25 research outputs found

    PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells

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    Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Brinkmeier, Michelle. University of Michigan; Estados UnidosFil: Mortensen, Amanda H. University of Michigan; Estados UnidosFil: Camper, Sally. University of Michigan; Estados Unido

    Characterizing sampling and quality screening biases in infrared and microwave limb sounding

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    This study investigates orbital sampling biases and evaluates the additional impact caused by data quality screening for the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and the Aura Microwave Limb Sounder (MLS). MIPAS acts as a proxy for typical infrared limb emission sounders, while MLS acts as a proxy for microwave limb sounders. These biases were calculated for temperature and several trace gases by interpolating model fields to real sampling patterns and, additionally, screening those locations as directed by their corresponding quality criteria. Both instruments have dense uniform sampling patterns typical of limb emission sounders, producing almost identical sampling biases. However, there is a substantial difference between the number of locations discarded. MIPAS, as a mid-infrared instrument, is very sensitive to clouds, and measurements affected by them are thus rejected from the analysis. For example, in the tropics, the MIPAS yield is strongly affected by clouds, while MLS is mostly unaffected. The results show that upper-tropospheric sampling biases in zonally averaged data, for both instruments, can be up to 10 to 30 %, depending on the species, and up to 3 K for temperature. For MIPAS, the sampling reduction due to quality screening worsens the biases, leading to values as large as 30 to 100 % for the trace gases and expanding the 3 K bias region for temperature. This type of sampling bias is largely induced by the geophysical origins of the screening (e.g. clouds). Further, analysis of long-term time series reveals that these additional quality screening biases may affect the ability to accurately detect upper-tropospheric long-term changes using such data. In contrast, MLS data quality screening removes sufficiently few points that no additional bias is introduced, although its penetration is limited to the upper troposphere, while MIPAS may cover well into the mid-troposphere in cloud-free scenarios. We emphasize that the results of this study refer only to the representativeness of the respective data, not to their intrinsic quality

    Effects of 3 mg/kg Body Mass of Caffeine on the Performance of Jiu-Jitsu Elite Athletes.

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    The effects of caffeine were investigated in judo, boxing, taekwondo and Brazilian jiu-jitsu. However, this substance was never investigated regarding traditional jiu-jitsu. Therefore, the aim of this research was to analyze the effects of caffeine in the Special Judo Fitness Test (SJFT) and technical variables during combat in traditional jiu-jitsu elite athletes. Methods: Twenty-two young professionals of traditional jiu-jitsu, 11 men and 11 women (age = 22 ± 4 (18–33) years, body mass = 66.6 ± 10.8 (46.2–86.1) kg, height = 1.70 ± 0.9 (1.55–1.85) m) with 15 ± 7 years of experience in traditional jiu-jitsu, participated in a double-blind, counterbalanced, crossover study. In two different conditions, the traditional jiu-jitsu athletes ingested 3 mg/kg body mass of caffeine or a placebo. After 60 min, they performed the SJFT test to measure throwing performance, and subsequently, combat to analyze offensive and defensive hitting techniques. Results: Caffeine had a main effect on the number of throws during the SJFT test (P < 0.01). In addition, it was effective in sets 2 (13 ± 2 vs. 14 ± 2; p = 0.01) and 3 (12 ± 2 vs. 13 ± 1; p = 0.03). There was also a main effect during the test on heart rate when caffeine was ingested (F = 12.48, p < 0.01). The effects of caffeine were similar compared to the placebo condition regarding performance during combat both in offensive and defensive fighting variables Conclusions: the pre-exercise ingestion of 3 mg/kg body mass of caffeine increased performance in the SJFT test, decreased fatigue perception, and increased power and endurance perception in professionally traditional jiu-jitsu athletes. However, it did not seem to improve offensive and defensive technical actions during combat.post-print1054 K

    Caffeine Doses of 3 mg/kg Increase Unilateral and Bilateral Vertical Jump Outcomes in Elite Traditional Jiu-Jitsu Athletes.

