Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 103
Filtrar
Más filtros

Intervalo de año de publicación
1.
J Cell Sci ; 137(7)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38469748

RESUMEN

Equal cell division relies upon astral microtubule-based centering mechanisms, yet how the interplay between mitotic entry, cortical force generation and long astral microtubules leads to symmetric cell division is not resolved. We report that a cortically located sperm aster displaying long astral microtubules that penetrate the whole zygote does not undergo centration until mitotic entry. At mitotic entry, we find that microtubule-based cortical pulling is lost. Quantitative measurements of cortical pulling and cytoplasmic pulling together with physical simulations suggested that a wavelike loss of cortical pulling at mitotic entry leads to aster centration based on cytoplasmic pulling. Cortical actin is lost from the cortex at mitotic entry coincident with a fall in cortical tension from ∼300pN/µm to ∼100pN/µm. Following the loss of cortical force generators at mitotic entry, long microtubule-based cytoplasmic pulling is sufficient to displace the aster towards the cell center. These data reveal how mitotic aster centration is coordinated with mitotic entry in chordate zygotes.


Asunto(s)
Semen , Huso Acromático , Masculino , Humanos , Microtúbulos , Citoplasma , División Celular
2.
Plant J ; 114(1): 23-38, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35574650

RESUMEN

Bean leaf crumple virus (BLCrV) is a novel begomovirus (family Geminiviridae, genus Begomovirus) infecting common bean (Phaseolus vulgaris L.), threatening bean production in Latin America. Genetic resistance is required to ensure yield stability and reduce the use of insecticides, yet the available resistance sources are limited. In this study, three common bean populations containing a total of 558 genotypes were evaluated in different yield and BLCrV resistance trials under natural infection in the field. A genome-wide association study identified the locus BLC7.1 on chromosome Pv07 at 3.31 Mbp, explaining 8 to 16% of the phenotypic variation for BLCrV resistance. In comparison, whole-genome regression models explained 51 to 78% of the variation and identified the same region on Pv07 to confer resistance. The most significantly associated markers were located within the gene model Phvul.007G040400, which encodes a leucine-rich repeat receptor-like kinase subfamily III member and is likely to be involved in the innate immune response against the virus. The allelic diversity within this gene revealed five different haplotype groups, one of which was significantly associated with BLCrV resistance. As the same genome region was previously reported to be associated with resistance against other geminiviruses affecting common bean, our study highlights the role of previous breeding efforts for virus resistance in the accumulation of positive alleles against newly emerging viruses. In addition, we provide novel diagnostic single-nucleotide polymorphism markers for marker-assisted selection to exploit BLC7.1 for breeding against geminivirus diseases in one of the most important food crops worldwide.


Asunto(s)
Estudio de Asociación del Genoma Completo , Phaseolus , Resistencia a la Enfermedad/genética , Fitomejoramiento , Genotipo , Phaseolus/genética , Hojas de la Planta , Enfermedades de las Plantas/genética
3.
Bioinformatics ; 39(12)2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37991849

RESUMEN

SUMMARY: ChromaX is a Python library that enables the simulation of genetic recombination, genomic estimated breeding value calculations, and selection processes. By utilizing GPU processing, it can perform these simulations up to two orders of magnitude faster than existing tools with standard hardware. This offers breeders and scientists new opportunities to simulate genetic gain and optimize breeding schemes. AVAILABILITY AND IMPLEMENTATION: The documentation is available at https://chromax.readthedocs.io. The code is available at https://github.com/kora-labs/chromax.


Asunto(s)
Genómica , Programas Informáticos , Genoma , Biblioteca de Genes , Simulación por Computador
4.
Cladistics ; 40(2): 192-203, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38041646

