132 research outputs found
Endosperm Evolution by Duplicated and Neofunctionalized Type I MADS-Box Transcription Factors
MADS-box transcription factors (TFs) are present in nearly all major eukaryotic groups. They are divided into Type I and Type II that differ in domain structure, functional roles, and rates of evolution. In flowering plants, major evolutionary innovations like flowers, ovules, and fruits have been closely connected to Type II MADS-box TFs. The role of Type I MADS-box TFs in angiosperm evolution remains to be identified. Here, we show that the formation of angiosperm-specific Type I MADS-box clades of M gamma and M gamma-interacting M alpha genes (M alpha*) can be tracked back to the ancestor of all angiosperms. Angiosperm-specific M gamma and M alpha* genes were preferentially expressed in the endosperm, consistent with their proposed function as heterodimers in the angiosperm-specific embryo nourishing endosperm tissue. We propose that duplication and diversification of Type I MADS genes underpin the evolution of the endosperm, a developmental innovation closely connected to the origin and success of angiosperms
Alismatales da bacia do alto e médio rio Araguaia (Brasil)
The present study deals with a survey of the order Alismatales (except Araceae) in the upper and middle Araguaia River region located between the states of Mato Grosso and Goiás, Brazil. Field expeditions were carried out during the rainy and dry seasons. The route covered approximately 2,000 km and 41 aquatic environments were visited. Thirteen taxa, representing the families Alismataceae (nine), Hydrocharitaceae (three) and Najadaceae (one) were identified. Keys for the identification of families and species in field, brief diagnoses, schematic illustrations and relevant comments were elaborated based on field observations as well as on the analysis of the specimens collected.Realizou-se o levantamento de espécies da ordem Alismatales (exceto Araceae) ocorrentes na região do alto e médio rio Araguaia, entre os estados de Mato Grosso e Goiás, Brasil. As expedições para coleta de material, ocorridas tanto na época de chuvas quanto na seca, totalizaram cerca de 2.000 km percorridos, abrangendo 41 ambientes aquáticos. Foram identificados treze táxons pertencentes às famílias Alismataceae (nove), Hydrocharitaceae (três) e Najadaceae (uma). Foram elaboradas chaves para identificação em campo das famílias e espécies, descrições breves, ilustrações esquemáticas e comentários relevantes, baseados em dados levantados em campo e através da análise do material coletado.43945
Updated Phylogeny and Protein Structure Predictions Revise the Hypothesis on the Origin of MADS-box Transcription Factors in Land Plants
MADS-box transcription factors (TFs), among the first TFs extensively studied, exhibit a wide distribution across eukaryotes and play diverse functional roles. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). Type I and II genes have been considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing availability of eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs were lost in the MRCA of Archaeplastida (the kingdom Plantae sensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type before the divergence of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. The recruitment of these originally stress-responsive TFs into developmental programs, including those underlying reproduction, may have facilitated the adaptation to the terrestrial environment
Loss of Xenopus cadherin-11 leads to increased Wnt/β-catenin signaling and up-regulation of target genes c-myc and cyclin D1 in neural crest
AbstractXenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member, which is predominantly expressed in cranial neural crest cells (NCCs). Apart from mediating cell–cell adhesion it promotes cranial NCC migration by initiating filopodia and lamellipodia formation. Here, we demonstrate an unexpected function of Xcadherin-11 in NCC specification by interfering with canonical Wnt/β-catenin signaling. Loss-of-function experiments, using a specific antisense morpholino oligonucleotide against Xcadherin-11, display a nuclear β-catenin localization in cranial NCCs and a broader expression domain of the proto-oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and Sox10. Thereby, we could allocate NCC proliferation and specification to different gene functions. To clarify which domain in Xcadherin-11 is required for early NCC development we tested different deletion mutants for their rescue ability in Xcadherin-11 morphants. We identified the cytoplasmic tail, specifically the β-catenin binding domain, to be necessary for proper NCC development. We propose that Xcadherin-11 is necessary for controlled NCC proliferation and early NCC specification in tuning the expression of the canonical Wnt/β-catenin target genes cyclin D1 and c-myc by regulating the concentration of the nuclear pool of β-catenin
SAIPy: A Python Package for single station Earthquake Monitoring using Deep Learning
Seismology has witnessed significant advancements in recent years with the
application of deep learning methods to address a broad range of problems.
