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1.
Anim Genet ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436096

RESUMO

Local species exhibit distinctive indigenous characteristics while showing unique productive and phenotypic traits. However, the advent of commercialization has posed a substantial threat to the survival of indigenous species. Anxi cattle, an endangered native breed in China, have evolved unique growth and reproductive characteristics in extreme desert and semidesert ecosystems. In this study, we conducted a genomic comparison of 10 Anxi cattle genomes with those of five other global populations/breeds to assess genetic diversity and identify candidate genomic regions in Anxi cattle. Population structure and genetic diversity analyses revealed that Anxi cattle are part of the East Asian cattle clade, exhibiting higher genetic diversity than commercial breeds. Through selective sweep analysis, we identified specific genetic variations linked to the environmental adaptability of Anxi cattle. Notably, we identified several candidate genes, including CERS3 involved in regulating skin permeability and antimicrobial functions, RBFOX2 associated with cardiac development, SLC16A7 participated in the regulation of pancreatic endocrine function, and SPATA3 related to reproduction. Our findings revealed the distinctive genomic features of Anxi cattle in dryland environments, provided invaluable insights for further research and breed preservation, and had important significance for enriching the domestic cattle breeding gene bank.

2.
Nano Lett ; 24(14): 4108-4116, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38536003

RESUMO

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

3.
Angew Chem Int Ed Engl ; 63(14): e202318926, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38381597

RESUMO

To date, locking the shape of liquids into non-equilibrium states usually relies on jamming nanoparticle surfactants at an oil/water interface. Here we show that a synthetic water-soluble zwitterionic Gemini surfactant can serve as an alternative to nanoparticle surfactants for stabilizing, structuring and additionally lubricating liquids. By having a high binding energy comparable to amphiphilic nanoparticles at the paraffin oil/water interface, the surfactant can attain near-zero interfacial tensions and ultrahigh surface coverages after spontaneous adsorption. Owing to the strong association between neighboring surfactant molecules, closely packed monolayers with high mechanical elasticity can be generated at the oil/water interface, thus allowing the surfactant to produce not only ultra-stable emulsions but also structured liquids with various geometries by using extrusion printing and 3D printing techniques. By undergoing tribochemical reactions at its sulfonic terminus, the surfactant can endow the resultant emulsions with favorable lubricity even under high load-bearing conditions. Our study may provide new insights into creating complex liquid devices and new-generation lubricants capable of combining the characteristics of both liquid and solid lubricants.

4.
Intensive Crit Care Nurs ; 82: 103656, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38359599

RESUMO

OBJECTIVE: Sufficient knowledge is crucial for nurses in intensive care unit to prevent medical device related pressure injuries. This study was aimed to explore the Chinese intensive care nurses' perceptions and knowledge of medical device related pressure injury prevention and identify associated factors. METHODS: This descriptive cross-sectional study included a convenience sample of 1286 intensive care nurses recruited from professional networks across China. Participants completed the demographic data form and the adapted 23-item Medical device related pressure injury Knowledge Assessment Questionnaire (MKAQ) questionnaire. Multiple linear regression was used to determine the associated factors. RESULTS: The medical device related pressure injury knowledge assessment questionnaire scores among intensive care nurses were relatively high, with a correct rate of 78.3 %. Multiple regression analysis revealed that management position (ß = 0.131, P < 0.001) was the strongest associated factor of knowledge scores, followed by academic position (ß = 0.114, P = 0.009) and received training on medical device related pressure injury (ß = 0.112, P < 0.001). Hospital level (ß = 0.087, P = 0.004) and sex (ß = 0.068, P = 0.016) were also significant associated factors. Collectively, these five variables accounted for 18.2 % of the variance in knowledge scores. CONCLUSION: Sufficient knowledge is a prerequisite for safe nursing practice. Although nurses demonstrated relatively high level of knowledge, it is essential for nursing managers to implement specific measures to enhance the knowledge among junior nursing staff, especially in non-tertiary hospitals, to promote medical device related pressure injury prevention in all intensive care settings. IMPLICATIONS FOR CLINICAL PRACTICE: This study highlights the importance of sociodemographic and professional characteristics in promoting satisfactory perception and knowledge of preventing medical device related pressure injury among intensive care nurses. It is necessary for nurse managers and leaders to develop strategic interventions, along with targeted training programs and quality improvement plans that correspond to the actual training needs to improve the medical device related pressure injury prevention.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem no Hospital , Lesão por Pressão , Humanos , Estudos Transversais , Lesão por Pressão/etiologia , Lesão por Pressão/prevenção & controle , Unidades de Terapia Intensiva , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde , Percepção
5.
Environ Res ; 246: 118108, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38184061