RESUMEN

Most arthropod species are undescribed and hidden in specimen-rich samples that are difficult to sort to species using morphological characters. For such samples, sorting to putative species with DNA barcodes is an attractive alternative, but needs cost-effective techniques that are suitable for use in many laboratories around the world. Barcoding using the portable and inexpensive MinION sequencer produced by Oxford Nanopore Technologies (ONT) could be useful for presorting specimen-rich samples with DNA barcodes because it requires little space and is inexpensive. However, similarly important is user-friendly and reliable software for analysis of the ONT data. It is here provided in the form of ONTbarcoder 2.0 that is suitable for all commonly used operating systems and includes a Graphical User Interface (GUI). Compared with an earlier version, ONTbarcoder 2.0 has three key improvements related to the higher read quality obtained with ONT's latest flow cells (R10.4), chemistry (V14 kits) and basecalling model (super-accuracy model). First, the improved read quality of ONT's latest flow cells (R10.4) allows for the use of primers with shorter indices than those previously needed (9 bp vs. 12-13 bp). This decreases the primer cost and can potentially improve PCR success rates. Second, ONTbarcoder now delivers real-time barcoding to complement ONT's real-time sequencing. This means that the first barcodes are obtained within minutes of starting a sequencing run; i.e. flow cell use can be optimized by terminating sequencing runs when most barcodes have already been obtained. The only input needed by ONTbarcoder 2.0 is a demultiplexing sheet and sequencing data (raw or basecalled) generated by either a Mk1B or a Mk1C. Thirdly, we demonstrate that the availability of R10.4 chemistry for the low-cost Flongle flow cell is an attractive option for users who require only 200-250 barcodes at a time.


Asunto(s)
Nanoporos , Análisis de Secuencia de ADN/métodos , Código de Barras del ADN Taxonómico/métodos , Programas Informáticos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
5.
Cult Health Sex ; : 1-15, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012361

RESUMEN

Despite growing understanding and acceptance of the concept of Undetectable = Untransmittable (U = U) among gay men, HIV stigma remains a burden for people living with HIV. This study explored perceptions of HIV among HIV seronegative gay men in Sweden in this new context. Using snowball sampling, 15 gay men born between 1980 and 2000 were recruited to the study. Semi-structured interviews were conducted and data were subjected to reflexive thematic analysis. Men grew up experiencing gay stigma and were repeatedly informed by parents, schools, communities, peers, and popular culture about the dangers of HIV, and that gay men were a high-risk group. As men grew older, and the premise of HIV shifted dramatically due to U = U, some remained emotionally anchored to the pre-U = U era, while others realigned their perceptions, often after a process of reconciling emotional responses (e.g. HIV = death) with the logical-rational claims made about U = U. The study highlights key areas for future efforts, namely establishing a balance between HIV education strategies and stigma reduction initiatives. Study findings underscore the need to care for the memory of those lost during the crisis years, while also addressing the stigma faced by those currently living with HIV.

6.
J Insect Sci ; 24(4)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38989844

RESUMEN

The Canary Islands is a Macaronesian volcanic archipelago with a depauperate community of three species of Kalotermitidae, including Kalotermes dispar. A total of 54 Kalotermes colonies were collected from Gran Canaria, Tenerife, La Gomera, La Palma, and El Hierro islands. Soldiers and imagos were morphologically examined and sequenced for four mitochondrial markers. Although morphological differences could not be detected, phylogenetic analysis of both cox1/tRNA/cox2 and rrnL markers revealed two distinct clades of K. dispar, suggesting cryptic diversity. The diversification within the Canary Kalotermes lineage most likely occurred around 7.5 Mya, while the divergence within the two clades was reconstructed at about 3.6 Mya and 1.9 Mya. Kalotermes approximatus from the southeastern Nearctic constitutes a sister to the Canary Kalotermes, while the Palearctic K. flavicollis, K. italicus, and K. phoenicae form a separate clade. It is hypothesized that a faunal exchange of Kalotermes from the Nearctic to the Canary Islands occurred via transoceanic rafting during the mid-Miocene.


Asunto(s)
Cucarachas , Filogenia , Animales , España , Cucarachas/clasificación
7.
J Org Chem ; 88(24): 16803-16816, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38050850

