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OBJECTIVE: To promote public speaking skills, a pediatrics residency program developed a longitudinal public speaking curriculum grounded in deliberate practice and reflective practice. METHODS: Residents delivered annual presentations and received formal feedback. Audience evaluation forms from 2005-2017 were included for analysis. The form used 5-point scales (5= best) for specific presentation elements (clarity, eye contact/body language, pace, succinct text, minimally distracting delivery, clear conclusion, appropriate learning objectives, achieving learning objectives, and answering questions) and for overall quality. Longitudinal changes in scores were analyzed with paired t tests. RESULTS: Overall, 5,771 evaluations of 276 presentations given by 97 residents were analyzed. Between post-graduate year (PGY)-1 and PGY-3 presentations, mean overall rating increased from 4.38 to 4.59 (P<.001, d=0.51). The median percentage of 5-point scores increased from 50.0% (IQR, 24.3%-65.4%) to 72.5% (IQR, 53.3%-81.2%). Eight of 9 specific elements showed significant increases (median effect size 0.55). Residents whose initial presentations ranked in the bottom quartile had larger improvements than residents initially ranked in the top quartile. CONCLUSIONS: After pediatric residents participated in a public speaking curriculum with targeted objectives, formal feedback, and repeated practice, their public speaking skills improved. Public speaking curricula can and should be adopted more broadly in graduate medical education.
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The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult. In microbes, assessing the effect of mutations on growth can be especially instructive, as this complex phenotype is closely linked to fitness in clonally evolving organisms. Here, we perform high-throughput time-lapse microscopy on cells from mutation-accumulation strains to precisely infer the distribution of mutational effects on growth rate in the budding yeast, Saccharomyces cerevisiae. We show that mutational effects on growth rate are overwhelmingly negative, highly skewed towards very small effect sizes, and frequent enough to suggest that deleterious hitchhikers may impose a significant burden on evolving lineages. By using lines that accumulated mutations in either wild-type or slippage repair-defective backgrounds, we further disentangle the effects of 2 common types of mutations, single-nucleotide substitutions and simple sequence repeat indels, and show that they have distinct effects on yeast growth rate. Although the average effect of a simple sequence repeat mutation is very small (approximately 0.3%), many do alter growth rate, implying that this class of frequent mutations has an important evolutionary impact.
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Aptitud Genética , Repeticiones de Microsatélite , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Repeticiones de Microsatélite/genética , Mutación/genética , Acumulación de MutacionesRESUMEN
The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology is rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimizing radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.
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Juvenile myelomonocytic leukemia (JMML) is a hematologic malignancy of young children caused by mutations that increase Ras signaling output. Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment, but patients with relapsed or refractory (advanced) disease have dismal outcomes. This phase II trial evaluated the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in patients with advanced JMML. Ten infants and children were enrolled, and the objective response rate was 50%. Four patients with refractory disease proceeded to HSCT after receiving trametinib. Three additional patients completed all 12 cycles permitted on study and continue to receive off-protocol trametinib without HSCT. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Transcriptomic and proteomic analyses provided novel insights into the mechanisms of response and resistance to trametinib in JMML. ClinicalTrials.gov Identifier: NCT03190915. Significance: Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates. Seven of 10 patients completed the maximum 12 cycles of therapy or used trametinib as a bridge to HSCT and are alive with a median follow-up of 24 months.
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This retrospective study aimed to evaluate the performance of hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows that received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than that for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) < 3.75 after treatment and loose-housed cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than that in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.
