Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets

Mucopolysaccharidoses (MPSs) constitute a heterogeneous group of lysosomal storage disorders characterized by the lysosomal accumulation of glycosaminoglycans (GAGs). Although lysosomal dysfunction is mainly affected, several cellular organelles such as mitochondria, endoplasmic reticulum, Golgi apparatus, and their related process are also impaired, leading to the activation of pathophysiological cascades. While supplying missing enzymes is the mainstream for the treatment of MPS, including enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), or gene therapy (GT), the use of modulators available to restore affected organelles for recovering cell homeostasis may be a simultaneous approach. This review summarizes the current knowledge about the cellular consequences of the lysosomal GAGs accumulation and discusses the use of potential modulators that can reestablish normal cell function beyond ERT-, HSCT-, or GT-based alternatives.     

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.     

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.     

An ultrastructural study of spermiogenesis in two species of Sitophilus (Coleoptera: Curculionidae).

The spermiogenesis of Sitophilus zeamais and Sitophilus oryzae, the maize and the rice weevil, respectively, was studied by light microscopy and scanning and transmission electron microscopy. Sitophilus spp. is the most widespread and destructive primary pest of stored cereals in the world. The spermiogenesis occurs within cysts. There are approximately 256 germ line cells per cyst. Inside each cysts, all the spermatids are in the same stage of maturation. The ultrastructure of the spermatozoa of S. zeamais and S. oryzae is similar to that described for other beetles. The head is formed by a three-layered acrosome with the perforatorium, the acrosomal vesicle, the extra-acrosomal layer and the nucleus. The flagellum has the typical axoneme formed by a 9+9+2 microtubules arrangement, two mitochondrial derivatives and two accessory bodies. The typical pattern for Curculionidae spermatozoa described here may provide useful information for future phylogenetic analysis of the superfamily Curculionoidea.     

Tuning the pKa of the antihistaminic drug chlorpheniramine maleate by supramolecular interactions with water-soluble polymers

The interaction of the pharmacologically important chlorpheniramine maleate (CPM) with polyanions containing sulfonate groups such as poly(sodium 4-styrenesulfonate) (PSS), poly(sodium vinylsulfonate) (PVS), and the more hydrophobic poly(sodium 2-(N-acrylamido)-2-methyl-propanesulfonate) (PAMPS) has been studied by ¹H NMR. It was found that the pK_a of the low-molecular weight molecule (LMWM) may be modified by its interaction with the polyanions, changing from 3 to 5, due to electric charge compensation. Interestingly, the interaction of CPM with PSS produces changes in CPM resonances, such as a general broadening and upfield shifts of the signals, and NOE effects between the LMWM and the water-soluble polymer (WSP) that indicate the presence of π-π interactions.     

The disposition of nifurtimox in the rat isolated perfused liver: effect of dose size

The disposition of nifurtimox was studied in the rat isolated perfused liver using a recirculating system. The drug was administered as a bolus (5.0, 15.0 or 30.0 micrograms mL-1), and its disappearance was monitored by analysing perfusate samples. In all experiments perfusate disappearance was monoexponential, and no significant difference was found between the three doses for the elimination constant (0.016, 0.011 and 0.012 min-1, respectively), half-life (46.6, 65.8 and 66.8 min, respectively), extraction rate (0.128, 0.091 and 0.099, respectively) and distribution volume (41.1, 47.3 and 30.7 mL g-1, respectively). At 30 micrograms mL-1 the hepatic clearance was lower than the other concentrations of nifurtimox (0.66, 0.51 and 0.34 mL min-1 g-1, respectively). Relatively little parent drug was recovered from the liver at the end of the perfusions. In summary, nifurtimox is cleared slowly from the rat isolated perfused liver, is poorly extracted by hepatocyte cells and is completely metabolized from 2 to 4 h after perfusion.     

