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1.
Adv Exp Med Biol ; 1354: 25-48, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34807435

RESUMO

Precise cell-specific spatio-temporal molecular signaling cascades regulate the establishment and maintenance of pregnancy. Importantly, the mechanisms regulating uterine receptivity, conceptus apposition and adhesion to the uterine luminal epithelia/superficial glandular epithelia and, in some species, invasion into the endometrial stroma and decidualization of stromal cells, are critical prerequisite events for placentation which is essential for the appropriate regulation of feto-placental growth for the remainder of pregnancy. Dysregulation of these signaling cascades during this critical stage of pregnancy can lead to pregnancy loss, impaired growth and development of the conceptus, and alterations in the transplacental exchange of gasses and nutrients. While many of these processes are conserved across species, significant variations in the molecular mechanisms governing maternal recognition of pregnancy, conceptus implantation, and placentation exist. This review addresses the complexity of key mechanisms that are critical for the establishment and maintenance of a successful pregnancy in humans, rodents, sheep, and pigs. Improving understanding of the molecular mechanisms governing these processes is critical to enhancing the fertility and reproductive health of humans and livestock species.


Assuntos
Placentação , Roedores , Animais , Implantação do Embrião , Endométrio , Feminino , Humanos , Placenta , Gravidez , Ovinos , Suínos , Útero
2.
Braz. J. Biol. ; 81(4): 989-998, Oct.-Dec. 2021. tab, graf
Artigo em Inglês | VETINDEX | ID: vti-762622

RESUMO

This checklist of parasites of Kerodon rupestris, an endemic rodent from the Brazilian semiarid region, revealed records of 25 enteroparasite taxa comprising Cestoda (Anoplocephalidae), Trematoda, Acanthocephala and Nematoda (Ancylostomidae, Ascarididae, Heterakidae, Oxyuridae, Pharyngodonidae, Trichuridae, Capillariidae, Trichostrongylidae, and Strongyloididae), and two taxa of coccidian. Paleoparasitological and parasitological studies published until 2019 were assessed in the present study and locality information, site of infection, sample dating, and host data were summarized from each reference. Analyses of recent feces and coprolites revealed the highest species richness in the Piauí State. The chronological data corroborated that Trichuris spp. and oxyurids are part of the parasitic fauna of K. rupestris. This represents the first checklist of intestinal parasites from K. rupestris.(AU)


Este levantamento de parasitos intestinais de Kerodon rupestris, um roedor endêmico da região semiárida brasileira, revelou registros de 25 táxons de enteroparasitos compreendendo Cestoda (Anoplocephalidae), Trematoda, Acanthocephala e Nematoda (Ancylostomidae, Ascarididae, Heterakidae, Oxyuridae, Pharyngodonidae, Trichuridae, Capillariidae, Trichostrongylidae, and Strongyloididae), e dois táxons de coccídios. Os estudos paleoparasitológicos e parasitológicos publicados até 2019 foram avaliados no presente trabalho e as informações de localização, local da infecção, datação da amostra e dados do hospedeiro, foram resumidas a partir de cada referência. Análises de fezes recentes e coprólitos revelaram a maior riqueza de espécies no estado do Piauí. Os dados cronológicos corroboram que Trichuris spp. e oxiurídeos fazem parte da fauna parasitária de K. rupestris. Essa é a primeira lista de verificação de parasitos intestinais de K. rupestris.(AU)


Assuntos
Animais , Roedores/parasitologia , Helmintíase Animal , Helmintos/classificação , Biodiversidade
3.
Zootaxa ; 5057(3): 29-63, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811205

RESUMO

Six mite species of the genus Leptotrombidium Nagayo, Miyagawa, Mitamura and Imamura, 1916 and one species from each of the genera Lorillatum Nadchatram, 1963 and Trombiculindus Radford, 1948, incompletely described by Schluger et al. (1960b, 1963) from rodents and tree shrews in North Vietnam, are re-described based on type series. Lectotypes and paralectotypes have been designated for all redescribed species. Two new synonyms have been established: Leptotrombidium magnum (Schluger, 1960) (= Leptotrombidium dooleyi Nadchatram, 1970, syn. nov.; = Leptotrombidium submagnum Wang, Li and Shi, 1988, syn. nov.).


