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1.
Cell ; 186(13): 2911-2928.e20, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37269832

RESUMO

Animals with complex nervous systems demand sleep for memory consolidation and synaptic remodeling. Here, we show that, although the Caenorhabditis elegans nervous system has a limited number of neurons, sleep is necessary for both processes. In addition, it is unclear if, in any system, sleep collaborates with experience to alter synapses between specific neurons and whether this ultimately affects behavior. C. elegans neurons have defined connections and well-described contributions to behavior. We show that spaced odor-training and post-training sleep induce long-term memory. Memory consolidation, but not acquisition, requires a pair of interneurons, the AIYs, which play a role in odor-seeking behavior. In worms that consolidate memory, both sleep and odor conditioning are required to diminish inhibitory synaptic connections between the AWC chemosensory neurons and the AIYs. Thus, we demonstrate in a living organism that sleep is required for events immediately after training that drive memory consolidation and alter synaptic structures.


Assuntos
Caenorhabditis elegans , Odorantes , Animais , Caenorhabditis elegans/fisiologia , Olfato , Sono/fisiologia , Sinapses/fisiologia
2.
Proc Natl Acad Sci U S A ; 120(29): e2206837120, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37428909

RESUMO

Alluvial rivers are conveyor belts of fluid and sediment that provide a record of upstream climate and erosion on Earth, Titan, and Mars. However, many of Earth's rivers remain unsurveyed, Titan's rivers are not well resolved by current spacecraft data, and Mars' rivers are no longer active, hindering reconstructions of planetary surface conditions. To overcome these problems, we use dimensionless hydraulic geometry relations-scaling laws that relate river channel dimensions to flow and sediment transport rates-to calculate in-channel conditions using only remote sensing measurements of channel width and slope. On Earth, this offers a way to predict flow and sediment flux in rivers that lack field measurements and shows that the distinct dynamics of bedload-dominated, suspended load-dominated, and bedrock rivers give rise to distinct channel characteristics. On Mars, this approach not only predicts grain sizes at Gale Crater and Jezero Crater that overlap with those measured by the Curiosity and Perseverance rovers, it enables reconstructions of past flow conditions that are consistent with proposed long-lived hydrologic activity at both craters. On Titan, our predicted sediment fluxes to the coast of Ontario Lacus could build the lake's river delta in as little as ~1,000 y, and our scaling relationships suggest that Titan's rivers may be wider, slope more gently, and transport sediment at lower flows than rivers on Earth or Mars. Our approach provides a template for predicting channel properties remotely for alluvial rivers across Earth, along with interpreting spacecraft observations of rivers on Titan and Mars.

3.
BMC Vet Res ; 19(1): 281, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124157

RESUMO

BACKGROUND: Feline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids.  The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography. RESULTS: Both the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions. CONCLUSION: The study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.


Assuntos
Doenças do Gato , Doenças Inflamatórias Intestinais , Microbiota , Gatos , Animais , Ácidos Graxos/análise , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Ácidos Graxos Voláteis/análise , Doenças Inflamatórias Intestinais/veterinária , Fezes/microbiologia
4.
J Am Anim Hosp Assoc ; 59(6): 255-284, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37883677

RESUMO

These guidelines present a systematic approach to diagnosis, treatment, and management of allergic skin diseases in dogs and cats. The guidelines describe detailed diagnosis and treatment plans for flea allergy, food allergy, and atopy in dogs and for flea allergy, food allergy, and feline atopic skin syndrome in cats. Management of the allergic patient entails a multimodal approach with frequent and ongoing communication with the client. Obtaining a comprehensive history is crucial for diagnosis and treatment of allergic skin diseases, and the guidelines describe key questions to ask when presented with allergic canine and feline patients. Once a detailed history is obtained, a physical examination should be performed, a minimum dermatologic database collected, and treatment for secondary infection, ectoparasites, and pruritus (where indicated) initiated. The process of diagnosing and managing allergic skin disease can be prolonged and frustrating for clients. The guidelines offer recommendations and tips for client communication and when referral to a dermatologist should be considered, to improve client satisfaction and optimize patient outcomes.


