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1.
Int J Mol Sci ; 24(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37569698

RESUMO

Individuals with ASD are known to have a tendency to have tactile sensory processing issues that could be associated with their impairment as regards social communication. The alterations in tactile processing in autistic subjects are usually accompanied by hypersensitivity and other unpleasant emotions induced by tactile contact. In our study, we investigated the impact of the velocity and the force of a tactile stroke received impersonally by a custom-built robotic device. A total of 21 adults with ASD and 22 adults from a control group participated in our study. The participants' responses were assessed according to subjective scales, EEG changes, and the dynamics of saliva antioxidants and oxytocin. It was found that the oxytocin level was significantly lower in subjects with ASD but increased after tactile stimulation. However, contrary to expectations, the increase in the oxytocin level in the target group negatively correlated with the subjective pleasantness of tactile stimulation and was probably associated with a stress-induced effect. The basic levels of antioxidants did not differ between the TD and ASD groups; however, these had significantly increased in individuals with ASD by the end of the study. The EEG findings, which revealed enhanced antioxidant levels, contributed to the relief of the cognitive control during the study.


Assuntos
Transtorno do Espectro Autista , Procedimentos Cirúrgicos Robóticos , Humanos , Adulto , Tato/fisiologia , Transtorno do Espectro Autista/psicologia , Antioxidantes , Ocitocina
2.
Adv Urol ; 2023: 2205306, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37214228

RESUMO

Fast track surgery (FTS), as well as ERAS (enhanced recovery after surgery/rapid recovery programs), is the latest multimodal treatment strategy, designed to reduce the disability period and improve the medical care quality. The study aims to analyze the enhanced recovery protocol effectiveness in a comparative study of elective urethral stricture surgery. A prospective study included 54 patients with an established diagnosis of urethral stricture in 2019-2020 in the urological hospital of the Irkutsk City Clinical Hospital No. 1. All 54 patients have completed the study. There were two groups of patients FTS-group (group II, n = 25) and standard group (group I, n = 29). In terms of preoperative parameters, the comparison groups have statistical homogeneity. The comparative intergroup efficacy analysis of the treatment based on the criteria established in the study demonstrated good treatment results for 5 (17.2%) patients of group I and 20 (80%) patients of group II (p=0.004). The overall efficacy of urethroplasty surgeries, regardless of the treatment protocol, was comparable (86.2% vs 92%; p=0.870), as well as the likelihood of relapse within two years (p=0.512). The predictors of recurrence were technical complications and urethral suture failure (OR 4.36; 95% CI 1.6; 7.11; p=0.002). The FTS protocol reduced the treatment period (p < 0.001) and decreased the severity of postoperative pain (p < 0.001). The use of the "fast track surgery" protocol in urethroplasty with generally similar treatment results makes it possible to achieve a better functional and objective condition of patients in the postoperative period due to less pain, shorter catheterization, and hospitalization.

3.
Sci Rep ; 12(1): 20630, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36450804

RESUMO

The family Glossiphoniidae is a diverse and widespread clade of freshwater leeches, playing a significant role in functioning of aquatic ecosystems. The taxonomy and biogeography of leeches from temperate, subtropical, and tropical regions attracted much attention of zoologists, while their taxonomic richness and distribution in the Arctic are poorly understood. Here, we present an overview of the Eurasian Arctic Glossiphoniidae based on the most comprehensive occurrence and DNA sequence datasets sampled to date. This fauna contains 14 species, belonging to five genera and three subfamilies. One genus and five species are new to science and described here. The world's northernmost occurrences of glossiphoniids are situated on the Taymyr Peninsula at 72° N, although further records at higher latitudes are expected. Most Arctic leeches are characterized by broad ranges crossing several climatic zones (e.g., Glossiphonia balcanica and G. nebulosa), although the distribution of two new species may be confined to the high-latitude areas. The Taymyr Peninsula with the nearby Putorana Plateau represents the most species-rich area (totally 9 species), while the European Arctic, Iceland, Kolyma Highland, and Chukotka Peninsula house depleted faunas (2-4 species per subregion). Finally, we show that the high-latitude melanism is a common phenomenon in glossiphoniid leeches.


