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1.
Ecol Evol ; 14(7): e11643, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957700

RESUMO

Marine sponges play a vital role in the reef's benthic community; however, understanding how their diversity and abundance vary with depth is a major challenge, especially on marginal reefs in areas deeper than 30 m. To help bridge this gap, we used underwater videos at 24 locations between 2- and 62-meter depths on a marginal reef system in the Southwestern Atlantic to investigate the effect of depth on the sponge metacommunity. Specifically, we quantified the abundance, density, and taxonomic composition of sponge communities, and decomposed their gamma (γ) diversity into alpha (α) and beta (ß) components. We also assessed whether beta diversity was driven by species replacement (turnover) or by nesting of local communities (nestedness). We identified 2020 marine sponge individuals, which belong to 36 species and 24 genera. As expected, deep areas (i.e., those greater than 30 m) presented greater sponge abundance and more than eightfold the number of sponges per square meter compared to shallow areas. About 50% of the species that occurred in shallow areas (<30 m) also occurred in deep areas. Contrarily to expectations, alpha diversity of rare (0 D α), typical (1 D α), or dominant (2 D α) species did not vary with depth, but the shallow areas had greater beta diversity than the deep ones, especially for typical (1 D ß) and dominant (2 D ß) species. Between 92.7% and 95.7% of the beta diversity was given by species turnover both inside and between shallow and deep areas. Our results support previous studies that found greater sponge abundance and density in deep areas and reveal that species sorting is stronger at smaller depths, generating more beta diversity across local communities in shallow than deep areas. Because turnover is the major driver at any depth, the entire depth gradient should be considered in management and conservation strategies.

2.
MRS Commun ; 14(3): 261-266, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966401

RESUMO

Microelectrode arrays (MEAs) have applications in drug discovery, toxicology, and basic research. They measure the electrophysiological response of tissue cultures to quantify changes upon exposure to biochemical stimuli. Unfortunately, manual addition of chemicals introduces significant noise in the recordings. Here, we report a simple-to-fabricate fluidic system that addresses this issue. We show that cell cultures can be successfully established in the fluidic compartment under continuous flow conditions and that the addition of chemicals introduces minimal noise in the recordings. This dynamic cell culture system represents an improvement over traditional tissue culture wells used in MEAs, facilitating electrophysiology measurements.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38972069

RESUMO

Understanding the dynamics of ion migration and volume change is crucial to studying the functionality and long-term stability of soft polymeric materials operating at liquid interfaces, but the subsurface characterization of swelling processes in these systems remains elusive. In this work, we address the issue using modulated electrochemical atomic force microscopy as a depth-sensitive technique to study electroswelling effects in the high-performance actuator material polypyrrole doped with dodecylbenzenesulfonate (Ppy:DBS). We perform multidimensional measurements combining local electroswelling and electrochemical impedance spectroscopies on microstructured Ppy:DBS actuators. We interpret charge accumulation in the polymeric matrix with a quantitative model, giving access to both the spatiotemporal dynamics of ion migration and the distribution of electroswelling in the electroactive polymer layer. The findings demonstrate a nonuniform distribution of the effective ionic volume in the Ppy:DBS layer depending on the film morphology and redox state. Our findings indicate that the highly efficient actuation performance of Ppy:DBS is caused by rearrangements of the polymer microstructure induced by charge accumulation in the soft polymeric matrix, increasing the effective ionic volume in the bulk of the electroactive film for up to two times the value measured in free water.

4.
Lancet Reg Health Am ; 35: 100806, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38948323

RESUMO

During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies' characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

5.
Vet Sci ; 11(6)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38922024

RESUMO

Seizures are a common presentation seen in small animal practices. Seizures require prompt management including initial interventions for triage, stabilization, and treatment with first-line anticonvulsant (AC) drugs like benzodiazepines. Concurrently, ruling out metabolic or extracranial causes with point-of-care diagnostics can help guide further diagnostics and treatments. Analysis of the history and a physical exam are also necessary to rule out common "look-alikes" that require specific diagnostic workup and treatments. Typically, causes of seizures can be grouped into intracranial and extracranial causes, with the latter being easier to diagnose with commonly available tests. This review presents a systematic approach to the diagnosis and treatment of single seizures, cluster seizures, and status epilepticus in dogs and cats.

