A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL.

We previously described a somatic cell expressing a variant H-2Dd molecule that did not serve as a target for alloreactive anti-Dd CTL. The mutant cell line had been isolated by its failure to express a serological epitope present on the H-2Dd alpha 3 domain. In the present study the alpha 3 domain of the Dd molecule of this somatic cell variant was sequenced and a single nucleotide change resulting in a glutamic acid to lysine substitution at residue 227 was identified. This change was reproduced in the cloned H-2Dd gene by oligonucleotide-directed mutagenesis. Cells transfected with this mutant gene were not killed by anti-H-2Dd CTL. Because previous studies using hybrid H-2 class I molecules had established that the alpha 3 domain does not express allele-specific determinants recognized by CTL, our results raise the possibility that residues in the alpha 3 domain of H-2 class I molecules are critical for CTL recognition and constitute a conserved (or monomorphic) determinant recognized by CTL

Socio-Economic Characteristics and Level of Awareness and Perception on Reducing Emissions from Deforestation and Forest Degradation Programme (REDD+) by Rural Communities in Akure Forest Reserve, Nigeria

Rural communities around Akure forest reserve depend mostly on forest and its products for their livelihoods, which results in its high rate of deforestation. Meanwhile, the Reducing Emissions from Deforestation and forest Degradation programme (REDD+), one of the international forest-governance initiatives to address sustainable forest  anagement and climate change mitigation has been introduced to the reserve. This research investigated the socio-economic status of the communities in Akure forest reserve, level of dependence on the forest resources and their level of awareness and perception about the REDD+ project. Six communities were selected randomly from around the reserve which were in the readiness phase of the REDD+ project. Data were collected through household survey with the use of semi-structured questionnaire administered to 120 respondents (household heads) selected randomly from the communities as well as information from 6 key informants (village heads). Descriptive Statistics and Chi Square test were used in the analysis of the data and the result showed that the main income-generating activity in the communities was farming accounting for 70.8% of the respondents. This affirms that the high level of the households’ dependence on forest resources is traceable to their socio-economic characteristics. Considering the level of awareness of REDD+ project, results revealed that the level of awareness of the key informants about REDD+ was very high (83.3%) while it was very low at the local community level with only 35% of the respondents being aware of the REDD+ project among which 23.3% found it beneficial. Therefore, to enhance the level of effectiveness of REDD+ project implementation, there should be an increase in the level of awareness in the communities. Keywords: Forest Communities, Awareness, REDD+ Project, Rural livelihood, Deforestatio

Nasal Carriage of Staphylococcus aureus and Antibiotic Susceptibility Pattern among Children in Freetown, Sierra Leone

Nasal carriage of Staphylococcus aureus has been demonstrated to be a major risk factor for invasive S. aureus infections in various population including children. The extent of S. aureus carriage in Sierra Leonean children is largely unknown. To determine the prevalence and pattern of antibiotic susceptibility of nasal S. aureus among children in Freetown, Sierra Leone, samples were collected from anterior nares of children less than two years at the Ola During Children’s Hospital between October 2008 and April 2009. Of the 116 children screened during the study period, S. aureus isolates were found in the nasal specimens of 40 (34.5%) of the children. Antimicrobial susceptibility testing to norfloxacin, gentamycin, erythromycin, trimethoprim-sulfamethazole, doxycycline, tetracycline and amoxycillin-clavulanic acid were observed to be 95, 35, 30, 20, 15, 7.5 and 2.5% respectively. All the isolates were susceptible to oxacillin and resistant to chloramphenicol, penicillin G, amoxycillin and ampiclox. Regular monitoring of antimicrobial susceptibility pattern may be useful. Keywords: Antibiotic Susceptibility, Children, Nasal carriage, Staphylococcus aureu

Socio-Economic Characteristics and Level of Awareness and Perception on Reducing Emissions from Deforestation and Forest Degradation Programme (REDD+) by Rural Communities in Akure Forest Reserve, Nigeria

Rural communities around Akure forest reserve depend mostly on forest and its products for their livelihoods, which results in its high rate of deforestation. Meanwhile, the Reducing Emissions from Deforestation and forest Degradation programme (REDD+), one of the international forest-governance initiatives to address sustainable forest management and climate change mitigation has been introduced to the reserve. This research investigated the socio-economic status of the communities in Akure forest reserve, level of dependence on the forest resources and their level of awareness and perception about the REDD+ project. Six communities were selected randomly from around the reserve which were in the readiness phase of the REDD+ project. Data were collected through household survey with the use of semi-structured questionnaire administered to 120 respondents (household heads) selected randomly from the communities as well as information from 6 key informants (village heads). Descriptive Statistics and Chi Square test were used in the analysis of the data and the result showed that the main income-generating activity in the communities was farming accounting for 70.8% of the respondents. This affirms that the high level of the households\u2019 dependence on forest resources is traceable to their socio-economic characteristics. Considering the level of awareness of REDD+ project, results revealed that the level of awareness of the key informants about REDD+ was very high (83.3%) while it was very low at the local community level with only 35% of the respondents being aware of the REDD+ project among which 23.3% found it beneficial. Therefore, to enhance the level of effectiveness of REDD+ project implementation, there should be an increase in the level of awareness in the communities