RESUMEN

The visible light-induced perfluoroalkyl (RF) radical reactions on peracetylglycals derived from hexoses and pentoses (galactal, glucal, arabinal, and xylal derivatives) were investigated. Various photocatalysts and perfluoroalkyl iodides (RF-I) were employed as sources of RF radicals with LEDs as the irradiation source. Particularly noteworthy was the use of an Iridium photocatalyst, Ir[dF(CF3)ppy]2(dtbpy))PF6, which yielded two distinct product types when applied to glucal. On the one hand, the 2-RF-substituted glucal was formed, a trend observed even when utilizing organic dyes as photocatalysts. On the other hand, the unexpected addition product, namely the 1-RF-2-iodo-α-manno-configured C-glycosyl derivative, was also obtained, as a result of a highly regioselective addition reaction of the RF moiety into the anomeric carbon, followed by attachment of the iodine atom on C-2 in axial disposition. This result contrasted with other radical reactions carried out on 2-unsubstituted glycals, where the incipient radical adds to C-2, generating a stabilized 1-glycosyl radical. The photocatalyzed radical perfluoroalkylations of peracetyl glycals derived from galactose, arabinose, and xylose all afforded the 2-RF-substituted glycals in good yields as a result of the expected vinylic substitution reaction. Mechanistic studies revealed that the 1-RF-2-iodo-α-manno-configured C-glycosyl derivatives arise from a radical chain reaction, whereas the 2-RF-substituted glycals proceed from inefficient chain processes.

8.
Proc Biol Sci ; 289(1975): 20220489, 2022 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-35582805

RESUMEN

Dispersal ability is known to influence geographical structuring of genetic variation within species, with a direct relationship between low vagility and population genetic structure, which can potentially give rise to allopatric speciation. However, our general understanding of the relationship between dispersal ability, population differentiation and lineage diversification is limited. To address this issue, we sampled mitochondrial DNA variation within lineages of beetles and spiders across the Canary Islands to explore the relationships between dispersal ability, differentiation within lineages and diversification. We found positive relationships between population genetic structure and diversification for both beetles and spiders. Comparisons between dispersive and non-dispersive lineages revealed significant differences for both lineage differentiation and diversification. For both taxa, non-dispersive lineages had stronger population genetic structure. Genus-level endemic species richness and proxies for diversification rate within genera were higher in non-dispersive taxa for both beetles and spiders. Comparisons of average and maximum node divergences within genera suggest that species turnover may be higher in non-dispersive genera. Our results reveal a model where dispersal limitation may shape the diversity of lineages across evolutionary timescales by positively influencing intraspecific and species diversity, moderated by higher extinction rates compared to more dispersive lineages.


Asunto(s)
Escarabajos , Arañas , Animales , Evolución Biológica , Escarabajos/genética , Especiación Genética , Variación Genética , Genética de Población , Filogenia , Arañas/genética
9.
Malar J ; 21(1): 74, 2022 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-35255896

RESUMEN

BACKGROUND: The World Health Organization (WHO) provides protocols for the diagnosis of malaria. One of them is related to the staining process of blood samples to guarantee the correct parasite visualization. Ensuring the quality of the staining procedure on thick blood smears (TBS) is a difficult task, especially in rural centres, where there are factors that can affect the smear quality (e.g. types of reagents employed, place of sample preparation, among others). This work presents an analysis of an image-based approach to evaluate the coloration quality of the staining process of TBS used for malaria diagnosis. METHODS: According to the WHO, there are different coloration quality descriptors of smears. Among those, the background colour is one of the best indicators of how well the staining process was conducted. An image database with 420 images (corresponding to 42 TBS samples) was created for analysing and testing image-based algorithms to detect the quality of the coloration of TBS. Background segmentation techniques were explored (based on RGB and HSV colour spaces) to separate the background and foreground (leukocytes, platelets, parasites) information. Then, different features (PCA, correlation, Histograms, variance) were explored as image criteria of coloration quality on the extracted background information; and evaluated according to their capability to classify images as with Good or Bad coloration quality from TBS. RESULTS: For background segmentation, a thresholding-based approach in the SV components of the HSV colour space was selected. It provided robustness separating the background information independently of its coloration quality. On the other hand, as image criteria of coloration quality, among the 19 feature vectors explored, the best one corresponds to the 15-bins histogram of the Hue component with classification rates of > 97%. CONCLUSIONS: An analysis of an image-based approach to describe the coloration quality of TBS was presented. It was demonstrated that if a robust background segmentation is conducted, the histogram of the H component from the HSV colour space is the best feature vector to discriminate the coloration quality of the smears. These results are the baseline for automating the estimation of the coloration quality, which has not been studied before, but that can be crucial for automating TBS's analysis for assisting malaria diagnosis process.