Assuntos
Sanguessugas , Lepidópteros , Melanose , Animais , Ecossistema , Sanguessugas/genética , Islândia
4.
Pol Przegl Chir ; 93(5): 1-5, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34552031

RESUMO

<b>Aim:</b> The aim of this research is to improve the results of surgical treatment of incisional ventral hernia by applying a case-specific approach and a new method of plastic repair of the anterior abdominal wall.<br/> <br/> <b>Methods:<b/> The prospective controlled dynamic study is based on incisional ventral hernia treatment results with the use of meshed endoprostheses among 219 patients. On-lay alloplasty was used in patients younger than 60 years of age, without severe concomitant pathology, with small and medium hernias and anterior abdominal wall defect of up to 10 cm (W1-W2).<br/> <br/> <b>Results:<b/> The article shows a selection algorithm for anterior abdominal wall plastic repair method. It goes through advantages of the author's proprietary technique. The article displays frequency and patterns of complications, with life quality of the patients after various prosthetic plastic repairs. In the main group, positive treatment results were observed in 65.0%, longterm results of the operation were observed in 88.4%, complications occurred in 13.6%, relapse in 4.5%. «Onlay¼ treatment tactics showed positive results in 59.4%, long-term results of the operation were observed in 74.7%, complications occurred in 40%, relapse in 3.1%. After «sublay¼ intervention, excellent results were observed in 40.0% of patients, long-term results of the operation were observed in 81.9%, complications occurred in 12%, and relapse in 1.4%<br/> <br/>.


Assuntos
Parede Abdominal , Hérnia Ventral , Hérnia Incisional , Parede Abdominal/cirurgia , Hérnia Ventral/cirurgia , Humanos , Hérnia Incisional/cirurgia , Estudos Prospectivos , Resultado do Tratamento
5.
Int J Surg Protoc ; 25(1): 114-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250322

RESUMO

BACKGROUND: The research aims to improve the surgical treatment results of incisional ventral hernia by applying a case-specific approach and a new method of anterior abdominal wall surgery. MATERIALS AND METHODS: The paper reports the results of the prospective dynamic cohort study on 219 patients under 60 years of age, with small and medium hernias and up to 10 cm defects in the anterior abdominal wall (W1-W2), who underwent incisional ventral hernia treatment with mesh endoprostheses. RESULTS: The paper offers a selection algorithm for anterior abdominal wall repair surgery and an original proprietary technique. We have developed and described in detail a new 'extra-sublay' technique of surgical intervention. The paper displays the frequency and pattern of complications, as well as the quality of life of patients after different prosthetic surgeries. In the main group, 65.0% of patients showed improvement, 88.4% showed long-term surgical success, 13.6% faced complications, and 4.5% experienced recurrence. CONCLUSION: After receiving the "on lay" treatment, 59.4% of patients showed positive results, 74.7% showed long-term surgical success, 40% had complications, and 3.1% experienced recurrence. After the "sub lay" intervention, 40.0% of patients demonstrated excellent results, 81.9% reached long-term success, 12% had complications, and 1.4% encountered recurrence. HIGHLIGHTS: The article shows a selection algorithm for anterior abdominal wall plastic repair method.One of the factors that cause relapses and ventral hernias themselves is obesity.The authors' method of the VH surgical treatment has shown good results.Excellent indicators showed 65.0% of patients of the main group.

