RESUMEN
The craniocaudal (CC) length of the right lobe of the liver (RLL), liver texture, size of the main portal vein, and hemodynamics of the hepatic artery, were sonographically evaluated in female diabetic and non-diabetic patients. A One-way ANOVA, a Tukey's post-hoc test, and a Kruskal-Wallis with post-hoc Dunn's test, were employed. Non-symptomatic differences in liver anatomy were detected among non-controlled type 2 diabetes patients. They exhibited the longest CC length of the RLL (p = 0.04) as well as an enlarged main portal vein (p = 0.04). Hepatic artery resistive index (RI) was higher among controlled type 2 diabetes patients (p = 0.04). These differences were not attributed to fatty infiltration. Non-controlled type 2 diabetes patients exhibited significantly higher alanine aminotransferase, lower high-density lipoprotein cholesterol, and higher triglyceride levels, than in non-type 2 diabetes patients. Longitudinal sonography may provide valuable diagnostic information in the management of type 2 diabetes.
RESUMEN
The liver is one of the principal organs of our body involved in over 500 physiological functions related to metabolism, digestion, immunity, and storage of nutrients, which makes it an essential organ to preserve life. Given that there are a number of approaches to measure liver length through diagnostic 2D sonography, this work aims to determine the most accurate measurement of this organ. Cadaveric specimens (n = 21) were employed to assess measurements in midclavicular line (MCL) and midaxillary line (MAL). Each measurement was calculated in anteroposterior (AP) and craniocaudal (CC) planes. In addition, in situ measurements were obtained by accessing the organ through the anterior thoracoabdominal wall. Statistical differences were detected between MCL and MAL measurements (p < 0.05), a positive correlation between MAL CC and in situ anterior measurements were noted (r = 0.97). Liver size, as assessed through in situ measurements, varied as a funtion of BMI and waist circumference (p < 0.05). It is concluded that CC measurement of the RLL in MAL from the uppermost right hemi-diaphragm to the inferior tip of the right lobe through a horizontal line parallel to the anterior liver wall is the most accurate measurement of the organ by sonography.
RESUMEN
Developing effective assessments of student learning is a challenging task for faculty and even more difficult for those in emerging disciplines that lack readily available resources and standards. With the power of technology-enhanced education and accessible digital learning platforms, instructors are also looking for assessments that work in an online format. This article will be useful for all teachers, but especially for entry-level instructors, in addition to more mature instructors who are looking to become more well versed in assessment, who seek a succinct summary of assessment types to springboard the integration of new forms of assessment of student learning into their courses. In this paper, ten assessment types, all appropriate for face-to-face, blended, and online modalities, are discussed. The assessments are mapped to a set of bioinformatics core competencies with examples of how they have been used to assess student learning. Although bioinformatics is used as the focus of the assessment types, the question types are relevant to many disciplines.
RESUMEN
Antifungal drug discovery and design is very challenging because of the considerable similarities in genetic features and metabolic pathways between fungi and humans. However, cell wall composition represents a notable point of divergence. Therefore, a research strategy was designed to improve our understanding of the mechanisms for maintaining fungal cell wall integrity, and to identify potential targets for new drugs that modulate the underlying protein-protein interactions in Saccharomyces cerevisiae This study defines roles for Wsc2p and Wsc3p and their interacting protein partners in the cell wall integrity signaling and cell survival mechanisms that respond to treatments with fluconazole and hydrogen peroxide. By combined genetic and biochemical approaches, we report the discovery of 12 novel protein interactors of Wsc2p and Wsc3p Of these, Wsc2p interacting partners Gtt1p and Yck2p, have opposing roles in the resistance and sensitivity to fluconazole treatments respectively. The interaction of Wsc2p with Ras2p was confirmed by iMYTH and IP-MS approaches and is shown to play a dominant role in response to oxidative stress induced by hydrogen peroxide. Consistent with an earlier study, Ras2p was also identified as an interacting partner of Wsc1p and Mid2p cell wall integrity signaling proteins. Collectively, this study expands the interaction networks of the mechanosensory proteins of the Cell Wall Integrity pathway.
Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Pared Celular/metabolismo , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
Saccharomyces cerevisiae, the budding yeast, must remodel initial cell shape and cell wall integrity during vegetative growth and pheromone-induced morphogenesis. The cell wall remodeling is monitored and regulated by the cell wall integrity (CWI) signaling pathway. Wsc1p, together with Wsc2p and Wsc3p, belongs to a family of highly O-glycosylated cell surface proteins that function as stress sensors of the cell wall in S. cerevisiae. These cell surface proteins have the main role of activating the CWI signaling pathway by stimulating the small G-protein Rho1p, which subsequently activates protein kinase C (Pkc1p) and a mitogen activated protein (MAP) kinase cascade that activates downstream transcription factors of stress-response genes. Wsc1p, Wsc2p, and Wsc3p possess a cytoplasmic domain where two conserved regions of the sequence have been assessed to be important for Rom2p interaction. Meanwhile, other research groups have also proposed that these transmembrane proteins could support protein-protein interactions with Ras2p. Molecular structures of the cytoplasmic domain of Wsc1p, Wsc2p and Wsc3p were generated using the standard and fully-automated ORCHESTAR procedures provided by the Sybyl-X 2.1.1 program. The tridimensional structure of full length Ras2p was also generated with Phyre2. These protein models were validated with Procheck-PDBsum and ProSA-web tools and subsequently used in docking-based modeling of protein-protein and protein-compound interfaces for extensive structural and functional characterization of their interaction. The results retrieved from STRING 10.5 suggest that the Wsc-family is involved in protein-protein interactions with each other and with Ras2p. Docking-based studies also validated the existence of protein-protein interactions mainly between Motif I (Wsc3p > Wsc1p > Wsc2p) and Ras2p, in agreement with the data provided by STRING 10.5. Additionally, it has shown that Calcofluor White preferably binds to Wsc1p (-9.5 kcal/mol), meanwhile Caspofungin binds to Wsc3p (-9.1 kcal/mol), Wsc1p (-9.1 kcal/mol) and more weakly Wsc2p (-6.9 kcal/mol). Thus, these data suggests Caspofungin as a common inhibitor for the Wsc-family. MTiOpenScreen database has provided a list of new compounds with energy scores higher than those compounds used in our docking studies, thus suggesting these new compounds have a better affinity towards the cytoplasmic domains and Ras2p. Based on these data, there are new and possibly more effective compounds that should be considered as therapeutic agents against yeast infection.
