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1.
Pest Manag Sci ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38624134

RESUMEN

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 GC-EAD analyses of whole-body extracts of virgin female H. cinchonae, two compounds elicited EAG responses from male antennae. These were identified as hexyl (R)-3-acetoxybutyrate and (R)-1-acetoxy-5-butyroxyhexane using 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. This article is protected by copyright. All rights reserved.

2.
Nat Commun ; 15(1): 3284, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627386

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales , Complicaciones Posoperatorias , Humanos , Mutación , SARS-CoV-2/genética , Anticuerpos Neutralizantes , Anticuerpos Antivirales
3.
ACS Appl Mater Interfaces ; 16(15): 19283-19297, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38578950

RESUMEN

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.

4.
Adv Mater ; : e2402289, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38581139

RESUMEN

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%.

5.
Aging (Albany NY) ; 16(7): 5829-5855, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38613792

RESUMEN

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.


Asunto(s)
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/farmacología
6.
bioRxiv ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38617257

RESUMEN

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.

7.
New Phytol ; 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515228

RESUMEN

Evolutionary radiation, a pivotal aspect of macroevolution, offers valuable insights into evolutionary processes. The genus Pinus is the largest genus in conifers with c . $$ c. $$ 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.

8.
J Med Econ ; 27(1): 519-530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38466204

RESUMEN

OBJECTIVE: The availability of targeted therapies for oncology patients is increasing. Available genomic tests to identify treatment-eligible patients include single gene tests and gene panel tests, including the whole-exome, whole-transcriptome OncoExTra test. We assessed the costs and clinical benefits of test choice. METHODS: A Microsoft Excel-based model was developed to evaluate test choice in patients with advanced/metastatic non-small cell lung cancer (NSCLC), breast, prostate, and colorectal cancer. Treatment pathways were based on NCCN guidelines and medical expert opinion. Inputs were derived from published literature. Annual economic results and lifetime clinical results with OncoExTra testing were projected per-tested-patient and compared with single gene testing and no testing. Separately, results were estimated for a US health plan without the OncoExTra test and with its use in 5% of patients. RESULTS: Compared with no genomic testing, OncoExTra test use increased costs by $4,915 per patient; however, 82%-92% of individuals across tumour types were identified as eligible for targeted therapy or a clinical trial. Compared with single gene testing, OncoExTra test use decreased costs by $9,966 per-patient-tested while increasing use of approved or investigational targeted therapies by 20%. When considering a hypothetical health plan with 1 million members, 858 patients were eligible for genomic testing. Using the OncoExTra test in 5% of those eligible, per-member per-month costs decreased by $0.003, ranging from cost-savings of $0.026 in NSCLC patients to a $0.009 increase in prostate cancer patients. Cost-savings were driven by reduced treatment costs with increased clinical trial enrolment and reduced direct and indirect medical costs associated with targeted treatments. LIMITATIONS: Limitations include the required simplifications in modelling complex conditions that may not fully reflect evolving real-world testing and treatment patterns. CONCLUSIONS: Compared to single-gene testing, results indicate that using next generation sequencing test such as OncoExTra identified more actionable alterations, leading to improved outcomes and reduced costs.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias de la Próstata , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias de la Próstata/genética , Femenino , Ensayos Clínicos como Asunto
9.
JAMA Netw Open ; 7(3): e244170, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38546643

RESUMEN

Importance: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma. Objective: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma. Design, Setting, and Participants: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023. Exposure: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set of 63 autosomal-dominant CPGs. Main Outcomes and Measures: Overall survival (OS) and event-free survival (EFS) were the main outcomes, using the Kaplan-Meier estimator to assess survival probabilities and the Cox proportional hazards regression model to adjust for clinical covariates. Analyses were stratified by tumor histology and the fusion status of PAX3 or PAX7 to the FOXO1 gene. Results: In this study of 580 individuals with rhabdomyosarcoma, the median patient age was 5.9 years (range, 0.01-23.23 years), and the male-to-female ratio was 1.5 to 1 (351 [60.5%] male). For patients with CPVs in rhabdomyosarcoma-associated CPGs, EFS was 48.4% compared with 57.8% for patients without a CPV (P = .10), and OS was 53.7% compared with 65.3% for patients without a CPV (P = .06). After adjustment, patients with CPVs had significantly worse OS (adjusted hazard ratio [AHR], 2.49 [95% CI, 1.39-4.45]; P = .002), and the outcomes were not better among patients with embryonal histology (EFS: AHR, 2.25 [95% CI, 1.25-4.06]; P = .007]; OS: AHR, 2.83 [95% CI, 1.47-5.43]; P = .002]). These associations were not due to the development of a second malignant neoplasm, and importantly, patients with fusion-negative rhabdomyosarcoma who harbored a CPV had similarly inferior outcomes as patients with fusion-positive rhabdomyosarcoma without CPVs (EFS: AHR, 1.35 [95% CI, 0.71-2.59]; P = .37; OS: AHR, 1.71 [95% CI, 0.84-3.47]; P = .14). There were no significant differences in outcome by CPV status of the 63 CPG set. Conclusions and Relevance: This cohort study identified a group of patients with embryonal rhabdomyosarcoma who had a particularly poor outcome. Other important clinical findings included that individuals with TP53 had poor outcomes independent of second malignant neoplasms and that patients with fusion-negative rhabdomyosarcoma who harbored a CPV had outcomes comparable to patients with fusion-positive rhabdomyosarcoma. These findings suggest that germline CPV testing may aid in clinical prognosis and should be considered in prospective risk-based clinical trials.


