Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF.

Macrophages and dendritic cells (DCs), although ontogenetically distinct, have overlapping functions and exhibit substantial cell-to-cell heterogeneity that can complicate their identification and obscure innate immune function. In this study, we report that M-CSF-differentiated murine bone marrow-derived macrophages (BMDMs) exhibit extreme heterogeneity in the production of IL-12, a key proinflammatory cytokine linking innate and adaptive immunity. A microwell secretion assay revealed that a small fraction of BMDMs stimulated with LPS secrete most IL-12p40, and we confirmed that this is due to extremely high expression of Il12b, the gene encoding IL-12p40, in a subset of cells. Using an Il12b-YFP reporter mouse, we isolated cells with high LPS-induced Il12b expression and found that this subset was enriched for genes associated with the DC lineage. Single-cell RNA sequencing data confirmed a DC-like subset that differentiates within BMDM cultures that is transcriptionally distinct but could not be isolated by surface marker expression. Although not readily apparent in the resting state, upon LPS stimulation, this subset exhibited a typical DC-associated activation program that is distinct from LPS-induced stochastic BMDM cell-to-cell heterogeneity. Overall, our findings underscore the difficulty in distinguishing macrophages and DCs even in widely used in vitro murine BMDM cultures and could affect the interpretation of some studies that use BMDMs to explore acute inflammatory responses.

Highlights of the 'I Congress ecancer Choosing Wisely' March 30 and 31, 2022 Santa Cruz, Bolivia.

The ecancer 'Choosing Wisely' conference was held for the first time in Latin America in Santa Cruz, Bolivia. The event had more than 150 registered attendees in addition to 22 speakers from different countries and different specialities in the field of oncology, who presented topics on prevention, oncological surgery, clinical oncology and palliative care, in order to demonstrate the current evidence of how to approach a patient in daily clinical practice based on the human resources, materials and drugs available, trying to offer the maximum benefit to the patient based on current scientific evidence. In addition to addressing issues of vital importance in breast cancer, during the 2 days of the event, updated information generated in recent years was presented, the results of which will change clinical practice. All the experts were in favour of developing strategies and methods that help us to properly select treatments to optimise resources and reduce the economic toxicity of the most modern and current treatments. This conference was an event of vital importance because it was the first face-to-face event for ecancer and the physicians after difficult years due to COVID-19.

Body Weight May Have a Role on Neuropathy and Mobility after Moderate to Severe COVID-19: An Exploratory Study.

Background and Objectives: Among the extra-pulmonary manifestations of COVID-19, neuromuscular signs and symptoms are frequent. We aimed to assess the correlation between neuromuscular abnormalities (electrophysiological) and mobility measures (Berg Balance Scale and Timed-Up-and-Go test) twice, at least 6 weeks after hospital discharge and 6 months later, taking into account cognitive performance, nutrition, muscle strength, and submaximal exercise capacity. Materials and Methods: 43 patients (51.4 ± 9.3 years old) accepted to participate in the study; they had a dyspnea score ≤ 3 (Borg scale), and no history of neurology/neuromuscular/orthopedic disorders, but high frequency of overweight/obesity and weight loss during hospital stay. The two evaluations included physical examination, cognitive assessment, nutritional evaluation, muscle strength (hand-grip and quadriceps dynamometry), electromyography, Barthel Index, Six-Minute- Walk-Test (6MWT), Berg Balance Scale and Timed-Up-and-Go test. Bivariate and repeated measures covariance analyses were performed (significance level of 0.05). Results: Electrophysiological abnormalities were evident in 67% of the patients, which were associated with diminished performance on the 6MWT, the Berg Balance Scale and the Timed-Up-and-Go test. At each evaluation and between evaluations, scores on the Berg Balance Scale were related to the body mass index (BMI) at hospital admission and the 6MWT (MANCoVA R ≥ 0.62, p = 0.0001), while the time to perform the Timed-Up-and-Go test was related to the electrophysiological abnormalities, weight loss during hospital stay, sex, handgrip strength, and the 6MWT (MANCoVA, R ≥ 0.62, p < 0.0001). We concluded that, after hospital discharge, patients with moderate to severe COVID-19 may have neuromuscular abnormalities that can be related to BMI/weight loss, and contribute to mobility decrease. In patients with moderate to severe COVID-19 and high BMI/ large weight loss, neuromuscular and intended mobility assessments could be required to provide early rehabilitation. Apart from the 6MWT, handgrip dynamometry and the Timed-Up-and-Go test were useful tools to quickly assess fitness and mobility.