RESUMO

The ecological risks of organic ultraviolet absorbents (UVAs) have been of increasing concern. Studies have found that these chemicals could be accumulated in terrestrial animals and pose toxicities. However, tissue distribution of UVAs in terrestrial species was far from well understood. In this study, free-range chickens and domestic pigeons were selected to investigate the occurrence and tissue distribution of UVAs. Total concentrations of eleven UVAs in muscles ranged from 778 to 2874 (mean 1413 ± 666) ng/g lipid weight, which were higher than those in aquatic species worldwide. Since low UVA concentrations in local environment were previously reported, the results implied the strong accumulation of UVAs in studied species. Brain, stomach and kidney were main target organs for studied UVAs, differentiating from the strong liver sequestration in aquatic species. The mean tissue-to-muscle ratios of 1.02-4.23 further indicated the preferential accumulation of target UVAs in these tissues. The tissue-to-blood ratios of benzophenone (BP), 2-ethylhexyl salicylate (EHS) and homosalate (HMS) in brain were 370, 1207 and 52.0, respectively, implying their preferential accumulation in brain. More research is needed to characterize the toxicokinetics and tissue distribution of UVAs in terrestrial wild species, in order to further understand their potential risks.


Assuntos
Peixes , Poluentes Químicos da Água , Animais , Columbidae , Galinhas , Distribuição Tecidual , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , China
6.
Sci Total Environ ; 912: 168838, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38030011

RESUMO

Methylsiloxanes are accumulated easily in aquatic organisms and may pose potential risks. However, available information on their uptake and accumulation in terrestrial species remains scarce. This study investigated the uptake, elimination and accumulation of eight typical methylsiloxanes in hens after a single oral exposure. At 1440 min after oral exposure, methylsiloxanes were mainly accumulated in kidney, liver and ovary, representing for 29.5 %, 20.4 % and 17.4 % of the summed methylsiloxanes in all tissues, respectively; all investigated chemicals were also detected in brains and unformed yolks. We found much higher mass uptake fractions (MUFs) of cyclic (27.5-66.5 %) than linear chemicals (9.9-17.3 %) by hens via this exposure, and the observed MUFs of individual cyclic congeners were comparable to the higher values of those reported for rats or fish previously. However, the metabolic half-life (t1/2) of these chemicals in hen tissues were in the range of 1.04-57.5 h based on kinetic analyses, indicating higher clearances in comparison with those reported for fish and rats. More research is needed on the metabolic mechanism of these chemicals in hens. Our findings provide important information for further understanding of transportation and transformation of these chemicals in terrestrial organisms and the associated potential risks.


Assuntos
Galinhas , Ovário , Animais , Ratos , Feminino , Galinhas/metabolismo , Cinética , Fígado/metabolismo , Transporte Biológico
7.
Oncogene ; 43(2): 77-91, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38081962

RESUMO

Gastrointestinal (GI) cancer is a formidable malignancy with significant morbidity and mortality rates. Recent studies have shed light on the complex interplay between the nervous system and the GI system, influencing various aspects of GI tumorigenesis, such as the malignance of cancer cells, the conformation of tumor microenvironment (TME), and the resistance to chemotherapies. The discussion in this review first focused on exploring the intricate details of the biological function of the nervous system in the development of the GI tract and the progression of tumors within it. Meanwhile, the cancer cell-originated feedback regulation on the nervous system is revealed to play a crucial role in the growth and development of nerve cells within tumor tissues. This interaction is vital for understanding the complex relationship between the nervous system and GI oncogenesis. Additionally, the study identified various components within the TME that possess a significant influence on the occurrence and progression of GI cancer, including microbiota, immune cells, and fibroblasts. Moreover, we highlighted the transformation relationship between non-neuronal cells and neuronal cells during GI cancer progression, inspiring the development of strategies for nervous system-guided anti-tumor drugs. By further elucidating the deep mechanism of various neuroregulatory signals and neuronal intervention, we underlined the potential of these targeted drugs translating into effective therapies for GI cancer treatment. In summary, this review provides an overview of the mechanisms of neuromodulation and explores potential therapeutic opportunities, providing insights into the understanding and management of GI cancers.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Humanos , Neoplasias Gastrointestinais/patologia , Carcinogênese , Transformação Celular Neoplásica , Antineoplásicos/uso terapêutico , Neurônios , Microambiente Tumoral
8.
Sci Adv ; 9(47): eadg8876, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38000020

