N-terminal cleavage of GSK-3 by calpain: a new form of GSK-3 regulation

Although GSK-3 activity can be regulated by phosphorylation and through interaction with GSK-3-binding proteins, here we describe N-terminal proteolysis as a novel way to regulate GSK-3. When brain extracts were exposed to calcium, GSK-3 was truncated, generating two fragments of approximately 40 and 30 kDa, a proteolytic process that was inhibited by specific calpain inhibitors. Interestingly, instead of inhibiting this enzyme, GSK-3 truncation augmented its kinase activity. When we digested recombinant GSK-3 alpha and GSK-3beta protein with calpain, each isoform was cleaved differently, yet the truncated GSK-3 isoforms were still active kinases. We also found that lithium, a GSK-3 inhibitor, inhibits full-length and cleaved GSK-3 isoforms with the same IC(50) value. Calpain removed the N-terminal ends of His-tagged GSK-3 isoenzymes, and exposing cultured cortical neurons with ionomycin, glutamate, or N-methyl-d-aspartate led to the truncation of GSK-3. This truncation was blocked by the calpain inhibitor calpeptin, at the same concentration at which it inhibits calpain-mediated cleavage of NMDAR-2B and of p35 (the regulatory subunit of CDK5). Together, our data demonstrate that calpain activation produces a truncation of GSK-3 that removes an N-terminal inhibitory domain. Furthermore, we show that GSK-3 alpha and GSK-3beta isoenzymes have a different susceptibility to this cleavage, suggesting a means to specifically regulate these isoenzymes. These data provide the first direct evidence that calpain promotes GSK-3 truncation in a way that has implications in signal transduction, and probably in pathological disorders such as Alzheimer disease.     

Nematode parasites reduce carotenoid-based signalling in male red grouse

Carotenoids determine the yellow-red colours of many ornaments, which often function as signals of quality. Carotenoid-based signalling may reliably advertise health and should be particularly sensitive to parasite infections. Nematodes are among the commonest parasites of vertebrates, with well-documented negative effects on their hosts. However, to date, little is known about the effects that these parasites may have on carotenoid-based signalling. Tetraonid birds (grouse) exhibit supra-orbital combs, which are bright integumentary ornaments pigmented by carotenoids. We tested the effect of the nematode parasite Trichostrongylus tenuis on signalling in free-living male red grouse Lagopus lagopus scoticus. We show that experimentally reduced nematode infection increases plasma carotenoid concentration and comb redness, demonstrating for the first time that nematodes can influence carotenoid-based signals.     

Backbone assignment of human proliferating cell nuclear antigen

PCNA is an essential factor for DNA replication, repair, chromatin metabolism, and effector of cell-cycle regulatory signals. The assignment of backbone ¹H_N, ¹³C_α, ¹³CO, and ¹⁵N, and sidechain ¹³C_β resonances of the human PCNA homotrimeric ring (∼90 kDa, 261 residues) is reported here.     

Determination of cocaine and cocaethylene in plasma by solid-phase microextraction and gas chromatography-mass spectrometry

The present paper describes a method for the simultaneous determination of cocaine and cocaethylene in plasma. It was based in the extraction of the analytes by solid-phase microextraction (SPME), and gas chromatography-mass spectrometry (GC-MS) was used to identify and quantify the analytes in selected ion monitoring (SIM) mode. The method showed to be very simple, rapid and sensitive. The method was validated for the two compounds, including linearity (range 25-1000 ng/mL) and the main precision parameters. It was applied to ten plasma samples from cocaine and alcohol users, obtaining positive results in all cases.     

Psychophysiological and Psychosocial Profile of Patients Attending Drug Addiction Centers

Drug treatment centres provide the highest level of rehab services for patients diagnosed with drug addictions. Most inpatient drug rehab programs focus on medical detox and mental health interventions. However, how to optimize the later remains a challenge. The aim of this study was to examine the psychophysiological and psychosocial profile of patients attending drug addiction centres in comparation with the general population. A total of 105 inpatient drug rehab patients and 50 participants from the general population were compared based on standardized psychophysiological and psychosocial measures. Results of this study suggest that patients attending drug addiction centers differ from general population in several different psychophysiological and psychosocial factors. Patients reported significantly lower levels of physical activity and increased sympathetic responsiveness, and significantly higher levels in loneliness, psychologically inflexibility and neuroticism. The results of this study highlight the importance of address healthy lifestyle behaviors such as sport practice and psychological variables such as loneliness, psychological (in)flexibility and neuroticism to improve current programs aim to prevent or reduce problematic drug consumptions.