Asunto(s)
Malaria , Parásitos , Algoritmos , Animales , Procesamiento de Imagen Asistido por Computador , Malaria/diagnóstico , Manejo de Especímenes/métodos , Coloración y Etiquetado
10.
Teach Learn Med ; 33(1): 1-9, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32856468

RESUMEN

Phenomenon: Mental health problems among medical students are a worrisome issue; recent studies have shown that one-third may be suffering major depressive disorder and one out of ten had suicidal ideation. Few studies have evaluated the association of medical students' mental health and their sexual orientation. This study aimed to evaluate differences in mental health indicators among medical students with diverse sexual orientations at a South American medical school. Approach: This study is a secondary analysis of cross-sectional data obtained through an electronic survey. The survey assessed demographics, academic variables, and several mental health scales and indexes, including: World Health Organization Well-being Index, Satisfaction With Life Scale, Family APGAR (Adaptability, Partnership, Growth, Affection, and Resolve), Self-Reporting Questionnaire, Athens Insomnia Scale, Eating Attitudes Test, and Alcohol Use Disorders Identification Test. Sexual orientation was assessed using self-identification and responses dichotomized as heterosexual and non-heterosexual. Findings: 554 students completed the survey (response rate: 70%). Mean age was 20.6 years, and the sample was 58.7% women. Eighty-two participants (14.8%) self-identified as non-heterosexual; this group comprised mostly males, fewer of whom lived with their family, and more of whom used loans or scholarships to pay university tuition fees. After adjustment for sex and tuition fee payment, non-heterosexual orientation was significantly associated (adjusted Odds Ratios [aOR] above 3.00) with rating mental health as bad, self-perceiving a need for mental health evaluation/treatment, and reporting last-year use of psychiatric medication. Lastly, non-heterosexual respondents reported more frequent psychiatric symptoms (depression/anxiety scores, suicidal ideation, eating disorder symptoms and substance use) with an aOR between 2.17 and 2.51. Insights: This study suggests that self-identified non-heterosexual medical students exhibit worse mental health outcomes evaluated through validated self-report scales and subjective perception of mental health status. This report specifically indicates that non-heterosexual medical students report family dysfunction more often and have less social support, which serve as additional risk factors. Future studies must assess social support, clarify the impact of family and peer support in mental health problems, and explore students' views on their sexual identity and the burden imposed by experiences of discrimination.


Asunto(s)
Trastornos Mentales/epidemiología , Salud Mental/estadística & datos numéricos , Conducta Sexual/psicología , Minorías Sexuales y de Género/psicología , Estudiantes de Medicina/psicología , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Colombia , Estudios Transversales , Femenino , Humanos , Masculino , Calidad de Vida/psicología , Autoimagen , Conducta Sexual/estadística & datos numéricos , Minorías Sexuales y de Género/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Adulto Joven
11.
Psychol Health Med ; 26(3): 375-380, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32314943

RESUMEN

There are not many direct comparisons of anxiety and depression symptoms between medicine students and the general population. This study aimed to determine the type of anxiety and depression symptoms at a medical school in Bogota (Colombia), and to compare the findings with population data. All students enrolled at a medical school were invited to participate in 2017. The Self-Reporting Questionnaire was applied to measure anxious and depressive symptoms. These findings were compared with data from the National Survey of Mental Health 2015 that were obtained with the same instrument in the same age range (18-25 years). A total of 554 students participated in the survey (70% response rate); 477 were between 18 and 25 years old. Anxiety symptoms (≥5) were reported by 44.9% of the medical students and 6.8% of the general population, and depression symptoms (≥7) were reported by 33.9% and 2.6%, respectively. The most prevalent symptoms reported by the medical students were fatigue, lack of sleep, and feeling tired all the time. In turn, the general population reported headaches, fear, nervousness, tension, and uneasiness. All comparisons showed p-values < 0.01. As prevalence is higher and symptom profile is different, specific policies are needed to reduce risk throughout medical degree programmes.