RESUMO

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas with limited treatment options, and new effective therapeutic strategies are desperately needed. We observe antiproliferative potency of genetic depletion of PTPN11 or pharmacological inhibition using the SHP2 inhibitor (SHP2i) TNO155. Our studies into the signaling response to SHP2i reveal that resistance to TNO155 is partially mediated by reduced RB function, and we therefore test the addition of a CDK4/6 inhibitor (CDK4/6i) to enhance RB activity and improve TNO155 efficacy. In combination, TNO155 attenuates the adaptive response to CDK4/6i, potentiates its antiproliferative effects, and converges on enhancement of RB activity, with greater suppression of cell cycle and inhibitor-of-apoptosis proteins, leading to deeper and more durable antitumor activity in in vitro and in vivo patient-derived models of MPNST, relative to either single agent. Overall, our study provides timely evidence to support the clinical advancement of this combination strategy in patients with MPNST and other tumors driven by loss of NF1.


Assuntos
Neurofibrossarcoma , Humanos , Transdução de Sinais , Ciclo Celular , Linhagem Celular Tumoral , Quinase 4 Dependente de Ciclina/genética
9.
Nat Commun ; 14(1): 7803, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38016956

RESUMO

Indicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle.


Assuntos
Evolução Biológica , Ecossistema , Animais , Bovinos , Alelos , Variação Genética , Sequenciamento Completo do Genoma , Polimorfismo de Nucleotídeo Único
10.
Zhongguo Gu Shang ; 36(10): 996-1004, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37881935

RESUMO

OBJECTIVE: To systematically review the clinical efficacy of total ankle arthroplasty (TAA) and ankle arthrodesis (AA) in the treatment of end-stage ankle arthritis. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched for articles published in the treatment of end-stage ankle arthritis with AA or TAA from the establishment of the database to June 2021. Bias risk tool was used to evaluate the quality of the literature. The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale(AOFAS), visual analog scale (VAS), ankle osteoarthritis scale(AOS), gait analysis (pace, frequency, stride), range of motion (ROM), satisfaction, complications and reoperation rate were analyzed by meta-analysis between AA and TAA groups by RevMan 5.3 software. RESULTS: A total of 12 articles were included, including 1 050 patients in the AA group and 3 760 patients in the TAA group, totaling 4 810 patients. Meta-analysis showed that the total score of AOFAS[MD=-3.12, 95%CI(-9.02, 2.96), P=0.31], pain score [MD=1.60, 95%CI(-1.35, 4.54), P=0.29], alignmentl score[MD=-0.04, 95%CI(-0.52, 0.44), P=0.88], VAS[MD=0.10, 95%CI(-0.49, 0.68), P=0.74], and AOS total score [MD=-4.01, 95%CI(-8.28, 0.25), P=0.06], the difference was not statistically significant (P>0.05). The score of AOFAS functional in TAA group was significantly higher than that in TAA group[MD=44.22, 95%CI(-8.01, -0.43), P=0.03]. There was no significant difference in gait analysis between the two groups (P>0.05). Postoperative ROM [MD=-4.93, 95%CI(-6.35, -3.52), P<0.000 01] and change in ROM from preoperative to follow-up[MD=-5.74, 95%CI(-8.88, -2.61), P=0.0003] between two groups, the difference was statistically significant. There was no significant difference in satisfaction between the two groups [OR=1.011, 95%CI(0.46, 2.23), P=0.98]. Complications [OR=1.61, 95%CI(1.26, 2.06), P=0.0002] and non-revision reoperation [OR=1.61, 95%CI(1.17, 2.21), P=0.003] were significantly lower in the TAA group than in the AA group. There was no significant difference in the rate of revision and reoperation(P>0.05) between the two groups [OR=1.02, 95%CI(0.37, 2.78), P=0.97]. CONCLUSION: The clinical efficacy of AA is similar to that of TAA, but the non revision reoperation rate and main surgical complications of TAA are significantly reduced. Therefore, further high-quality methodological research and long-term follow-up are needed to confirm this conclusion.