Asunto(s)
Neoplasias Primarias Secundarias , Rabdomiosarcoma , Niño , Humanos , Femenino , Masculino , Estudios de Cohortes , Estudios Prospectivos , Rabdomiosarcoma/genética , Rabdomiosarcoma/terapia , Pruebas Genéticas , Células Germinativas
10.
Genetics ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38467475

RESUMEN

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 C. elegans PLM neurons. The synaptic vesicle anterograde kinesin motor UNC-104/KIF1A regulates this vesicle behaviour 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 behaviour at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight towards the asynaptic end. This suggests that the neuron optimises UNC-104 levels on the cargo surface to maximise the fraction of vesicles entering the branch and minimise the fraction going to the asynaptic end.

11.
Environ Entomol ; 53(2): 249-258, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38309712

RESUMEN

Knowledge of insect pest ecology and biology is important for maximizing crop protection and reducing crop losses. Currently, we lack an efficient control program for the cocoa mirid Sahlbergella singularis Haglund (Hemiptera: Miridae), the principal insect pest of cocoa in West and Central Africa. A 2-yr study was conducted in 11 plantations across Ayos and Konye, two of the largest cocoa growing areas of Cameroon. We evaluated the effects of mirid sex pheromone and climatic variations on mirid population dynamics and their associated cocoa damage. Sex pheromone traps caught 1.5-fold higher mirids in Ayos than in Konye, with more overall counts in 2015 than in 2016. Cocoa pod counts were also significantly higher in 2015 than in 2016 and were negatively correlated with temperature and relative humidity. In both localities, mirid populations and associated cocoa pod damage were suppressed in plantations where sex pheromone traps were used. Damage incidence was positively correlated with mirid counts, confirming that the cocoa pod is the preferential site for mirid feeding and reproduction. As such, damage incidence could be used as proxy for comparative mirid population level due to the mirid's cryptic habit. Of the recorded weather variables, only relative humidity was correlated (negatively) with damage severity. Our data on the relationships between damage caused by mirids and their population dynamics and sex pheromone trap catches suggest that an effective control strategy using mass trapping could be developed for mirid management in cocoa plantations.


Asunto(s)
Cacao , Hemípteros , Heterópteros , Atractivos Sexuales , Animales , Feromonas , Camerún , Control de Insectos
12.
Pest Manag Sci ; 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38348748

RESUMEN

BACKGROUND: Spotted wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), is an economically important pest of soft and stone fruit crops. The aim of this study was to identify repellents, formulated in dispensers, which could protect crops from D. suzukii. Fourteen potential repellents were screened against summer- and winter-morph D. suzukii through electroantennography and behavioural bioassays. Repellents effective in the laboratory were tested in polytunnels to determine their efficacy in reducing catches in fruit-baited traps. Further trials of three potential repellents were conducted to determine the distances over which repellent dispensers could reduce D. suzukii emergence in a strawberry crop. RESULTS: All 14 chemicals screened were detected by the antennae of both D. suzukii morphs. Hexyl acetate and geosmin both elicited a significantly greater corrected EAG response in summer morphs than winter morphs. Summer-morph D. suzukii were repelled by butyl acetate, ethyl propionate, methyl N,N-dimethyl anthranilate, geosmin, methyl salicylate, DEET and benzaldehyde at one or more doses test in laboratory bioassays. Winter morphs were repelled by ethyl propionate, methyl anthranilate, methyl N,N-dimethyl anthranilate, DEET, benzaldehyde and butyl anthranilate at one or more of the doses tested in the laboratory. Ethyl propionate, methyl N,N-dimethylanthranilate and benzaldehyde repelled both morphs from fruit-baited traps in polytunnel trapping trials. Ethyl propionate and methyl N,N-dimethylanthranilate reduced emergence of D. suzukii in a strawberry crop over 3-5 m. CONCLUSIONS: Ethyl propionate and methyl N,N-dimethylanthranilate may protect strawberry crops against D. suzukii. Future work should test these repellents in combination with attractants in a 'push-pull' strategy. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

13.
Nat Commun ; 15(1): 1546, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413604

RESUMEN

A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the chemical connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode has evolved to respond to harsh environments by developing a quantitatively and qualitatively differentiated connectome.