6.
Can Commun Dis Rep ; 50(5): 121-134, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38835503

RESUMO

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.

7.
Clin Nutr ; 43(7): 1782-1790, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38861891

RESUMO

INTRODUCTION: While therapies based on endogenous gut peptides such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have been compelling therapeutic agents for obesity and type 2 diabetes (T2D), only a few have achieved long-term weight loss and all have shown significant side-effects, including nausea/malaise and gastrointestinal ailments. OBJECTIVE: As the pathophysiology of obesity is driven by dysregulation of multiple, inter-related, pathways, we tested a novel peptide targeting multiple receptors of complementary neurocircuits regulating the controls of energy balance. METHODS: Response to daily injections of GEP44, a GLP-1R and neuropeptide Y1R and Y2R receptor (Y1R/Y2R) triple agonist was tested vs. the GLP-1R agonist liraglutide (LIRA) in diet-induced obese (DIO) male and female rats. Glucose tolerance tests after intraperitoneal injection of glucose (IPGTT) were performed at baseline and after 14-d of treatment in GEP44 treated rats. Other metabolic parameters were assessed in blood at the end of a 28-d intervention. RESULTS: Upon conclusion at 28-d, body weight reduction compared to vehicle was -15.6%/-11.9% in response to GEP44, vs. -9.7%/-5.1% after LIRA, males, and females, respectively. Significant reductions of cumulative food intake occurred over 28-d in female rats treated with GEP44 (-30%; p < 0.0001), vs. LIRA (-10%), and in male rats GEP44 (-39%; p < 0.0001), vs. LIRA (-20%; p = 0.003). In IPGTTs, a similar stimulation glucose induced insulin secretion was noted in rats treated with GEP44 and LIRA. CONCLUSION: The strong reductions of body weight in response to long-term applications of the triple agonist GEP44 confirms the therapeutic potential of targeting multiple receptors for achieving more robust and potentially more sustained improvement of energy balance.


Assuntos
Ingestão de Alimentos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Liraglutida , Obesidade , Animais , Obesidade/tratamento farmacológico , Masculino , Ratos , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Liraglutida/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores de Neuropeptídeo Y/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Insulina/sangue , Teste de Tolerância a Glucose
8.
Sci Adv ; 10(26): eado9576, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38924408

RESUMO

Lip language recognition urgently needs wearable and easy-to-use interfaces for interference-free and high-fidelity lip-reading acquisition and to develop accompanying data-efficient decoder-modeling methods. Existing solutions suffer from unreliable lip reading, are data hungry, and exhibit poor generalization. Here, we propose a wearable lip language decoding technology that enables interference-free and high-fidelity acquisition of lip movements and data-efficient recognition of fluent lip language based on wearable motion capture and continuous lip speech movement reconstruction. The method allows us to artificially generate any wanted continuous speech datasets from a very limited corpus of word samples from users. By using these artificial datasets to train the decoder, we achieve an average accuracy of 92.0% across individuals (n = 7) for actual continuous and fluent lip speech recognition for 93 English sentences, even observing no training burn on users because all training datasets are artificially generated. Our method greatly minimizes users' training/learning load and presents a data-efficient and easy-to-use paradigm for lip language recognition.


Assuntos
Fala , Dispositivos Eletrônicos Vestíveis , Humanos , Idioma , Lábio/fisiologia , Movimento , Masculino , Feminino , Adulto , Leitura Labial , Captura de Movimento
9.
Biomaterials ; 310: 122624, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38805956

RESUMO

The proliferation of medical wearables necessitates the development of novel electrodes for cutaneous electrophysiology. In this work, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is combined with a deep eutectic solvent (DES) and polyethylene glycol diacrylate (PEGDA) to develop printable and biocompatible electrodes for long-term cutaneous electrophysiology recordings. The impact of printing parameters on the conducting properties, morphological characteristics, mechanical stability and biocompatibility of the material were investigated. The optimised eutectogel formulations were fabricated in four different patterns -flat, pyramidal, striped and wavy- to explore the influence of electrode geometry on skin conformability and mechanical contact. These electrodes were employed for impedance and forearm EMG measurements. Furthermore, arrays of twenty electrodes were embedded into a textile and used to generate body surface potential maps (BSPMs) of the forearm, where different finger movements were recorded and analysed. Finally, BSPMs for three different letters (B, I, O) in sign-language were recorded and used to train a logistic regressor classifier able to reliably identify each letter. This novel cutaneous electrode fabrication approach offers new opportunities for long-term electrophysiological recordings, online sign-language translation and brain-machine interfaces.