These techniques have demonstrated their remarkable ability to effectively
extract statistical properties from extensive datasets, surpassing the
capabilities of traditional approaches to an extent. In this study, we present
SAIPy, an open source Python package specifically developed for fast data
processing by implementing deep learning. SAIPy offers solutions for multiple
seismological tasks, including earthquake detection, magnitude estimation,
seismic phase picking, and polarity identification. We introduce upgraded
versions of previously published models such as CREIMERT capable of identifying
earthquakes with an accuracy above 99.8 percent and a root mean squared error
of 0.38 unit in magnitude estimation. These upgraded models outperform state of
the art approaches like the Vision Transformer network. SAIPy provides an API
that simplifies the integration of these advanced models, including CREIMERT,
DynaPickerv2, and PolarCAP, along with benchmark datasets. The package has the
potential to be used for real time earthquake monitoring to enable timely
actions to mitigate the impact of seismic events. Ongoing development efforts
aim to enhance the performance of SAIPy and incorporate additional features
that enhance exploration efforts, and it also would be interesting to approach
the retraining of the whole package as a multi-task learning problem
Automated bolus advisor control and usability study (ABACUS): does use of an insulin bolus advisor improve glycaemic control in patients failing multiple daily insulin injection (MDI) therapy? [NCT01460446]
BACKGROUND: People with T1DM and insulin-treated T2DM often do not follow and/or adjust their insulin regimens as needed. Key contributors to treatment non-adherence are fear of hypoglycaemia, difficulty and lack of self-efficacy associated with insulin dose determination. Because manual calculation of insulin boluses is both complex and time consuming, people may rely on empirical estimates, which can result in persistent hypoglycaemia and/or hyperglycaemia. Use of automated bolus advisors (BA) has been shown to help insulin pump users to more accurately meet prandial insulin dosage requirements, improve postprandial glycaemic excursions, and achieve optimal glycaemic control with an increased time within optimal range. Use of a BA containing an early algorithm based on sliding scales for insulin dosing has also been shown to improve HbA1c levels in people treated with multiple daily insulin injections (MDI). We designed a study to determine if use of an automated BA can improve clinical and psychosocial outcomes in people treated with MDI. METHODS/DESIGN: The Automated Bolus Advisor Control and Usability Study (ABACUS) is a 6-month, prospective, randomised, multi-centre, multi-national trial to determine if automated BA use improves glycaemic control as measured by a change in HbA1c in people using MDI with elevated HbA1c levels (#62;7.5%). A total of 226 T1DM and T2DM participants will be recruited. Anticipated attrition of 20% will yield a sample size of 90 participants, which will provide #62;80% power to detect a mean difference of 0.5%, with SD of 0.9%, using a one-sided 5% t-test, with 5% significance level. Other measures of glycaemic control, self-care behaviours and psychosocial issues will also be assessed. DISCUSSION: It is critical that healthcare providers utilise available technologies that both facilitate effective glucose management and address concerns about safety and lifestyle. Automated BAs may help people using MDI to manage their diabetes more effectively and minimise the risk of long-term diabetes related complications. Findings from a recent study suggest that BA use positively addresses both safety and lifestyle concerns; however, randomised trials are needed to confirm these perceptions and determine whether bolus advisor use improves clinical outcomes. Our study is designed to make these assessments. TRIAL REGISTRATION: NCT0146044
Significância prognóstica da expressão de ki-67, receptores de estrógeno e receptores de progesterona em pacientes com melanoma cutâneo / Prognostic significance of ki-67, estrogen receptors and progesterone receptors expression in patients with cutaneous melanoma