Assuntos
Artroplastia de Substituição do Tornozelo , Osteoartrite , Humanos , Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Resultado do Tratamento , Osteoartrite/cirurgia , Artrodese , Estudos Retrospectivos
11.
Vet Q ; 43(1): 1-10, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37869782

RESUMO

High-protein diets may aid weight loss and weight maintenance programs in both humans and dogs, although the effect of dietary protein levels on gut metabolism and functionality has not been studied in depth. The current study aimed to investigate the effect of an altered dietary protein:carbohydrate ratio on gut function in adult dogs by means of faecal metabolomic fingerprinting. More specifically, functional metabolic differences in dogs fed a high-protein/low-carbohydrate (HPLC) vs. low-protein/high-carbohydrate (LPHC) diet were studied by equally allocating twelve clinically healthy (6 lean and 6 obese) Beagles into two groups in a cross-over design, with each group receiving two isocaloric diets for four weeks. The faecal metabolome revealed that different protein:carbohydrate ratio can influence host and/or gut microbiome metabolism and function, while no effect was observed on the body condition. Targeted analysis demonstrated that the HPLC diet significantly increased the concentration of indole, spermidine, and pipecolinic acid and decreased the concentration of azelaic acid, D-fructose, mannose, and galactose (p < 0.05). Multivariate modelling (OPLS-DA) of the untargeted faecal metabolome revealed distinctly different metabolomic profiles following the HPLC vs. LPHC diet, with 18 altered pathways. The HPLC diet influenced amino acid and lipid metabolism, potentially promoting weight loss and immune function, whereas the LPHC diet affected carbohydrate fermentation and may promote anti-oxidative function.


Assuntos
Carboidratos , Proteínas na Dieta , Humanos , Cães , Animais , Carboidratos/análise , Proteínas na Dieta/análise , Dieta/veterinária , Redução de Peso , Metaboloma , Fezes
12.
Anim Genet ; 54(6): 731-742, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37796667

RESUMO

Over the years, indigenous cattle have not only played an essential role in securing primary food sources but have also been utilized for labor by humans, making them invaluable genetic resources. The Zhaotong cattle, a native Chinese breed from the Yunnan province, possess excellent meat quality and resistance to heat and humidity. Here we used whole genome sequencing data of 104 animals to delve into the population structure, genomic diversity and potential positive selection signals in Zhaotong cattle. The findings of this study demonstrate that the genetic composition of Zhaotong cattle was primarily derived from Chinese indicine cattle and East Asian cattle. The nucleotide diversity of Zhaotong cattle was only lower than that of Chinese indicine cattle, which was much higher than that of other taurine cattle. Genome-wide selection scans detected a series of positive candidate regions containing multiple key genes related to bone development and metabolism (CA10, GABRG3, GLDN and NOTUM), meat quality traits (ALG8, LINGO2, MYO5B, PRKG1 and GABRB1), immune response (ADA2, BMF, LEF1 and PAK6) and heat resistance (EIF2AK4 and LEF1). In summary, this study supplies essential genetic insights into the genome diversity within Zhaotong cattle and provides a foundational framework for comprehending the genetic basis of indigenous cattle breeds.


Assuntos
Genoma , Polimorfismo de Nucleotídeo Único , Humanos , Bovinos/genética , Animais , China , Genômica , Fenótipo , Proteínas Serina-Treonina Quinases/genética
13.
Stress Biol ; 3(1): 30, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37676416

RESUMO

The majority of native cattle are taurine × indicine cattle of diverse phenotypes in the central region of China. Sanjiang cattle, a typical breed in the central region, play a central role in human livelihood and have good adaptability, including resistance to dampness, heat, roughage, and disease, and are thus regarded as an important genetic resource. However, the genetic history of the successful breed remains unknown. Here, we sequenced 10 Sanjiang cattle genomes and compared them to the 70 genomes of 5 representative populations worldwide. We characterized the genomic diversity and breed formation process of Sanjiang cattle and found that Sanjiang cattle have a mixed ancestry of indicine (55.6%) and taurine (33.2%) dating to approximately 30 generations ago, which has shaped the genome of Sanjiang cattle. Through ancestral fragment inference, selective sweep and transcriptomic analysis, we identified several genes linked to lipid metabolism, immune regulation, and stress reactions across the mosaic genome of Sanjiang cattle showing an excess of taurine or indicine ancestry. Taurine ancestry might contribute to meat quality, and indicine ancestry is more conducive to adaptation to hot climate conditions, making Sanjiang cattle a valuable genetic resource for the central region of China. Our results will help us understand the evolutionary history and ancestry components of Sanjiang cattle, which will provide a reference for resource conservation and selective breeding of Chinese native cattle.

