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1.
PLoS Genet ; 20(6): e1011154, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38900713

RESUMO

Lager yeasts are limited to a few strains worldwide, imposing restrictions on flavour and aroma diversity and hindering our understanding of the complex evolutionary mechanisms during yeast domestication. The recent finding of diverse S. eubayanus lineages from Patagonia offers potential for generating new lager yeasts with different flavour profiles. Here, we leverage the natural genetic diversity of S. eubayanus and expand the lager yeast repertoire by including three distinct Patagonian S. eubayanus lineages. We used experimental evolution and selection on desirable traits to enhance the fermentation profiles of novel S. cerevisiae x S. eubayanus hybrids. Our analyses reveal an intricate interplay of pre-existing diversity, selection on species-specific mitochondria, de-novo mutations, and gene copy variations in sugar metabolism genes, resulting in high ethanol production and unique aroma profiles. Hybrids with S. eubayanus mitochondria exhibited greater evolutionary potential and superior fitness post-evolution, analogous to commercial lager hybrids. Using genome-wide screens of the parental subgenomes, we identified genetic changes in IRA2, IMA1, and MALX genes that influence maltose metabolism, and increase glycolytic flux and sugar consumption in the evolved hybrids. Functional validation and transcriptome analyses confirmed increased maltose-related gene expression, influencing greater maltotriose consumption in evolved hybrids. This study demonstrates the potential for generating industrially viable lager yeast hybrids from wild Patagonian strains. Our hybridization, evolution, and mitochondrial selection approach produced hybrids with high fermentation capacity and expands lager beer brewing options.


Assuntos
Cerveja , Fermentação , Hibridização Genética , Saccharomyces cerevisiae , Cerveja/microbiologia , Fermentação/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces/genética , Saccharomyces/metabolismo , Etanol/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Genoma Fúngico , Evolução Molecular , Variação Genética , Maltose/metabolismo , Mutação
2.
Ecol Evol ; 14(3): e10901, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435006

RESUMO

Worldwide climate-driven shifts in the distribution of species is of special concern when it involves habitat-forming species. In the coastal environment, large Laminarian algae-kelps-form key coastal ecosystems that support complex and diverse food webs. Among kelps, Macrocystis pyrifera is the most widely distributed habitat-forming species and provides essential ecosystem services. This study aimed to establish the main drivers of future distributional changes on a global scale and use them to predict future habitat suitability. Using species distribution models (SDM), we examined the changes in global distribution of M. pyrifera under different emission scenarios with a focus on the Southeast Pacific shores. To constrain the drivers of our simulations to the most important factors controlling kelp forest distribution across spatial scales, we explored a suite of environmental variables and validated the predictions derived from the SDMs. Minimum sea surface temperature was the single most important variable explaining the global distribution of suitable habitat for M. pyrifera. Under different climate change scenarios, we always observed a decrease of suitable habitat at low latitudes, while an increase was detected in other regions, mostly at high latitudes. Along the Southeast Pacific, we observed an upper range contraction of -17.08° S of latitude for 2090-2100 under the RCP8.5 scenario, implying a loss of habitat suitability throughout the coast of Peru and poleward to -27.83° S in Chile. Along the area of Northern Chile where a complete habitat loss is predicted by our model, natural stands are under heavy exploitation. The loss of habitat suitability will take place worldwide: Significant impacts on marine biodiversity and ecosystem functioning are likely. Furthermore, changes in habitat suitability are a harbinger of massive impacts in the socio-ecological systems of the Southeast Pacific.