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    Caffeine increases vertical jump, although its effects on kinetics and kinematics during different phases of bilateral and unilateral jumps remain unclear. The aim of this study was to identify the effects of 3 mg/kg on kinetic, kinematic and temporal variables in the concentric and eccentric phases of bilateral and unilateral countermovement jumps. A total of 16 Spanish national team traditional Jiu-Jitsu athletes took part in two experimental trials (3 mg/kg caffeine or placebo) in a randomized, double-blind crossover study. Sixty minutes after ingestion, bilateral and unilateral jumps were performed on a force platform. Compared to the placebo, caffeine increased bilateral jump height (p = 0.008; D% = 4.40), flight time (p = 0.008; D% = 2.20), flight time:contraction time (p = 0.029; D% = 8.90), concentric impulse (p = 0.018; D% = 1.80), peak power (p = 0.049; D% = 2.50), RSI-modified (p = 0.011; D% = 11.50) and eccentric mean braking force (p = 0.045; D% = 4.00). Additionally, caffeine increased unilateral RSI-mod in both legs (Left: p = 0.034; D% = 7.65; Right: p = 0.004; D% = 11.83), left leg flight time (p = 0.044; D% = 1.91), left leg jump height (p = 0.039; D% = 3.75) and right leg FT:CT (p = 0.040; D% = 9.72). Caffeine in a dose of 3 mg/kg BM in elite Jiu- Jitsu athletes is a recommended ergogenic aid as it increased performance of bilateral and unilateral vertical jumps. These increases were also accompanied by modified jump execution during the different phases of the countermovement prior to take-off.post-print746 K

    First evidence of middle atmospheric HO_2 response to 27 day solar cycles from satellite observations

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    HO_2 and OH, also known as HO_x, play an important role in controlling middle atmospheric O_3. Due to their photochemical production and short chemical lifetimes, HO_x are expected to respond rapidly to solar irradiance changes, resulting in O_3 variability. While OH solar cycle signals have been investigated, HO_2 studies have been limited by the lack of reliable observations. Here we present the first evidence of HO_2 variability during solar 27 day cycles by investigating the recently developed HO_2 data from the Aura Microwave Limb Sounder (MLS). We focus on 2012–2015, when solar variability is strong near the peak of Solar Cycle 24. The features of HO_2 variability, with the strongest signals at 0.01–0.068 hPa, correlate well with those of solar Lyman α. When continuous MLS OH observations are not available, the new HO_2 data could be a promising alternative for investigating HO_x variability and the corresponding impacts on O_3 and the climate

    Genetics of combined pituitary hormone deficiency: Roadmap into the genome era

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    The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. Weexpect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity.Wediscuss approaches for future research in the genetics of CPHD.Fil: Fang, Qing. University of Michigan; Estados UnidosFil: George, Akima S.. University of Michigan; Estados UnidosFil: Brinkmeier, Michelle L.. University of Michigan; Estados UnidosFil: Mortensen, Amanda H.. University of Michigan; Estados UnidosFil: Gergics, Peter. University of Michigan; Estados UnidosFil: Cheung, Leonard Y.M.. University of Michigan; Estados UnidosFil: Daly, Alexandre Z.. University of Michigan; Estados UnidosFil: Ajmal, Adnan. University of Michigan; Estados UnidosFil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Bilge Ozel, A.. University of Michigan; Estados UnidosFil: Kitzman, Jacob. University of Michigan; Estados UnidosFil: Mills, Ryan E.. University of Michigan; Estados UnidosFil: Li, Jun Z.. University of Michigan; Estados UnidosFil: Camper, Sally. University of Michigan; Estados Unido

    La modernización del campo y la globalización económica

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    El presente libro incluye las ponencias presentadas en el del XIV Seminario de Economía Agrícola del Tercer Mundo, en el cual participan distinguidos especialistas nacionales y extranjeros, atentos a la dinámica y a la problemática actual de la producción primaria y el desarrollo rural de México y el mundo. El interés se centró en la elaboración de análisis críticos y propositivos en torno a los cambios ocurridos durante los últimos años en el sector rural mexicano a la luz del proceso de modernización y globalización económica en que está inmerso nuestro país. Los trabajos presentados en el Seminario muestran un consenso básico en torno a la importancia estratégica del sector agropecuario y rural para la construcción de un proyecto de desarrollo nacional sostenido, equilibrado y democrático

    Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients

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    Wearable device for automatic detection and monitoring of freezing in Parkinson’s disease

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    Freezing of gait (FOG) in Parkinson’s disease (PD) is described as a short-term episode of absence or considerable decrease of movement despite the intention of moving forward. FOG is related to risk of falls and low quality of life for individuals with PD. FOG has been studied and analyzed through different techniques, including inertial movement units (IMUs) and motion capture systems (MOCAP), both along with robust algorithms. Still, there is not a standardized methodology to identify nor quantify freezing episodes (FEs). In a previous work from our group, a new methodology was developed to differentiate FEs from normal movement using position data obtained from a motion capture system. The purpose of this study is to determine if this methodology is equally effective identifying FEs when using IMUs. Twenty subjects with PD will perform two different gait-related tasks. Trials will be tracked by IMUs and filmed by a video camera; data from IMUs will be compared to the time occurrence of FEs obtained from the videos. We expect this methodology will successfully detect FEs with IMUs’ data. Results would allow the development of a wearable device able to detect and monitor FOG. It is expected that the use of this type of devices would allow clinicians to better understand FOG and improve patients’ care
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