Assuntos
Doenças do Gato , Dermatite Atópica , Doenças do Cão , Hipersensibilidade Alimentar , Humanos , Animais , Gatos , Cães , Dermatite Atópica/diagnóstico , Dermatite Atópica/terapia , Dermatite Atópica/veterinária , Doenças do Gato/diagnóstico , Doenças do Gato/terapia , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Prurido/terapia , Prurido/veterinária , Hipersensibilidade Alimentar/veterinária , Alérgenos
5.
Plant J ; 106(1): 245-257, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33458870

RESUMO

The maize (Zea mays) genome encodes three indole-3-glycerolphosphate synthase enzymes (IGPS1, 2, and 3) catalyzing the conversion of 1-(2-carboxyphenylamino)-l-deoxyribulose-5-phosphate to indole-3-glycerolphosphate. Three further maize enzymes (BX1, benzoxazinoneless 1; TSA, tryptophan synthase alpha subunit; and IGL, indole glycerolphosphate lyase) convert indole-3-glycerolphosphate to indole, which is released as a volatile defense signaling compound and also serves as a precursor for the biosynthesis of tryptophan and defense-related benzoxazinoids. Phylogenetic analyses showed that IGPS2 is similar to enzymes found in both monocots and dicots, whereas maize IGPS1 and IGPS3 are in monocot-specific clades. Fusions of yellow fluorescent protein with maize IGPS enzymes and indole-3-glycerolphosphate lyases were all localized in chloroplasts. In bimolecular fluorescence complementation assays, IGPS1 interacted strongly with BX1 and IGL, IGPS2 interacted primarily with TSA, and IGPS3 interacted equally with all three indole-3-glycerolphosphate lyases. Whereas IGPS1 and IGPS3 expression was induced by insect feeding, IGPS2 expression was not. Transposon insertions in IGPS1 and IGPS3 reduced the abundance of both benzoxazinoids and free indole. Spodoptera exigua (beet armyworm) larvae show improved growth on igps1 mutant maize plants. Together, these results suggest that IGPS1 and IGPS3 function mainly in the biosynthesis of defensive metabolites, whereas IGPS2 may be involved in the biosynthesis of tryptophan. This metabolic channeling is similar to, though less exclusive than, that proposed for the three maize indole-3-glycerolphosphate lyases.


Assuntos
Benzoxazinas/metabolismo , Indol-3-Glicerolfosfato Sintase/metabolismo , Indóis/metabolismo , Triptofano/metabolismo , Zea mays/metabolismo , Indol-3-Glicerolfosfato Sintase/genética
6.
Plant Physiol ; 186(1): 655-676, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33576792

RESUMO

Addressing the looming global food security crisis requires the development of high-yielding crops. In agricultural soils, deficiency in the micronutrient copper significantly decreases grain yield in wheat (Triticum aestivum), a globally important crop. In cereals, grain yield is determined by inflorescence architecture, flower fertility, grain size, and weight. Whether copper is involved in these processes, and how it is delivered to the reproductive organs is not well understood. We show that copper deficiency alters not only the grain set but also flower development in both wheat and its recognized model, Brachypodium distachyon. We then show that the Brachypodium yellow stripe-like 3 (YSL3) transporter localizes to the phloem, transports copper in frog (Xenopus laevis) oocytes, and facilitates copper delivery to reproductive organs and grains. Failure to deliver copper, but not iron, zinc, or manganese to these structures in the ysl3 CRISPR-Cas9 mutant results in delayed flowering, altered inflorescence architecture, reduced floret fertility, grain size, weight, and protein accumulation. These defects are rescued by copper supplementation and are complemented by YSL3 cDNA. This knowledge will help to devise sustainable approaches for improving grain yield in regions where soil quality is a major obstacle for crop production. Copper distribution by a phloem-localized transporter is essential for the transition to flowering, inflorescence architecture, floret fertility, size, weight, and protein accumulation in seeds.


Assuntos
Brachypodium/fisiologia , Cobre/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Plantas/genética , Sementes/crescimento & desenvolvimento , Brachypodium/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Plantas/metabolismo , Reprodução
7.
Vet Dermatol ; 32(4): 389-e111, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34033160

RESUMO

Erythema multiforme is a rare hypersensitivity reaction that is reported in several domestic animal species, and not in goats. This case report describes the clinical and histopathological features of erythema multiforme and secondary bacterial skin infection in a goat.


Un érythème polymorphe est une réaction d 'hypersensibilité rare décrite chez plusieurs espèces d'animaux domestiques mais pas chez la chèvre. Cet article décrit les données cliniques et histopathologiques d'un érythème polymorphe et d'une infection bactérienne secondaire chez une chèvre.