Asunto(s)
Antifúngicos/farmacología , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Proteínas de la Membrana/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Proteínas de Saccharomyces cerevisiae/antagonistas & inhibidores , Saccharomyces cerevisiae/efectos de los fármacos , Proteínas ras/antagonistas & inhibidores , Antifúngicos/química , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas ras/metabolismoRESUMEN
In order to obtain a wider perspective of iron homeostasis in the eye, a comparative study was undertaken of several iron-related parameters (Total Iron, TI; Total Iron Binding Capacity, TIBC; Transferrin, Tf; and saturation of Tf) both in blood serum and in ocular tissues (lens, cornea, iris-ciliary body, retina) and fluids (vitreous body, aqueous humor) of several animal species (pig, cow and rat). The relative degree of oxidative stress of tissues and fluids was evaluated based on the criteria that high values of TI and Tf saturation, and low values of TIBC and Tf, would promote iron-related oxidative stress. The inclusion of both diurnal (pig, cow) and nocturnal (rat) animal species in this comparative work provided the opportunity to explore if iron homeostasis parameters are in some way influenced by the higher oxidative stress level expected in animals with diurnal living habits. This project involved also the design of new and very sensitive methods of analyses, given the fact that in many cases very small amounts of sample (i.e., aqueous humor), and/or low concentration of analytes (i.e., transferrin) are available. All results were expressed as concentration relative to mg protein as determined with the Bradford method (microplate assay). When analyzing TI/TIBC it was possible to define a loosely bound iron pool (LBIP) in ocular tissues that was proportional to the degree of vascularization of the tissues analyzed. The comparison of iron related parameters patterns within the eye and among species allowed us to reach the following conclusions: (1) The aqueous humor and vitreous body of cow and pig exhibited highest concentration of Tf and a very low saturation of Tf, while the lowest value of Tf was detected in all species in the lens; (2) TI showed the tendency to be highest in the vitreous body of cow and pig, and lowest in the lens of all three species. The very low iron concentration in the lens may effectively counteract the risk of having a low Tf level; (3) The pattern of distribution of TIBC is the same for the cow and the pig; (4) Saturation of Tf was very high in the rat aqueous, also high in the rat lens and serum; (5) Highest differences in the pattern of distribution of iron parameters in the eye among the three species studied were found between the rat and the other two species, suggesting that the nocturnal habit of living is influencing iron related parameters in the rat. Lacking the full effect of UV light on the eye, the rat apparently lives exposed to high risk iron parameters without overt pathology, but its antioxidant reserves must be minimal. For example, the combination of high TI aqueous with relatively low Tf, gives a dangerous high saturation of Tf (82%) in the rat; (6) The posterior part of the lens is exposed to high levels of iron and Tf in diurnal animals, with saturation of Tf in the vitreous in the 40% level. This could facilitate postvitrectomy cataracts in addition to the documented increase in vitreous level of oxygen under those conditions.
Asunto(s)
Ojo/metabolismo , Hierro/metabolismo , Animales , Bovinos , Ratas , PorcinosRESUMEN
Shugoshin-2 (SGOL2) is one of the two mammalian orthologs of the Shugoshin/Mei-S322 family of proteins that regulate sister chromatid cohesion by protecting the integrity of the multiprotein cohesin complexes. This protective system is essential for faithful chromosome segregation during mitosis and meiosis, which is the physical basis of Mendelian inheritance. Regardless of its evolutionary conservation from yeast to mammals, little is known about the in vivo relevance and specific role that SGOL2 plays in mammals. Here we show that disruption of the gene encoding mouse SGOL2 does not cause any alteration in sister chromatid cohesion in embryonic cultured fibroblasts and adult somatic tissues. Moreover, mutant mice develop normally and survive to adulthood without any apparent alteration. However, both male and female Sgol2-deficient mice are infertile. We demonstrate that SGOL2 is necessary for protecting centromeric cohesion during mammalian meiosis I. In vivo, the loss of SGOL2 promotes a premature release of the meiosis-specific REC8 cohesin complexes from anaphase I centromeres. This molecular alteration is manifested cytologically by the complete loss of centromere cohesion at metaphase II leading to single chromatids and physiologically with the formation of aneuploid gametes that give rise to infertility.