3.
Cureus ; 16(1): e52977, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38406131

RESUMO

Objective This retrospective study aims to present the audiologic outcomes of patients aged 18 years and above who underwent treatment for sudden sensorineural hearing loss (SSNHL) at the tertiary Hospital Central Sur Petróleos Mexicanos in Mexico City, Mexico, between January 2000 and December 2015. Main outcome measures The main outcome measures were patient demographics (age, sex, comorbidities) time from symptom onset to diagnosis and treatment initiation, initial threshold, treatment details (type, dosage, duration), adverse effects, audiometry at diagnosis and at the end of treatment, follow-up duration, and pure-tone average. Results A total of 72 patients were included, with a mean follow-up duration of four months. Comorbidities such as type 2 diabetes mellitus, hypertension, and hypertriglyceridemia were observed in a significant portion of patients. However, these conditions and the use of salvage therapy and adjuvant drugs did not impact hearing recovery. A longer delay from symptom onset to medical attention was associated with a lower gain in decibels (p=0.307). Diabetic patients who received steroid treatment showed a significant gain of at least 15 dB, indicating the greatest benefit in this subgroup. Conclusions Adjuvant drugs may be unnecessary and ineffective in treating SSNHL. Metabolic disorders may be linked to the development of SSNHL. Steroid treatment is the only effective therapeutic option for improving hearing recovery in diabetic patients. Early initiation of treatment after symptom onset is crucial for maximizing auditory recovery.

4.
Radiother Oncol ; 190: 110049, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072365

RESUMO

BACKGROUND AND PURPOSE: Immunotherapy is actively explored in glioblastoma (GBM) to improve patient prognosis. Tumor-associated macrophages (TAMs) are abundant in GBM and harnessing their function for anti-tumor immunity is of interest. They are plastic cells that are influenced by the tumor microenvironment, by radio-chemotherapy and by their own phagocytic activity. Indeed, the engulfment of necrotic cells promotes pro-inflammatory (and anti-tumoral) functions while the engulfment of apoptotic cells promotes anti-inflammatory (and pro-tumoral) functions through efferocytosis. MATERIALS AND METHODS: To model the effect of radio-chemotherapy on the GBM microenvironment, we exposed human macrophages to supernatant of treated GBM cells in vitro. Macrophages were derived from human monocytes and GBM cells from patient-resected tumors. GBM cells were exposed to therapeutically relevant doses of irradiation and chemotherapy. Apoptosis and phagocytic activity were assessed by flow cytometry. RESULTS: The phagocytic activity of macrophages was increased, and it was correlated with the proportion of apoptotic GBM cells producing the supernatant. Whether uptake of apoptotic tumor cells could occur would depend upon the expression of efferocytosis-associated receptors. Indeed, we showed that efferocytosis-associated receptors, such as AXL, were upregulated. CONCLUSIONS AND PERSPECTIVES: We showed that macrophage phagocytic activity increased when exposed to supernatant from GBM cells treated by radio-chemotherapy. However, as efferocytosis-associated receptors were up-regulated, this effect could be deleterious for the anti-GBM immune response. We speculate that by inducing GBM cell apoptosis in parallel to an increase in efferocytosis receptor expression, the impact of radio-chemotherapy on phagocytic activity could promote anti-inflammatory and pro-tumoral TAM functions.


Assuntos
Glioblastoma , Humanos , Glioblastoma/patologia , Macrófagos , Fagocitose , Apoptose , Anti-Inflamatórios/metabolismo , Microambiente Tumoral
5.
Front Genet ; 14: 1304974, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090153

RESUMO

In response to inequality in access to genomics research, efforts are underway to include underrepresented minorities, but explicit (and enforcing) guidelines are mostly targeted toward the Global North. In this work, we elaborate on the need to return scientific results to indigenous communities, reporting the actions we have taken in a recent genomic study with Mapuche communities in Chile. Our approach acknowledged the social dynamics perpetuating colonial hierarchies. We framed genetic results to empower indigenous knowledge and communities' history and identities. A fundamental step in our strategy has been sharing the results with the communities before publishing the scientific paper, which allowed us to incorporate community perspectives. We faced the challenge of translating genetic concepts like admixture, emphasizing the distinction between identity and biology. To reach a broad and diverse audience, we disseminated the study results to single community members, cultural representatives, and high schools, highlighting the importance of the history of the region before the European contact. To facilitate results dissemination, we prepared didactic material and a report in Spanish written in non-specialized language, targeting a wider Latin American readership. This work illustrates the benefits of discussing scientific findings with indigenous communities, demonstrating that a collaborative and culturally sensitive approach fosters knowledge sharing and community empowerment and challenges power dynamics in genetic research. Bridging the gap between academia and indigenous communities promotes equity and inclusion in scientific endeavors.

