw proportions followed by the inverse with the random-effects model to combine the transformed proportions and generate the pooled prevalence and 95% confidence interval (CI)., Results: We included 24 studies for a total of 5203 patients who underwent AF ablation. Among these patients, 54.6% (n = 2842) underwent PFA and 45.4% (n = 2361) underwent thermal ablation. There were significantly fewer periprocedural complications in the PFA group (2.05%; 95% CI 0.94-3.46) compared to the thermal ablation group (7.75%; 95% CI 5.40-10.47) ( P = .001). When comparing AF recurrence up to 1 year, there was a statistically insignificant trend toward a lower prevalence of recurrence in the PFA group (14.24%; 95% CI 6.97-23.35) compared to the thermal ablation group (25.98%; 95% CI 15.75-37.68) ( P = .132)., Conclusion: Based on the results of this meta-analysis, PFA was associated with lower rates of periprocedural complications and similar rates of acute procedural success and recurrent AF with up to 1 year of follow-up compared to ablation with thermal energy sources., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline ( p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis.

Background and Objectives: Biocompatible nanoparticles have been increasingly used in a variety of medical applications, including photodynamic therapy. Although the impact of synthesis parameters and purification methods is reported in previous studies, it is still challenging to produce a reliable protocol for the fabrication, purification, and characterization of nanoparticles in the 200-300 nm range that are highly monodisperse for biomedical applications., Study Design/materials and Methods: We investigated the synthesis of chitosan nanoparticles in the 200-300 nm range by evaluating the chitosan to sodium tripolyphosphate (TPP) mass ratio and acetic acid concentration of the chitosan solution. Chitosan nanoparticles were also crosslinked to rose bengal and incubated with human breast cancer cells (MCF-7) to test photodynamic activity using a green laser (λ = 532 nm, power = 90 mW)., Results: We established a simple protocol to fabricate and purify biocompatible nanoparticles with the most frequent size occurring between 200 and 300 nm. This was achieved using a chitosan to TPP mass ratio of 5:1 in 1% v/v acetic acid at a pH of 5.5. The protocol involved the formation of nanoparticle coffee rings that showed the particle shape to be spherical in the first approximation. Photodynamic treatment with rose bengal-nanoparticles killed ~98% of cancer cells., Conclusion: A simple protocol was established to prepare and purify spherical and biocompatible chitosan nanoparticles with a peak size of ~200 nm. These have remarkable antitumor activity when coupled with photodynamic treatment., (© 2022 Wiley Periodicals LLC.)

Background: Ascertainment of hospitalizations is critical to assess quality of care and the effectiveness and adverse effects of various therapies. Smartphones, mobile geolocators that are ubiquitous, have not been leveraged to ascertain hospitalizations. Therefore, we evaluated the use of smartphone-based geofencing to track hospitalizations., Methods and Results: Participants aged ≥18 years installed a mobile application programmed to geofence all hospitals using global positioning systems and cell phone tower triangulation and to trigger a smartphone-based questionnaire when located in a hospital for ≥4 hours. An in-person study included consecutive consenting patients scheduled for electrophysiology and cardiac catheterization procedures. A remote arm invited Health eHeart Study participants who consented and engaged with the study via the internet only. The accuracy of application-detected hospitalizations was confirmed by medical record review as the reference standard. Of 22 eligible in-person patients, 17 hospitalizations were detected (sensitivity 77%; 95% confidence interval, 55%-92%). The length of stay according to the application was positively correlated with the length of stay ascertained via the electronic medical record ( r =0.53; P =0.03). In the remote arm, the application was downloaded by 3443 participants residing in all 50 US states; 243 hospital visits at 119 different hospitals were detected through the application. The positive predictive value for an application-reported hospitalization was 65% (95% confidence interval, 57%-72%)., Conclusions: Mobile application-based ascertainment of hospitalizations can be achieved with modest accuracy. This first proof of concept may ultimately be applicable to geofencing other types of prespecified locations to facilitate healthcare research and patient care., (© 2017 American Heart Association, Inc.)

Mutations in dynamin-2 (DNM2) cause autosomal dominant centronuclear myopathy (CNM). We report a series of 12 patients from eight families with CNM in whom we have identified a number of novel features that expand the reported clinicopathological phenotype. We identified two novel and five recurrent missense mutations in DNM2. Early clues to the diagnosis include relative weakness of neck flexors, external ophthalmoplegia and ptosis, although these are not present in all patients. Pes cavus was present in two patients, and in another two members of one family there was mild slowing of nerve conduction velocities. Whole-body MRI examination in two children and one adult revealed a similar pattern of involvement of selective muscles in head (lateral pterygoids), neck (extensors), trunk (paraspinal) and upper limbs (deep muscles of forearm). Findings in lower limbs and pelvic region were similar to that previously reported in adults with DNM2 mutations. Two patients presented with dystrophic changes as the predominant pathological feature on muscle biopsies; one of whom had a moderately raised creatine kinase, and both patients were initially diagnosed as congenital muscular dystrophy. DNM2 mutation analysis should be considered in patients with a suggestive clinical phenotype despite atypical histopathology, and MRI findings can be used to guide genetic testing. Subtle neuropathic features in some patients suggest an overlap with the DNM2 neuropathy phenotype. Missense mutations in the C-terminal region of the PH domain appear to be associated with a more severe clinical phenotype evident from infancy., (Copyright 2010 Elsevier B.V. All rights reserved.)

Phosphatidylinositol 3-kinase (PI 3-kinase) plays a role in late stages of endocytosis as well as in cellular proliferation and transformation. The SH3 domain of its regulatory p85 subunit stimulates the GTPase activity of dynamin in vitro. Dynamin is a GTPase enzyme required for endocytosis of activated growth factor receptors. An interaction between these proteins has not been demonstrated in vivo. Here, we report that dynamin associates with PI 3-kinase in hematopoietic cells. We detected both p85 and PI 3-kinase activity in dynamin immune complexes from IL-3-dependent BaF3 cells. However, this association was significantly reduced in BaF3 cells transformed with the BCR/abl oncogene. After transformation only a 4-fold increase in PI 3-kinase activity was detected in dynamin immune complexes, whereas grb2 associated activity was elevated 20-fold. Furthermore, dynamin inhibited the activity of both purified recombinant and immunoprecipitated PI 3-kinase. In BaF3 cells expressing a temperature-sensitive mutant of BCR/abl, a significant decrease in p85 and dynamin association was observed 4 h after the induction of BCR/abl activity. In contrast, in IL-3-stimulated parental BaF3 cells, this association was increased. Our results demonstrate an in vivo association of PI 3-kinase with dynamin and this interaction regulates the activity of PI 3-kinase.