Assuntos
Trombiculidae , Animais , Roedores , Vietnã
4.
Zootaxa ; 5027(2): 175-210, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34811235

RESUMO

Nephelomys albigularis is a sigmodontine rodent of the tribe Oryzomyini distributed in the Andean forests from central Ecuador to central Peru. Although several studies recognize this species as monotypic, significant morphological variation has been reported in Peruvian populations that were not properly assessed by direct comparisons with the type series from central Ecuador. We present a preliminary review of N. albigularis with an integrative approach and emphasis on Peruvian populations. We analyzed specimens using morphological and morphometric methods, complemented with phylogenetic analyses and species delimitation using sequence data from the cytochrome-b gene. Our results reveal that N. albigularis (sensu lato) comprises two taxa: N. albigularis s.s., from the montane forests in central and southern Ecuador and northwestern Peru, and Nephelomys sp. nov. from montane forest east of the Maran River. These taxa are morphologically distinct and are separated by a genetic distance of 5.90 1.01%. Nephelomys sp. nov. differs from N. albigularis s.s. by longer rump hairs, narrow hypothenar pads, faintly bicolor tail; absent interorbital ridges, low zygomatic plates, smoothly squared posterior margin of the hard palate or with a small median postpalatal process, smoothly edged ventral margin of the external auditory meatus, and slightly angular mandibular sigmoid notches. In this work, we present a diagnosis and description of the new species of Nephelomys and discuss the role of the Maran River as a potential driver for speciation in the genus Nephelomys.


Assuntos
Arvicolinae , Roedores , Animais , Florestas , Peru , Filogenia
5.
Curr Protoc ; 1(11): e285, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34748292

RESUMO

In vivo rodent, whole peripheral nerve models are useful for studying the electrical conduction of sensory and motor fibers under normal physiological conditions as well as for assessing neurological outcomes after the application of physical alterations or pharmacological agents to the nervous system. Significant literature has focused on single-neuron and central nervous system electrophysiology protocol development. However, creation and development of in vivo whole-nerve electrophysiological recording protocols are sparse in the scientific literature. Here, detailed protocols for designing and building an in vivo whole-nerve electrophysiology system are described, including straightforward techniques to create working stimulation and recording electrodes that may be adapted to numerous study designs. Further, we include details for rodent anesthesia, surgical dissection (for the sciatic nerve), compound action potential signal optimization, data acquisition, data analyses, and troubleshooting tips. © 2021 Wiley Periodicals LLC. Basic Protocol 1: In vivo electrophysiology system wiring, hardware, and software setups Support Protocol 1: Design and 3D printing of electrophysiology base electrodes Support Protocol 2: Building needle electrodes Basic Protocol 2: Rodent anesthesia and surgery for nerve exposure Basic Protocol 3: Compound action potential recording and troubleshooting using WinWCP Basic Protocol 4: Compound action potential data analysis using WinWCP.


Assuntos
Análise de Dados , Roedores , Potenciais de Ação , Animais , Eletrofisiologia Cardíaca , Nervo Isquiático
6.
Rev Bras Parasitol Vet ; 30(4): e012721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755807

RESUMO

This study aimed to investigate the genetic diversity of Hepatozoon spp. in rodents from Valdivia, Chile. A total of 74 rodents (synanthropic n=38; wild n=36) were trapped in Valdivia. We performed conventional PCR assays for Apicomplexa organisms targeting two overlapping 18S rDNA gene fragments (600 bp and 900 bp) followed by sequencing of selected amplicons. Hepatozoon spp. occurrence was 82.43% (61/74). Twelve sequences obtained from the 600 bp and ten from the 900 bp 18S rDNA fragments were identified as Hepatozoon sp. Six sequences obtained from 18S rDNA-based overlapping PCR protocols were used for concatenated (1,400 bp) phylogenetic, haplotype and distance analyses. Hepatozoon spp. 18S rDNA concatenated sequences from the present study were detected in Oligoryzomys longicaudatus, Rattus norvegicus, Mus musculus, and Abrothrix longipilis grouped with Hepatozoon species earlier described in rodents and reptiles from Chile and Brazil. Nucleotide polymorphism of the six 18S rDNA sequences (1,400 bp) from this study, and other Chilean sequences from rodents and rodent's ticks, showed high diversity with a total of nine Chilean haplotypes. Three haplotypes from Valdivia were identified for the first time in this study, suggesting the circulation of novel haplotypes in rodents from southern Chile.