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Extracellular vesicles (EVs) are submicron membranous structures and key mediators of intercellular communication.1,2 Recent research has highlighted roles for cilia-derived EVs in signal transduction, underscoring their importance as bioactive extracellular organelles containing conserved ciliary signaling proteins.3,4 Members of the transient receptor potential (TRP) channel polycystin-2 (PKD-2) family are found in ciliary EVs of the green algae Chlamydomonas and the nematode Caenorhabditis elegans5,6 and in EVs in the mouse embryonic node and isolated from human urine.7,8 In C. elegans, PKD-2 is expressed in male-specific EV-releasing sensory neurons, which extend ciliary tips to ciliary pore and directly release EVs into the environment.6,9 Males release EVs in a mechanically stimulated manner, regulate EV cargo content in response to mating partners, and deposit PKD-2::GFP-labeled EVs on the vulval cuticle of hermaphrodites during mating.9,10 Combined, our findings suggest that ciliary EV release is a dynamic process. Herein, we identify mechanisms controlling dynamic EV shedding using time-lapse imaging. Cilia can sustain the release of PKD-2-labeled EVs for 2 h. This extended release doesn't require neuronal transmission. Instead, ciliary intrinsic mechanisms regulate PKD-2 ciliary membrane replenishment and dynamic EV release. The kinesin-3 motor kinesin-like protein 6 (KLP-6) is necessary for initial and extended EV release, while the transition zone protein NPHP-4 is required only for sustained EV release. The dynamic replenishment of PKD-2 at the ciliary tip is key to sustained EV release. Our study provides a comprehensive portrait of real-time ciliary EV release and mechanisms supporting cilia as proficient EV release platforms.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cilios , Vesículas Extracelulares , Células Receptoras Sensoriales , Canales Catiónicos TRPP , Animales , Cilios/metabolismo , Cilios/fisiología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/fisiología , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , MasculinoRESUMEN
INTRODUCTION: Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial. METHODS: The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes. ETHICS AND DISSEMINATION: PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: PACTR202104532026017).
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Metformina , Preeclampsia , Humanos , Embarazo , Femenino , Metformina/uso terapéutico , Preeclampsia/prevención & control , Método Doble Ciego , Sudáfrica , Hipoglucemiantes/uso terapéutico , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Resultado del EmbarazoAsunto(s)
Hernia Umbilical , Humanos , Hernia Umbilical/cirugía , Remisión Espontánea , Factores de Tiempo , Lactante , Niño , PreescolarRESUMEN
Endemic infectious diseases remain a major challenge for dairy producers worldwide. For effective disease control programs, up-to-date prevalence estimates are of utmost importance. The objective of this study was to estimate the herd-level prevalence of bovine leukemia virus (BLV), Salmonella Dublin, and Neospora caninum in dairy herds in Alberta, Canada using a serial cross-sectional study design. Bulk tank milk samples from all Alberta dairy farms were collected 4 times, in December 2021 (n = 489), April 2022 (n = 487), July 2022 (n = 487), and October 2022 (n = 480), and tested for antibodies against BLV, S. Dublin, and N. caninum using ELISAs. Herd-level apparent prevalence was calculated as positive samples divided by total tested samples at each time point. A mixed effect modified Poisson regression model was employed to assess the association of prevalence with region, herd size, herd type, and type of milking system. Apparent prevalence of BLV was 89.4, 88.7, 86.9 and 86.9% in December, April, July, and October, respectively, whereas for S. Dublin apparent prevalence was 11.2, 6.6, 8.6, and 8.5%, and for N. caninum apparent prevalence was 18.2, 7.4, 7.8, and 15.0%. For BLV, S. Dublin and N. caninum, a total of 91.7, 15.6, and 28.1% of herds, respectively, were positive at least once, whereas 82.5, 3.6, and 3.0% of herds were ELISA-positive at all 4 times. Compared with the north region, central Alberta had a high prevalence (prevalence ratio (PR) = 1.13) of BLV-antibody positive herds, whereas south Alberta had a high prevalence (PR = 2.56) of herds positive for S. Dublin antibodies. Furthermore, central (PR = 0.52) and south regions (PR = 0.46) had low prevalence of N. caninum-positive herds compared with the north. Hutterite colony herds were more frequently BLV-positive (PR = 1.13) but less frequently N. caninum-positive (PR = 0.47). Large herds (>7,200 L/day milk delivered â¼ > 250 cows) were 1.1 times more often BLV-positive, whereas small herds (≤3,600 L/day milk delivered â¼ ≤ 125 cows) were 3.2 times more often N. caninum-positive. For S. Dublin, Hutterite-colony herds were less frequently (PR = 0.07) positive than non-colony herds only in medium and large stratum but not in small stratum. Moreover, larger herds were more frequently (PR = 2.20) S. Dublin-positive than smaller herds only in non-colony stratum but not in colony stratum. Moreover, N. caninum prevalence was 1.6 times higher on farms with conventional milking systems compared with farms with an automated milking system. These results provide up-to-date information of the prevalence of these infections that will inform investigations of within-herd prevalence of these infections and help in devising evidence-based disease control strategies.