Asunto(s)
Ansiedad/epidemiología , Depresión/epidemiología , Estudiantes de Medicina/psicología , Adolescente , Adulto , Colombia/epidemiología , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Prevalencia , Estudiantes de Medicina/estadística & datos numéricos , Adulto Joven
12.
BMC Genomics ; 21(1): 799, 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33198642

RESUMEN

BACKGROUND: Common bean is an important staple crop in the tropics of Africa, Asia and the Americas. Particularly smallholder farmers rely on bean as a source for calories, protein and micronutrients. Drought is a major production constraint for common bean, a situation that will be aggravated with current climate change scenarios. In this context, new tools designed to understand the genetic basis governing the phenotypic responses to abiotic stress are required to improve transfer of desirable traits into cultivated beans. RESULTS: A multiparent advanced generation intercross (MAGIC) population of common bean was generated from eight Mesoamerican breeding lines representing the phenotypic and genotypic diversity of the CIAT Mesoamerican breeding program. This population was assessed under drought conditions in two field trials for yield, 100 seed weight, iron and zinc accumulation, phenology and pod harvest index. Transgressive segregation was observed for most of these traits. Yield was positively correlated with yield components and pod harvest index (PHI), and negative correlations were found with phenology traits and micromineral contents. Founder haplotypes in the population were identified using Genotyping by Sequencing (GBS). No major population structure was observed in the population. Whole Genome Sequencing (WGS) data from the founder lines was used to impute genotyping data for GWAS. Genetic mapping was carried out with two methods, using association mapping with GWAS, and linkage mapping with haplotype-based interval screening. Thirteen high confidence QTL were identified using both methods and several QTL hotspots were found controlling multiple traits. A major QTL hotspot located on chromosome Pv01 for phenology traits and yield was identified. Further hotspots affecting several traits were observed on chromosomes Pv03 and Pv08. A major QTL for seed Fe content was contributed by MIB778, the founder line with highest micromineral accumulation. Based on imputed WGS data, candidate genes are reported for the identified major QTL, and sequence changes were identified that could cause the phenotypic variation. CONCLUSIONS: This work demonstrates the importance of this common bean MAGIC population for genetic mapping of agronomic traits, to identify trait associations for molecular breeding tool design and as a new genetic resource for the bean research community.


Asunto(s)
Phaseolus , África , Asia , Mapeo Cromosómico , Sequías , Phaseolus/genética , Fenotipo , Fitomejoramiento , Sitios de Carácter Cuantitativo
13.
Clin Gastroenterol Hepatol ; 18(3): 700-709.e3, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31323381

RESUMEN

BACKGROUND & AIMS: Clearance of hepatitis B surface antigen (HBsAg) from serum is the most desirable end point and a proposed definition of functional cure for hepatitis B virus (HBV) infection. However, little is known about the long-term durability of HBsAg loss, and there is controversy over whether the development of antibodies against HBsAg (anti-HBs) is required for maintenance. We aimed to assess the durability of spontaneous or treatment-related (interferon or nucleos(t)ide analogue [NA]) loss of HBsAg. METHODS: We performed a retrospective study of patients with chronic HBV infection followed up at the National Institutes of Health from February 1980 through November 2017. We identified those with HBsAg loss, confirmed on 2 visits at least 24 weeks apart. Patients with hepatitis C virus, hepatitis D virus, human immunodeficiency virus, or human T lymphocyte virus co-infection or HBsAg loss after liver transplantation were excluded. Patients were assigned to the following groups: spontaneous clearance (cleared HBsAg without ever receiving treatment or those who received treatment with a NA or interferon and discontinued therapy >5 years before HBsAg loss), interferon-treated (cleared HBsAg either during treatment or ≤5 years after stopping interferon), and NA-treated (cleared HBsAg either during treatment or ≤5 years after stopping NA). RESULTS: Among the 787 HBsAg-positive patients, 89 achieved HBsAg loss; 65 of 89 had confirmed HBsAg loss, which was spontaneous in 19 of the patients (29%), after interferon in 22 (34%), and after NA in 24 (37%). Of the 65 patients with confirmed loss of HBsAg, 62 patients (95%) remained HBsAg negative after a mean time of 9.6 years from the first negative HBsAg test result. HBsAg seroreversion occurred in 3 of the 46 treated patients (7%) (1 interferon and 2 NA), 1 of whom was positive for anti-HBs. At the time of HBsAg loss, 33 of 65 (51%) were anti-HBs positive. At the last follow-up evaluation, anti-HBs was detectable in 50 of the 62 patients (81%) assessed. The rate of development of anti-HBs was proportionally higher among interferon-treated patients (19 of 21; 90%) than NA-treated patients (17 of 22; 77%) or patients with spontaneous loss of HBsAg (14 of 19; 74%). CONCLUSIONS: In a retrospective study of 787 HBsAg-positive patients, loss of HBsAg (either spontaneous or after treatment) was confirmed in 8% and was durable. Seroconversion to anti-HBs increased over time and appeared to be more frequent after interferon treatment. HBsAg loss is therefore a robust end point for functional cure.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Antivirales/efectos adversos , ADN Viral , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Estudios Retrospectivos
14.
J Anim Ecol ; 89(9): 1992-1996, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-33448375