6.
Psychophysiology ; 58(9): e13854, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34061347

RESUMO

A pleasant touch reduces psychoemotional stress via the oxytocin mechanism due to its anti-inflammatory and antioxidant effects. Our research is aimed to reveal the correlations between the subjectively perceived pleasantness of touch, the antioxidant potential of saliva, and salivary oxytocin. A total of 56 healthy volunteers aged 18-38 years participated in the study. The control group consisted of 24 volunteers. The participants were subjected to tactile stimulation using a specially designed protocol. They ranked the touch pleasantness on a scale from 1 to 10. Heart rate variability and low-frequency/high-frequency ratios from the power spectral density of ECG were determined to assess psychoemotional relaxation. Salivary oxytocin and antioxidant capacity were quantified before and after the touch test. We found a significant increase in salivary antioxidant potential and oxytocin after pleasant tactile stimulation for the participants compared to the control group. The difference in antioxidant capacity values before and after the test positively correlated with mean pleasantness in the touch test (r = 0.57) and the difference in heart rate variability (r = 0.67); it negatively correlated with the difference in low-frequency/high-frequency ECG band ratio (r = -0.59). Oxytocin ratio positively correlated with the difference in antioxidant capacity values (r = 0.47). As a result of tactile stimulation, a significant increase in the antioxidant capacity of saliva and salivary oxytocin was found in the test group compared to the control group. These findings support further studies of the effects of pleasant touch on hormonal and oxidative metabolism.


Assuntos
Antioxidantes/metabolismo , Frequência Cardíaca/fisiologia , Ocitocina/metabolismo , Prazer/fisiologia , Saliva/metabolismo , Percepção do Tato/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
7.
Exp Brain Res ; 238(10): 2257-2268, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32719908

RESUMO

Affective touch plays an important role in human social bonding, affiliative behavior, and in general emotional well-being. A system of unmyelinated low-threshold mechanosensitive C-type afferents innervating hairy skin (C-tactile or CT system) is postulated to provide the neurophysiological background of affective touch perception. C-tactile afferents respond optimally to soft and slow strokes, and this response correlates positively with pleasure ratings of tactile stimuli. As gentle touch is consistently associated with oxytocin release further promoting prosocial behavior, it has been suggested that this effect is mediated by the response of C-tactile afferents. This study assesses a possible link between CT-optimal touch, its subjective pleasantness, EEG indices of cortical arousal, and peripheral oxytocin response. EEG was recorded in 28 healthy volunteers during resting state and tactile stimulation[gentle slow brush strokes on forearm (CT-targeted touch) and palm (non-CT-targeted touch)]. Saliva samples were collected before and after the touch stimulation. Oxytocin concentration increase was significantly associated with greater subjective ratings of CT-targeted touch but not of non-CT-targeted touch, and with lower peak alpha frequency values indicating decreased cortical arousal. The findings suggest that CT-targeted stimulation triggers oxytocin release but only when the touch is perceived at an individual level as having clearly positive affective salience. This corresponds to previous studies reporting that oxytocin response to touch can be related to different personality factors, and bears important implications for planning touch-based interventions in social and medical care.


Assuntos
Ocitocina , Percepção do Tato , Nível de Alerta , Eletroencefalografia , Emoções , Humanos , Estimulação Física
8.
Sci Rep ; 10(1): 3072, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080260

RESUMO

Freshwater mussels are ecosystem engineers and keystone species in aquatic environments. Unfortunately, due to dramatic declines this fauna is among the most threatened globally. Here, we clarify the taxonomy and biogeography of Russian Unionidae species based on the most comprehensive multi-locus dataset sampled to date. We revise the distribution and assess the conservation status for each species. This fauna comprises 16 native species from 11 genera and 4 tribes: Anodonta, Pseudanodonta (Anodontini); Amuranodonta, Beringiana, Buldowskia, Cristaria, Sinanodonta (Cristariini); Middendorffinaia, Nodularia, Unio (Unionini); and Lanceolaria (Lanceolariini). No country-level endemic species are known in Russia, except for Buldowskia suifunica that may also occur in China. Sinanodonta woodiana, a non-native species, was introduced from China. Russia comprises the northern parts of Western and Eastern Palearctic subregions. The first subregion with six species encompasses a huge area from the western boundary of Russia to the Lena Basin in Siberia. The second subregion with 10 species covers the Amur Basin, rivers east of the Lena Basin, coastal basins of the Japan Sea, and the North Pacific Islands. The fauna of Russia primarily includes widespread generalist species that are here considered Least Concern (LC). However, Buldowskia suifunica and Sinanodonta lauta have restricted distributions and are assessed here as Vulnerable (VU) and Endangered (EN), respectively.