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Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS-altered CRCs, there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC were evaluated in a cohort of 925 patients with CRC, 277 (30.0%) of whom were ≤50 years old, and 454 (49.1%) who had RAS-altered tumors. For 3 biomarkers, RNF43, APC, and microsatellite instability (MSI), the association with RAS status was significantly modified by age after adjustment for multiple testing. Specifically, younger patients with RAS-altered tumors were more likely to be MSI-high, RNF43 mutated, and APC wild type. These differences might contribute to the observed pattern of diminished survival in younger versus older patients with CRC with RAS-mutated tumors undergoing liver metastasis resection.
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An economic simulation was carried out over 183 milk-producing countries to estimate the global economic impacts of 12 dairy cattle diseases and health conditions: mastitis (subclinical and clinical), lameness, paratuberculosis (Johne's disease), displaced abomasum, dystocia, metritis, milk fever, ovarian cysts, retained placenta, and ketosis (subclinical and clinical). Estimates of disease impacts on milk yield, fertility, and culling were collected from the literature, standardized, meta-analyzed using a variety of methods ranging from simple averaging to random-effects models, and adjusted for comorbidities to prevent overestimation. These comorbidity-adjusted disease impacts were then combined with a set of country-level estimates for lactational incidence or prevalence or both, herd characteristics, and price estimates within a series of Monte Carlo simulations that estimated and valued the economic losses due to these diseases. It was estimated that total annual global losses are US$65 billion (B). Subclinical ketosis, clinical mastitis, and subclinical mastitis were the costliest diseases modeled, resulting in mean annual global losses of approximately US$18B, US$13B, and US$9B, respectively. Estimated global annual losses due to clinical ketosis, displaced abomasum, dystocia, lameness, metritis, milk fever, ovarian cysts, paratuberculosis, and retained placenta were estimated to be US$0.2B, US$0.6B, US$0.6B, US$6B, US$5B, US$0.6B, US$4B, US$4B, and US$3B, respectively. Without adjustment for comorbidities, when statistical associations between diseases were disregarded, mean aggregate global losses would have been overestimated by 45%. Although annual losses were greatest in India (US$12B), the United States (US$8B), and China (US$5B), depending on the measure of losses used (losses as a percentage of gross domestic product, losses per capita, losses as a percentage of gross milk revenue), the relative economic burden of these dairy cattle diseases across countries varied markedly.
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Enfermedades de los Bovinos , Industria Lechera , Mastitis Bovina , Bovinos , Animales , Enfermedades de los Bovinos/economía , Enfermedades de los Bovinos/epidemiología , Femenino , Industria Lechera/economía , Mastitis Bovina/economía , Mastitis Bovina/epidemiología , Leche/economía , Lactancia , Comorbilidad , Cetosis/veterinaria , Cetosis/economía , EmbarazoRESUMEN
Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant in cilia, and its dysregulation may contribute to ciliopathies and neurodegeneration. Mutation of the deglutamylase CCP1 causes infantile-onset neurodegeneration. In C. elegans, ccpp-1 loss causes age-related ciliary degradation that is suppressed by a mutation in the conserved NEK10 homolog nekl-4. NEKL-4 is absent from cilia, yet it negatively regulates ciliary stability via an unknown, glutamylation-independent mechanism. We show that NEKL-4 was mitochondria-associated. Additionally, nekl-4 mutants had longer mitochondria, a higher baseline mitochondrial oxidation state, and suppressed ccpp-1∆ mutant lifespan extension in response to oxidative stress. A kinase-dead nekl-4(KD) mutant ectopically localized to ccpp-1∆ cilia and rescued degenerating microtubule doublet B-tubules. A nondegradable nekl-4(PEST∆) mutant resembled the ccpp-1∆ mutant with dye-filling defects and B-tubule breaks. The nekl-4(PEST∆) Dyf phenotype was suppressed by mutation in the depolymerizing kinesin-8 KLP-13/KIF19A. We conclude that NEKL-4 influences ciliary stability by activating ciliary kinesins and promoting mitochondrial homeostasis.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cilios , Microtúbulos , Mitocondrias , Neuronas , Animales , Microtúbulos/metabolismo , Microtúbulos/genética , Mitocondrias/metabolismo , Mitocondrias/genética , Cilios/metabolismo , Cilios/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Neuronas/metabolismo , Mutación/genéticaRESUMEN
Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.