Introdução: O Melanoma Cutâneo (MC) é a forma mais agressiva de câncer de pele. Pouco se conhece sobre marcadores biológicos que representam uma maior ou menor agressividade desta neoplasia. Estudos indicam uma relação entre os hormônios sexuais e o índice de proliferação celular (Ki-67) com o MC. Objetivo: Analisar o perfil molecular de pacientes com MC invasor, verificando a significância prognóstica dos Receptores de Estrógeno (RE), Receptores de Progesterona (RP) e Ki-67. Métodos: Trata-se de um estudo caso-controle que analisou 179 casos de MC invasor, que ocorreram na região dos Campos Gerais – PR, Brasil, no período de 2002 a 2014. Foi construído um banco de dados com informações anatomopatológicas, clínicas, e imuno-histoquímicas. Posteriormente, os dados foram analisados pelos testes Kolmogorov-Smirnov, Student uni-caudal e exato de Fisher. Resultados: A incidência de metástases foi maior nos casos de Ki-67 alto (p=0,021). Observou-se que a marcação citoplasmática, tanto pelo RE, quanto pelo RP, está associada com pacientes que não possuem metástases (p=0,006; 0,001 respectivamente). Sexo masculino, sítio anatômico, estadiamento clínico, nível de Clark, espessura de Breslow, ulceração e invasão linfática foram os fatores que apresentaram significância estatística como preditores de metástases. Não foi evidenciada correlação entre o Ki- 67 e os outros marcadores. Conclusão: Este estudo foi estatisticamente significante, corroborando as evidências do envolvimento dos hormônios sexuais e do Ki-67 na progressão do MC. Novos estudos devem ser realizados para comprovar os reais papéis do Ki-67 e dos hormônios sexuais, assim como os mecanismos de ação por eles adotados
Reviewing the environmental and human health knowledge base of carbon nanotubes.
Carbon nanotubes (CNTs) are considered one of the most promising materials in nanotechnology, with attractive properties for many technologic applications. The different synthesis, purification, and postprocessing methods produce CNTs with different physical characteristics, which can be applied in different fields ranging from composite materials, medical applications, and electronics to energy storage. The widespread projected use of CNTs makes it important to understand their potential harmful effects. In this environmental health review we observed a remarkable range of results of some of the toxicology studies. The comparability should be improved by further standardization and introduction of reference materials. However, at present the findings of this review suggest several key points: a) there are different types of CNTs, and therefore they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. The properties of CNTs suggest a possible accumulation along the food chain and high persistence. In organisms the absorption, distribution, metabolism, excretion, and toxicity of CNTs depend on the inherent physical and chemical characteristics such as CNT functionalization, coating, length, and agglomeration state that are influenced by the external environmental conditions during CNT production, use, and disposal stages. Characterized exposure scenarios could therefore be useful when conducting toxicologic studies. However, CNTs produce a toxic response upon reaching the lungs in sufficient quantity; this reaction is produced in a time-and dose-dependent manner. The identification of possible risks to human health and environment is a prerequisite for a successful introduction of CNTs in future applications
Pulsed pressure perturbations, an extra dimension in NMR spectroscopy of proteins
The introduction of multidimensional NMR spectroscopy was a breakthrough in biological NMR methodology because it allowed the unequivocal correlation of different spin states of the system. The introduction of large pressure perturbations in the corresponding radio frequency (RF) pulse sequences adds an extra structural dimension into these experiments. We have developed a microprocessor-controlled pressure jump unit that is able to introduce fast, strong pressure changes at any point in the pulse sequences. Repetitive pressure changes of 80 MPa in the sample tube are thus feasible in less than 30 ms. Two general forms of these experiments are proposed here, the pressure perturbation transient state spectroscopy (PPTSS) and the pressure perturbation state correlation spectroscopy (PPSCS). PPTSS can be used to measure the rate constants and the activation energies and activation volumes for the transition between different conformational states including the folded and unfolded state of proteins, for polymerization-depolymerization processes, and for ligand binding at atomic resolution. PPSCS spectroscopy correlates the NMR parameters of different pressure-induced states of the system, thus allowing the measurement of properties of a given pressure induced state such as a folding intermediate in a different state, for example, the folded state. Selected examples for PPTSS and PPSCS spectroscopy are presented in this Article.DFGBFSFC
IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (T-reg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in T-reg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector T-reg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity
- …