Bacillus subtilis RarA Acts as a Positive RecA Accessory Protein

Ubiquitous RarA AAA+ ATPases play crucial roles in the cellular response to blocked replication forks in pro- and eukaryotes. Here, we provide evidence that RarA regulates the activity of the central player in homologous recombination (HR), RecA, in response to DNA damage. During unperturbed growth, absence of RarA reduced the viability of recA, recO and recF15 cells, and during repair of H2O2- or MMS-induced DNA damage, rarA was epistatic to recA, recO and recF. Conversely, the inactivation of rarA partially suppressed the HR defect of mutants lacking end-resection (addAB, recJ, recQ, recS) or branch migration (ruvAB, recG, radA) activity. RarA contributes to RecA thread formation, that are thought to be the active forms of RecA during homology search. The absence of RarA reduced RecA accumulation, and the formation of visible RecA threads in vivo upon DNA damage. When rarA was combined with mutations in genuine RecA accessory genes, RecA accumulation was further reduced in rarA recU and rarA recX double mutant cells, and was blocked in rarA recF15 cells. These results suggest that RarA contributes to the assembly of RecA nucleoprotein filaments onto single-stranded DNA (ssDNA), in concert with RecF, and possibly antagonizes RecA filament disassembly by RecX or RecU.Peer reviewe

A cost utility analysis alongside a cluster-randomised trial evaluating a minor ailment service compared to usual care in community pharmacy.

BACKGROUND: Minor ailments are "self-limiting conditions which may be diagnosed and managed without a medical intervention". A cluster randomised controlled trial (cRCT) was designed to evaluate the clinical, humanistic and economic outcomes of a Minor Ailment Service (MAS) in community pharmacy (CP) compared with usual care (UC). METHODS: The cRCT was conducted for 6 months from December 2017. The pharmacist-patient intervention consisted of a standardised face-to-face consultation on a web-based program using co-developed protocols, pharmacists' training, practice change facilitators and patients' educational material. Patients requesting a non-prescription medication (direct product request) or presenting minor ailments received MAS or UC and were followed-up by telephone 10-days after the consultation. The primary economic outcomes were incremental cost-utility ratio (ICUR) of the service and health related quality of life (HRQoL). Total costs included health system, CPs and patient direct costs: health professionals' consultation time, medication costs, pharmacists' training costs, investment of the pharmacy and consultation costs within the 10 days following the initial consultation. The HRQoL was obtained using the EuroQoL 5D-5L at the time of the consultation and at 10-days follow up. A sensitivity analysis was carried out using bootstrapping. There were two sub-group analyses undertaken, for symptom presentation and direct product requests, to evaluate possible differences. RESULTS: A total of 808 patients (323 MAS and 485 UC) were recruited in 27 CPs with 42 pharmacists (20 MAS and 22 UC). 64.7% (n = 523) of patients responded to follow-up after their consultation in CP. MAS patients gained an additional 0.0003 QALYs (p = 0.053). When considering only MAS patients presenting with symptoms, the ICUR was 24,733€/QALY with a 47.4% probability of cost-effectiveness (willingness to pay of 25,000€/QALY). Although when considering patients presenting for a direct product request, MAS was the dominant strategy with a 93.69% probability of cost-effectiveness. CONCLUSIONS: Expanding community pharmacists' scope through MAS may benefit health systems. To be fully cost effective, MAS should not only include consultations arising from symptom presentation but also include an oversight of self-selected products by patients. MAS increase patient safety through the appropriate use of non-prescription medication and through the direct referral of patients to GP. TRIAL REGISTRATION: ISRCTN, ISRCTN17235323 . Registered 07/05/2021 - Retrospectively registered