6.
Front Vet Sci ; 10: 1271240, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869492

RESUMO

The modulation of inflammation is pivotal for uterine homeostasis. Here we evaluated the effect of the oestrus cycle on the expression of pro-inflammatory and anti-inflammatory markers in a cellular model of induced fibrosis. Mare endometrial stromal cells isolated from follicular or mid-luteal phase were primed with 10 ng/mL of TGFß alone or in combination with either IL1ß, IL6, or TNFα (10 ng/mL each) or all together for 24 h. Control cells were not primed. Messenger and miRNA expression were analyzed using real-time quantitative PCR (RT-qPCR). Cells in the follicular phase primed with pro-inflammatory cytokines showed higher expression of collagen-related genes (CTGF, COL1A1, COL3A1, and TIMP1) and mesenchymal marker (SLUG, VIM, CDH2, and CDH11) genes; p < 0.05. Cells primed during the mid-luteal overexpressed genes associated with extracellular matrix, processing, and prostaglandin E synthase (MMP2, MMP9, PGR, TIMP2, and PTGES; p < 0.05). There was a notable upregulation of pro-fibrotic miRNAs (miR17, miR21, and miR433) in the follicular phase when the cells were exposed to TGFß + IL1ß, TGFß + IL6 or TGFß + IL1ß + IL6 + TNFα. Conversely, in cells from the mid-luteal phase, the treatments either did not or diminished the expression of the same miRNAs. On the contrary, the anti-fibrotic miRNAs (miR26a, miR29b, miR29c, miR145, miR378, and mir488) were not upregulated with treatments in the follicular phase. Rather, they were overexpressed in cells from the mid-luteal phase, with the highest regulation observed in TGFß + IL1ß + IL6 + TNFα treatment groups. These miRNAs were also analyzed in the extracellular vesicles secreted by the cells. A similar trend as seen with cellular miRNAs was noted, where anti-fibrotic miRNAs were downregulated in the follicular phase, while notably elevated pro-fibrotic miRNAs were observed in extracellular vesicles originating from the follicular phase. Pro-inflammatory cytokines may amplify the TGFß signal in the follicular phase resulting in significant upregulation of extracellular matrix-related genes, an imbalance in the metalloproteinases, downregulation of estrogen receptors, and upregulation of pro-fibrotic factors. Conversely, in the luteal phase, there is a protective role mediated primarily through an increase in anti-fibrotic miRNAs, a decrease in SMAD2 phosphorylation, and reduced expression of fibrosis-related genes.

7.
iScience ; 26(9): 107644, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37701811

RESUMO

The Miocene was a key time in the evolution of African ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here, we report the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique. We provide the first 1) radiometric ages of the Mazamba Formation, 2) reconstructions of paleovegetation in the region based on pedogenic carbonates and fossil wood, and 3) descriptions of fossil teeth. Gorongosa is unique in the East African Rift in combining marine invertebrates, marine vertebrates, reptiles, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossils including new species.