El eritema multiforme es una reacción de hipersensibilidad rara que se ha descrito en diversas especies de animales domésticos, pero no en cabras. Este artículo describe las características clínicas e histopatológicas de eritema multiforme e infección cutánea bacteriana secundaria en una cabra.


O eritema multiforme é uma reação de hipersensibilidade rara relatada em várias espécies de animais domésticos, e não em cabras. Este relato de caso descreve as características clínicas e histopatológicas de eritema multiforme e infecção bacteriana secundária da pele em uma cabra.


Assuntos
Eritema Multiforme , Foliculite , Doenças das Cabras , Dermatopatias Bacterianas , Animais , Eritema Multiforme/diagnóstico , Eritema Multiforme/veterinária , Foliculite/diagnóstico , Foliculite/veterinária , Doenças das Cabras/diagnóstico , Cabras , Dermatopatias Bacterianas/veterinária
8.
Vet Dermatol ; 32(2): 188-e48, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33185315

RESUMO

BACKGROUND: Lodderomyces elongisporus is a yeast with a worldwide distribution that has been reported as a cause of infection in immunocompromised humans and in a dog that had been quilled by a porcupine. OBJECTIVES: The objective of this report is to describe the clinical presentation, diagnosis and treatment of dermatitis caused by L. elongisporus in a North American porcupine (Erethizon dorsatum). ANIMAL: One wild adult male North American porcupine from New York state, USA. METHODS AND MATERIALS: The porcupine was presented for alopecia and scaling dermatitis over the caudal dorsum. Diagnostic testing included cytological evaluation, trichogram, bacterial and fungal culture, and histopathological examination of skin biopsies. RESULTS: Histopathological findings from skin specimens demonstrated mild eosinophilic perivascular-to-interstitial dermatitis with superficial dermal fibrosis, mild epidermal hyperplasia with moderate-to-marked intracorneal and intrafollicular yeast. Fungal culture with matrix-assisted laser desorption/ionization confirmed L. elongisporus as the cause of the dermatitis. The porcupine was treated with a six week course of oral itraconazole with clinical resolution. CLINICAL RELEVANCE: Infection with L. elongisporus should be included as a differential diagnosis for North American porcupines exhibiting signs of dermatitis including scaling and alopecia. This case report may be relevant for the diagnosis and treatment of porcupines with dermatitis and for animals or humans that have been quilled by a porcupine.


Assuntos
Dermatite , Doenças do Cão , Porcos-Espinhos , Doenças dos Roedores , Alopecia/veterinária , Animais , Dermatite/veterinária , Doenças do Cão/diagnóstico , Cães , Masculino , América do Norte , Saccharomycetales
9.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672907

RESUMO

HKT channels are a plant protein family involved in sodium (Na+) and potassium (K+) uptake and Na+-K+ homeostasis. Some HKTs underlie salt tolerance responses in plants, while others provide a mechanism to cope with short-term K+ shortage by allowing increased Na+ uptake under K+ starvation conditions. HKT channels present a functionally versatile family divided into two classes, mainly based on a sequence polymorphism found in the sequences underlying the selectivity filter of the first pore loop. Physiologically, most class I members function as sodium uniporters, and class II members as Na+/K+ symporters. Nevertheless, even within these two classes, there is a high functional diversity that, to date, cannot be explained at the molecular level. The high complexity is also reflected at the regulatory level. HKT expression is modulated at the level of transcription, translation, and functionality of the protein. Here, we summarize and discuss the structure and conservation of the HKT channel family from algae to angiosperms. We also outline the latest findings on gene expression and the regulation of HKT channels.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Proteínas de Plantas/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Simportadores/metabolismo , Proteínas de Transporte de Cátions/classificação , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica de Plantas , Transporte de Íons , Magnoliopsida/genética , Magnoliopsida/metabolismo , Microalgas/genética , Microalgas/metabolismo , Filogenia , Proteínas de Plantas/genética , Simportadores/classificação , Simportadores/genética
10.
Vet Anaesth Analg ; 48(2): 223-229, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33536139