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Caenorhabditis elegans , Longevidad , Estrés Oxidativo , Animales , Longevidad/efectos de los fármacos , Longevidad/genética , Estrés Oxidativo/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Resveratrol/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Antecedentes Genéticos , Natación , Piperazinas/farmacología , Estilbenos/farmacologíaRESUMEN
BACKGROUND: Helopeltis cinchonae (Hemiptera: Miridae) is a major pest of tea plantations in Asia. Conventional control of pests with pesticides is unsustainable. Therefore, safe and eco-friendly alternatives, such as pheromones, are required to manage the pest. RESULTS: In gas chromatography-electroantennographic detection (GC-EAD) analysis of whole-body extracts of virgin female H. cinchonae, two compounds elicited electroantennogram (EAG) responses from male antennae. These were identified as hexyl (R)-3-acetoxybutyrate and (R)-1-acetoxy-5-butyroxyhexane using gas chromatography-mass spectrometry (GC-MS) analysis compared to synthetic compounds. This is the first study to report 1-acetoxy-5-butyroxyhexane as an insect pheromone component. The synthetic compounds elicited dose-dependent EAG responses from the antennae of male H. cinchonae. In two field trapping experiments, the individual compounds were highly attractive to male H. cinchonae when dispensed from polyethylene vials. However, higher catches were obtained with blends of the two compounds in a 1:10 ratio. The blend of racemic compounds was as attractive as the blend of (R)-enantiomers. CONCLUSIONS: We reported that 1-acetoxy-5-butyroxyhexane and hexyl 3-acetoxybutyrate are components of the female-produced sex pheromone of H. cinchonae, but further work is required on the blend and loading of pheromone and on trap design to provide an optimized system for monitoring and control of this pest. The results may also facilitate the identification of the pheromones of other Helopeltis species, which are major pests in many crops. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Heterópteros , Atractivos Sexuales , Animales , Atractivos Sexuales/farmacología , Atractivos Sexuales/química , Femenino , Masculino , Heterópteros/fisiología , Cromatografía de Gases y Espectrometría de Masas , Control de Insectos/métodos , Camellia sinensis/químicaRESUMEN
Narrowband emissive multiresonant thermally activated delayed fluorescence (MR-TADF) emitters are a promising solution to achieve the current industry-targeted color standard, Rec. BT.2020-2, for blue color without using optical filters, aiming for high-efficiency organic light-emitting diodes (OLEDs). However, their long triplet lifetimes, largely affected by their slow reverse intersystem crossing rates, adversely affect device stability. In this study, a helical MR-TADF emitter (f-DOABNA) is designed and synthesized. Owing to its π-delocalized structure, f-DOABNA possesses a small singlet-triplet gap, ΔEST, and displays simultaneously an exceptionally faster reverse intersystem crossing rate constant, kRISC, of up to 2 × 106 s-1 and a very high photoluminescence quantum yield, ΦPL, of over 90% in both solution and doped films. The OLED with f-DOABNA as the emitter achieved a narrow deep-blue emission at 445 nm (full width at half-maximum of 24 nm) associated with Commission Internationale de l'Éclairage (CIE) coordinates of (0.150, 0.041), and showed a high maximum external quantum efficiency, EQEmax, of ≈20%.