8.
Sci Rep ; 13(1): 13839, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620368

RESUMO

Y chromosome markers can shed light on male-specific population dynamics but for many species no such markers have been discovered and are available yet, despite the potential for recovering Y-linked loci from available genome sequences. Here, we investigated how effective available bioinformatic tools are in recovering informative Y chromosome microsatellites from whole genome sequence data. In order to do so, we initially explored a large dataset of whole genome sequences comprising individuals at various coverages belonging to different species of baboons (genus: Papio) using Y chromosome references belonging to the same genus and more distantly related species (Macaca mulatta). We then further tested this approach by recovering Y-STRs from available Theropithecus gelada genomes using Papio and Macaca Y chromosome as reference sequences. Identified loci were validated in silico by a) comparing within-species relationships of Y chromosome lineages and b) genotyping male individuals in available pedigrees. Each STR was selected not to extend in its variable region beyond 100 base pairs, so that loci can be developed for PCR-based genotyping of non-invasive DNA samples. In addition to assembling a first set of Papio and Theropithecus Y-specific microsatellite markers, we released TYpeSTeR, an easy-to-use script to identify and genotype Y chromosome STRs using population genomic data which can be modulated according to available male reference genomes and genomic data, making it widely applicable across taxa.


Assuntos
Metagenômica , Theropithecus , Humanos , Masculino , Animais , Papio , Macaca mulatta , Repetições de Microssatélites/genética
9.
Cureus ; 15(6): e40329, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37448424

RESUMO

Pubis osteomyelitis is an uncommon disease, accounting for less than 1% of all bone infections. It occurs secondarily to hematogenous bacterial planting or direct inoculation. Clinically, it presents with intense acute pubic pain, limited mobility, and high fever, so it is rarely suspected initially. Its diagnosis can be easily confused with pubalgia, that do not respond to treatment. We present the case of a 17-year-old patient who sought consultation for three weeks of coxalgia associated with general discomfort and fever. Following a laboratory and imageological study, the diagnosis of acute pubis osteomyelitis was determined, which required surgical intervention and a subsequent pharmacological therapy for six weeks.

10.
Curr Biol ; 33(13): 2602-2615.e5, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37279753

RESUMO

The southernmost regions of South America harbor some of the earliest evidence of human presence in the Americas. However, connections with the rest of the continent and the contextualization of present-day indigenous ancestries remain poorly resolved. In this study, we analyze the genetic ancestry of one of the largest indigenous groups in South America: the Mapuche. We generate genome-wide data from 64 participants from three Mapuche populations in Southern Chile: Pehuenche, Lafkenche, and Huilliche. Broadly, we describe three main ancestry blocks with a common origin, which characterize the Southern Cone, the Central Andes, and Amazonia. Within the Southern Cone, ancestors of the Mapuche lineages differentiated from those of the Far South during the Middle Holocene and did not experience further migration waves from the north. We find that the deep genetic split between the Central and Southern Andes is followed by instances of gene flow, which may have accompanied the southward spread of cultural traits from the Central Andes, including crops and loanwords from Quechua into Mapudungun (the language of the Mapuche). Finally, we report close genetic relatedness between the three populations analyzed, with the Huilliche characterized additionally by intense recent exchanges with the Far South. Our findings add new perspectives on the genetic (pre)history of South America, from the first settlement through to the present-day indigenous presence. Follow-up fieldwork took these results back to the indigenous communities to contextualize the genetic narrative alongside indigenous knowledge and perspectives. VIDEO ABSTRACT.


Assuntos
Fluxo Gênico , Grupos Populacionais , Humanos , Chile , Peru , Genética Populacional
11.
World J Transplant ; 12(7): 142-156, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36051452

RESUMO

Cardiovascular diseases (CVD) form a principal consideration in patients with end-stage liver disease (ESLD) undergoing evaluation for liver transplant (LT) with prognostic implications in the peri- and post-transplant periods. As the predominant etiology of ESLD continues to evolve, addressing CVD in these patients has become increasingly relevant. Likewise, as the number of LTs increase by the year, the proportion of older adults on the waiting list with competing comorbidities increase, and the demographics of LT candidates evolve with parallel increases in their CVD risk profiles. The primary goal of cardiac risk assessment is to preemptively reduce the risk of cardiovascular morbidity and mortality that may arise from hemodynamic stress in the peri- and post-transplant periods. The complex hemodynamics shared by ESLD patients in the pre-transplant period with adverse cardiovascular events occurring in only some of these recipients continue to challenge currently available guidelines and their uniform applicability. This review focusses on cardiac assessment of LT candidates in a stepwise manner with special emphasis on preoperative patient optimization. We hope that this will reinforce the importance of cardiovascular optimization prior to LT, prevent futile LT in those with advanced CVD beyond the stage of optimization, and thereby use the finite resources prudently.