Assuntos
Eucoccidiida , Roedores , Animais , Chile , Eucoccidiida/genética , Variação Genética , Camundongos , Filogenia , RNA Ribossômico 18S/genética , Ratos
7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(7): 1266-1273, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814542

RESUMO

Objective: To explore the genetic characteristics and evolution of hantavirus carried by rodents in port area of Ningde in Fujian province in the summer of 2020. Methods: Rodents were captured in the port area of Ningde, the RNA was extracted from rodent lung tissues and detected by using specific kit. The positive samples were used for whole-genome sequencing of the virus. Bioinformatics software was used for the analysis on the similarity and genetic variation of the sequences. Results: A total of 112 rodents were captured, including 5 Rattus norvegicus and 2 Rattus flavipectus, the positive rate of hantavirus was 6.25% (7/112). By virus gene sequencing, two hantavirus complete genome sequences were obtained (named as FJ35 and FJ36, GenBank accession numbers: MW449188-MW449193). The genetic analysis results showed that the hantavirus detected in positive samples were SEOV and shared 99% nucleotide similarity with hantavirus strains LZSF21 and JX20140581 isolated from Shandong province. Phylogenetic analysis using the maximum likelihood method showed that the hantavirus detected in positive samples belonged to S3 subtype, sharing the same subtype with hantavirus strains Z37 from Zhejiang province, LZSF21 from Shandong province, and zy27 and Gongzhuling 415 from northeastern China. Compared with FJ372, the amino acid variation of N259S was observed at sites 251-264 of nucleoprotein, which might be related to antigenicity. Another variation of Q81R was observed in glycoprotein compared with SEOV 80-39 segment of coded amino acid of international reference strain, which might also cause the change in antigenicity. Conclusion: The high positive rate of hantavirus in rodents in the port area of Ningde- would increase the risk of natural human infection and epidemic in local area. The hantavirus positive rodents in this focus might be from an endemic area in Shandong. It is necessary to strengthen the imported rodent control in the port area of Ningde. The virus detected in 2 positive samples belonged to SEOV subtype Ⅲ and shared high homologies of nucleotides and amino acid sequences with the hantavirus strains in surrounding area. However, some slight variations occurred in glycoprotein and nucleoprotein amino acid sequences, which might cause changes in its antigeniity.


Assuntos
Infecções por Hantavirus , Hantavirus , Animais , China/epidemiologia , Hantavirus/genética , Infecções por Hantavirus/epidemiologia , Filogenia , RNA Viral/genética , Ratos , Roedores
8.
Curr Protoc ; 1(10): e268, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34679249

RESUMO

Sequential and cue-directed response learning in rodents have been previously shown to depend on intact striatal signaling. In particular, these behaviors rely on striatal dopamine and acetylcholine release, with an impairment of sequential response learning evident in animal models with alterations in the two systems. Here we provide a protocol for testing sequential response/response chain learning using the rodent touchscreen system. Specifically, the present protocol is designed to implement the heterogeneous sequence task, adapted from Keeler et al. (2014), in the rodent touchscreen apparatus. This task has been used previously to assess complex motor learning and response selection in mice. In the following protocol, the task is performed in touchscreen-based automated chambers with five response locations using food reinforcers to maintain performance. The sequence task requires the subject to make five nose pokes to white square stimuli appearing in five different locations sequentially from left to right. © 2021 Wiley Periodicals LLC. Basic Protocol: Implementation of the heterogeneous sequence task Support Protocol: Creation of the heterogeneous sequence task ABET II touchscreen schedule.


Assuntos
Aprendizagem , Roedores , Animais , Corpo Estriado , Camundongos
9.
Int J Mol Sci ; 22(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34639043

RESUMO

Studies have shown that bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into dermal fibroblasts to participate in skin-repairing. However, at present, little is known about how microgravity affects dermal fibroblastic differentiation of BMSCs in space. The aim of this study was to investigate the effect of simulated microgravity (SMG) on the differentiation of BMSCs into dermal fibroblasts and the related molecular mechanism. Here, using a 2D-clinostat device to simulate microgravity, we found that SMG inhibited the differentiation and suppressed the Wnt/ß-catenin signaling and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2). After upregulating the Wnt/ß-catenin signaling with lithium chloride (LiCl) treatment, we found that the effect of the differentiation was restored. Moreover, the Wnt/ß-catenin signaling was upregulated when phosphorylation of ERK1/2 was activated with tert-Butylhydroquinone (tBHQ) treatment. Taken together, our findings suggest that SMG inhibits dermal fibroblastic differentiation of BMSCs by suppressing ERK/ß-catenin signaling pathway, inferring that ERK/ß-catenin signaling pathway may act as a potential intervention target for repairing skin injury under microgravity conditions.


