Placenta-Specific miR-125b Overexpression Leads to Increased Rates of Pregnancy Loss in Mice

Pregnancy loss (PL) is one of the common complications that women can experience during pregnancy, with an occurrence rate of 1 to 5%. The potential causes of pregnancy loss are unclear, with no effective treatment modalities being available. It has been previously reported that the level of miR-125b was significantly increased in placentas of PL patients. However, the role of miR-125b in the development of PL still remains unknown. In the current study, an miR-125b placenta-specific over-expression model was constructed by lentiviral transfecting zona-free mouse embryos followed by embryo transfer. On gestation day 15, it was observed that the placenta was significantly smaller in the miR-125b placenta-specific overexpression group than the control group. Additionally, the abortion rate of the miR-125b placenta-specific overexpression group was markedly higher than in the control group. The blood vessel diameter was larger in the miR-125b-overexpressing specific placenta. In addition, miR-125b-overexpressing HTR8 and JEG3 cell lines were also generated to analyze the migration and invasion ability of trophoblasts. The results showed that miR-125b overexpression significantly suppressed the migration and invasion ability of HTR8 and JEG3 cells. Overall, our results demonstrated that miR-125b can affect embryo implantation through modulating placenta angiogenesis and trophoblast cell invasion capacity that can lead to PL.

Heterogeneous recruitment abilities to RNA polymerases generate nonlinear scaling of gene expression with cell volume

While most genes’ expression levels are proportional to cell volumes, some genes exhibit nonlinear scaling between their expression levels and cell volume. Therefore, their mRNA and protein concentrations change as the cell volume increases, which often have crucial biological functions such as cell-cycle regulation. However, the biophysical mechanism underlying the nonlinear scaling between gene expression and cell volume is still unclear. In this work, we show that the nonlinear scaling is a direct consequence of the heterogeneous recruitment abilities of promoters to RNA polymerases based on a gene expression model at the whole-cell level. Those genes with weaker (stronger) recruitment abilities than the average ability spontaneously exhibit superlinear (sublinear) scaling with cell volume. Analysis of the promoter sequences and the nonlinear scaling of Saccharomyces cerevisiae’s mRNA levels shows that motifs associated with transcription regulation are indeed enriched in genes exhibiting nonlinear scaling, in concert with our model.

Caracterización de un modelo murino de enterocolitis necrotizante

Introducción: La enterocolitis necrotizante (ECN) es la patología gastrointestinal de las más comunes y devastadoras en recién nacido con muy bajo peso al nacer (rango entre 500-1500g) y se caracteriza por inflamación y necrosis intestinal. Los objetivos de este estudio fueron desarrollar un modelo murino de ECN así como un modelo de sobreexpresión de proteínas en el intestino mediante la administración enteral mediante sonda de vectores lentivirales. Métodos: Para el modelo de ECN se utilizaron cepas de ratón C57BL6 y CD1 a los cuales se les trató por 6 veces cada dos horas con una dosis de anoxia con CO2 al 100% durante 10 o 7.5 minutos seguida una reoxigenación mediante hiperoxia al 95% por 5 minutos. Además, para activar el sistema inmune se administró LPS en las primeras dos dosis. Para la sobreexpresión de prolactina (PRL) en el intestino se administraron vectores lentivirales que sobreexpresan GFP (como control) o PRL por vía enteral a ratones CD1 en edades postnatales P2 y P3. Posteriormente se analizó la presencia de GFP y prolactina de las muestras de intestino mediante visualización por microscopia de fluorescencia y Western blot, respectivamente. Resultados: Se obtuvo una mortalidad del 45% y una eficiencia de desarrollo de ECN entre los animales vivos del 100% en ratones CD1 de edad postnatal P1, en contraste con la mortalidad de 85% y la eficiencia de desarrollo de ECN entre los animales vivos del 0% en ratones C57Bl6 de P1. En relación al modelo de sobreexpresión de proteínas en el intestino, se detectó GFP en el intestino de ratones administrados con 106 TU/ml vectores lentivirales para la sobreexpresión de GFP en el día P2 y evaluados 24 horas después. No se observó la sobreexpresión de PRL en el intestino de ratones administrados con 106 y 108 TU/ml vectores lentivirales para la sobreexpresión de PRL en los días P2 y P3 y evaluados 48 horas después. Conclusión: El modelo de ECN en ratones CD1 de P1 tuvo una efectividad del 100% a pesar de una mortalidad elevada. Además, se logró estandarizar el método para la sobreexpresión de proteínas en el intestino de ratones en P2 24 horas después de la administración de vectores lentivirales por la via enteral. La determinación de sobreexpresión de PRL en el intestino no fue conclusiva. Background: Necrotizating enterocolitis (NEC) is one of the most common and devastating gastrointestinal disease in newborns with very low weight birth (range among 500 -1500 g). NEC is characterized by intestinal inflammation and necrosis. Our aims of this study were to develop a NEC murine model and a intestinal protein expression model by means of enteral administration of lentiviral vectors. Method: For the NEC model were used C57BL6 and CD1 mice which were treated with anoxia with 100% CO2 for 10 or 7.5 minutes followed by 95% O2 for 5 minutes. This treatment was repeated six times with a 2 hours interval. Moreover, to activate the immune system, LPS was administrated orally in the first two doses. For the overexpression of prolactin (PRL) in the intestine, lentiviral vectors that overexpress GFP (as a control) or PRL were administered by orally to CD1 mice at postnatal ages P2 and P3. Then, the presence of GFP and prolactin in the intestine samples was analyzed by fluorescence microscopy and Western blot, respectively. Result: Mortality of 45% and a NEC development efficiency of 100% was obtained among live animals in CD1 mice of P1 postnatal age, in contrast to the mortality of 85% and development efficiency of 0% among live animals in C57BL6 mice of P1 age. In relation to the protein overexpression model in the intestine, GFP was detected in the mice gut administrated with 106 lentiviral vectors for the GFP overexpression on P2 evaluated 24 hours later. PRL overexpression was not observed in mice that received on day P1 postnatal 106 and 108 TU/ml of lentiviral vectors for the overexpression of PRL and evaluated on days P2 and P3. Conclusion: NEC model had an effectiveness of 100% in CD1 mice of 1 day of life, despite the high mortality. Moreover, a method for protein overexpression in the intestine was standardized. Lenviral vectors were orally administered 24 hours after birth and the expression of the protein was detected 24 hours later. Prolactin overexpression determination was not conclusive.