14.
Int Emerg Nurs ; 70: 101327, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37597279

RESUMO

INTRODUCTION: Optimal nutritional support is becoming increasingly important in Emergency Departments (EDs) as over half of patients presenting to ED are reported to be malnourished or at risk of malnutrition. Few studies have examined the barriers and facilitators to nutritional support in ED. AIM: To identify barriers and facilitators to providing optimal nutritional support in the ED from nurse and physician perspectives. METHODS: A cross-sectional 31-item electronic survey was developed, validated, and distributed nationally in August 2021 in China. RESULTS: A total of 1766 eligible respondents completed the survey, including 846 ED nurses and 920 ED physicians from 155 hospitals. Barriers to optimal nutrition were moderate (2.72/5 ± 0.88); the most common barrier was lack of multidisciplinary team-work support. Facilitators to support optimal nutrition were moderately high (3.58/5 ± 1.08); the most common facilitator was technical/professional support and organizational management. Respondents who received recent nutrition training and those with higher levels of nutrition knowledge (self-rated) perceived fewer barriers overall to optimal nutrition in ED (P < 0.01). CONCLUSION: Context specific barriers and facilitators both hinder and support optimal nutrition in ED. Further research is required to develop tailored interventions to address specific barriers to optimal nutrition and enhance facilitators in the ED context.

16.
J Clin Nurs ; 32(19-20): 6863-6878, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37300246

RESUMO

BACKGROUND: Current evidence shows that medical device-related pressure injury (MDRPI) has a high prevalence (10%) and incidence (12%), and much research has been done to prevent MDRPI in recent years. However, to our knowledge, there is limited systematic review available on interventions and strategies to prevent MDRPI. AIM: To synthesise research evidence on interventions and strategies used to prevent MDRPI. METHODS: This systematic review adhered to the PRISMA Guidelines. We searched six databases including Medline, CINAHL, EMBASE, Cochrane library, Web of Science and ProQuest with no restriction to year of publication. Data were extracted and checked by two authors independently. A narrative summary technique was used to describe the findings. Implementation strategies were grouped into six classifications: dissemination/implementation process/integration/capacity building/sustainability/scale-up strategies. RESULTS: Twenty-four peer-reviewed papers met the inclusion criteria, which comprised of 11 quality improvement projects and 13 original research. Types of devices included respiratory devices (non-invasive ventilation mask, CPAP/BiPAP mask, endotracheal tube), gastrointestinal/urinary devices and other devices. Interventions used included the use of dressing, hyperoxygenated fatty acids, full-face mask, training, and/or multidisciplinary education, use of special securement devices or tube holder, repositioning, application of stockinette, early removal and foam ring use. Common implementation strategies included ongoing staff education, audit and standardising documentation or guideline development. CONCLUSION: Much work on MDRPI prevention strategies has been undertaken. There were a variety of devices reported, however, it is evident that higher quality research is needed. RELEVANCE TO CLINICAL PRACTICE: Current evidence shows that interventions including use of dressing or special securement device, repositioning, and training/multidisciplinary education can be beneficial for MDRPI prevention. High-quality research, such as randomised controlled trials are needed to test the effectiveness of the interventions and their implementation strategies. No patient or public contribution.


Assuntos
Lesão por Pressão , Humanos , Adulto , Lesão por Pressão/etiologia , Lesão por Pressão/prevenção & controle , Bandagens
17.
bioRxiv ; 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37205414

RESUMO

Background: Major depressive disorder (MDD), along with related mood disorders, is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels of mood disorders, stress-mediated disruptions in brain function that precipitate these illnesses remain elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with depressive symptoms, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding precise roles for serotonin in the precipitation of mood disorders. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this phenomenon has not yet been explored following stress and/or AD exposures. Methods: We employed a combination of genome-wide and biochemical analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress to examine the impact of stress exposures on H3K4me3Q5ser dynamics, as well as associations between the mark and stress-induced gene expression. We additionally assessed stress-induced regulation of H3K4me3Q5ser following AD exposures, and employed viral-mediated gene therapy to reduce H3K4me3Q5ser levels in DRN and examine the impact on stress-associated gene expression and behavior. Results: We found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity. Chronically stressed mice displayed dysregulated H3K4me3Q5ser dynamics in DRN, with both AD- and viral-mediated disruption of these dynamics proving sufficient to rescue stress-mediated gene expression and behavior. Conclusions: These findings establish a neurotransmission-independent role for serotonin in stress-/AD-associated transcriptional and behavioral plasticity in DRN.