Assuntos
Bivalves/classificação , Conservação dos Recursos Naturais , Filogeografia , Exoesqueleto/anatomia & histologia , Animais , Biodiversidade , Bivalves/genética , Água Doce , Loci Gênicos , Funções Verossimilhança , Federação Russa , Especificidade da Espécie
9.
Sci Rep ; 9(1): 16449, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712612

RESUMO

Freshwater mussels (Unionida) are one of the most imperiled animal groups worldwide, revealing the fastest rates of extinction. Habitat degradation, river pollution and climate change are the primary causes of global decline. However, biological threats for freshwater mussels are still poorly known. Here, we describe a diverse ecological group of leeches (Hirudinea: Glossiphoniidae) inhabiting the mantle cavity of freshwater mussels. So far, examples of mussel-associated leech species are recorded from East Asia, Southeast Asia, India and Nepal, Africa, and North America. This group comprises a dozen glossiphoniid species with a hidden life style inside the mantle cavity of their hosts largely overlooked by researchers. We show that the association with freshwater mussels evolved independently in three leech clades, i.e. Batracobdelloides, Hemiclepsis, and Placobdella, at least since the Miocene. Seven mussel-associated leech species and two additional free-living taxa are described here as new to science.


Assuntos
Biodiversidade , Bivalves/parasitologia , Água Doce , Sanguessugas/classificação , Animais , Evolução Biológica , Parasitologia de Alimentos , Alimentos Marinhos/parasitologia
10.
Zookeys ; (794): 23-30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30416338

RESUMO

Associations of various invertebrate species with bryozoans and sponges are a well-known marine phenomenon but such epizooic communities are far less diverse in freshwater environments. Here an occurrence of numerous leeches Alboglossiphoniacf.papillosa (Braun, 1805), in interstitial spaces between zooids of a colony of the freshwater bryozoan species Plumatellaaff.fungosa (Pallas, 1768) in Eastern Siberia is described. To the best of our knowledge, this record appears to be the first known example of a leech-bryozoan association, although such relationships deserve further research.

11.
Sci Rep ; 8(1): 11199, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-30046044

RESUMO

The radicine pond snails represent a species-rich and widely distributed group, many species of which are key vectors of human and animal trematodoses. Here we clarify the taxonomy, distribution and evolutionary biogeography of the radicine lymnaeids in the Old World based on the most comprehensive multi-locus molecular dataset sampled to date. We show that the subfamily Amphipepleinae is monophyletic and contains at least ten genus-level clades: Radix Montfort, 1810, Ampullaceana Servain, 1881, Peregriana Servain, 1881, Tibetoradix Bolotov, Vinarski & Aksenova gen. nov., Kamtschaticana Kruglov & Starobogatov, 1984, Orientogalba Kruglov & Starobogatov, 1985, Cerasina Kobelt, 1881, Myxas G. B. Sowerby I, 1822, Bullastra Bergh, 1901, and Austropeplea Cotton, 1942. With respect to our phylogeny, species-delimitation model and morphological data, the Old World fauna includes 35 biological species of radicines. Tibet and Eastern Europe harbor the richest faunas, while East Asia and Africa appear to be the most species-poor areas. The radicine clade could have originated near the Cretaceous - Paleocene boundary. The Miocene great lakes in Eurasia seems to be the most important evolutionary hotspots shaping spatial patterns of recent species richness. Finally, we present the first DNA barcode reference library for the reliable molecular identification of species within this group.


