Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains

INTRODUCTION: Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. METHODS: The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. RESULTS: During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. CONCLUSION: The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.     

Effect of polysaccharide structure on mechanical and thermal properties of galactomannan-based films

Films were prepared from guar gum and locust bean gum galactomannans. In addition, enzymatic modification was applied to guar gum to obtain structurally different galactomannans. Cohesive and flexible films were formed from galactomannans plasticized with 20-60% (w/w of polymer) glycerol or sorbitol. Galactomannans with lower galactose content (locust bean gum, modified guar gum) produced films with higher elongation at break and tensile strength. The mechanical properties of films were improved statistically significantly by decreasing the degree of polymerization of guar gum with mannanase treatments (4 h) of 2 and 10 nkat/g, whereas 50 nkat/g produced films with low elongation at break and tensile strength. Galactomannans with approximately 6 galactose units per 10 mannose backbone units resulted in films with 2 peaks in loss modulus spectra, whereas films from galactomannans with approximately 2 galactose groups per 10 mannose units behaved as a single phase in dynamic mechanical analysis.     

Safeguarding marine life: conservation of biodiversity and ecosystems

Reviews in Fish Biology and Fisheries - Marine ecosystems and their associated biodiversity sustain life on Earth and hold intrinsic value. Critical marine ecosystem services include maintenance of...     

The COP9 signalosome is vital for timely repair of DNA double-strand breaks

The DNA damage response is vigorously activated by DNA double-strand breaks (DSBs). The chief mobilizer of the DSB response is the ATM protein kinase. We discovered that the COP9 signalosome (CSN) is a crucial player in the DSB response and an ATM target. CSN is a protein complex that regulates the activity of cullin ring ubiquitin ligase (CRL) complexes by removing the ubiquitin-like protein, NEDD8, from their cullin scaffold. We find that the CSN is physically recruited to DSB sites in a neddylation-dependent manner, and is required for timely repair of DSBs, affecting the balance between the two major DSB repair pathways—nonhomologous end-joining and homologous recombination repair (HRR). The CSN is essential for the processivity of deep end-resection—the initial step in HRR. Cullin 4a (CUL4A) is recruited to DSB sites in a CSN- and neddylation-dependent manner, suggesting that CSN partners with CRL4 in this pathway. Furthermore, we found that ATM-mediated phosphorylation of CSN subunit 3 on S410 is critical for proper DSB repair, and that loss of this phosphorylation site alone is sufficient to cause a DDR deficiency phenotype in the mouse. This novel branch of the DSB response thus significantly affects genome stability.     

Important marine habitat off east Antarctica revealed by two decades of multi‐species predator tracking

Satellite telemetry data are a key source of animal distribution information for marine ecosystem management and conservation activities. We used two decades of telemetry data from the East Antarctic sector of the Southern Ocean. Habitat utilization models for the spring/summer period were developed for six highly abundant, wide‐ranging meso‐ and top‐predator species: Adélie Pygoscelis adeliae and emperor Aptenodytes forsteri penguins, light‐mantled albatross Phoebetria palpebrata, Antarctic fur seals Arctocephalus gazella, southern elephant seals Mirounga leonina, and Weddell seals Leptonychotes weddellii. The regional predictions from these models were combined to identify areas utilized by multiple species, and therefore likely to be of particular ecological significance. These areas were distributed across the longitudinal breadth of the East Antarctic sector, and were characterized by proximity to breeding colonies, both on the Antarctic continent and on subantarctic islands to the north, and by sea‐ice dynamics, particularly locations of winter polynyas. These areas of important habitat were also congruent with many of the areas reported to be showing the strongest regional trends in sea ice seasonality. The results emphasize the importance of on‐shore and sea‐ice processes to Antarctic marine ecosystems. Our study provides ocean‐basin‐scale predictions of predator habitat utilization, an assessment of contemporary habitat use against which future changes can be assessed, and is of direct relevance to current conservation planning and spatial management efforts.     

Pheromone-encoding mRNA is transported to the yeast mating projection by specific RNP granules

Association of messenger RNAs with large complexes such as processing bodies (PBs) plays a pivotal role in regulating their translation and decay. Little is known about other possible functions of these assemblies. Exposure of haploid yeast cells, carrying mating type “a,” to “α pheromone” stimulates polarized growth resulting in a “shmoo” projection; it also induces synthesis of “a pheromone,” encoded by MFA2. In this paper, we show that, in response to α pheromone, MFA2 mRNA is assembled with two types of granules; both contain some canonical PB proteins, yet they differ in size, localization, motility, and sensitivity to cycloheximide. Remarkably, one type is involved in mRNA transport to the tip of the shmoo, whereas the other—in local translation in the shmoo. Normal assembly of these granules is critical for their movement, localization, and for mating. Thus, MFA2 mRNAs are transported to the shmoo tip, in complex with PB-like particles, where they are locally translated.     

Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages

Tissue macrophages are derived exclusively from blood monocytes, which as monocyte-derived macrophages support HIV-1 replication. However, among human tissue macrophages only intestinal macrophages are non-permissive to HIV-1, suggesting that the unique microenvironment in human intestinal mucosa renders lamina propria macrophages non-permissive to HIV-1. We investigated this hypothesis using blood monocytes and intestinal extracellular matrix (stroma)-conditioned media (S-CM) to model the exposure of newly recruited monocytes and resident macrophages to lamina propria stroma, where the cells take up residence in the intestinal mucosa. Exposure of monocytes to S-CM blocked up-regulation of CD4 and CCR5 expression during monocyte differentiation into macrophages and inhibited productive HIV-1 infection in differentiated macrophages. Importantly, exposure of monocyte-derived macrophages simultaneously to S-CM and HIV-1 also inhibited viral replication, and sorted CD4+ intestinal macrophages, a proportion of which expressed CCR5+, did not support HIV-1 replication, indicating that the non-permissiveness to HIV-1 was not due to reduced receptor expression alone. Consistent with this conclusion, S-CM also potently inhibited replication of HIV-1 pseudotyped with vesicular stomatitis virus glycoprotein, which provides CD4/CCR5-independent entry. Neutralization of TGF-β in S-CM and recombinant TGF-β studies showed that stromal TGF-β inhibited macrophage nuclear translocation of NF-κB and HIV-1 replication. Thus, the profound inability of intestinal macrophages to support productive HIV-1 infection is likely the consequence of microenvironmental down-regulation of macrophage HIV-1 receptor/coreceptor expression and NF-κB activation.