Assuntos
Diferenciação Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ausência de Peso , beta Catenina/metabolismo , Animais , Derme/citologia , Modelos Biológicos , Roedores , Transdução de Sinais
10.
Transl Psychiatry ; 11(1): 538, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663781

RESUMO

Early life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS). Specifically, we show that in control rats but not after MS, endogenous activity of GluK1 subunit containing KARs disinhibit LA principal neurons during activation of cortical afferents. GluK1 antagonism attenuated excitability of parvalbumin (PV)-expressing interneurons, resulting in loss of PV-dependent inhibitory control and an increase in firing of somatostatin-expressing interneurons. Inactivation of Grik1 expression locally in the adult amygdala reduced ongoing GABAergic transmission and was sufficient to produce a mild anxiety-like behavioral phenotype. Interestingly, MS and GluK1-dependent phenotypes showed similar gender specificity, being detectable in male but not female rodents. Our data identify a novel KAR-dependent mechanism for cell-type and projection-specific functional modulation of the LA GABAergic microcircuit and suggest that the loss of GluK1 KAR function contributes to anxiogenesis after ELS.


Assuntos
Experiências Adversas da Infância , Receptores de Ácido Caínico , Tonsila do Cerebelo/metabolismo , Animais , Ansiedade , Regulação para Baixo , Interneurônios/metabolismo , Masculino , Privação Materna , Ratos , Receptores de Ácido Caínico/metabolismo , Roedores/metabolismo
11.
J Vis Exp ; (176)2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34661572

RESUMO

Glutamate removal from the extracellular space by high-affinity Na+-dependent transporters is essential to ensure that the brain's intrinsic connectivity mechanisms work properly and homeostasis is maintained. The hippocampus is a unique brain structure that manages higher cognitive functions, and is the subject of several studies regarding neurologic diseases. The investigation of physiological and pathological mechanisms in rodent models can benefit from acute hippocampal slice (AHS) preparations. AHS has the advantage of providing reliable information on cell function since the cytoarchitecture and synaptic circuits are preserved. Although AHS preparations are commonly used in neurochemistry laboratories, it is possible to find some methodological differences in the literature. Considering that distinctive slice preparation protocols might change the hippocampal regions analyzed, this current protocol proposes a standard technique for obtaining transverse AHS from resected hippocampus. This simple-to-perform protocol may be used in mice and rats' experimental models and allow several ex vivo approaches investigating neurochemical dynamics (in dorsal, intermediate and ventral hippocampus) in different backgrounds (e.g., transgenic manipulations) or after in vivo manipulations (e.g., pharmacological treatments or suitable rodent models to study clinical disorders). After dissecting the hippocampus from the rodent brain, transverse slices along the septo-temporal axis (300 µm thick) were obtained. These AHS contain distinct parts of the hippocampus and were subjected to an individual neurochemical investigation (as an example: neurotransmitter transporters using their respective substrates). As the hippocampus presents a high density of excitatory synapses, and glutamate is the most important neurotransmitter in the brain, the glutamatergic system is an interesting target for in vivo observed phenomena. Thus, the current protocol provides detailed steps to explore glutamate uptake in ex vivo AHS using L-[3H]-Glutamate. Using this protocol to investigate hippocampal function may help to better understand the influence of glutamate metabolism on mechanisms of neuroprotection or neurotoxicity.


Assuntos
Ácido Glutâmico , Roedores , Animais , Hipocampo , Camundongos , Ratos , Sinapses
12.
J Vis Exp ; (175)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34633389

RESUMO

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of transplant with the potential to deliver durable heart valves capable of somatic growth with no requirement for anticoagulation. However, the immunobiology of heart valve transplants remains unexplored, highlighting the need for animal models to study this new type of transplant. Previous rat models for heterotopic aortic valve transplantation into the abdominal aorta have been described, though they are technically challenging and costly. For addressing this challenge, a renal subcapsular transplant model was developed in rodents as a practical and more straightforward method for studying heart valve transplant immunobiology. In this model, a single aortic valve leaflet is harvested and inserted into the renal subcapsular space. The kidney is easily accessible, and the transplanted tissue is securely contained in a subcapsular space that is well vascularized and can accommodate a variety of tissue sizes. Furthermore, because a single rat can provide three donor aortic leaflets and a single kidney can provide multiple sites for transplanted tissue, fewer rats are required for a given study. Here, the transplantation technique is described, providing a significant step forward in studying the transplant immunology of heart valve transplantation.