Fitness cost and reversion of resistance Leucoptera coffeella (Lepidoptera: Lyonetiidae) to chlorpyrifos.

A better understanding of fitness costs and insecticide resistance reversion has practical applications for improving resistance management approaches. The coffee leaf miner, Leucoptera coffeella, is one of the most important coffee pests worldwide. Chlorpyrifos is still used to control L. coffeella despite studies showing resistance in this pest. The current study investigated the fitness costs and reversion of resistance to chlorpyrifos in L. coffeella populations in coffee. The control failure of this insecticide was evaluated in 15 field populations. Selection of resistant and susceptible L. coffeella (G1-G10), with and without chlorpyrifos exposure, was evaluated. The following parameters were investigated: consumed leaf area, adult longevity, number of eggs per female, and egg viability. The present study showed control failures of chlorpyrifos and low (< 31-folds) to high levels (> 80-folds) of resistance in all field populations tested. The resistant population showed less fitness than the susceptible population. The fitness of the resistant population decreased significantly after 10 generations of chlorpyrifos selection. Specifically, the number of eggs per female, larvae hatched, and adult longevity were reduced by factors of 5, 2.3 and 3, respectively. Furthermore, the chlorpyrifos-resistant L. coffeella population consumed more than the susceptible population. Therefore, we concluded that non-exposing L. coffeella populations to chlorpyrifos insecticide leads to rapid reversion of resistance and susceptibility. In addition, resistant populations show reduced reproductive fitness and longevity, while consuming more, probably to meet greater metabolic demands.

Sendai voluntary commitments: landslide stakeholders and the all-of-society approach enhanced by UNDRR.

The resilience of communities and nations is a necessary condition for sustainable development. Building resilience, however, is not always a straightforward process and requires joint efforts, an all-of-society approach. Thus, the commitment, goodwill, knowledge, experience, and resources of all stakeholders contributing to disaster risk reduction (DRR) are crucial. In UNDRR's Sendai Framework Voluntary Commitments online platform, the work of all stakeholders can be showcased and tracked. Using novel data from this platform, this article presents descriptive information about the types of commitments made by stakeholders working on landslides. Results suggest that landslide is the third most covered hazard. Commitments working on this hazard have a more balanced distribution of global, regional, and local actions as compared with the whole sample. Also, landslide commitments tend to display higher levels of collaboration (as measured by the number of organizations involved) and longer duration (a commitment will last 7.6 years on average). Common issues being addressed include capacity development, risk management, and community-based DRR. When looking at specific regions and countries, there are opportunities for increased partnerships and effectiveness in topics such as knowledge sharing and technology solutions. The systemic nature of risks is increasingly apparent, and this article may stimulate further studies analyzing complexity and the joint action of all stakeholders committed to accelerate the implementation of the Sendai Framework.

Genomics of Clostridium taeniosporum, an organism which forms endospores with ribbon-like appendages.

Clostridium taeniosporum, a non-pathogenic anaerobe closely related to the C. botulinum Group II members, was isolated from Crimean lake silt about 60 years ago. Its endospores are surrounded by an encasement layer which forms a trunk at one spore pole to which about 12-14 large, ribbon-like appendages are attached. The genome consists of one 3,264,813 bp, circular chromosome (with 26.6% GC) and three plasmids. The chromosome contains 2,892 potential protein coding sequences: 2,124 have specific functions, 147 have general functions, 228 are conserved but without known function and 393 are hypothetical based on the fact that no statistically significant orthologs were found. The chromosome also contains 101 genes for stable RNAs, including 7 rRNA clusters. Over 84% of the protein coding sequences and 96% of the stable RNA coding regions are oriented in the same direction as replication. The three known appendage genes are located within a single cluster with five other genes, the protein products of which are closely related, in terms of sequence, to the known appendage proteins. The relatedness of the deduced protein products suggests that all or some of the closely related genes might code for minor appendage proteins or assembly factors. The appendage genes might be unique among the known clostridia; no statistically significant orthologs were found within other clostridial genomes for which sequence data are available. The C. taeniosporum chromosome contains two functional prophages, one Siphoviridae and one Myoviridae, and one defective prophage. Three plasmids of 5.9, 69.7 and 163.1 Kbp are present. These data are expected to contribute to future studies of developmental, structural and evolutionary biology and to potential industrial applications of this organism.