Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task

The use of stimulants (methylphenidate and amphetamine) as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose) in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations) given with and without methylphenidate (20 mg, oral). Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less). This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering) was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering) or impaired (i.e., attention deficit hyperactivity disorder), but it could be detrimental when brain activity is already optimally focused. This would explain why methylphenidate has beneficial effects in some individuals and contexts and detrimental effects in others.     

Drosophila p24 homologues eclair and baiser are necessary for the activity of the maternally expressed Tkv receptor during early embryogenesis

p24 proteins are assumed to play an important role in the transport of secreted and transmembrane proteins into membranes. However, only few cargo proteins are known that partially, but in no case completely require p24 proteins for membrane transport. Here, we show that two p24 proteins are essential for dorsoventral patterning of Drosophila melanogaster embryo. Mutations in the genes, eclair (eca) and baiser (bai), encoding two p24 proteins reduce signalling by the TGF-beta homologue, Dpp, in early embryos. This effect is strictly maternal and specific to early embryogenesis, as Dpp signalling in other contexts is not notably affected. We provide genetic evidence that in the absence of eca or bai function in the oocyte, the maternally expressed type I TGF-beta receptor Tkv is not active. We propose that during early embryogenesis eca and bai are specifically required for the activity of the maternal Tkv, while the zygotic Tkv is not affected in the mutant embryos. Mutations in either eca or bai are sufficient for the depletion of Tkv activity and no enhancement of the phenotypes was observed in embryos derived from oocytes mutant for both genes. The dependence of maternal Tkv protein on the products of p24 genes may serve as an in vivo model for studying p24 proteins.     

ABA may affect the dormancy in triticale caryopses by inhibition of embryo class I RNases,enzymes involved in P<Subscript>i</Subscript> release

The main objective of this study was to analyze the differences in profiles of RNase activities from triticale embryos (Triticosecale, cv. Ugo) between dormant and non-dormant caryopses and to determine the influence of exogenous abscisic acid (ABA) on the activities of these enzymes. The major RNase from the examined tissue was detected following SDS-PAGE, with substrate-based gel assay, described by Yen and Green (Plant Physiol 97:1487–1493, 1991). The activities of enzymes were characterized according to their pH optima, ion dependence, EDTA sensitivity and DNase activity. In embryos with arrested growth (in a natural way by dormancy or artificially by ABA treatment), the activity of two enzymes—24 and 27 kDa—belonging to class I RNases was completely inhibited, whereas that of two other RNases of this family—23 and 25 kDa—was detectable. However, the activity of the class I ribonucleases (enzymes responsible for cellular P_i release) was very low. Moreover, in contrast with non-dormant caryopses, imbibing embryos of dormant or ABA-treated seeds contained 13- and 14-kDa enzymes. These enzymes have not been classified so far, and their specific properties are different from the generally accepted properties of ribonucleolytic enzymes. In addition to the above results, the P_i content in the analyzed samples was determined by the Ames (Methods Enzymol 8:115–118, 1966) method. The results suggest a very low and constant level of inorganic phosphate in dormant samples as well as an evidently decreasing P_i content in embryos under the influence of ABA treatment. The inhibition of the class I RNases activity induced by abscisic acid implies that one of the roles of ABA in seed dormancy may consist in arresting the catabolic release of P_i, which results in retarding the embryo’s growth.     

Different contributions of HtrA protease and chaperone activities to Campylobacter jejuni stress tolerance and physiology

The microaerophilic bacterium Campylobacter jejuni is the most common cause of bacterial food-borne infections in the developed world. Tolerance to environmental stress relies on proteases and chaperones in the cell envelope, such as HtrA and SurA. HtrA displays both chaperone and protease activities, but little is known about how each of these activities contributes to stress tolerance in bacteria. In vitro experiments showed temperature-dependent protease and chaperone activities of C. jejuni HtrA. A C. jejuni mutant lacking only the protease activity of HtrA was used to show that the HtrA chaperone activity is sufficient for growth at high temperature or under oxidative stress, whereas the HtrA protease activity is essential only under conditions close to the growth limit for C. jejuni. However, the protease activity was required to prevent induction of the cytoplasmic heat shock response even under optimal growth conditions. Interestingly, the requirement of HtrA at high temperatures was found to depend on the oxygen level, and our data suggest that HtrA may protect oxidatively damaged proteins. Finally, protease activity stimulates HtrA production and oligomer formation, suggesting that a regulatory role depends on the protease activity of HtrA. Studying a microaerophilic organism encoding only two known periplasmic chaperones (HtrA and SurA) revealed an efficient HtrA chaperone activity and proposed multiple roles of the protease activity, increasing our understanding of HtrA in bacterial physiology.     