Assuntos
Evolução Biológica , Filogeografia , Caramujos/genética , Caramujos/fisiologia , África , Animais , Classificação/métodos , DNA Mitocondrial/genética , Lagos , Lagoas , Caramujos/classificação , Especificidade da Espécie
12.
Sci Rep ; 8(1): 35, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29311629

RESUMO

The effects of climate change on oligotrophic rivers and their communities are almost unknown, albeit these ecosystems are the primary habitat of the critically endangered freshwater pearl mussel and its host fishes, salmonids. The distribution and abundance of pearl mussels have drastically decreased throughout Europe over the last century, particularly within the southern part of the range, but causes of this wide-scale extinction process are unclear. Here we estimate the effects of climate change on pearl mussels based on historical and recent samples from 50 rivers and 6 countries across Europe. We found that the shell convexity may be considered an indicator of the thermal effects on pearl mussel populations under warming climate because it reflects shifts in summer temperatures and is significantly different in viable and declining populations. Spatial and temporal modeling of the relationship between shell convexity and population status show that global climate change could have accelerated the population decline of pearl mussels over the last 100 years through rapidly decreasing suitable distribution areas. Simulation predicts future warming-induced range reduction, particularly in southern regions. These results highlight the importance of large-scale studies of keystone species, which can underscore the hidden effects of climate warming on freshwater ecosystems.


Assuntos
Bivalves , Mudança Climática , Densidade Demográfica , Rios , Algoritmos , Animais , Ecossistema , Água Doce , Geografia , Modelos Teóricos
14.
Radiat Prot Dosimetry ; 173(1-3): 10-15, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27884938

RESUMO

The Russian Radiobiological Human Tissue Repository (RHTR) at the Southern Urals Biophysics Institute in Ozyorsk, Russia, was established to collect and store biospecimens supporting research on health consequences of chronic, low-dose radiation exposures. The purpose of this paper is to describe the RHTR resources and the availability of high-quality biological specimens. RHTR has enrolled two groups of subjects from 1951 to the present time: exposed workers at the Mayak Production Association facilities and residents of Ozyorsk who were never occupationally exposed to ionizing radiation (controls). Biospecimens are collected with informed consent of participants and are annotated with demographic, occupational, dosimetry and medical information. To date, 900 individuals have provided surgical tissues and 1000 have provided autopsy tissues. Blood samples are also collected and stored. Familial DNA is available from parent-offspring triads. Biospecimens and annotated data are available to interested scientists worldwide, via the RHTR website.


Assuntos
Exposição Ocupacional , Plutônio , Bancos de Tecidos , Humanos , Radiação Ionizante , Radiobiologia , Federação Russa
15.
Biol Rev Camb Philos Soc ; 92(1): 572-607, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26727244

RESUMO

Freshwater mussels of the Order Unionida provide important ecosystem functions and services, yet many of their populations are in decline. We comprehensively review the status of the 16 currently recognized species in Europe, collating for the first time their life-history traits, distribution, conservation status, habitat preferences, and main threats in order to suggest future management actions. In northern, central, and eastern Europe, a relatively homogeneous species composition is found in most basins. In southern Europe, despite the lower species richness, spatially restricted species make these basins a high conservation priority. Information on freshwater mussels in Europe is unevenly distributed with considerable differences in data quality and quantity among countries and species. To make conservation more effective in the future, we suggest greater international cooperation using standardized protocols and methods to monitor and manage European freshwater mussel diversity. Such an approach will not only help conserve this vulnerable group but also, through the protection of these important organisms, will offer wider benefits to freshwater ecosystems.