12.
Front Psychol ; 13: 934600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092118

RESUMO

Pre and perinatal administration of Tetrahydrocannabinol (THC) in rodents and their offspring has many effects that have been studied using different methods that have not been integrated using quantitative methods. The effect of THC administration on behavior can be better understood by meta-analytic techniques. We examined whether there is an overall effect on the behavior of the offspring when THC is administered to mothers. Eligibility criteria included experiments using an experimental design with a control group without THC, in which THC is administered to mothers during pregnancy and lactation in rodents, and in which at least one type of behavioral (locomotor, emotional or cognitive) measurement in the offspring was implemented. Cohen's d was obtained for each study, then each individual study was weighted, and moderator analysis was performed. Analysis was performed using fixed and random effect models, and the heterogeneity was assessed by calculating Qb, I 2 and the prediction interval. Furthermore, 3 sub-meta-analyses were carried out according to the type of behavior. The general analysis determined a low weighted effect size of THC on the behavior of the offspring, moderated by type of rat strain. The sub-meta-analyses showed a medium effect for cognitive effects of THC in the offspring, and a low effect on locomotor activity and emotional behavior. In addition, publication bias was not detected. More research is needed to contribute to the understanding of the effect of THC exposure on offspring.

13.
Internet Interv ; 28: 100532, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35646607

RESUMO

Introduction: Personality disorders (PD) have a serious impact on the lives of individuals who suffer from them and those around them. It is common for family members to experience high levels of burden, anxiety, and depression, and deterioration in their quality of life. It is curious that few interventions have been developed for family members of people with PD. However, Family Connections (FC) (Hoffman and Fruzzetti, 2005) is the most empirically supported intervention for family members of people with Borderline Personality Disorder (BPD). Aim: The aim of this study is to explore the effectiveness of online vs face-to-face FC. Given the current social constraints resulting from SARS-CoV-2, interventions have been delivered online and modified. Method: This was a non-randomized pilot study with a pre-post evaluation and two conditions: The sample consisted of 45 family members distributed in two conditions: FC face-to-face (20) performed by groups before the pandemic, and FC online (25), performed by groups during the pandemic. All participants completed the evaluation protocol before and after the intervention. Results: There is a statistically significant improvement in levels of burden (η 2 = 0.471), depression, anxiety, and stress (η 2 = 0.279), family empowerment (η 2 = 0.243), family functioning (η 2 = 0.345), and quality of life (µ2 η 2 = 0.237). There were no differences based on the application format burden (η 2 = 0.134); depression, anxiety, and stress (η 2 = 0.087); family empowerment (η 2 = 0,27), family functioning (η 2 = 0.219); and quality of life (η 2 = 0.006), respectively). Conclusions: This study provides relevant data about the possibility of implementing an intervention in a sample of family members of people with PD in an online format without losing its effectiveness. During the pandemic, and despite the initial reluctance of family members and the therapists to carry out the interventions online, this work shows the effectiveness of the results and the satisfaction of the family members. These results are particularly relevant in a pandemic context, where there was no possibility of providing help in other ways. All of this represents a great step forward in terms of providing psychological treatment.