Assuntos
Eletrodos , Aprendizado de Máquina , Poliestirenos , Impressão Tridimensional , Têxteis , Humanos , Poliestirenos/química , Condutividade Elétrica , Dispositivos Eletrônicos Vestíveis , Compostos Bicíclicos Heterocíclicos com Pontes/química , Géis/química , Polímeros/química , Polietilenoglicóis/química , Eletromiografia/métodos , Materiais Biocompatíveis/química
10.
Sci Adv ; 10(19): eadl1230, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38718109

RESUMO

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.


Assuntos
Traumatismos da Medula Espinal , Medula Espinal , Animais , Medula Espinal/fisiologia , Ratos , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Humanos , Estimulação Elétrica/métodos , Eletrodos Implantados
11.
J Am Vet Med Assoc ; : 1, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749473

RESUMO

OBJECTIVE: To provide a video tutorial detailing how to perform "blind" and ultrasound-guided abdominocentesis for diagnostic and therapeutic guidance, and to provide a brief demonstration of intra-abdominal pressure measurement (IAP). ANIMALS: Any cat or dog with suspicion of free abdominal effusion or patients requiring measurement of IAP. METHODS: Abdominocentesis should be performed when there is high suspicion for peritoneal effusion based on physical exam and/or diagnostic imaging. The 4-quadrant tap uses 20-gauge or larger needles placed blindly in ≥ 1 of the 4 quadrants of the abdomen to collect abdominal fluid. In contrast, ultrasound allows visualization of fluid in the abdomen prior to percutaneous insertion of a needle and syringe to collect fluid. Regardless of collection technique, fluid should have immediate cytologic analysis and later can be submitted for biochemical parameters, additional cellular analysis by a pathologist, and culture and sensitivity (in rare cases if indicated). Intravesicular bladder pressure measurement using a manometer-urinary catheter system approximates the IAP when there is concern for organ hypoperfusion and compartment syndrome. RESULTS: Abdominocentesis can be performed with and without the use of ultrasound guidance. Intravesicular bladder pressure measurement is used to diagnose and trend IAP values before and after treatments are performed. CLINICAL RELEVANCE: Abdominocentesis is a simple and safe technique that all small animal clinicians should be comfortable performing. Effusion sampling can guide further diagnostics and treatments. Measurement of IAP is simple and requires no specialized equipment.

12.
Curr Probl Cardiol ; 49(6): 102560, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583791

RESUMO

Spontaneous coronary artery dissection (SCAD) is an underdiagnosed cause of acute coronary syndrome (ACS) that usually presents in young female patients. Risk factors include female sex, physical and emotional stressors, and fibromuscular dysplasia, and diagnosis is usually made by coronary angiography aided by intravascular ultrasound (IVUS) or optical coherence tomography (OCT). While conservative treatment is usually preferred over percutaneous coronary intervention or surgery, medical management of SCAD has been under debate. This comprehensive review aims to summarize findings from recent studies exploring various medical treatment approaches for the management of SCAD. Antiplatelet therapy with aspirin is generally safe and beneficial for SCAD patients, with dual antiplatelet (DAPT) being recommended for patients undergoing PCI. In the absence of intervention, DAPT may be given for a short period followed by a longer single-antiplatelet (SAPT) therapy with aspirin. Beta-blockers appear to be safe and effective for SCAD patients. On the other hand, fibrinolytics, anticoagulants, and glycoprotein IIa/IIIb inhibitors are contraindicated. Cardiovascular medications such as renin-angiotensin-aldosterone system (RAAS) inhibitors, mineralocorticoid receptor antagonists, and statins are not recommended in the absence of left ventricular dysfunction. Hormonal therapy is contraindicated for patients who develop SCAD during pregnancy and future pregnancy is discouraged in that patient population.


