Structural insights into polyamine spermidine uptake by the ABC transporter PotD-PotABC.

Polyamines, characterized by their polycationic nature, are ubiquitously present in all organisms and play numerous cellular functions. Among polyamines, spermidine stands out as the predominant type in both prokaryotic and eukaryotic cells. The PotD-PotABC protein complex in Escherichia coli, belonging to the adenosine triphosphate-binding cassette transporter family, is a spermidine-preferential uptake system. Here, we report structural details of the polyamine uptake system PotD-PotABC in various states. Our analyses reveal distinct "inward-facing" and "outward-facing" conformations of the PotD-PotABC transporter, as well as conformational changes in the "gating" residues (F222, Y223, D226, and K241 in PotB; Y219 and K223 in PotC) controlling spermidine uptake. Therefore, our structural analysis provides insights into how the PotD-PotABC importer recognizes the substrate-binding protein PotD and elucidates molecular insights into the spermidine uptake mechanism of bacteria.

Cryo-EM structure of the SPFH-NfeD family protein complex QmcA-YbbJ.

The SPFH (stomatin, prohibitin, flotillin, and HflK/C) protein family is universally present and encompasses the evolutionarily conserved SPFH domain. These proteins are predominantly localized in lipid raft and implicated in various biological processes. The NfeD (nodulation formation efficiency D) protein family is often encoded in tandem with SPFH proteins, suggesting a close functional relationship. Here, we elucidate the cryoelectron microscopy (cryo-EM) structure of the Escherichia coli QmcA-YbbJ complex belonging to the SPFH and NfeD families, respectively. Our findings reveal that the QmcA-YbbJ complex forms an intricate cage-like structure composed of 26 copies of QmcA-YbbJ heterodimers. The transmembrane helices of YbbJ act as adhesive elements bridging adjacent QmcA molecules, while the oligosaccharide-binding domain of YbbJ encapsulates the SPFH domain of QmcA. Our structural study significantly contributes to understanding the functional role of the NfeD protein family and sheds light on the interplay between SPFH and NfeD family proteins.

Food insecurity among low-income households in Addis Ababa, Ethiopia.

With the rapid urbanization in developing countries, poverty and food insecurity are becoming increasing prevalent, posing a major challenge to urban areas. The COVID-19 pandemic induced job losses and reduced income combined with inflation have further exacerbated the household food insecurity situation, particularly in cities of low-income countries. Our study aims to assess the extent of food insecurity and its determinants among low-income household in Addis Ababa, Ethiopia. We conducted a community-based cross-sectional study among a sample of 578 households in Addis Ababa. We estimated the household food insecurity status using the Household Food Insecurity Access Scale (HFIAS). An ordinal logistic regression model was used to assess the relationship between household food insecurity status and the socioeconomic and demographic covariates. The STATA 14 software package was used for data analysis. We found that household food insecurity was prevalent among low-income households in Addis Ababa, with a prevalence rate of 92.4 % (95 % CI: 90.2-94.6 %). Of these households, 33.6 % (95 % CI: 29.7-37.4 %) were severely food insecure. To cope with the food shortage, households were forced to reduce their food quantity and quality. We also found that respondent's education, engagement in income generating activities, and household wealth were independently associated with household food insecurity. We conclude that although supporting people living below the poverty line (pro-poor) remains the top priority for social protection programs, adapting the program to accommodate the working poor (informal sector employees and casual workers) is crucial, especially during shocks.

Ribosomal RNA modification enzymes stimulate large ribosome subunit assembly in E. coli.

Ribosomal RNA modifications are introduced by specific enzymes during ribosome assembly in bacteria. Deletion of individual modification enzymes has a minor effect on bacterial growth, ribosome biogenesis, and translation, which has complicated the definition of the function of the enzymes and their products. We have constructed an Escherichia coli strain lacking 10 genes encoding enzymes that modify 23S rRNA around the peptidyl-transferase center. This strain exhibits severely compromised growth and ribosome assembly, especially at lower temperatures. Re-introduction of the individual modification enzymes allows for the definition of their functions. The results demonstrate that in addition to previously known RlmE, also RlmB, RlmKL, RlmN and RluC facilitate large ribosome subunit assembly. RlmB and RlmKL have functions in ribosome assembly independent of their modification activities. While the assembly stage specificity of rRNA modification enzymes is well established, this study demonstrates that there is a mutual interdependence between the rRNA modification process and large ribosome subunit assembly.

Mapping a research-advocacy-policy agenda on human rights and albinism: a mixed methods project.

