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We present approaches using stochastic processes for the calculation of line broadening in plasmas. The derivation of model microfield methods (MMM) based on analytic formulations is recalled, as well as an approach using a simulation of the stochastic process. We discuss the possibility of an improvement of the stochastic process by comparing our first results to ab initio particle simulations coupled to a numerical integration of the emitters Schrödinger equation.

IntroductionA health and lifestyle advisor service embedded within primary care was piloted in Kingston-upon-Hull from January 2021. We aimed to evaluate the first two years of service delivery by identifying patient demographics referred to the service, reason for referral, determine uptake and retention rates, and monitor individual lifestyle-related risk factor changes following discharge.MethodsAnonymised data were extracted from the SystmOne database for all patients referred to the service between January 2021 and January 2023.ResultsIn the initial two years of the service, 705 unique patients were referred at a mean rate of ∼29 per month. Each unique patient received a median (robust median absolute deviation; [MAD]) of 3 (Steel N, et al 2018) planned consultations prior to discharge over this period. The majority of referrals were for symptom management and health promotion purposes (95%). Of those referred, 69% attended their appointments, and 14% did not attend. The majority of referrals were white British (55%), however, the service did receive a substantial number of referrals from minority ethnic groups, with only 67% of referrals speaking English as their main language. Eighteen distinct languages were spoken. Most referrals were classified as class I obese (59.4%). Across initial and final appointments, median (robust MAD) systolic blood pressure was 130 (15) mmHg and 130 (15) mmHg, and median (robust MAD) waist circumference was 103.0 (13.3) cm and 101.0 (13.3) cm.ConclusionThe evaluation highlighted the demand for this service embedded within primary care settings in Kingston-upon-Hull. Service engagement was evident, and a large proportion of those who engaged were from minority ethnic groups. A high proportion of referrals presented with obesity and/or hypertension which requires further investigation.

Abstract Background Halorubrum lacusprofundi is a cold-adapted halophilic archaeon isolated from Deep Lake, a perennially cold and hypersaline lake in Antarctica. Its genome sequencing project was recently completed, providing access to many genes predicted to encode polyextremophilic enzymes active in both extremely high salinity and cold temperatures. Results Analysis of the genome sequence of H. lacusprofundi showed a gene cluster for carbohydrate utilization containing a glycoside hydrolase family 42 β-galactosidase gene, named bga. In order to study the biochemical properties of the β-galactosidase enzyme, the bga gene was PCR amplified, cloned, and expressed in the genetically tractable haloarchaeon Halobacterium sp. NRC-1 under the control of a cold shock protein (cspD2) gene promoter. The recombinant β-galactosidase protein was produced at 20-fold higher levels compared to H. lacusprofundi, purified using gel filtration and hydrophobic interaction chromatography, and identified by SDS-PAGE, LC-MS/MS, and ONPG hydrolysis activity. The purified enzyme was found to be active over a wide temperature range (−5 to 60°C) with an optimum of 50°C, and 10% of its maximum activity at 4°C. The enzyme also exhibited extremely halophilic character, with maximal activity in either 4 M NaCl or KCl. The polyextremophilic β-galactosidase was also stable and active in 10–20% alcohol-aqueous solutions, containing methanol, ethanol, n-butanol, or isoamyl alcohol. Conclusion The H. lacusprofundi β-galactosidase is a polyextremophilic enzyme active in high salt concentrations and low and high temperature. The enzyme is also active in aqueous-organic mixed solvents, with potential applications in synthetic chemistry. H. lacuprofundi proteins represent a significant biotechnology resource and for developing insights into enzyme catalysis under water limiting conditions. This study provides a system for better understanding how H. lacusprofundi is successful in a perennially cold, hypersaline environment, with relevance to astrobiology.