RESUMO

OBJECTIVE: To collect data about the current practice of recovering horses from general anesthesia and recovery personnel safety. STUDY DESIGN: Online survey. METHODS: An online questionnaire, including questions on general demographic data, recovery drugs, modality and characteristics of equine recovery and morbidity and mortality, was designed and distributed via e-mail to equine practitioners worldwide. RESULTS: Practitioners from 22 countries completed 373 questionnaires; 53% of the participants were board-certified equine surgeons, and the remainder were board-certified anesthesiologists (18%), large animal residents (8%), general practitioners (7%), large animal interns (6%), anesthesia residents (4.5%) and veterinary technicians (1.6%). Respondents were employed by academia (58%) or private practice (42%). Of the respondents employed at a university, 93% had a board-certified anesthesiologist on staff compared with 7% of respondents employed at a private practice. Most of the respondents assist horses during recovery, with 23% assisting every recovery and 44% assisting recovery in the majority of cases. Reasons for choosing to assist horses during recovery were: orthopedic procedures (57%), neurological deficits (49%), bad health (47%), history of poor recovery (44%), foals (42%), draft breeds (30%), magnetic resonance imaging (17%) and computed tomography (16%). Unacceptable recoveries were reported by 77% of participants. Commonly reported complications during recovery with any method were: orthopedic injury (66%), myopathy (54%), skin abrasion (53%) and airway obstruction (37%). The incidences of unacceptable quality of recovery (p = 0.09) or personnel injury (p = 0.56) were not different between assisted and nonassisted recoveries; however, more equine fatalities were reported for assisted recoveries (p < 0.006). Practitioners in academia reported more unacceptable recoveries (p < 0.0007) and personnel injuries (p < 0.002) compared with those in private practice. CONCLUSIONS: The method of recovery differs among hospitals. Recovery personnel injuries associated with assisting horses during recovery are an important and previously unreported finding.


Assuntos
Anestesia Geral , Doenças dos Cavalos , Período de Recuperação da Anestesia , Anestesia Geral/veterinária , Animais , Cavalos , Inquéritos e Questionários
11.
Vet Dermatol ; 30(6): 536-e163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31441172

RESUMO

BACKGROUND: Culicoides hypersensitivity (CH), an intensely pruritic and seasonal allergic dermatitis, is a common allergic disease affecting horses worldwide. Currently, there is no validated clinical scoring system for the quantification of clinical signs associated with CH. OBJECTIVES: To (i) determine the best cut-off point of three scoring systems, (ii) test the accuracy of each system when compared to the clinical diagnosis of an experienced veterinarian and (iii) assess agreement between systems. ANIMALS: Icelandic horses (n = 20); eight with CH and 12 unaffected, from a research herd receiving no treatments for allergic dermatitis. METHODS AND MATERIALS: Lesion scores were recorded biweekly from April until September with three clinical scoring systems (A, B and C) by a single observer initially blinded to CH status. Separate logistic regression analyses for each time point were used to determine appropriate cut-offs for CH classification. Spearman's rho and Cohen's kappa were calculated to analyze correlation of scores and agreement of CH categorization between systems, respectively. RESULTS: The best allergic cut-off scores for system A, B and C were determined to be three, eight and 12, respectively. For each system median areas under the curve (>0.85) were excellent and discriminatory ability for correctly classifying CH status was strong. Excellent correlation between scores for each system (Spearman's rho > 0.96) and excellent intersystem agreement for CH categorization (kappa ≥ 0.73) were found across scoring time points. CONCLUSION AND CLINICAL IMPORTANCE: Results support the use of these scoring systems as templates for the future standardization of a CH clinical scoring system.


Assuntos
Ceratopogonidae/imunologia , Dermatite Atópica/veterinária , Doenças dos Cavalos/diagnóstico , Hipersensibilidade/veterinária , Animais , Dermatite Atópica/diagnóstico , Feminino , Doenças dos Cavalos/imunologia , Cavalos/imunologia , Hipersensibilidade/diagnóstico , Islândia , Imunoglobulina E , Mordeduras e Picadas de Insetos
12.
Neuroimage ; 89: 81-91, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24296331

RESUMO

The apolipoprotein E ε4 allele is a well established genetic risk factor for sporadic Alzheimer's disease. It is associated with structural and functional brain changes in healthy young, middle-aged and elderly subjects. In the current study, we assessed the impact of the ApoE genotype on brain macro- and microstructure, cognitive functioning and brain activity in fifty healthy young subjects (25 ApoE ε4 (ε4+) carriers and 25 non-carriers (ε4-), mean age 26.4±4.6years). We used diffusion tensor imaging (DTI) and voxel based morphometry (VBM) to assess brain structure, an extensive neuropsychological battery to test cognitive functioning and event-related functional magnetic resonance imaging (fMRI) to capture brain activity during episodic memory encoding and retrieval. ApoE ε4 carriers differed from non-carriers in fMRI activations but not in cognitive performance nor in brain micro- and macrostructure. These results suggest functional alterations in the episodic memory network that are modulated by the ε4 allele and might precede clinical or structural neurodegeneration.