BACKGROUND: Persons with albinism face challenges to their wellbeing, safety, and security, ranging from vision impairment and skin cancer to stigma and discrimination. In some regions, they also face human rights atrocities including mutilation and murder. Research on human rights and albinism is a relatively new field that has gained momentum since the United Nations appointment of an Independent Expert on the enjoyment of human rights by persons with albinism. In this paper, we present the results of a mixed methods study undertaken to identify priorities for research, advocacy, and policy on albinism and human rights. METHODS: The first component was a synthesis of peer-reviewed and grey literatures at the nexus of albinism, spiritual/cultural beliefs and practices, and human rights. We then conducted a priority-setting survey, informed by Delphi methods, on extant knowledge-practice gaps and research, advocacy, and policy priorities. Inclusion criteria included demonstrated expertise in the field (e.g., peer-reviewed publications, funded research), membership on national or international associations, or advocacy (civil society organizations) of more than 2 years in albinism and human rights. Thereafter, we gathered leading researchers, policy-makers, and civil society stakeholders for a Roundtable to gain consensus on these priorities. RESULTS: Access to skin and vision care, and education were not deemed high priority for research, likely because the evidence supporting the need for these is well established. However, they were priorities for advocacy and policy: what is needed is mobilization of this evidence through advocacy and implementation of such services (policy). Other social determinants of health (rurality, poverty, and gender equality) are present as subtext in the findings, more so than priorities for research, advocacy, or policy, despite their preponderance in the lives of persons with albinism. Research was prioritized on stigma and discrimination; advocacy; and witchcraft, but with some differentiation between Global North and Global South priorities. Priorities for research, advocacy, and policy vary in keeping with the explanatory frameworks at play, including how harmful practices and witchcraft are viewed. CONCLUSIONS: The lived experience of albinism is profoundly shaped by the social determinants of health (SDOH). Threats to the security and well-being of persons with albinism should be viewed through a human rights lens that encompasses the explanatory frameworks at play.

The association Between Sleep Quality, Fatigue and Periodontal Status: a pilot study / La asociación entre la calidad del sueño, la fatiga y el estado periodontal: un estudio piloto

Abstract Reduced sleep duration, poor sleep quality and fatigue are related to reduced immunity and increased inflammatory markers. Due to its potential to influence inflammation, poor sleep quality and fatigue could be factors for periodontitis and quality of life. Ninety-three individuals with untreated periodontitis and thirty-one individuals with healthy gingiva were included in the study. The research involved a clinical examination and a questionnaire. Demographic information, information on oral health, oral hygiene habits, the Pittsburgh Sleep Quality Index, Jenkins Sleep Scale, Multidimensional Assessment of Fatigue Scale, and Oral Health Impact Profile-14 were included in the questionnaire. Patients were diagnosed based on the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. No statistically significant difference was revealed between sleep quality, fatigue, oral health related quality of life, and stage-grade of periodontitis (p<0.05). However, periodontitis group had higher Oral Health Impact Profile-14 scores (p<0.05). A statistically significantly lower sleep duration was observed in stage IV periodontitis group than the other groups (p<0.05). A statistically significant positive correlation was observed between the Pittsburgh Sleep Quality Index and the scores of the other questionnaires (p<0.05). The stage of periodontitis may impact sleep duration.

Resumen La reducción de la duración del sueño, la mala calidad del sueño y la fatiga están relacionados con una inmunidad reducida y un aumento de los marcadores inflamatorios. Debido a su potencial para influir en la inflamación, la mala calidad del sueño y la fatiga podrían ser factores determinantes en el desarrollo de la periodontitis e incidir en la calidad de vida. Noventa y tres personas con periodontitis no tratada, además de treinta y una personas con encía sana se incluyeron en el estudio. La investigación involucró un examen clínico y un cuestionario. En el cuestionario se incluyeron información demográfica, información sobre salud bucal, hábitos de higiene bucal, el índice de calidad del sueño de Pittsburgh, la escala de sueño de Jenkins, la escala de evaluación multidimensional de la fatiga y el perfil de impacto en la salud bucal-14. Los pacientes fueron diagnosticados en base al Taller Mundial 2017 sobre la Clasificación de Enfermedades y Condiciones Periodontales y Periimplantarias. No se revelaron diferencias estadísticamente significativas entre la calidad del sueño, la fatiga, la calidad de vida relacionada con la salud bucal y el grado de etapa de la periodontitis (p<0,05). Sin embargo, el grupo de periodontitis tuvo puntajes más altos en el Perfil de Impacto en la Salud Oral-14 (p<0.05). Se observó una duración del sueño significativamente menor desde el punto de vista estadístico en el grupo de periodontitis en estadio IV que en los otros grupos (p<0,05). Se observó una correlación positiva estadísticamente significativa entre el Índice de Calidad del Sueño de Pittsburgh y las puntuaciones de los otros cuestionarios (p<0,05). La etapa de la periodontitis puede afectar la duración del sueño.