Assuntos
Transplante de Coração , Roedores , Animais , Valva Aórtica/cirurgia , Modelos Animais , Ratos , Transplante Heterotópico
13.
J Agric Food Chem ; 69(44): 13246-13254, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34702032

RESUMO

There is limited information available about the physiological content of glyceraldehyde, a precursor of toxic advanced glycation end products. The conventional derivatization method for aldoses using 1-phenyl-3-methyl-5-pyrazolone did not allow reproducible quantification of glyceraldehyde due to the instability of glyceraldehyde compared to other aldoses. We optimized the derivatization condition to achieve high and reproducible recovery of derivatives for liquid chromatography tandem mass spectrometry quantification. Based on the stability of glyceraldehyde during sample preparation and high recovery of spiked standard, the present method provides reproducible quantification of glyceraldehyde in the body. The glyceraldehyde contents in fasting conditions in the rodent liver (mice: 50.0 ± 3.9 nmol/g; rats: 35.5 ± 4.9 nmol/g) were higher than those in plasma (9.4 ± 1.7 and 7.2 ± 1.2 nmol/mL). The liver glyceraldehyde levels significantly increased after food consumption (p < 0.05) but remained constant in the plasma. High fat diet feeding significantly increased plasma glyceraldehyde levels in mice (p < 0.005). In healthy human volunteers, the plasma glyceraldehyde levels remained unchanged after the consumption of steamed rice. In patients with type 2 diabetes, the plasma glyceraldehyde level was positively correlated with the plasma glucose level (r = 0.84; p < 0.0001).


Assuntos
Diabetes Mellitus Tipo 2 , Gliceraldeído , Animais , Jejum , Produtos Finais de Glicação Avançada , Humanos , Camundongos , Ratos , Roedores
14.
Viruses ; 13(10)2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34696405

RESUMO

Coronaviruses (CoVs) are widespread and highly diversified in wildlife and domestic mammals and can emerge as zoonotic or epizootic pathogens and consequently host shift from these reservoirs, highlighting the importance of veterinary surveillance. All genera can be found in mammals, with α and ß showing the highest frequency and diversification. The aims of this study were to review the literature for features of CoV surveillance in animals, to test widely used molecular protocols, and to identify the most effective one in terms of spectrum and sensitivity. We combined a literature review with analyses in silico and in vitro using viral strains and archive field samples. We found that most protocols defined as pan-coronavirus are strongly biased towards α- and ß-CoVs and show medium-low sensitivity. The best results were observed using our new protocol, showing LoD 100 PFU/mL for SARS-CoV-2, 50 TCID50/mL for CaCoV, 0.39 TCID50/mL for BoCoV, and 9 ± 1 log2 ×10-5 HA for IBV. The protocol successfully confirmed the positivity for a broad range of CoVs in 30/30 field samples. Our study points out that pan-CoV surveillance in mammals could be strongly improved in sensitivity and spectrum and propose the application of a new RT-PCR assay, which is able to detect CoVs from all four genera, with an optimal sensitivity for α-, ß-, and γ-.


Assuntos
Alphacoronavirus/genética , Infecções por Coronavirus/veterinária , Deltacoronavirus/genética , Gammacoronavirus/genética , SARS-CoV-2/genética , Animais , Animais Selvagens/virologia , Betacoronavirus/genética , COVID-19/veterinária , Quirópteros/virologia , Genoma Viral/genética , Humanos , Gado/virologia , Roedores/virologia
15.
J Vet Med Sci ; 83(11): 1790-1794, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34645726

RESUMO

From 2012 to 2021, prevalence of pathogenic Yersinia in wild rodents captured in Fukushima Prefecture, Japan was investigated twice a year to clarify the ecology of this pathogen in wild rodent populations. Pathogenic Yersinia enterocolitica O8 was isolated from 13 (1.7%) of 755 wild rodents. The Y. enterocolitica O8 isolates harbored three virulent genes (ail, fyuA, and virF). This pathogen was isolated repeatedly from wild rodents in April 2015, 2016, and 2017, in June and November 2020, and in April 2021, which was 6 of 19 times of observations. All Y. enterocolitica O8 isolates showed the same PFGE patterns. These results indicated that the same clone of pathogenic Y. enterocolitica O8 has been maintained in wild rodent populations in Fukushima Prefecture. Therefore, wild rodent populations contribute substantially to the continuous transmission of Y. enterocolitica O8 and its persistence in the ecosystem. This is the first report on the isolation of pathogenic Y. enterocolitica O8 in wild rodents in Fukushima Prefecture, Japan.