Assuntos
Anomalias dos Vasos Coronários , Doenças Vasculares , Doenças Vasculares/congênito , Humanos , Doenças Vasculares/diagnóstico , Doenças Vasculares/etiologia , Anomalias dos Vasos Coronários/diagnóstico , Anomalias dos Vasos Coronários/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Gerenciamento Clínico , Angiografia Coronária/métodos , Antagonistas Adrenérgicos beta/uso terapêutico , Intervenção Coronária Percutânea/métodos , Fatores de Risco
13.
Clin Med Res ; 22(1): 19-27, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38609144

RESUMO

Musculoskeletal conditions of the upper and lower extremities are commonly treated with corticosteroid injections. Ketorolac, a parenteral nonsteroidal anti-inflammatory drug, represents an alternative injectant for common shoulder, hip, and knee conditions. A review of the current literature was conducted on the efficacy of ketorolac injection in musculoskeletal diseases. Several studies support the use and efficacy of ketorolac injection in subacromial bursitis, adhesive capsulitis, and hip and knee osteoarthritis. Given the systemic effects of glucocorticoid injections, ketorolac may be a safe and effective alternative in patients with musculoskeletal disease. However, more evidence is required to better understand the effects ketorolac has on the human body during inflammatory processes.


Assuntos
Bursite , Doenças Musculoesqueléticas , Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Cetorolaco/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Bursite/tratamento farmacológico , Doenças Musculoesqueléticas/tratamento farmacológico
14.
EBioMedicine ; 103: 105097, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608515

RESUMO

BACKGROUND: Extended-spectrum cephalosporins (ESCs) are third and fourth generation cephalosporin antimicrobials used in humans and animals to treat infections due to multidrug-resistant (MDR) bacteria. Resistance to ESCs (ESC-R) in Enterobacterales is predominantly due to the production of extended-spectrum ß-lactamases (ESBLs) and plasmid-mediated AmpC ß-lactamases (AmpCs). The dynamics of ESBLs and AmpCs are changing across countries and host species, the result of global transmission of ESC-R genes. Plasmids are known to play a key role in this dissemination, but the relative importance of different types of plasmids is not fully understood. METHODS: In this study, Escherichia coli with the major ESC-R genes blaCTX-M-1, blaCTX-M-15, blaCTX-M-14 (ESBLs) and blaCMY-2 (AmpC), were selected from diverse host species and other sources across Canada, France and Germany, collected between 2003 and 2017. To examine in detail the vehicles of transmission of the ESC-R genes, long- and short-read sequences were generated to obtain complete contiguous chromosome and plasmid sequences (n = 192 ESC-R E. coli). The types, gene composition and genetic relatedness of these plasmids were investigated, along with association with isolate year, source and geographical origin, and put in context with publicly available plasmid sequences. FINDINGS: We identified five epidemic resistance plasmid subtypes with distinct genetic properties that are associated with the global dissemination of ESC-R genes across multiple E. coli lineages and host species. The IncI1 pST3 blaCTX-M-1 plasmid subtype was found in more diverse sources than the other main plasmid subtypes, whereas IncI1 pST12 blaCMY-2 was more frequent in Canadian and German human and chicken isolates. Clonal expansion also contributed to the dissemination of the IncI1 pST12 blaCMY-2 plasmid in ST131 and ST117 E. coli harbouring this plasmid. The IncI1 pST2 blaCMY-2 subtype was predominant in isolates from humans in France, while the IncF F31:A4:B1 blaCTX-M-15 and F2:A-:B- blaCTX-M-14 plasmid subtypes were frequent in human and cattle isolates across multiple countries. Beyond their epidemic nature with respect to ESC-R genes, in our collection almost all IncI1 pST3 blaCTX-M-1 and IncF F31:A4:B1 blaCTX-M-15 epidemic plasmids also carried multiple antimicrobial resistance (AMR) genes conferring resistance to other antimicrobial classes. Finally, we found genetic signatures in the regions surrounding specific ESC-R genes, identifying the predominant mechanisms of ESC-R gene movement, and using publicly available databases, we identified these epidemic plasmids from widespread bacterial species, host species, countries and continents. INTERPRETATION: We provide evidence that epidemic resistance plasmid subtypes contribute to the global dissemination of ESC-R genes, and in addition, some of these epidemic plasmids confer resistance to multiple other antimicrobial classes. The success of these plasmids suggests that they may have a fitness advantage over other plasmid types and subtypes. Identification and understanding of the vehicles of AMR transmission are crucial to develop and target strategies and interventions to reduce the spread of AMR. FUNDING: This project was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), through the Medical Research Council (MRC, MR/R000948/1), the Canadian Institutes of Health Research (CFC-150770), and the Genomics Research and Development Initiative (Government of Canada), the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709, the French Agency for food environmental and occupational health & safety (Anses), and the French National Reference Center (CNR) for antimicrobial resistance. Support was also provided by the Biotechnology and Biological Sciences Research Council (BBSRC) through the BBSRC Institute Strategic Programme Microbes in the Food ChainBB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain).