Assuntos
Bivalves/fisiologia , Conservação dos Recursos Naturais , Ecossistema , Distribuição Animal , Animais , Conservação dos Recursos Naturais/tendências , Europa (Continente) , Água Doce
16.
Zootaxa ; 4132(4): 588-90, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27395696

RESUMO

The strigeid digenean species Australapatemon burti (Miller, 1923) (Trematoda: Digenea: Strigeidae) was originally described from North America, but recorded in the Neotropical region (Drago et al. 2007; Hernández-Mena et al. 2014; Blasco-Costa et al. 2016) and in Central Europe (Faltýnková et al. 2007). In Europe, this species is rare, and there is not much information about its range (Faltýnková et al. 2007; Soldánová et al. 2012). Australapatemon burti has a complex life cycle with three larval stages, two of which (sporocyst and cercaria) use several species of freshwater snails, and the third stage (metacercaria) use non-specific host hirudineans (Dubois 1968; Davies & Ostrowski de Núñez 2012; Blasco-Costa et al. 2016). Adult flukes are parasitic in the intenstines of various waterfowl species, such as ducks and swans (Drago et al. 2007; Hernández-Mena et al. 2014). Currently, the molecular data on this parasite species includes only nucleotide sequences of four adult specimens from Mexico (Hernández-Mena et al. 2014). Their hosts were Mexican duck, Anas diazi Ridgway, American Wigeon, Anas americana Gmelin, Cinnamon Teal, Anas cyanoptera Vieillot, and Ruddy Duck, Oxyura jamaicensis (Gmelin) (Anserformes: Anatidae).


Assuntos
Gastrópodes/parasitologia , Estágios do Ciclo de Vida , Trematódeos/classificação , Trematódeos/crescimento & desenvolvimento , Trematódeos/genética , Animais , Doenças das Aves/parasitologia , Patos/parasitologia , Europa (Continente) , Filogenia , Trematódeos/anatomia & histologia
17.
Health Phys ; 103(1): 28-36, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22647909

RESUMO

The objective of this research was quantitative assessment of serum and membrane regulatory proteins in blood from nuclear workers as markers of radiation-induced alterations in immune homeostasis in the late period after protracted exposure of nuclear workers with different doses. The effector and regulatory lymphocytes were measured using a flow cytofluorometer in workers from the main facilities of the Mayak PA (aged ∼60 y up to 80 y) in the late period after combined exposure to external gamma-rays and internal alpha-radiation from incorporated 239Pu. The control group included non-occupationally exposed members of the Ozyorsk population matched by gender and age to the group of Mayak workers. Thirty serum proteins involved in regulation of immune homeostasis, such as growth factors, multifunctional interleukins, pro- and anti-inflammatory cytokines, and their receptors, were measured using ELISA in blood serum specimens from the Radiobiology Human Tissue Repository. The dosimetry estimates were obtained using Doses-2005. The correlation analysis revealed a statistically significant direct relationship of T-killers and plutonium body burden and a decreasing level of T-helpers with accumulated external dose in exposed individuals. There were differences in expression of membrane markers in young regulatory cells (double null T-lymphocytes, NKT-lymphocytes, regulatory T-cells, and an increase of activated forms of T-lymphocytes), which indicated an active role of regulatory cells in maintaining immune homeostasis in terms of protracted exposure. The assessment of regulatory proteins in blood indicated that growth factors (EGF, TGF-ß1, PDGF), multifunctional interleukins (IL-17A, IL-18), and pro-inflammatory cytokines (IL-1ß and INF-γ) could be potential markers of radiation-induced alterations in protein status. An imbalance of pro- and antiinflammatory proteins in blood and variations of protein profiles at the lower exposure levels (gamma-ray dose <1 Gy, plutonium body burden <0.74 kBq) in the late period after protracted exposure were less pronounced than at the higher exposure levels, which was probably explained by compensatory-adaptive responses in the late period among senile individuals with polypathology.