Focus on Metformin: Its Role and Safety in Pregnancy and Beyond.

Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.

Measurements of the associated production of a W boson and a charm quark in proton-proton collisions at s = 8 TeV.

Measurements of the associated production of a W boson and a charm ( c ) quark in proton-proton collisions at a centre-of-mass energy of 8 TeV are reported. The analysis uses a data sample corresponding to a total integrated luminosity of 19.7 fb - 1 collected by the CMS detector at the LHC. The W bosons are identified through their leptonic decays to an electron or a muon, and a neutrino. Charm quark jets are selected using distinctive signatures of charm hadron decays. The product of the cross section and branching fraction σ ( pp → W + c + X ) B ( W → ℓ ν ) , where ℓ = e or µ , and the cross section ratio σ ( pp → W + + c ¯ + X ) / σ ( pp → W - + c + X ) are measured in a fiducial volume and differentially as functions of the pseudorapidity and of the transverse momentum of the lepton from the W boson decay. The results are compared with theoretical predictions. The impact of these measurements on the determination of the strange quark distribution is assessed.

First Search for Exclusive Diphoton Production at High Mass with Tagged Protons in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search for exclusive two-photon production via photon exchange in proton-proton collisions, pp→pγγp with intact protons, is presented. The data correspond to an integrated luminosity of 9.4 fb^{-1} collected in 2016 using the CMS and TOTEM detectors at a center-of-mass energy of 13 TeV at the LHC. Events are selected with a diphoton invariant mass above 350 GeV and with both protons intact in the final state, to reduce backgrounds from strong interactions. The events of interest are those where the invariant mass and rapidity calculated from the momentum losses of the forward-moving protons match the mass and rapidity of the central, two-photon system. No events are found that satisfy this condition. Interpreting this result in an effective dimension-8 extension of the standard model, the first limits are set on the two anomalous four-photon coupling parameters. If the other parameter is constrained to its standard model value, the limits at 95% confidence level are |ζ_{1}|<2.9×10^{-13} GeV^{-4} and |ζ_{2}|<6.0×10^{-13} GeV^{-4}.

Metastatic malignant melanoma of the breast: report of a case and review of the literature.

Melanoma is the most rapidly increasing cancer in the world. Associated morbidity and mortality are mainly related to metastatic potential. Metastases to the breast from malignant melanoma are rare and represent only 1.3%-2.7% of reported cases. The aim of this study was to present a rare case of metastatic malignant melanoma to the breast. A 51-year-old woman was admitted for management of a palpable mass of the left breast. The past medical history referred to a sizable nodular melanoma that was removed from her back. Classification of the breast lesion was BI-RADS 5. Core needle biopsy was compatible with the diagnosis of malignant melanoma. Immunohistochemical evaluation was positive for Mart1 and Ki67. Subsequent staging was indicative of multiple secondary foci in the liver and bones. The patient was administered a combination of PD L1 inhibitor nivolumab with the anti-CTLA4 inhibitor ipilimumab followed by additional targeted therapy with the BRAF inhibitor vemurafenib. Metastasis to the breast from malignant melanoma is extremely rare. Nevertheless, breast metastases must be suspected in patients with a history of malignant melanoma. Moreover, recent breakthroughs in the Braf and MEK inhibitors and immune checkpoint inhibition therapies have impressively improved prognosis in patients affected by melanoma.

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton-proton collisions at s = 13 TeV.

A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton-proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 , at a center-of-mass energy s = 13 TeV . No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported.

Using Z Boson Events to Study Parton-Medium Interactions in Pb-Pb Collisions.

The spectra measurements of charged hadrons produced in the shower of a parton originating in the same hard scattering with a leptonically decaying Z boson are reported in lead-lead nuclei (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Both Pb-Pb and pp data sets are recorded by the CMS experiment at the LHC and correspond to an integrated luminosity of 1.7 nb^{-1} and 320 pb^{-1}, respectively. Hadronic collision data with one reconstructed Z boson candidate with the transverse momentum p_{T}>30 GeV/c are analyzed. The Z boson constrains the initial energy and direction of the associated parton. In heavy ion events, azimuthal angular distributions of charged hadrons with respect to the direction of a Z boson are sensitive to modifications of the in-medium parton shower and medium response. compared to reference data from pp interactions, the results for central Pb-Pb collisions indicate a modification of the angular correlations. The measurements of the fragmentation functions and p_{T} spectra of charged particles in Z boson events, which are sensitive to medium modifications of the parton shower longitudinal structure, are also reported. Significant modifications in central Pb-Pb events compared to the pp reference data are also found for these observables.

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV.

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses.

Plasticity and conditional essentiality of modification enzymes for domain V of Escherichia coli 23S ribosomal RNA.