Assuntos
Apolipoproteína E4/genética , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Memória Episódica , Adulto , Mapeamento Encefálico , Imagem de Tensor de Difusão , Feminino , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Adulto Jovem
13.
J Interpers Violence ; 39(11-12): 2687-2707, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38189155

RESUMO

Approximately one in five college women experience a sexual assault (SA), though a meaningful percentage of survivors do not acknowledge or label their experience as such. Research indicates that acknowledgment status is often influenced by how closely SA incidents align with the "real rape" script and degree of survivor rape myth acceptance (RMA). However, studies evaluating acknowledgment paired with other attitudes and health outcomes among survivors is sparse. The current study examined the relation between acknowledgment status, RMA, weight-related constructs, and psychological well-being among three groups of college women (N = 584): non-survivors, unacknowledged survivors, and acknowledged survivors. Findings indicate that, among survivors, acknowledged compared to unacknowledged SA is significantly associated with diminished body appreciation, self-esteem, and increased internalized weight bias, though no differences in psychological distress were found.


Assuntos
Imagem Corporal , Estupro , Autoimagem , Estudantes , Sobreviventes , Humanos , Feminino , Adulto Jovem , Estudantes/psicologia , Sobreviventes/psicologia , Estupro/psicologia , Universidades , Imagem Corporal/psicologia , Adulto , Vítimas de Crime/psicologia , Adolescente , Preconceito de Peso/psicologia , Delitos Sexuais/psicologia
14.
PLoS One ; 19(3): e0300628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517838

RESUMO

In the emerging field of whole-brain imaging at single-cell resolution, which represents one of the new frontiers to investigate the link between brain activity and behavior, the nematode Caenorhabditis elegans offers one of the most characterized models for systems neuroscience. Whole-brain recordings consist of 3D time series of volumes that need to be processed to obtain neuronal traces. Current solutions for this task are either computationally demanding or limited to specific acquisition setups. Here, we propose See Elegans, a direct programming algorithm that combines different techniques for automatic neuron segmentation and tracking without the need for the RFP channel, and we compare it with other available algorithms. While outperforming them in most cases, our solution offers a novel method to guide the identification of a subset of head neurons based on position and activity. The built-in interface allows the user to follow and manually curate each of the processing steps. See Elegans is thus a simple-to-use interface aimed at speeding up the post-processing of volumetric calcium imaging recordings while maintaining a high level of accuracy and low computational demands. (Contact: enrico.lanza@iit.it).


Assuntos
Caenorhabditis elegans , Neurônios , Animais , Neurônios/fisiologia , Caenorhabditis elegans/fisiologia , Microscopia de Fluorescência/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Algoritmos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38593404

RESUMO

The cell plasma membrane is a two-dimensional, fluid mosaic material composed of lipids and proteins that create a semipermeable barrier defining the cell from its environment. Compared with soluble proteins, the methodologies for the structural and functional characterization of membrane proteins are challenging. An emerging tool for studies of membrane proteins in mammalian systems is a "plasma membrane on a chip," also known as a supported lipid bilayer. Here, we create the "plant-membrane-on-a-chip,″ a supported bilayer made from the plant plasma membranes of Arabidopsis thaliana, Nicotiana benthamiana, or Zea mays. Membrane vesicles from protoplasts containing transgenic membrane proteins and their native lipids were incorporated into supported membranes in a defined orientation. Membrane vesicles fuse and orient systematically, where the cytoplasmic side of the membrane proteins faces the chip surface and constituents maintain mobility within the membrane plane. We use plant-membrane-on-a-chip to perform fluorescent imaging to examine protein-protein interactions and determine the protein subunit stoichiometry of FLOTILLINs. We report here that like the mammalian FLOTILLINs, FLOTILLINs expressed in Arabidopsis form a tetrameric complex in the plasma membrane. This plant-membrane-on-a-chip approach opens avenues to studies of membrane properties of plants, transport phenomena, biophysical processes, and protein-protein and protein-lipid interactions in a convenient, cell-free platform.