Evaluation of Genotype-Based Gene Expression Model Performance: A Cross-Framework and Cross-Dataset Study

Predicting gene expression from genotyped data is valuable for studying inaccessible tissues such as the brain. Herein we present eGenScore, a polygenic/poly-variation method, and compare it with PrediXcan, a method based on regularized linear regression using elastic nets. While both methods have the same purpose of predicting gene expression based on genotype, they carry important methodological differences. We compared the performance of expression quantitative trait loci (eQTL) models to predict gene expression in the frontal cortex, comparing across these frameworks (eGenScore vs. PrediXcan) and training datasets (BrainEAC, which is brain-specific, vs. GTEx, which has data across multiple tissues). In addition to internal five-fold cross-validation, we externally validated the gene expression models using the CommonMind Consortium database. Our results showed that (1) PrediXcan outperforms eGenScore regardless of the training database used; and (2) when using PrediXcan, the performance of the eQTL models in frontal cortex is higher when trained with GTEx than with BrainEAC.

Clouds of bubbles in a viscoplastic fluid

Viscoplastic fluids can hold bubbles/particles stationary by balancing the buoyancy stress with the yield stress – the key parameter here is the yield number $Y$ , the ratio of the yield stress to the buoyancy stress. In the present study, we investigate a suspension of bubbles in a yield-stress fluid. More precisely, we compute how much is the gas fraction $\phi$ that could be held trapped in a yield-stress fluid without motion. Here the goal is to shed light on how the bubbles feel their neighbours through the stress field and to compute the critical yield number for a bubble cloud beyond which the flow is suppressed. We perform two-dimensional computations in a full periodic box with randomized positions of the monosized circular bubbles. A large number of configurations are investigated to obtain statistically converged results. We intuitively expect that for higher volume fractions, the critical yield number is larger. Not only here do we establish that this is the case, but also we show that short-range interactions of bubbles increase the critical yield number even more dramatically for bubble clouds. The results show that the critical yield number is a linear function of volume fraction in the dilute regime. An algebraic expression model is given to approximate the critical yield number (semi-empirically) based on the numerical experiment in the studied range of $0\le \phi \le 0.31$ , together with lower and upper estimates.

The Dynamic Changes of Transcription Factors During the Development Processes of Human Biparental and Uniparental Embryos

Previous studies have revealed that transcription factors (TFs) play important roles in biparental (BI) early human embryogenesis. However, the contribution of TFs during early uniparental embryo development is still largely unknown. Here we systematically studied the expression profiles of transcription factors in early embryonic development and revealed the dynamic changes of TFs in human biparental and uniparental embryogenesis by single-cell RNA sequencing (scRNA-seq). In general, the TF expression model of uniparental embryos showed a high degree of conformity with biparental embryos. The detailed network analysis of three different types of embryos identified that 10 out of 17 hub TFs were shared or specifically owned, such as ZNF480, ZNF581, PHB, and POU5F1, were four shared TFs, ZFN534, GTF3A, ZNF771, TEAD4, and LIN28A, were androgenic (AG) specific TFs, and ZFP42 was the only one parthenogenetic (PG) specific TF. All the four shared TFs were validated using human embryonic stem cell (hESC) differentiation experiments; most of their target genes are responsible for stem cell maintenance and differentiation. We also found that Zf-C2H2, HMG, and MYB were three dominant transcription factor families that appeared in early embryogenesis. Altogether, our work provides a comprehensive regulatory framework and better understanding of TF function in human biparental and uniparental embryogenesis.