Asunto(s)
Conectoma , Nematodos , Animales , Caenorhabditis elegans/fisiología , Sinapsis , Neuronas Motoras
14.
bioRxiv ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38405845

RESUMEN

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 mutation in the conserved NEK10 homolog nekl-4. NEKL-4 is absent from cilia, yet negatively regulates ciliary stability via an unknown, glutamylation-independent mechanism. We show that NEKL-4 was mitochondria-associated. 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(PESTΔ) mutant resembled the ccpp-1 mutant with dye filling defects and B-tubule breaks. The nekl-4(PESTΔ) 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.

15.
New Phytol ; 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38308133

RESUMEN

Scots pine is the foundation species of diverse forested ecosystems across Eurasia and displays remarkable ecological breadth, occurring in environments ranging from temperate rainforests to arid tundra margins. Such expansive distributions can be favored by various demographic and adaptive processes and the interactions between them. To understand the impact of neutral and selective forces on genetic structure in Scots pine, we conducted range-wide population genetic analyses on 2321 trees from 202 populations using genotyping-by-sequencing, reconstructed the recent demography of the species and examined signals of genetic adaptation. We found a high and uniform genetic diversity across the entire range (global FST 0.048), no increased genetic load in expanding populations and minor impact of the last glacial maximum on historical population sizes. Genetic-environmental associations identified only a handful of single-nucleotide polymorphisms significantly linked to environmental gradients. The results suggest that extensive gene flow is predominantly responsible for the observed genetic patterns in Scots pine. The apparent missing signal of genetic adaptation is likely attributed to the intricate genetic architecture controlling adaptation to multi-dimensional environments. The panmixia metapopulation of Scots pine offers a good study system for further exploration into how genetic adaptation and plasticity evolve under gene flow and changing environment.

16.
bioRxiv ; 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-37398149

RESUMEN

Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion over long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses. It is assumed that neurons' possess this capacity, but ultrastructural data over substantial portions of a neuron's extent that would allow for tests of such hypotheses are scarce. Here, we mined the Caenorhabditis elegans electron micrographs of John White and Sydney Brenner and found systematic differences in average mitochondrial length (ranging from 1.3 to 2.4 µm), volume density (3.7% to 6.5%) and diameter (0.18 to 0.24 µm) between neurons of different neurotransmitter type and function, but found limited differences in mitochondrial morphometrics between axons and dendrites of the same neurons. Analyses of distance intervals found mitochondria to be distributed randomly with respect to presynaptic specializations, and an indication that mitochondria were displaced from postsynaptic specializations. Presynaptic specializations were primarily localized to varicosities, but mitochondria were no more likely to be found in synaptic varicosities than non-synaptic varicosities. Consistently, mitochondrial volume density was no greater in varicosities with synapses. Therefore, beyond the capacity to disperse mitochondria throughout their length, at least in C. elegans, fine caliber neurons manifest limited sub-cellular control of mitochondrial size and distribution.

17.
Geroscience ; 46(2): 2239-2251, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37923874

RESUMEN

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies-for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.


Asunto(s)
Antioxidantes , Caenorhabditis , Animales , Humanos , Anciano , Antioxidantes/farmacología , Masoprocol/farmacología , Masoprocol/metabolismo , Caenorhabditis elegans/genética , Longevidad , Promoción de la Salud , Extractos Vegetales/farmacología , Té/metabolismo , Mamíferos
18.
Laryngoscope ; 134(3): 1299-1307, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37668315

RESUMEN

OBJECTIVE: With the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model. METHODS: An animal study was designed using 21 healthy male New Zealand rabbits. Gallium-68-labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa (n = 6) or lateral tongue (n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non-nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection. RESULTS: Buccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1-5) were identified. In addition, an average of 16.9 ± 3.3 non-sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent-of-injected dose (%ID) compared with non-sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48-h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative. CONCLUSION: Fluorescent-labeled Tc-99 m-tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1299-1307, 2024.


Asunto(s)
Neoplasias de la Boca , Ganglio Linfático Centinela , Masculino , Animales , Conejos , Biopsia del Ganglio Linfático Centinela/métodos , Ganglios Linfáticos/patología , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/patología
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