Assuntos
Proteínas Sanguíneas/metabolismo , Centrais Nucleares , Exposição Ocupacional/efeitos adversos , Idoso , Biomarcadores/sangue , Carga Corporal (Radioterapia) , Homeostase/imunologia , Homeostase/efeitos da radiação , Humanos , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/efeitos da radiação , Plutônio/metabolismo , Federação Russa , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/efeitos da radiação , Fatores de Tempo
18.
Genome Res ; 20(5): 623-35, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20308636

RESUMO

Structural variation (SV) is a rich source of genetic diversity in mammals, but due to the challenges associated with mapping SV in complex genomes, basic questions regarding their genomic distribution and mechanistic origins remain unanswered. We have developed an algorithm (HYDRA) to localize SV breakpoints by paired-end mapping, and a general approach for the genome-wide assembly and interpretation of breakpoint sequences. We applied these methods to two inbred mouse strains: C57BL/6J and DBA/2J. We demonstrate that HYDRA accurately maps diverse classes of SV, including those involving repetitive elements such as transposons and segmental duplications; however, our analysis of the C57BL/6J reference strain shows that incomplete reference genome assemblies are a major source of noise. We report 7196 SVs between the two strains, more than two-thirds of which are due to transposon insertions. Of the remainder, 59% are deletions (relative to the reference), 26% are insertions of unlinked DNA, 9% are tandem duplications, and 6% are inversions. To investigate the origins of SV, we characterized 3316 breakpoint sequences at single-nucleotide resolution. We find that approximately 16% of non-transposon SVs have complex breakpoint patterns consistent with template switching during DNA replication or repair, and that this process appears to preferentially generate certain classes of complex variants. Moreover, we find that SVs are significantly enriched in regions of segmental duplication, but that this effect is largely independent of DNA sequence homology and thus cannot be explained by non-allelic homologous recombination (NAHR) alone. This result suggests that the genetic instability of such regions is often the cause rather than the consequence of duplicated genomic architecture.


Assuntos
Pontos de Quebra do Cromossomo , Mapeamento Cromossômico , Elementos de DNA Transponíveis/genética , Variação Genética , Genoma , Duplicações Segmentares Genômicas/genética , Algoritmos , Animais , Sequência de Bases , Mapeamento Cromossômico/métodos , Biologia Computacional/métodos , Feminino , Genoma/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Análise de Sequência de DNA/métodos
19.
J Biol Chem ; 283(13): 8136-44, 2008 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-18218623

RESUMO

Mutations in the I-II loop of Ca(v)3.2 channels were discovered in patients with childhood absence epilepsy. All of these mutations increased the surface expression of the channel, whereas some mutations, and in particular C456S, altered the biophysical properties of channels. Deletions around C456S were found to produce channels that opened at even more negative potentials than control, suggesting the presence of a gating brake that normally prevents channel opening. The goal of the present study was to identify the minimal sequence of this brake and to provide insights into its structure. A peptide fragment of the I-II loop was purified from bacteria, and its structure was analyzed by circular dichroism. These results indicated that the peptide had a high alpha-helical content, as predicted from secondary structure algorithms. Based on homology modeling, we hypothesized that the proximal region of the I-II loop may form a helix-loop-helix structure. This model was tested by mutagenesis followed by electrophysiological measurement of channel gating. Mutations that disrupted the helices, or the loop region, had profound effects on channel gating, shifting both steady state activation and inactivation curves, as well as accelerating channel kinetics. Mutations designed to preserve the helical structure had more modest effects. Taken together, these studies showed that any mutations in the brake, including C456S, disrupted the structural integrity of the brake and its function to maintain these low voltage-activated channels closed at resting membrane potentials.


Assuntos
Canais de Cálcio Tipo T/química , Canais de Cálcio Tipo T/metabolismo , Ativação do Canal Iônico , Sequência de Aminoácidos , Canais de Cálcio Tipo T/genética , Linhagem Celular , Sequência Conservada , Eletrofisiologia , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutação/genética , Técnicas de Patch-Clamp , Estrutura Secundária de Proteína , Alinhamento de Sequência
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