Assuntos
Doenças dos Roedores , Yersiniose , Yersinia enterocolitica , Animais , Ecossistema , Japão/epidemiologia , Doenças dos Roedores/epidemiologia , Roedores , Yersinia , Yersiniose/epidemiologia , Yersiniose/veterinária , Yersinia enterocolitica/genética
16.
Biomaterials ; 278: 121140, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634661

RESUMO

The in vivo fate of nanoformulated drugs is governed by the physicochemical properties of the drug and the functionality of nanocarriers. Nanoformulations such as polymeric micelles, which physically encapsulate poorly soluble drugs, release their payload into the bloodstream during systemic circulation. This results in three distinct fractions of the drug-nanomedicine: encapsulated, protein-bound, and free drug. Having a thorough understanding of the pharmacokinetic (PK) profiles of each fraction is essential to elucidate mechanisms of nanomedicine-driven changes in drug exposure and PK/PD relationships pharmacodynamic activity. Here, we present a comprehensive preclinical assessment of the poly (2-oxazoline)-based polymeric micelle of paclitaxel (PTX) (POXOL hl-PM), including bioequivalence comparison to the clinically approved paclitaxel nanomedicine, Abraxane®. Physicochemical characterization and toxicity analysis of POXOL hl-PM was conducted using standardized protocols by the Nanotechnology Characterization Laboratory (NCL). The bioequivalence of POXOL hl-PM to Abraxane® was evaluated in rats and rhesus macaques using the NCL's established stable isotope tracer ultrafiltration assay (SITUA) to delineate the plasma PK of each PTX fraction. The SITUA study revealed that POXOL hl-PM and Abraxane® had comparable PK profiles not only for total PTX but also for the distinct drug fractions, suggesting bioequivalence in given animal models. The comprehensive preclinical evaluation of POXOL hl-PM in this study showcases a series of widely applicable standardized studies by NCL for assessing nanoformulations prior to clinical investigation.


Assuntos
Antineoplásicos Fitogênicos , Paclitaxel , Paclitaxel Ligado a Albumina , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Isótopos , Macaca mulatta , Micelas , Ratos , Roedores , Equivalência Terapêutica
17.
PLoS One ; 16(10): e0258474, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34634084

RESUMO

Rhipidomys (Sigmodontinae, Thomasomyini) has 25 recognized species, with a wide distribution ranging from eastern Panama to northern Argentina. Cytogenetic data has been described for 13 species with 12 of them having 2n = 44 with a high level of autosomal fundamental number (FN) variation, ranging from 46 to 80, assigned to pericentric inversions. The species are grouped in groups with low FN (46-52) and high FN (72-80). In this work the karyotypes of Rhipidomys emiliae (2n = 44, FN = 50) and Rhipidomys mastacalis (2n = 44, FN = 74), were studied by classical cytogenetics and by fluorescence in situ hybridization using telomeric and whole chromosome probes (chromosome painting) of Hylaeamys megacephalus (HME). Chromosome painting revealed homology between 36 segments of REM and 37 of RMA. We tested the hypothesis that pericentric inversions are the predominant chromosomal rearrangements responsible for karyotypic divergence between these species, as proposed in literature. Our results show that the genomic diversification between the karyotypes of the two species resulted from translocations, centromeric repositioning and pericentric inversions. The chromosomal evolution in Rhipidomys was associated with karyotypical orthoselection. The HME probes revealed that seven syntenic probably ancestral blocks for Sigmodontinae are present in Rhipidomys. An additional syntenic block described here is suggested as part of the subfamily ancestral karyotype. We also define five synapomorphies that can be used as chromosomal signatures for Rhipidomys.