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Mosquito-borne viruses cause more than 400 million annual infections and place over half of the world's population at risk. Despite this importance, the mechanisms by which arboviruses infect the mosquito host and disseminate to tissues required for transmission are not well understood. Here, we provide evidence that mosquito immune cells, known as hemocytes, play an integral role in the dissemination of dengue virus (DENV) and Zika virus (ZIKV) in the mosquito Aedes aegypti. We establish that phagocytic hemocytes are a focal point for virus infection and demonstrate that these immune cell populations facilitate virus dissemination to the ovaries and salivary glands. Additional transfer experiments confirm that virus-infected hemocytes confer a virus infection to non-infected mosquitoes more efficiently than free virus in acellular hemolymph, revealing that hemocytes are an important tropism to enhance virus dissemination in the mosquito host. These data support a "trojan horse" model of virus dissemination where infected hemocytes transport virus through the hemolymph to deliver virus to mosquito tissues required for transmission and parallels vertebrate systems where immune cell populations promote virus dissemination to secondary sites of infection. In summary, this study significantly advances our understanding of virus infection dynamics in mosquitoes and highlights conserved roles of immune cells in virus dissemination across vertebrate and invertebrate systems.
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The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called 'FLip' mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.
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Anticuerpos Monoclonales , Complicaciones Posoperatorias , Humanos , Mutación , SARS-CoV-2/genética , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
Lead-free BiFeO3-BaTiO3 (BF-BT) piezoceramics have sparked considerable interest in recent years due to their high piezoelectric performance and high Curie temperature. In this paper, we show how the addition of highly aligned porosity (between 40 and 60 vol %) improves the piezoelectric performance, sensing, and energy harvesting figures of merit in freeze-cast 0.70BiFeO3-0.30BaTiO3 piezoceramics compared to conventionally processed, nominally dense samples of the same composition. The dense and porous BF-BT ceramics had similar longitudinal piezoelectric coefficients (d33) immediately after poling, yet the dense samples were observed to age faster than those of porous ceramics. After 24 h, for example, the porous samples had significantly higher d33 values ranging from 112 to 124 pC/N, compared to 85 pC/N for the dense samples. Porous samples exhibited 3 and 5 times higher longitudinal piezoelectric voltage coefficient g33 and energy harvesting figure of merit d33g33 than dense samples due to the unexpected increase in d33 and decrease in relative permittivity with porosity. Spontaneous polarization (Ps) and remnant polarization (Pr) decrease as the porosity content increased from 37 to 59 vol %, as expected due to the lower volume of active material; however, normalized polarization values with respect to porosity level showed a slight increase in the porous materials relative to the dense BF-BT. Furthermore, the porous ceramics showed improved temperature-dependent strain-field response compared to the dense. As a result, these porous materials show excellent potential for use in high temperature sensing and harvesting applications.
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Asymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branches in vivo in wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point in Caenorhabditis elegans Posterior Lateral Mechanosensory neurons. The synaptic vesicle anterograde kinesin motor UNC-104/KIF1A regulates this vesicle behavior at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch. SAM-4/Myrlysin, which aids in recruitment/activation of UNC-104 on synaptic vesicles, regulates vesicle behavior at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight toward the asynaptic end. This suggests that the neuron optimizes UNC-104 levels on the cargo surface to maximize the fraction of vesicles entering the branch and minimize the fraction going to the asynaptic end.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cinesinas , Proteínas del Tejido Nervioso , Vesículas Sinápticas , Animales , Vesículas Sinápticas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Cinesinas/metabolismo , Cinesinas/genética , Neuronas/metabolismoRESUMEN
Evolutionary radiation, a pivotal aspect of macroevolution, offers valuable insights into evolutionary processes. The genus Pinus is the largest genus in conifers with c . 90% of the extant species emerged in the Miocene, which signifies a case of rapid diversification. Despite this remarkable history, our understanding of the mechanisms driving radiation within this expansive genus has remained limited. Using exome capture sequencing and a fossil-calibrated phylogeny, we investigated the divergence history, niche diversification, and introgression among 13 closely related Eurasian species spanning climate zones from the tropics to the boreal Arctic. We detected complex introgression among lineages in subsection Pinus at all stages of the phylogeny. Despite this widespread gene exchange, each species maintained its genetic identity and showed clear niche differentiation. Demographic analysis unveiled distinct population histories among these species, which further influenced the nucleotide diversity and efficacy of purifying and positive selection in each species. Our findings suggest that radiation in the Eurasian pines was likely fueled by interspecific recombination and further reinforced by their adaptation to distinct environments. Our study highlights the constraints and opportunities for evolutionary change, and the expectations of future adaptation in response to environmental changes in different lineages.