14.
BMC Ecol Evol ; 22(1): 44, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410131

RESUMO

BACKGROUND: Gorongosa National Park in Mozambique hosts a large population of baboons, numbering over 200 troops. Gorongosa baboons have been tentatively identified as part of Papio ursinus on the basis of previous limited morphological analysis and a handful of mitochondrial DNA sequences. However, a recent morphological and morphometric analysis of Gorongosa baboons pinpointed the occurrence of several traits intermediate between P. ursinus and P. cynocephalus, leaving open the possibility of past and/or ongoing gene flow in the baboon population of Gorongosa National Park. In order to investigate the evolutionary history of baboons in Gorongosa, we generated high and low coverage whole genome sequence data of Gorongosa baboons and compared it to available Papio genomes. RESULTS: We confirmed that P. ursinus is the species closest to Gorongosa baboons. However, the Gorongosa baboon genomes share more derived alleles with P. cynocephalus than P. ursinus does, but no recent gene flow between P. ursinus and P. cynocephalus was detected when available Papio genomes were analyzed. Our results, based on the analysis of autosomal, mitochondrial and Y chromosome data, suggest complex, possibly male-biased, gene flow between Gorongosa baboons and P. cynocephalus, hinting to direct or indirect contributions from baboons belonging to the "northern" Papio clade, and signal the presence of population structure within P. ursinus. CONCLUSIONS: The analysis of genome data generated from baboon samples collected in central Mozambique highlighted a complex set of evolutionary relationships with other baboons. Our results provided new insights in the population dynamics that have shaped baboon diversity.


Assuntos
Evolução Biológica , Papio ursinus , Alelos , Animais , Masculino , Moçambique , Papio/genética , Papio ursinus/anatomia & histologia
15.
Neurobiol Stress ; 17: 100440, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35252485

RESUMO

Stress-related disorders display differences at multiple levels according to sex. While most studies have been conducted in male rodents, less is known about comparable outcomes in females. In this study, we found that the chronic restraint stress model (2.5 h/day for 14 days) triggers different somatic responses in male and female adult rats. Chronic restraint produced a loss in sucrose preference and novel location preference in male rats. However, chronic restraint failed to produce loss of sucrose preference in females, while it improved spatial performance. We then characterized the molecular responses associated with these behaviors in the hippocampus, comparing the dorsal and ventral poles. Notably, sex- and hippocampal pole-specific transcriptional signatures were observed, along with a significant concordance between the female ventral and male dorsal profiles. Functional enrichment analysis revealed both shared and specific terms associated with each pole and sex. By looking into signaling pathways that were associated with these terms, we found an ample array of sex differences in the dorsal and, to a lesser extent, in the ventral hippocampus. These differences were mainly present in synaptic TrkB signaling, Akt pathway, and glutamatergic receptors. Unexpectedly, the effects of stress on these pathways were rather minimal and mostly dissociated from the sex-specific behavioral outcomes. Our study suggests that female rats are resilient and males susceptible to the restraint stress exposure in the sucrose preference and object location tests, while the activity of canonical signaling pathways is primarily determined by sex rather than stress in the dorsal and ventral hippocampus.

18.
Cranio ; 40(2): 166-173, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31726950

RESUMO

Objective: Painful post-traumatic trigeminal neuropathy (PTTN) is a clinical pain syndrome that occurs due to injuries to the peripheral branches of the trigeminal nerve and is characterized by a deep burning pain and accompanied by positive and negative neurological signs. In patients with recalcitrant PTTN, the sympathetic nervous system is a potential therapeutic target. The aim of this study was to investigate the therapeutic response of PTTN patients to pulsed radiofrequency treatment (PRF) of the superior cervical sympathetic ganglion (SCG).Methods: Thirty-five patients with PTTN who had a history of severe disabling facial neuropathic pain underwent PRF of the SCG under a new lateral fluoroscopic approach.Results: The patients' pain intensity post-PRF was 3.94 (± 3.11), compared with 8.82 (± 1.27) pre-PRF (p < 0.001).Conclusion: PRF of the SCG could be an effective method to treat chronic PTTN.