Escherichia coli rRNAs are post-transcriptionally modified at 36 positions but their modification enzymes are dispensable individually for growth, bringing into question their significance. However, a major growth defect was reported for deletion of the RlmE enzyme, which abolished a 2'O methylation near the peptidyl transferase center (PTC) of the 23S rRNA. Additionally, an adjacent 80-nt "critical region" around the PTC had to be modified to yield significant peptidyl transferase activity in vitro. Surprisingly, we discovered that an absence of just two rRNA modification enzymes is conditionally lethal (at 20°C): RlmE and RluC. At a permissive temperature (37°C), this double knockout was shown to abolish four modifications and be defective in ribosome assembly, though not more so than the RlmE single knockout. However, the double knockout exhibited an even lower rate of tripeptide synthesis than did the single knockout, suggesting an even more defective ribosomal translocation. A combination knockout of the five critical-region-modifying enzymes RluC, RlmKL, RlmN, RlmM, and RluE (not RlmE), which synthesize five of the seven critical-region modifications and 14 rRNA and tRNA modifications altogether, was viable (minor growth defect at 37°C, major at 20°C). This was surprising based on prior in vitro studies. This five-knockout combination had minimal effects on ribosome assembly and frameshifting at 37°C, but greater effects on ribosome assembly and in vitro peptidyl transferase activity at cooler temperatures. These results establish the conditional essentiality of bacterial rRNA modification enzymes and also reveal unexpected plasticity of modification of the PTC region in vivo.

Indoleamine-2,3-dioxygenase-related anti-inflammatory effects of 3-aminobenzamide and infliximab in experimental colitis

SUMMARY OBJECTIVE: This study aimed to investigate the presence of indoleamine-2,3-dioxygenase and bacterial translocation after the administration of 3-aminobenzamide and infliximab in the TNBS model of rat colitis. METHODS: The study group was divided into five categories as follows: group 1: (control), group 2: colitis+saline, group 3: colitis+3-aminobenzamide, group 4: colitis+infliximab, and group 5: colitis+3-aminobenzamide+infliximab. Intestinal mesenteric cultures were incubated on specific agar media plates under aerobic and anaerobic conditions, bacterial translocation was evaluated and assessed as colony-forming units per gram of tissue. Colonic tissue samples were evaluated by Western blotting method to detect the presence of indoleamine-2,3-dioxygenase. RESULTS: The results obtained were as follows: group 1: normal gut flora; group 2: eight of nine samples had bacterial translocation, of which six of them had positive indoleamine-2,3-dioxygenase protein; group 3: five of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; group 4: three of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; and group 5: only one sample had exact indoleamine-2,3-dioxygenase protein. CONCLUSION: Altered expression of indoleamine-2,3-dioxygenase results in a lower bacterial translocation via infliximab compared with 3-aminobenzamide treatment. Combined treatments emphasized different approaches for the new molecules related to indoleamine-2,3-dioxygenase.

Evidence for X(3872) in Pb-Pb Collisions and Studies of its Prompt Production at sqrt[s_{NN}]=5.02 TeV.

The first evidence for X(3872) production in relativistic heavy ion collisions is reported. The X(3872) production is studied in lead-lead (Pb-Pb) collisions at a center-of-mass energy of sqrt[s_{NN}]=5.02 TeV per nucleon pair, using the decay chain X(3872)→J/ψπ^{+}π^{-}→µ^{+}µ^{-}π^{+}π^{-}. The data were recorded with the CMS detector in 2018 and correspond to an integrated luminosity of 1.7 nb^{-1}. The measurement is performed in the rapidity and transverse momentum ranges |y|<1.6 and 15

Glycaemic control and novel technology management strategies in pregestational diabetes mellitus.

Introduction: Pregestational diabetes (PGDM) is an increasingly common and complex condition that infers risk to both mother and infant. To prevent serious morbidity, strict glycaemic control is essential. The aim of this review is to review the glucose sensing and insulin delivering technologies currently available for women with PGDM. Methods: We reviewed online databases for articles relating to technology use in pregnancy using a combination of keywords and MeSH headings. Relevant articles are included below. Results: A number of technological advancements have improved care and outcomes for women with PGDM. Real time continuous glucose monitoring (rtCGM) offers clear advantages in terms of infants size and neonatal intensive care unit admissions; and further benefits are seen when combined with continuous subcutaneous insulin delivery (insulin pump) and algorithms which continuously adjust insulin levels to glucose targets (hybrid closed loop). Other advancements including flash or intermittent scanning CGM (isCGM) and stand-alone insulin pumps do not confer as many advantages for women and their infants, however they are increasingly used outside of pregnancy and many women enter pregnancy already using these devices. Discussion: This article offers a discussion of the most commonly used technologies in pregnancy and evaluates their current and future roles.