16.
Nat Cell Biol ; 25(6): 904-916, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37188763

RESUMO

Insulin-producing ß cells created from human pluripotent stem cells have potential as a therapy for insulin-dependent diabetes, but human pluripotent stem cell-derived islets (SC-islets) still differ from their in vivo counterparts. To better understand the state of cell types within SC-islets and identify lineage specification deficiencies, we used single-nucleus multi-omic sequencing to analyse chromatin accessibility and transcriptional profiles of SC-islets and primary human islets. Here we provide an analysis that enabled the derivation of gene lists and activity for identifying each SC-islet cell type compared with primary islets. Within SC-islets, we found that the difference between ß cells and awry enterochromaffin-like cells is a gradient of cell states rather than a stark difference in identity. Furthermore, transplantation of SC-islets in vivo improved cellular identities overtime, while long-term in vitro culture did not. Collectively, our results highlight the importance of chromatin and transcriptional landscapes during islet cell specification and maturation.


Assuntos
Insulinas , Ilhotas Pancreáticas , Células-Tronco Pluripotentes , Humanos , Multiômica , Diferenciação Celular/genética , Células-Tronco Pluripotentes/metabolismo , Cromatina/genética , Cromatina/metabolismo , Insulinas/metabolismo
17.
J Neurotrauma ; 40(23-24): 2541-2551, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37350129

RESUMO

Abstract Approximately one in three traumatic spinal cord injuries (SCIs) occurs during or shortly after the consumption of alcohol. A small number of retrospective clinical studies report variable effects of alcohol intoxication on mortality, neurological recovery, and complications after SCI. Some of these studies demonstrate a protective effect of alcohol intoxication on SCI outcomes, whereas others show an increased complication risk. Pre-clinical studies in rat, ferret, and feline SCI models report a detrimental effect of ethanol intoxication on hemorrhage, motor recovery, and biochemical markers of tissue injury. However, no studies to date have investigated the neuropathological consequences of ethanol intoxication at the time of SCI or the reciprocal effect of SCI on ethanol metabolism. Therefore, we combined a pre-clinical mouse model of acute ethanol intoxication and experimental vertebral level T9 contusion SCI to investigate their interactive effects in female mice. We first investigated the effect of SCI on ethanol metabolism and found that T9 SCI does not alter ethanol metabolism. However, we did find that isoflurane anesthesia significantly slowed ethanol metabolism independent of SCI. We also determined how acute ethanol intoxication at the time of SCI alters locomotor recovery and lesion pathology. Using the Basso Mouse Scale (BMS) and CatWalk XT Gait Analysis System, we assessed locomotor recovery for 6 weeks after injury and observed that acute ethanol intoxication at the time of injury did not alter locomotor recovery. We also found no effect of ethanol intoxication on heat hyperalgesia development. There was, however, a detrimental effect of ethanol on tissue sparing after SCI. Therefore, we conclude that acute alcohol intoxication at the time of injury may contribute to the neuropathological consequences of SCI.


Assuntos
Intoxicação Alcoólica , Alcoolismo , Traumatismos da Medula Espinal , Camundongos , Animais , Ratos , Feminino , Gatos , Intoxicação Alcoólica/complicações , Estudos Retrospectivos , Furões , Traumatismos da Medula Espinal/patologia , Etanol/efeitos adversos , Recuperação de Função Fisiológica , Medula Espinal/patologia
18.
Trans Am Clin Climatol Assoc ; 123: 242-56, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23303991

RESUMO

Based on traditional microbiological methods, namely cultivation and microscopic analyses, the vaginal microbiota (VMB) has been defined as healthy when it is predominated by hydrogen peroxide-producing Lactobacillus spp., most prominently Lactobacillis crispatus. Similarly, the VMB has been defined as bacterial vaginosis (BV) when it is predominated by Gardnerella vaginalis as well as a number of other anaerobic bacterial species. BV is associated with a distinct vaginal discharge syndrome, poor pregnancy outcomes, pelvic inflammatory disease, post-operative wound infections, and endometritis after elective abortions. Additionally, BV predisposes women to infection by HIV as well as other sexually transmitted diseases (STDs). The application of molecular techniques over the last decade to studies of the VMB has significantly advanced our understanding of its structure and variation. It is now clear that the diversity of the VMB is far more complex than previously recognized; it is comprised of many heretofore unknown bacteria in addition to those previously identified by culture. Here we describe the application of 454 pyrosequencing technology to a study of vaginal specimens from 92 women attending the New Orleans STD clinic in an effort to obtain a more precise view of how different types of "trees" (bacteria) assemble to form a recognizable "forest" (VMB). This knowledge will be useful in the design of future clinical studies that investigate the mechanisms by which the vaginal microbiome influences human health and disease.