Assuntos
Tratamento por Radiofrequência Pulsada , Traumatismos do Nervo Trigêmeo , Neuralgia do Trigêmeo , Humanos , Dor , Tratamento por Radiofrequência Pulsada/métodos , Gânglio Cervical Superior , Resultado do Tratamento , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/terapia
19.
Brain Res ; 1775: 147727, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34788638

RESUMO

BACKGROUND: Our understanding of how balance control responds to levodopa over the course of a single day in people with Parkinson's disease (PD) is limited with the majority of studies focused on isolated comparisons of ON vs. OFF levodopa medication. OBJECTIVE: To evaluate the temporal dynamics of postural control following the first levodopa dose of the day during a challenging standing task in a group of people with PD. METHODS: Changes in postural control were evaluated by monitoring cortical activity (covering frontal, motor, parietal and occipital areas), body sway parameters (force platform), and lower limb muscle activity (tibialis anterior and gastrocnemius medialis) in 15 individuals with PD during a semi-tandem standing task. Participants were assessed during two 60 second trials every 30 minutes (ON-30 ON-60 etc.) for 3 hours after the first matinal dose (ON-180). RESULTS: Compared to when tested OFF-medication, cortical activity was increased across all four regions from ON-60 to ON-120 with early increases in alpha and beta band activity observed at ON-30. Levodopa was associated with increased gastrocnemius medialis activity (ON-30 to ON-120) and ankle co-contraction (ON-60 to ON-120). Changes in body sway outcomes (particularly in the anterior-posterior direction) were evident from ON-60 to ON-120. CONCLUSIONS: Our results reveal a 60-minute window within which postural control outcomes may be obtained that are different compared to OFF-state and remain stable (from 60-minutes to 120-minutes after levodopa intake). Identifying a window of opportunity for measurement when individuals are optimally medicated is important for observations in a clinical and research setting.


Assuntos
Antiparkinsonianos/administração & dosagem , Córtex Cerebral/efeitos dos fármacos , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Equilíbrio Postural/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Equilíbrio Postural/fisiologia
20.
ACS Chem Neurosci ; 12(16): 2981-3001, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34339164

RESUMO

We explored sex-biased effects of the primary stress glucocorticoid hormone corticosterone on the miRNA expression profile in the rat hippocampus. Adult adrenalectomized (ADX) female and male rats received a single corticosterone (10 mg/kg) or vehicle injection, and after 6 h, hippocampi were collected for miRNA, mRNA, and Western blot analyses. miRNA profiling microarrays showed a basal sex-biased miRNA profile in ADX rat hippocampi. Additionally, acute corticosterone administration triggered a sex-biased differential expression of miRNAs derived from genes located in several chromosomes and clusters on the X and 6 chromosomes. Putative promoter analysis unveiled that most corticosterone-responsive miRNA genes contained motifs for either direct or indirect glucocorticoid actions in both sexes. The evaluation of transcription factors indicated that almost 50% of miRNA genes sensitive to corticosterone in both sexes was under glucocorticoid receptor regulation. Transcription factor-miRNA regulatory network analyses identified several transcription factors that regulate, activate, or repress miRNA expression. Validated target mRNA analysis of corticosterone-responsive miRNAs showed a more complex miRNA-mRNA interaction network in males compared to females. Enrichment analysis revealed that several hippocampal-relevant pathways were affected in both sexes, such as neurogenesis and neurotrophin signaling. The evaluation of selected miRNA targets from these pathways displayed a strong sex difference in the hippocampus of ADX-vehicle rats. Corticosterone treatment did not change the levels of the miRNA targets and their corresponding tested proteins. Our data indicate that corticosterone exerts a sex-biased effect on hippocampal miRNA expression, which may engage in sculpting the basal sex differences observed at higher levels of hippocampal functioning.


Assuntos
Corticosterona , MicroRNAs , Adrenalectomia , Animais , Corticosterona/farmacologia , Feminino , Hipocampo/metabolismo , Masculino , MicroRNAs/genética , Ratos , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
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