Assuntos
Sigmodontinae , Animais , Hibridização in Situ Fluorescente , Roedores
18.
J Neural Eng ; 18(5)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34542029

RESUMO

Context.Long-term deep brain stimulation (DBS) studies in rodents are of crucial importance for research progress in this field. However, most stimulation devices require jackets or large head-mounted systems which severely affect mobility and general welfare influencing animals' behavior.Objective.To develop a preclinical neurostimulation implant system for long-term DBS research in small animal models.Approach.We propose a low-cost dual-channel DBS implant called software defined implantable platform (STELLA) with a printed circuit board size of Ø13 × 3.3 mm, weight of 0.6 g and current consumption of 7.6µA/3.1 V combined with an epoxy resin-based encapsulation method.Main results.STELLA delivers charge-balanced and configurable current pulses with widely used commercial electrodes. Whilein vitrostudies demonstrate at least 12 weeks of error-free stimulation using a CR1225 battery, our calculations predict a battery lifetime of up to 3 years using a CR2032. Exemplary application for DBS of the subthalamic nucleus in adult rats demonstrates that fully-implanted STELLA neurostimulators are very well-tolerated over 42 days without relevant stress after the early postoperative phase resulting in normal animal behavior. Encapsulation, external control and monitoring of function proved to be feasible. Stimulation with standard parameters elicited c-Fos expression by subthalamic neurons demonstrating biologically active function of STELLA.Significance.We developed a fully implantable, scalable and reliable DBS device that meets the urgent need for reverse translational research on DBS in freely moving rodent disease models including sensitive behavioral experiments. We thus add an important technology for animal research according to 'The Principle of Humane Experimental Technique'-replacement, reduction and refinement (3R). All hardware, software and additional materials are available under an open source license.


Assuntos
Estimulação Encefálica Profunda , Núcleo Subtalâmico , Animais , Eletrodos Implantados , Neuroestimuladores Implantáveis , Ratos , Roedores , Software
19.
Zool Res ; 42(5): 671-674, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34490760

RESUMO

All extant species in the rodent family Spalacidae are subterranean and have evolved various traits for underground life. However, the phylogenomic relationships among its three subfamilies (Myospalacinae, Spalacinae, and Rhizomyinae) and the molecular basis underlying their adaptations to underground life remain poorly understood. Here, we inferred the phylogenomic relationships among these subfamilies based on de novo sequencing the genome of the hoary bamboo rat ( Rhizomys pruinosus). Analyses showed that ~50% of the identified 11 028 one-to-one orthologous protein-coding genes and the concatenated sequences of these orthologous genes strongly supported a sister relationship between Myospalacinae and Rhizomyinae. The three subfamilies diversified from each other within ~2 million years. Compared with the non-subterranean controls with similar divergence dates, the spalacids shared more convergent genes with the African subterranean mole-rats at the genomic scale due to more rapid protein sequence evolution. Furthermore, these convergent genes were enriched in the functional categories of carboxylic acid transport, vascular morphogenesis, and response to oxidative stress, which are closely associated with adaptations to the hypoxic-hypercapnic underground environment. Our study presents a well-supported phylogenomic relationship among the three subfamilies of Spalacidae and offers new insights into the molecular adaptations of spalacids living underground.


Assuntos
Adaptação Fisiológica/genética , Comportamento Animal/fisiologia , Evolução Molecular , Genômica , Roedores/genética , Animais , Genoma , Filogenia , Roedores/fisiologia , Especificidade da Espécie
20.
Curr Microbiol ; 78(11): 3872-3876, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510223

RESUMO

The family Cycloposthiidae (Entodiniomorphida) comprises ciliated protists that are symbionts of the gastrointestinal tract of several herbivore mammals, such as rodents, elephants, equids, primates, hippopotamus, marsupials, rhinoceros and tapir, where they contribute to the digestion of their host's plant-based diet. Despite the significance of these ciliates to the evolution of their hosts, many characters used in the taxonomy of the group are homoplastic and most of the valid species do not have molecular data available. For these reasons the systematics of this family is poorly understood. Here, we sequenced the 18S-rDNA of ten cycloposthiids, including nine Cycloposthium spp. and Monoposthium cynodontum, all of them isolated from the cecum of a Brazilian capybara. Our phylogenetic analyses indicate that the family Cycloposthiidae might be polyphyletic, while M. cynodontum and Cycloposthium spp. constitute a single monophyletic group. Given the great morphological and molecular similarities between members of M. cynodontum and Cycloposthium ciliates, it is possible that this species, although it has been described in the genus Monoposthium, is actually a Cycloposthium ciliate.


Assuntos
Cilióforos , Roedores , Animais , Cilióforos/genética , DNA Ribossômico/genética , Trato Gastrointestinal , Filogenia
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