Assuntos
Metagenoma , Sistema Urogenital/microbiologia , Vagina/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Lactobacillus/isolamento & purificação , Nova Orleans , Estudos Retrospectivos , Shigella/isolamento & purificação
19.
Am J Pharm Educ ; 86(5): 8668, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34697014

RESUMO

Objective. To assess the current practices of US schools and colleges of pharmacy pertaining to teaching legislative advocacy; the engagement of staff, faculty, postgraduates, students, and administrators in legislative advocacy partnerships and activities; and their future goals for legislative advocacy involvement by academic pharmacy institutions.Methods. An electronic survey was distributed to deans of schools and colleges of pharmacy across the United States. Respondents were asked to complete 53 items about their school's involvement in, barriers to involvement in, and relative importance of involvement in legislative advocacy. Responses were evaluated using descriptive statistics.Results. The survey accrued responses from 48 of 143 (33%) schools and colleges of pharmacy. Sixteen percent of responding schools required a course on advocacy and approximately 50% offered an advocacy elective. A majority (58.8%) of responding institutions ranked their institution's involvement in legislative advocacy high (≥7 on a scale of 1-10), and 75.8% ranked the importance of legislative advocacy in external collaboration high. A majority of institutions (60%) ranked the importance of faculty, staff, and postgraduate roles in advocacy high; however, 42.3% did not rank involvement as strongly. Fifty percent of institutions plan to expand involvement in legislative advocacy.Conclusion. Respondents highly ranked the importance of legislative advocacy. Many perceived their institution's involvement as strong and having plans to expand. Moving forward, curricula and resource allocation should be reviewed to diminish the dissonance between an institution's perception of the importance of legislative advocacy and actual implementation of legislative advocacy components.


Assuntos
Educação em Farmácia , Farmácia , Estudantes de Farmácia , Currículo , Educação em Farmácia/métodos , Humanos , Instituições Acadêmicas , Faculdades de Farmácia , Inquéritos e Questionários , Estados Unidos
20.
Poult Sci ; 101(5): 101790, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35316649

RESUMO

Ethanol is one of the most widely used and abused drugs. Following ethanol consumption, ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. In the bloodstream, ethanol is cleared from the system by the liver. The primary metabolism of ethanol uses alcohol dehydrogenase (ADH). In mammals, females appear to have higher ADH activity in liver samples than males. The purpose of the first experiment was to analyze sex differences in ADH levels following 12 d of ethanol administration (i.e., water or 2 g/kg) in male and female quail. Following the last daily treatment of ethanol, quail were euthanized, their livers were extracted, and ADH was analyzed in liver homogenate samples. Results showed that female quail had higher ADH levels, heavier livers, and a greater liver to body weight ratio than male quail. In a second experiment, we aimed to develop a blood ethanol concentration (BEC) profile for both male and female quail. Quail were administered 0.75 or 2 g/kg of ethanol and blood was collected at 0.5, 1, 2, 4, 6, 8, 12, 24 h after gavage administration. Blood ethanol concentration was analyzed using an Analox. We found that quail had a fairly rapid increase in BECs followed by a steady and slow disappearance of ethanol from the blood samples. Female quail had a lower peak of ethanol concentration and a smaller area under the curve (AUC) than male quail. The current research suggests that higher ADH levels in female quail may be responsible for increased metabolism of ethanol. In general, quail appear to eliminate ethanol more slowly than rodents. Thus, as a model, they may allow for a prolonged window with which to investigate the effects of ethanol.


Assuntos
Álcool Desidrogenase , Concentração Alcoólica no Sangue , Álcool Desidrogenase/metabolismo , Animais , Galinhas/metabolismo , Coturnix/metabolismo , Etanol/metabolismo , Feminino , Fígado/metabolismo , Masculino , Mamíferos/metabolismo , Caracteres Sexuais
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