RESUMEN

In Focus: Scalercio, S., Cini, A., Menchetti, M., Voda, R., Bonelli, S., Bordoni, A., … Dapporto, L. (2020). How long is 3 km for a butterfly? Ecological constraints and functional traits explain high mitochondrial genetic diversity between Sicily and the Italian Peninsula. Journal of Animal Ecology. https://doi.org/10.1111/1365-2656.13196. Biotic and abiotic factors can shape geographical patterns of genetic variation within species, but few studies have addressed how this might generate common patterns at the level of communities of species. Scalercio et al. (2020) have combined mtDNA sequence data and life-history traits, to reveal a repeated pattern of genetic structure between Sicilian and southern Italian butterfly populations, which are separated by only 3 km of ocean. They reveal how intrinsic species traits and extrinsic environmental constraints explain this pattern, demonstrating an important role for wind. Moreover, the inclusion of almost 8,000 georeferenced sequences reveals that, in spite of also being present in southern Italy, almost half of Sicilian butterfly species are more closely related to populations from other parts of Europe, Asia or North Africa. We provide further discussion on the biogeographic barrier they identify, and the potential of community-level DNA barcoding to identify processes that structure genetic variation across communities.


Asunto(s)
Mariposas Diurnas , África del Norte , Animales , Mariposas Diurnas/genética , ADN Mitocondrial/genética , Europa (Continente) , Variación Genética , Italia , Filogenia
15.
PLoS Genet ; 13(7): e1006928, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28746375

RESUMEN

Meiotic chromosomes assemble characteristic "axial element" structures that are essential for fertility and provide the chromosomal context for meiotic recombination, synapsis and checkpoint signaling. Whether these meiotic processes are equally dependent on axial element integrity has remained unclear. Here, we investigated this question in S. cerevisiae using the putative condensin allele ycs4S. We show that the severe axial element assembly defects of this allele are explained by a linked mutation in the promoter of the major axial element gene RED1 that reduces Red1 protein levels to 20-25% of wild type. Intriguingly, the Red1 levels of ycs4S mutants support meiotic processes linked to axis integrity, including DNA double-strand break formation and deposition of the synapsis protein Zip1, at levels that permit 70% gamete survival. By contrast, the ability to elicit a meiotic checkpoint arrest is completely eliminated. This selective loss of checkpoint function is supported by a RED1 dosage series and is associated with the loss of most of the cytologically detectable Red1 from the axial element. Our results indicate separable roles for Red1 in building the structural axis of meiotic chromosomes and mounting a sustained recombination checkpoint response.


Asunto(s)
Dosificación de Gen/genética , Meiosis/genética , Recombinación Genética , Proteínas de Saccharomyces cerevisiae/genética , Emparejamiento Cromosómico , Cromosomas Fúngicos/genética , Roturas del ADN de Doble Cadena , Mutación , Saccharomyces cerevisiae/genética , Esporas Fúngicas/genética , Complejo Sinaptonémico/genética
16.
Hepatology ; 68(6): 2078-2088, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29704252