     

Designed and naturalised sward response to management: I. Patterns of herbage production

Pastures in the Appalachian region of the United States comprise a mix of grasses, legumes and forbs that tend to differ in productivity within and among years. A high degree of spatial variability in hill‐land pasture creates microsite conditions that influence botanical composition of pasture. The variation in sward composition presents logistical challenges to livestock producers who rely on a dependable supply of herbage mass and nutritive value to meet production goals. Our objective was to determine if forage communities sown for specific functions, for example, superior dry matter productivity, resource patch exploitation or targeted seasonal production, adapted to changing growing conditions within and among years. Productivity of communities differed among years reflecting the cumulative influences of time, ontogenetic and environmental variations. Maximum productivity was influenced by the specific forage community and less so by simple clipping and fertiliser management. Naturalised swards clipped to emulate hay management tended to have sustained herbage productivity but lower nutritive value when compared to sown communities. Rankings of dry matter productivity of communities were similar for each year where bioactive composition, high productivity and warm season tended to produce the most, and stoloniferous‐rhizomatous and naturalised pasture the least. Regardless of initial sward composition, effective number of species as an index of diversity increased when frequently clipped swards were not fertilised, and when infrequently clipped swards were fertilised. Dry matter production patterns were not influenced by the effective number of species in any forage community suggesting that key species sustained productivity with volunteer species making lesser contribution to total productivity. The species composition of forage plant communities appears to be more important than clipping or fertiliser management practices as a means to sustain forage productivity.     

Reduced Introgression of Sex Chromosome Markers in the Mexican Howler Monkey (Alouatta palliata × A. pigra) Hybrid Zone

International Journal of Primatology - Interspecific hybridization allows the introgression or movement of alleles from one genome to another. While some genomic regions freely exchange alleles...     

Abundance,distribution, and secondary production of the apple snail Pomacea flagellata (Say, 1829) in Bacalar Lake,a tropical karstic system in southern Mexico

Pomacea flagellata is a gastropod conspicuous in freshwater environments, and represents a fishing resource. To assess their abundance, distribution, and secondary production, monthly samplings were carried out in Bacalar Lake from June 2012 to May 2013 at 12 sampling sites. In each site, three random transects were marked parallel to the shore. All snails on transect were collected and shell length and wet weight measured. The highest density occurred in September (1.27 ind.m^?2), lowest in October (0.47 ind.m^?2). Shell lengths ranged from 2 to 56 mm, with recruitment in January–March. Growth parameters were L_∞ 59.50 mm, K 0.65.year^?1; the lifetime span was 3 years. Average biomass reached 5.57 wet g.m^?2 and secondary production was 6.025 wet g.m^?2.year^-1; annual renewal rate P/B 1.08. Highest abundance and secondary production was contributed by individuals between 31 and 41 mm in length. A potential biomass of 25.06 tons of snails was estimated in the lake. Snail densities, secondary production, and turnover were very low during the year, indicating that it is not viable to consider a commercial catch without affecting the population. A ban of 10 years is proposed, and aquaculture practices of snails are recommended to recover the resource.     

Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species

Plant Cell, Tissue and Organ Culture (PCTOC) - Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse...     

Widening the antimicrobial spectrum of esters of bicyclic amines: In vitro effect on gram-positive Streptococcus pneumoniae and gram-negative non-typeable Haemophilus influenzae biofilms

Antibiotic resistance is a global current threat of increasing importance. Moreover, biofilms represent a medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence, therefore demanding the development of novel antimicrobials. Esters of bicyclic amines (EBAs), which are strong inhibitors of Streptococcus pneumoniae growth, were initially designed as inhibitors of pneumococcal choline-binding proteins on the basis of their structural analogy to the choline residues in the cell wall. However, instead of mimicking the characteristic cell chaining phenotype caused by exogenously added choline on planktonic cultures of pneumococcal cells, EBAs showed an unexpected lytic activity. In this work we demonstrate that EBAs display a second, and even more important, function as cell membrane destabilizers. We then assayed the inhibitory and disintegrating activity of these molecules on pneumococcal biofilms. The selected compound (EBA 31) produced the highest effect on S. pneumoniae (encapsulated and non-encapsulated) biofilms at very low concentrations. EBA 31 was also effective on mixed biofilms of non-encapsulated S. pneumoniae plus non-typeable Haemophilus influenzae, two pathogens frequently forming a self-produced biofilm in the human nasopharynx. These results support the role of EBAs as a promising alternative for the development of novel, broad-range antimicrobial drugs encompassing both Gram-positive and Gram-negative pathogens.