18.
Neuro Oncol ; 25(11): 2044-2057, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37246765

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX). METHODS: Genomic analysis was performed on all PDX-tumor pairs. Selected PDX were harvested for assembly into 3D microtissues. Based on prior work in our labs, we evaluated drugs (trabectedin, olaparib, and mirdametinib) ex vivo and in vivo. For 3D microtissue studies, cell viability was the endpoint as assessed by Zeiss Axio Observer. For PDX drug studies, tumor volume was measured twice weekly. Bulk RNA sequencing was performed to identify pathways enriched in cells. RESULTS: We developed 13 NF1-associated MPNST-PDX and identified mutations or structural abnormalities in NF1 (100%), SUZ12 (85%), EED (15%), TP53 (15%), CDKN2A (85%), and chromosome 8 gain (77%). We successfully assembled PDX into 3D microtissues, categorized as robust (>90% viability at 48 h), good (>50%), or unusable (<50%). We evaluated drug response to "robust" or "good" microtissues, namely MN-2, JH-2-002, JH-2-079-c, and WU-225. Drug response ex vivo predicted drug response in vivo, and enhanced drug effects were observed in select models. CONCLUSIONS: These data support the successful establishment of a novel 3D platform for drug discovery and MPNST biology exploration in a system representative of the human condition.


Assuntos
Neoplasias de Bainha Neural , Neurofibromatose 1 , Neurofibrossarcoma , Humanos , Neurofibrossarcoma/patologia , Medicina de Precisão , Neurofibromatose 1/patologia , Neoplasias de Bainha Neural/patologia , Mutação
19.
Funct Plant Biol ; 50(7): 559-570, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37211614

RESUMO

Knowledge of the ionome of plant organs helps us understand a plant's nutritional status. However, the ionome of Macadamia (Proteaceae), which is an important nut-producing tree, remains unknown. We aimed to characterise the allocation of biomass and nutrient-partitioning patterns in three macadamia genotypes. We excavated 15 productive trees (three cultivars at 21years of age; two cultivars at 16years of age) in an orchard. Biomass, nutrient concentrations, and contents of roots, stems, branches, and leaves were analysed. Dry weight of roots, stems, branches and leaves accounted for 14-20%, 19-30%, 36-52%, and 12-18% of total plant weight, respectively. No significant difference was found in the total biomass among the cultivars at the same age. Compared with most crop plants, macadamia had low phosphorus (P) concentrations in all organs (<1gkg-1 ), and low leaf zinc (Zn) concentration (8mgkg-1 ). In contrast, macadamia accumulated large amounts of manganese (Mn), with a 20-fold higher leaf Mn concentration than what is considered sufficient for crop plants. Leaves exhibited the highest nutrient concentrations, except for iron and Zn, which exhibited the highest concentrations in roots. The organ-specific ionomics of Macadamia is characterised by low P and high Mn concentrations, associated with adaptation to P-impoverished habitats.


Assuntos
Macadamia , Proteaceae , Manganês , Biomassa , Plantas , Árvores , Fósforo
20.
bioRxiv ; 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36993231

RESUMO

Recent advances in protein engineering have provided a wealth of methods that allow for the site-specific manipulation of proteins in vitro and in cells. However, the efforts to expand these toolkits for use in live animals has been limited. Here, we report a new method for the semi-synthesis of site-specifically modified and chemically defined proteins in live animals. Importantly, we illustrate the usefulness of this methodology in the context of a challenging, chromatin bound N-terminal histone tail within rodent postmitotic neurons located in ventral striatum (Nucleus Accumbens/NAc). This approach provides the field with a precise and broadly applicable methodology for manipulating histones in vivo, thereby serving as a unique template towards examining chromatin phenomena that may mediate transcriptomic and physiological plasticity within mammals.

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