Low Cost BIST for Static and Dynamic Testing of ADCs

This paper presents a low cost test method for the static and dynamic characterization of analog-to-digital converters. The method is suitable for implementation in a SoC environment, as a built-in self test (BIST) solution. In the proposed approach, noise is used as the test signal. Theory of operation and practical results demonstrating the effectiveness of the method for INL, DNL, THD and SINAD characterization are presented. The BIST surface overhead caused by the noise generator is only 7.4% of the ADC total area. The reduced number of data samples required allows a reduction of about 7.5× in test time, in comparison to the histogram method.Maria da Gloria Cataldi Flores was born in Santa Maria, Brazil, in 1978. She received the electrical engineering degree in 2000 from Universidade Federal de Santa Maria (UFSM) and the M.S. degree engineering in 2003 from Universidade Federal do Rio Grande do Sul (UFRGS), Brazil. Since then, she has been working as a design engineer in an EAS Supply brazilian company. Her main research interests include mixed-signal and analog testing and digital signal processing.Marcelo Negreiros was born in Porto Alegre, Brazil, in 1969. He received the electrical engineering degree in 1992 and the M.S. degree engineering in 1994, both from Universidade Federal do Rio Grande do Sul (UFRGS), Brazil. Since then he was been working as an associate researcher in the Signal Processing Lab. (LaPSI) of the Electrical Engineering Department at UFRGS. Since 2000 he also works toward a Ph.D. in Computer Science from UFRGS. His main research interests include mixed-signal and analog testing and digital signal processing.Luigi Carro was born in Porto Alegre, Brazil, in 1962. He received the Electrical Engineering and the M.Sc. degrees from Universidade Federal do Rio Grande do Sul (UFRGS), Brazil, in 1985 and 1989, respectively. From 1989 to 1991 he worked at ST-Microelectronics, Agrate, Italy, in the R&D group. In 1996 he received the Ph.D. degree in the area of Computer Science from Universidade Federal do Rio Grande do Sul (UFRGS), Brazil. He is presently a lecturer at the Electrical Engineering Department of UFRGS, in charge of Digital Systems Design and Digital Signal processing disciplines at the graduate and undergraduate level. He is also a member of the Graduation Program in Computer Science of UFRGS, where he is responsible for courses in Embedded Systems, Digital Signal Processing, and VLSI Design. His primary research interests include mixed-signal design, digital signal processing, mixed-signal and analog testing, and fast system prototyping. He has published more than 90 technical papers in those topics and is the author of the book Digital Systems Design and Prototyping (in portuguese).Altamiro A Susin was born in Vacaria-RS, Brazil, in 1945. He received the Electrical Engineering and the MSc. degrees from Universidade Federal do Rio Grande do Sul (UFRGS), Brazil, in 1972 and 1977, respectively. Since 1968 he worked in the start up of Computer Centers of two local Universities. In 1981 he got his Dr. Eng degree from Institut National Polytechnique de Grenoble-France. He is presently a lecturer at the Electrical Engineering Department of UFRGS, in charge of Digital Systems Design disciplines at the graduate and undergraduate level. He is also a member of the Graduation Program in Computer Science of UFRGS, where he is responsible by courses in VLSI Architecture and is also thesis director. His main research interests are Integrated Circuit Architecture, Embedded Systems, Signal Processing with more than 50 technical papers published in those domains. He is/was responsible for several R&D projects either funded with public and/or industry resources.Felipe Ricardo Clayton received the B.S. degree in Electrical Engineering from State University of Campinas (UNICAMP), Brazil, in 1986. He worked at CPqD (Brazilian PTT R&D Center) till 1996 designing analog and mixed signal circuits for telecom and automotive applications. From 1997 to the second half of 1998, he worked at Instituto Superior Técnico (IST), Lisbon, Portugal, under the guidance of Prof. Carlos Azeredo Leme on development of CMOS RF circuits. Since October 1998 he had worked for Motorola SPS. Now he is head of the Power Managment Group at Freescale.Cristiano Benevento received his B.S. degree in Electrical Engineering from Universidade Estadual de Campinas (Unicamp), Brazil, in 1997. He worked at Motorola Cellular Infrastructure Group until August 2000 as a Systems Engineer. He joined Motorola Semiconductor Product Sector in August 2000 as IC Designer for Power Management Group and is now at Freescale.     

Are clinical psychologists prepared for service and research with ethnic minorities? Report of a decade of progress.

Longitudinal data on the status of training of clinical psychologists for service and research with ethnic minority populations were presented to assess progress. Data from an earlier survey by M. E. Bernal and A. M. Padilla (see record 1983-06520-001), which were collected in 1979–1980, were compared with similar survey data collected in 1990–1991. Results revealed a mixed picture of progress: key aspects of minority training have improved, and there is a substantial block of programs committed to minority training. However, 2 changes are needed: engagement in a change process leading to training for cultural competence rather than minimal exposure to culture, and a significant increase in the numbers of minority faculty, which can occur only by a sharp increase in the numbers of minority students admitted into the educational pipeline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)