Abstract Background Since the first genome of a halophilic archaeon was sequenced in 2000, biologists have been advancing the understanding of genomic characteristics that allow for survival in the harsh natural environments of these organisms. An increase in protein acidity and GC-bias in the genome have been implicated as factors in tolerance to extreme salinity, desiccation, and high solar radiation. However, few previous attempts have been made to identify novel genes that would permit survival in such extreme conditions. Results With the recent release of several new complete haloarchaeal genome sequences, we have conducted a comprehensive comparative genomic analysis focusing on the identification of unique haloarchaeal conserved proteins that likely play key roles in environmental adaptation. Using bioinformatic methods, we have clustered 31,312 predicted proteins from nine haloarchaeal genomes into 4,455 haloarchaeal orthologous groups (HOGs). We assigned likely functions by association with established COG and KOG databases in NCBI. After identifying homologs in four additional haloarchaeal genomes, we determined that there were 784 core haloarchaeal protein clusters (cHOGs), of which 83 clusters were found primarily in haloarchaea. Further analysis found that 55 clusters were truly unique (tucHOGs) to haloarchaea and qualify as signature proteins while 28 were nearly unique (nucHOGs), the vast majority of which were coded for on the haloarchaeal chromosomes. Of the signature proteins, only one example with any predicted function, Ral, involved in desiccation/radiation tolerance in Halobacterium sp. NRC-1, was identified. Among the core clusters, 33% was predicted to function in metabolism, 25% in information transfer and storage, 10% in cell processes and signaling, and 22% belong to poorly characterized or general function groups. Conclusion Our studies have established conserved groups of nearly 800 protein clusters present in all haloarchaea, with a subset of 55 which are predicted to be accessory proteins that may be critical or essential for success in an extreme environment. These studies support core and signature genes and proteins as valuable concepts for understanding phylogenetic and phenotypic characteristics of coherent groups of organisms.

Abstract Excitation-contraction coupling involves the faithful conversion of electrical stimuli to mechanical shortening in striated muscle cells, enabled by the ubiquitous second messenger, calcium. Crucial to this process are ryanodine receptors (RyRs), the sentinels of massive intracellular calcium stores contained within the sarcoplasmic reticulum. In response to sarcolemmal depolarization, RyRs release calcium into the cytosol, facilitating mobilization of the myofilaments and enabling cell contraction. In order for the cells to relax, calcium must be rapidly resequestered or extruded from the cytosol. The sustainability of this cycle is crucially dependent upon precise regulation of RyRs by numerous cytosolic metabolites and by proteins within the lumen of the sarcoplasmic reticulum and those directly associated with the receptors in a macromolecular complex. In addition to providing the majority of the calcium necessary for contraction of cardiac and skeletal muscle, RyRs act as molecular switchboards that integrate a multitude of cytosolic signals such as dynamic and steady calcium fluctuations, β-adrenergic stimulation (phosphorylation), nitrosylation and metabolic states, and transduce these signals to the channel pore to release appropriate amounts of calcium. Indeed, dysregulation of calcium release via RyRs is associated with life-threatening diseases in both skeletal and cardiac muscle. In this paper, we briefly review some of the most outstanding structural and functional attributes of RyRs and their mechanism of regulation. Further, we address pathogenic RyR dysfunction implicated in cardiovascular disease and skeletal myopathies.

The use of misidentified and contaminated cell lines continues to be a problem in biomedical research. Research Resource Identifiers (RRIDs) should reduce the prevalence of misidentified and contaminated cell lines in the literature by alerting researchers to cell lines that are on the list of problematic cell lines, which is maintained by the International Cell Line Authentication Committee (ICLAC) and the Cellosaurus database. To test this assertion, we text-mined the methods sections of about two million papers in PubMed Central, identifying 305,161 unique cell-line names in 150,459 articles. We estimate that 8.6% of these cell lines were on the list of problematic cell lines, whereas only 3.3% of the cell lines in the 634 papers that included RRIDs were on the problematic list. This suggests that the use of RRIDs is associated with a lower reported use of problematic cell lines.