Organic Anion Transporting Polypeptide 1B1 Is a Potential Reporter for Dual MR and Optical Imaging

Membrane proteins responsible for transporting magnetic resonance (MR) and fluorescent contrast agents are of particular importance because they are potential reporter proteins in noninvasive molecular imaging. Gadobenate dimeglumine (Gd-BOPTA), a liver-specific MR contrast agent, has been used globally for more than 10 years. However, the corresponding molecular transportation mechanism has not been validated. We previously reported that the organic anion transporting polypeptide (OATP) 1B3 has an uptake capability for both MR agents (Gd-EOB-DTPA) and indocyanine green (ICG), a clinically available near-infrared (NIR) fluorescent dye. This study further evaluated OATP1B1, another polypeptide of the OATP family, to determine its reporter capability. In the OATP1B1 transfected 293T transient expression model, both Gd-BOPTA and Gd-EOB-DTPA uptake were confirmed through 1.5 T MR imaging. In the constant OAPT1B1 and OATP1B3 expression model in the HT-1080 cell line, both HT-1080-OAPT1B1 and HT-1080-OATP1B3 were observed to ingest Gd-BOPTA and Gd-EOB-DTPA. Lastly, we validated the ICG uptake capability of both OATP1B1 and OATP1B3. OAPT1B3 exhibited a superior ICG uptake capability to that of OAPT1B1. We conclude that OATP1B1 is a potential reporter for dual MR and NIR fluorescent molecular imaging, especially in conjunction with Gd-BOPTA.

portugues Corpo criativo e eficaz no futebol é mais caosal: perspectivas pautadas na periodização tática sobre a propensão para o ato criativo (Creative and effective body in football is more chaosal: perspectives based on tactical periodization about the propensit

A metodologia Periodização Tática (PT) expressa, em geral, que o contexto Específico, com E maiúsculo, no qual o jogador está envolvido, serve como útero artificial para ações táticas criativas e eficazes. Por tais razões, o presente ensaio objetivou realizar uma reflexão crítica sobre a criatividade e eficácia das expressões corpóreas no treino e no jogo de futebol de acordo com os paradigmas científicos emergentes no século XX tais como o paradigma dos sistemas, do caos, fractais e das estruturas dissipativas. Este ensaio crítico foi regido por dois documentos: a obra de Paulo Cunha e Silva (2000) intitulada «A imprevisibilidade da Revisão: Causalidade, Casualidade e Caosalidade», utilizada para justificar as considerações aludidas por Vitor Frade (2010) no documento intitulado «Último Cântico» sobre a metodologia Periodização Tática (PT) como metodologia catalizadora deste corpo criativo e eficaz no futebol. Métodos: foi realizada uma revisão narrativa destes documentos a fim de vincular suas declarações sobre o corpo, criatividade, eficácia, treino e jogo de futebol. Desenvolvimento: perante a exposição dos conteúdos abordados pelas obras supracitadas, apontou-se para a importância do papel da Especificidade do treinamento defendida pela metodologia PT, a nutrir, numa dada intencionalidade prévia, as ações corpóreas criativas em condições caosais, i.e., caóticas e determinísticas. Comentários: a metodologia PT se apoia, fundamentada em várias asserções críticas aos paradigmas científicos clássicos, como uma contraposição em termos de metodologia de treinamento de futebol ao modelo de expressão corporal fechado como se aplicava anteriormente. Neste sentido, é fundamental que se considere a gestualidade do corpo do jogador de futebol, no seu contexto ecológico, como mais propicio à criatividade e, por consequência, mais eficaz. Abstract. The Tactical Periodization (PT) methodology expresses, in general, that the Specific context, with a capital E, in which the player is involved, serves as an artificial uterus for creative and effective tactical actions. For these reasons, this essay aimed to carry out a critical reflection on the creativity and effectiveness of body expressions in soccer training and games according to the scientific paradigms emerging in the 20th century such as the paradigm of systems, chaos, fractals and dissipative structures. This critical essay was governed by two documents: the work of Paulo Cunha e Silva (2000) entitled «The unpredictability of the Review: Causality, Casuality and Chaosality», used to justify the considerations referred to by Vitor Frade (2010) in the document entitled «Last Song «on the Tactical Periodization (PT) methodology as a catalyst for this creative and effective body in football. Methods: a narrative review of these documents was carried out in order to link their statements about the body, creativity, effectiveness, training and soccer game. Development: in view of the exposure of the content covered by the aforementioned works, the importance of the specificity of the training defended by the PT methodology was pointed out, to nurture, in a given previous intentionality, creative bodily actions in chaos, ie, chaotic and deterministic conditions . Comments: the PT methodology is supported, based on several critical assertions to the classic scientific paradigms, as a counterpoint in terms of football training methodology to the closed body expression model as previously applied. In this sense, it is essential to consider the gesturality of the football player’s body, in its ecological context, as more conducive to creativity and, consequently, more effective.