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies

Multimode fibre:Light-sheet microscopy at the tip of a needle

We also thank the UK Engineering and Physics Sciences Research Council for funding under grant EP/J01771X/1. Finally, we would like to thank EXCELLENT TEAMS (CZ.1.07/2.3.00/30.0005) from European Social Fund and CEITEC - Central European Institute of Technology (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund for support.Light-sheet fluorescence microscopy has emerged as a powerful platform for 3-D volumetric imaging in the life sciences. Here, we introduce an important step towards its use deep inside biological tissue. Our new technique, based on digital holography, enables delivery of the light-sheet through a multimode optical fibre - an optical element with extremely small footprint, yet permitting complex control of light transport processes within. We show that this approach supports some of the most advanced methods in light-sheet microscopy: by taking advantage of the cylindrical symmetry of the fibre, we facilitate the wavefront engineering methods for generation of both Bessel and structured Bessel beam plane illumination. Finally, we assess the quality of imaging on a sample of fluorescent beads fixed in agarose gel and we conclude with a proof-of-principle imaging of a biological sample, namely the regenerating operculum prongs of Spirobranchus lamarcki.Publisher PDFPeer reviewe

Laypersons' understanding of relative risk reductions: Randomised cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Despite increasing recognition of the importance of involving patients in decisions on preventive healthcare interventions, little is known about how well patients understand and utilise information provided on the relative benefits from these interventions. The aim of this study was to explore whether lay people can discriminate between preventive interventions when effectiveness is presented in terms of relative risk reduction (RRR), and whether such discrimination is influenced by presentation of baseline risk.</p> <p>Methods</p> <p>The study was a randomised cross-sectional interview survey of a representative sample (n = 1,519) of lay people with mean age 59 (range 40–98) years in Denmark. In addition to demographic information, respondents were asked to consider a hypothetical drug treatment to prevent heart attack. Its effectiveness was randomly presented as RRR of 10, 20, 30, 40, 50 or 60 percent, and half of the respondents were presented with quantitative information on the baseline risk of heart attack. The respondents had also been asked whether they were diagnosed with hypercholesterolemia or had experienced a heart attack.</p> <p>Results</p> <p>In total, 873 (58%) of the respondents consented to the hypothetical treatment. While 49% accepted the treatment when RRR = 10%, the acceptance rate was 58–60% for RRR>10. There was no significant difference in acceptance rates across respondents irrespective of whether they had been presented with quantitative information on baseline risk or not.</p> <p>Conclusion</p> <p>In this study, lay people's decisions about therapy were only slightly influenced by the magnitude of the effect when it was presented in terms of RRR. The results may indicate that lay people have difficulties in discriminating between levels of effectiveness when they are presented in terms of RRR.</p

Dasatinib in First- and Second-Line Therapy of Chronic Myeloid Leukemia: Efficacy, Safety and Quality of Life

Background & Aims. The article presents results of two observational, prospective, multicenter studies “Quality of Life, Symptom Profile, and Adherence to Treatment in Adult Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Receiving Dasatinib” (2012–2015) and “Quality of Life and Symptom Profile in Imatinib-Resistant or Intolerant Patients with Chronic Myeloid Leukemia” (2011–2014). Methods. Data of 107 patients with chronic myeloid leukemia in chronic phase were involved in the real-world analysis — 32 newly diagnosed patients on first-line treatment with dasatinib or after yearly switch to dasatinib after imatinib treatment failure and 75 imatinib-resistant or intolerant patients on second-line treatment with dasatinib. Treatment effectiveness and safety of dasatinib were assessed during first and second-line dasatinib treatment using clinical outcomes as well as quality of life and symptom profile assessment. Results. The real-world data obtained during observational study in limited population of CML patients conform the results of clinical trials devoted to evaluation of treatment efficacy and safety of dasatinib treatment in first and second-line treatment and demonstrate the importance of patient-reported outcomes. Patient’s quality of life improved within 12 months of the first-line dasatinib therapy according to the following scales: role physical functioning, pain, vitality, social functioning and role emotional functioning. The most pronounced and clinically significant improvement was observed for the role emotional functioning (51.1 vs. 68.9). During the second-line dasatinib treatment, stabilization of quality of life parameters was registered for the following scales: vitality, social functioning, mental health, and pain. Significant improvement of the Integral Quality of Life Index was observed (p < 0.05). Positive dynamics of relevant symptoms was registered. The symptom severity decreased during both the first and second-line therapy. Conclusion. Quality of life and symptom assessment in CML patients contribute to a better disease control in accordance with the principles of risk-adaptive therapy

Repeat-sequence turnover shifts fundamentally in species with large genomes

Given the 2,400-fold range of genome sizes (0.06–148.9 Gbp (gigabase pair)) of seed plants (angiosperms and gymnosperms) with a broadly similar gene content (amounting to approximately 0.03 Gbp), the repeat-sequence content of the genome might be expected to increase with genome size, resulting in the largest genomes consisting almost entirely of repetitive sequences. Here we test this prediction, using the same bioinformatic approach for 101 species to ensure consistency in what constitutes a repeat. We reveal a fundamental change in repeat turnover in genomes above around 10 Gbp, such that species with the largest genomes are only about 55% repetitive. Given that genome size influences many plant traits, habits and life strategies, this fundamental shift in repeat dynamics is likely to affect the evolutionary trajectory of species lineages.We thank Natural Environment Research Council (NE/G020256/1), the Czech Academy of Sciences (RVO:60077344) and Ramón y Cajal Fellowship (RYC-2017-2274) funded by the Ministerio de Ciencia y Tecnología (Gobierno de España) for support. We also thank Natural Environment Research Council for funding a studentship to S.D. and the China Scholarship Council for funding W.W.Abstract Main Methods Data availability Code availability References Acknowledgements Author information Ethics declarations Additional information Extended data Supplementary information Rights and permissions About this article Further readin