RESUMEN

Hepatitis C virus (HCV) infection induces interferon (IFN)-stimulated genes (ISGs) and downstream innate immune responses. This study investigated whether baseline and on-treatment differences in these responses predict response versus virological breakthrough during therapy with direct-acting antivirals (DAAs). Thirteen HCV genotype 1b-infected patients who had previously failed a course of pegylated IFN/ribavirin were retreated with asunaprevir/daclatasvir for 24 weeks. After pretreatment biopsy, patients were randomized to undergo a second biopsy at week 2 or 4 on therapy. Microarray and NanoString analyses were performed on paired liver biopsies and analyzed using linear mixed models. As biomarkers for peripheral IFN responses, peripheral blood natural killer cells were assessed for phosphorylated signal transducer and activator of transcription 1 (pSTAT1) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and degranulation. Nine of 13 (69%) patients achieved sustained virological response at 12 weeks off therapy (SVR12), and 4 experienced virological breakthroughs between weeks 4 and 12. Patients who achieved SVR12 displayed higher ISG expression levels in baseline liver biopsies and a higher frequency of pSTAT1 and TRAIL-expressing, degranulating natural killer cells in baseline blood samples than those who experienced virological breakthrough. Comparing gene expression levels from baseline and on-therapy biopsies, 408 genes (±1.2-fold, P < 0.01) were differentially expressed. Genes down-regulated on treatment were predominantly ISGs. Down-regulation of ISGs was rapid and correlated with HCV RNA suppression. Conclusion: An enhanced IFN signature is observed at baseline in liver and blood of patients who achieve SVR12 compared to those who experience a virological breakthrough; the findings suggest that innate immunity may contribute to clearance of HCV during DAA therapy by preventing the emergence of resistance-associated substitutions that lead to viral breakthrough during DAA therapy.


Asunto(s)
Antivirales/uso terapéutico , Expresión Génica , Hepatitis C/tratamiento farmacológico , Imidazoles/uso terapéutico , Inmunidad Innata , Isoquinolinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Carbamatos , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Hepatitis C/inmunología , Hepatitis C/metabolismo , Humanos , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Pirrolidinas , ARN Mensajero/metabolismo , Resultado del Tratamiento , Valina/análogos & derivados
19.
Neurobiol Learn Mem ; 131: 36-45, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26976088

RESUMEN

The strategies utilized to effectively perform a given task change with practice and experience. During a spatial navigation task, with relatively little training, performance is typically attentive enabling an individual to locate the position of a goal by relying on spatial landmarks. These (place) strategies require an intact hippocampus. With task repetition, performance becomes automatic; the same goal is reached using a fixed response or sequence of actions. These (response) strategies require an intact striatum. The current work aims to understand the activation patterns across these neural structures during this experience-dependent strategy transition. This was accomplished by region-specific measurement of activity-dependent immediate early gene expression among rats trained to different degrees on a dual-solution task (i.e., a task that can be solved using either place or response navigation). As expected, rats increased their reliance on response navigation with extended task experience. In addition, dorsal hippocampal expression of the immediate early gene Arc was considerably reduced in rats that used a response strategy late in training (as compared with hippocampal expression in rats that used a place strategy early in training). In line with these data, vicarious trial and error, a behavior linked to hippocampal function, also decreased with task repetition. Although Arc mRNA expression in dorsal medial or lateral striatum alone did not correlate with training stage, the ratio of expression in the medial striatum to that in the lateral striatum was relatively high among rats that used a place strategy early in training as compared with the ratio among over-trained response rats. Altogether, these results identify specific changes in the activation of dissociated neural systems that may underlie the experience-dependent emergence of response-based automatic navigation.


Asunto(s)
Proteínas del Citoesqueleto/metabolismo , Regulación de la Expresión Génica/fisiología , Genes Inmediatos-Precoces/fisiología , Hipocampo/metabolismo , Aprendizaje por Laberinto/fisiología , Neostriado/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Navegación Espacial/fisiología , Animales , Conducta Animal/fisiología , Masculino , Ratas , Ratas Long-Evans
20.
Exp Brain Res ; 234(12): 3509-3522, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27501731

RESUMEN

Research on the crossmodal correspondences has revealed that seemingly unrelated perceptual information can be matched across the senses in a manner that is consistent across individuals. An interesting extension of this line of research is to study how sensory information biases action. In the present study, we investigated whether different sounds (i.e. tones and piano chords) would bias participants' hand movements in a free movement task. Right-handed participants were instructed to move a computer mouse in order to represent three tones and two chords. They also had to rate each sound in terms of three visual analogue scales (slow-fast, unpleasant-pleasant, and weak-strong). The results demonstrate that tones and chords influence hand movements, with higher-(lower-)pitched sounds giving rise to a significant bias towards upper (lower) locations in space. These results are discussed in terms of the literature on forward models, embodied cognition, crossmodal correspondences, and mental imagery. Potential applications sports and rehabilitation are discussed briefly.


Asunto(s)
Percepción Auditiva/fisiología , Mano , Movimiento/fisiología , Sonido , Estimulación Acústica , Adolescente , Adulto , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Escala Visual Analógica , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA