In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic reticulum (ER) folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S) with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT), V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50–200 mg/kg/d intraperitoneally) had minor effects on increasing GCase activity in brain and liver (1.2-fold). Diltiazem treatment (10 mg/kg/d) had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold) in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses

Comparative Therapeutic Effects of Velaglucerase Alfa and Imiglucerase in a Gaucher Disease Mouse Model

Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid β-glucosidase (GCase). Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD) and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig) and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela), in a Gaucher mouse, D409V/null. About 80+% of either enzyme localized to the liver interstitial cells and <5% was recovered in spleens and lungs after bolus i.v. injections. Glucosylceramide (GC) levels and storage cell numbers were reduced in a dose (5, 15 or 60 U/kg/wk) dependent manner in livers (60–95%) and in spleens (∼10–30%). Compared to Vela, Imig (60 U/kg/wk) had lesser effects at reducing hepatic GC (p = 0.0199) by 4 wks; this difference disappeared by 8 wks when nearly WT levels were achieved by Imig. Anti-GCase IgG was detected in GCase treated mice at 60 U/kg/wk, and IgE mediated acute hypersensitivity and death occurred after several injections of 60 U/kg/wk (21% with Vela and 34% with Imig). The responses of GC levels and storage cell numbers in Vela- and Imig-treated Gaucher mice at various doses provide a backdrop for clinical applications and decisions

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys : First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).Peer reviewe

Reproductive ecology and size of sexual maturity in the anomuran crab Aegla parana (Decapoda: Aeglidae)

In Southern Brazil, Aegla parana Schmitt, 1942 is characterized by a broad distribution throughout the Iguacu River basin, particularly between the southern state of Parana and the northern state of Santa Catarina, preferentially inhabiting streams with rocky substrates. Although there has been an increase in the number of studies about the population biology of Aeglidae, many aspects about the reproductive biology of A. parana are still unknown. Therefore, the present study aimed to investigate the size at sexual maturity, reproductive seasonality and recruitment of A. parana from November, 2008 to December, 2009, in a tributary of the Iguacu River located in Uniao da Vitoria, Parana, Brazil. Basic environmental factors were investigated to determine their influence on the reproductive cycle of this species. Gonadal stages were characterized macroscopically, and the presence or absence of embryos in females (ovigerous females) from monthly samples was recorded. The entire sample was composed of 436 males and 211 females. Although the smallest ovigerous female was 16.2 mm, the average size (carapace length, CL) at sexual maturity (CL50%) was calculated at 17.4 mm. The greatest percentage of females with developed (mature, near spawning) gonads stage was observed from January to June, 2009, while ovigerous females were recorded from April to July, 2009, after which the reproductive period ended. Recruitment occurred from October to December, 2009. The presence of ovigerous females was negatively correlated with temperature (Spearman, p < 0.05). Females carrying embryos were generally collected during periods of lower temperatures, whereas recruits entered the population during periods of higher temperatures, when food for them is more abundant in the region studied

Decapod abundance and species richness in the bycatch of Xiphopenaeus kroyeri (Heller, 1862) fishery, Santa Catarina, southern Brazil

Abstract We aimed to analyze the crustacean bycatch from the Xiphopenaeus kroyeri fishery in the Santa Catarina State and compare the bycatch’s biomass to that of the target species. Shrimp and environmental factors were sampled monthly from July 2010 through June 2011. For each crustacean species, we calculated the number of individuals, the relative abundance and the occurrence frequency. The relative abundance was classified as very abundant (Va), abundant (Ab) or low abundance (La), while the occurrence frequency was labeled continuous (Co), accessory (Ac) or accidental (Ad). We observed a total richness of 28 species, which is considered high for a subtropical region. Brachyura was the most frequent taxon (74%) followed by Penaeiodea (18%). Five species were considered Va (Arenaeus cribrarius, Callinectes danae, C. ornatus, Isochelis sawayai and Pleoticus muelleri), and eight species were considered Co (A. cribrarius, C. danae, C. ornatus, Farfantepenaeus paulensis, Hepatus pudibundus, Libinia spinosa, Litopenaeus schmitti and Sicyonia dorsalis), suggesting that the studied environment is heterogeneous and provides a variety of microhabitats, enabling many species to coexist. Therefore, the high species richness observed demonstrates the ecological importance of this region and thus the necessity of strategies aiming to minimize the impacts caused by trawling fisheries

Lifespan and population dynamics of the endemic South American shrimpArtemesia longinaris (Crustacea: Penaeidae) in southeastern Brazil

ABSTRACT The present study investigated the growth, longevity and reproductive dynamics ofArtemesia longinaris in the southeastern coast of Brazil over a two-year period. Monthly collections were conducted in Ubatuba and Caraguatatuba using a shrimp fishing boat equipped with "double-rig" nets. Each region was divided into 7 sampling stations up to 35 m deep. Size frequency distributions, growth, longevity, sex ratio, and abundance of individuals in each demographic class, were compared. The relationship between abiotic factors and abundance of each demographic class was assessed using a Canonical Correlation Analysis. A total of 64,641 individuals were collected (6,928 measured) with an estimated longevity of 1.30 (Ubatuba) and 1.14 (Caraguatatuba) years for females and 1.03 years for males in both regions. There was a statistically significant bias in sex ratio toward females (Chi-squared test, p < 0.05) in both regions. The Canonical Correlation Analysis resulted in a canonical correlation coefficient of 0.31 (p = 0.00002). Salinity and temperature showed high correlation mainly with the presence of reproductive females. In general, this demographic class was most common in conditions of low temperature and high salinity. These findings, as well as other studies carried out in colder regions with the same species, are consistent with classical latitudinal paradigm