Assuntos
Resistência às Cefalosporinas , Infecções por Escherichia coli , Escherichia coli , Plasmídeos , Plasmídeos/genética , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/transmissão , Humanos , Resistência às Cefalosporinas/genética , Animais , beta-Lactamases/genética , Cefalosporinas/farmacologia , Antibacterianos/farmacologia , Alemanha/epidemiologia , Testes de Sensibilidade Microbiana , França/epidemiologia
15.
Nat Mater ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671159

RESUMO

Electrode arrays that interface with peripheral nerves are used in the diagnosis and treatment of neurological disorders; however, they require complex placement surgeries that carry a high risk of nerve injury. Here we leverage recent advances in soft robotic actuators and flexible electronics to develop highly conformable nerve cuffs that combine electrochemically driven conducting-polymer-based soft actuators with low-impedance microelectrodes. Driven with applied voltages as small as a few hundreds of millivolts, these cuffs allow active grasping or wrapping around delicate nerves. We validate this technology using in vivo rat models, showing that the cuffs form and maintain a self-closing and reliable bioelectronic interface with the sciatic nerve of rats without the use of surgical sutures or glues. This seamless integration of soft electrochemical actuators with neurotechnology offers a path towards minimally invasive intraoperative monitoring of nerve activity and high-quality bioelectronic interfaces.

16.
PLoS Genet ; 20(3): e1011140, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427688

RESUMO

During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that DSB clustering is abolished when meiotic prophase timing is extended via deletion of the NDT80 transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, when Tel1 is absent but Ndt80 is present and thus cells are able to rapidly exit meiotic prophase, genome-wide maps of Spo11-DSB formation are skewed towards pericentromeric regions and regions that load pro-DSB factors early-revealing regions of preferential priming-but this effect is abolished when NDT80 is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering-a phenomenon that is exacerbated in tel1Δ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control.


Assuntos
Quebras de DNA de Cadeia Dupla , Proteínas de Saccharomyces cerevisiae , DNA , Proteínas de Ligação a DNA/genética , Endodesoxirribonucleases/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Meiose/genética , Prófase/genética , Proteínas Serina-Treonina Quinases/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
18.
Life (Basel) ; 14(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38541676

RESUMO

Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice.

19.
Cureus ; 16(2): e53731, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38455821

RESUMO

Pediatric obesity is a global concern with distressing comorbid conditions, including mood disturbance, cardiovascular changes, endocrine imbalance, liver disease, sleep apnea, and orthopedic conditions. The primary treatment of this condition includes physical activity. Participating in organized sports has been shown to reduce weight and the complications of pediatric obesity more effectively than individual exercise.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38512306

RESUMO

Superstitious rituals are common in sports and can play a role in athletes' optimism, sense of control, and confidence in performance. Superstitious rituals have characteristics rooted in tradition and need for perfection. While superstitious rituals vary in type of activity, it is necessary to consider their impact on players and the team, and to guide athletes into positive forms of expression to optimize their performance and overall well-being when engaged in their athletic activities. This paper explores the potential benefits and challenges of superstitious rituals, and the ways in which positive alternative pathways can contribute to peak performance in athletes.

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