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

TweetLID : a benchmark for tweet language identification

Language identification, as the task of determining the language a given text is written in, has progressed substantially in recent decades. However, three main issues remain still unresolved: (1) distinction of similar languages, (2) detection of multilingualism in a single document, and (3) identifying the language of short texts. In this paper, we describe our work on the development of a benchmark to encourage further research in these three directions, set forth an evaluation framework suitable for the task, and make a dataset of annotated tweets publicly available for research purposes. We also describe the shared task we organized to validate and assess the evaluation framework and dataset with systems submitted by seven different participants, and analyze the performance of these systems. The evaluation of the results submitted by the participants of the shared task helped us shed some light on the shortcomings of state-of-the-art language identification systems, and gives insight into the extent to which the brevity, multilingualism, and language similarity found in texts exacerbate the performance of language identifiers. Our dataset with nearly 35,000 tweets and the evaluation framework provide researchers and practitioners with suitable resources to further study the aforementioned issues on language identification within a common setting that enables to compare results with one another

Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series

<p>Abstract</p> <p>Background</p> <p>Neurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment.</p> <p>Case Presentation</p> <p>The clinical and radiological pictures of six Mexican patients non-respondent to cysticidal treatment are presented.</p> <p>Conclusions</p> <p>The possible factors involved in the cysticidal non-response are discussed and hints are provided of potentially useful changes to therapeutic protocols.</p

Group-level selection increases cooperation in the public goods game

When groups compete for resources, some groups will be more successful than others, forcing out less successful groups. Group-level selection is the most extreme form of group competition, where the weaker group ceases to exist, becoming extinct. We implement group-level selection in a controlled laboratory experiment in order to study its impact on human cooperation. The experiment uses variations on the standard linear public goods game. Group-level selection operates through competition for survival: the least successful, lowest-earning groups become extinct, in the sense that they no longer are able to play the game. Additional control treatments include group comparison without extinction, and extinction of the least successful individuals across groups. We find that group-level extinction produces very high contributions to the provision of the public good, while group comparison alone or individual extinction fail to cause higher contributions. Our results provide stark evidence that group-level selection enhances within-group cooperation

ApoE and ApoE Nascent-Like HDL Particles at Model Cellular Membranes: Effect of Protein Isoform and Membrane Composition.

Apolipoprotein E (ApoE), an important mediator of lipid transportation in plasma and the nervous system, plays a large role in diseases such as atherosclerosis and Alzheimer's. The major allele variants ApoE3 and ApoE4 differ only by one amino acid. However, this difference has major consequences for the physiological behaviour of each variant. In this paper, we follow (i) the initial interaction of lipid-free ApoE variants with model membranes as a function of lipid saturation, (ii) the formation of reconstituted High-Density Lipoprotein-like particles (rHDL) and their structural characterisation, and (iii) the rHDL ability to exchange lipids with model membranes made of saturated lipids in the presence and absence of cholesterol [1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) with and without 20 mol% cholesterol]. Our neutron reflection results demonstrate that the protein variants interact differently with the model membranes, adopting different protein conformations. Moreover, the ApoE3 structure at the model membrane is sensitive to the level of lipid unsaturation. Small-angle neutron scattering shows that the ApoE containing lipid particles form elliptical disc-like structures, similar in shape but larger than nascent or discoidal HDL based on Apolipoprotein A1 (ApoA1). Neutron reflection shows that ApoE-rHDL do not remove cholesterol but rather exchange saturated lipids, as occurs in the brain. In contrast, ApoA1-containing particles remove and exchange lipids to a greater extent as occurs elsewhere in the body

Emirati women do not shy away from competition: evidence from a patriarchal society in transition

We explore gender attitudes towards competition in the United Arab Emirates—a traditionally patriarchal society which in recent times has adopted numerous policies to empower women and promote their role in the labor force. The experimental treatments vary whether individuals compete in single-sex or mixed-sex groups. In contrast to previous studies, women in our sample are not less willing to compete than men. In fact, once we control for individual performance, Emirati women are more likely to select into competition. Our analysis shows that neither women nor men shy away from competition, and both compete more than what would be optimal in monetary terms as the fraction of men in their group increases. We offer a detailed survey of the literature and discuss possible reasons for the lack of gender differences in our experiment