Review. Meiotic drive and sex determination: molecular and cytological mechanisms of sex ratio adjustment in birds

Differences in relative fitness of male and female offspring across ecological and social environments should favour the evolution of sex-determining mechanisms that enable adjustment of brood sex ratio to the context of breeding. Despite the expectation that genetic sex determination should not produce consistent bias in primary sex ratios, extensive and adaptive modifications of offspring sex ratio in relation to social and physiological conditions during reproduction are often documented. Such discordance emphasizes the need for empirical investigation of the proximate mechanisms for modifying primary sex ratios, and suggests epigenetic effects on sex-determining mechanisms as the most likely candidates. Birds, in particular, are thought to have an unusually direct opportunity to modify offspring sex ratio because avian females are heterogametic and because the sex-determining division in avian meiosis occurs prior to ovulation and fertilization. However, despite evidence of strong epigenetic effects on sex determination in pre-ovulatory avian oocytes, the mechanisms behind such effects remain elusive. Our review of molecular and cytological mechanisms of avian meiosis uncovers a multitude of potential targets for selection on biased segregation of sex chromosomes, which may reflect the diversity of mechanisms and levels on which such selection operates in birds. Our findings indicate that pronounced differences between sex chromosomes in size, shape, size of protein bodies, alignment at the meiotic plate, microtubule attachment and epigenetic markings should commonly produce biased segregation of sex chromosomes as the default state, with secondary evolution of compensatory mechanisms necessary to maintain unbiased meiosis. We suggest that it is the epigenetic effects that modify such compensatory mechanisms that enable context-dependent and precise adjustment of primary sex ratio in birds. Furthermore, we highlight the features of avian meiosis that can be influenced by maternal hormones in response to environmental stimuli and may account for the precise and adaptive patterns of offspring sex ratio adjustment observed in some species.     

Highly branched polymers with polymyxin end groups responsive to Pseudomonas aeruginosa

Polymyxin peptide conjugated to the end groups of highly branched poly(N-isopropyl acrylamide) was shown to bind to a Gram negative bacterium, Pseudomonas aeruginosa . The nonbound polymer had a lower critical solution temperature (LCST) above 60 °C. However, binding caused aggregation, which was disrupted on cooling of the bacteria and polymer mixture. The data indicate that polymer binding of bacteria occurred by interaction of the end groups with lipopolysaccharide and that the binding decreased the LCST to below 37 °C. Cooling then progressed the polymer/bacteria aggregate through a bound LCST into an open polymer coil conformation that was not adhesive to P. aeruginosa .     

Influences of sea level changes and volcanic eruptions on Holocene vegetation in Tonga

Here, we investigate Mid- to Late-Holocene vegetation changes in low-lying coastal areas in Tonga and how changing sea levels and recurrent volcanic eruptions have influenced vegetation dynamics on four islands of the Tongan archipelago (South Pacific). To investigate past vegetation and environmental change at Ngofe Marsh (‘Uta Vava’u), we examined palynomorphs (pollen and spores), charcoal (fire), and sediment characteristics (volcanic activity) from a 6.7-m-long sediment core. Radiocarbon dating indicated the sediments were deposited over the last 7700 years. We integrated the Ngofe Marsh data with similar previously published data from Avai’o’vuna Swamp on Pangaimotu Island, Lotofoa Swamp on Foa Island, and Finemui Swamp on Ha’afeva Island. Plant taxa were categorized as littoral, mangrove, rainforest, successional/ disturbance, and wetland groups, and linear models were used to examine relationships between vegetation, relative sea level change, and volcanic eruptions (tephra). We found that relative sea level change has impacted vegetation on three of the four islands investigated. Volcanic eruptions were not identified as a driver of vegetation change. Rainforest decline does not appear to be driven by sea level changes or volcanic eruptions. From all sites analyzed, vegetation at Finemui Swamp was most sensitive to changes in relative sea level. While vegetation on low-lying Pacific islands is sensitive to changing sea levels, island characteristics, such as area and elevation, are also likely to be important factors that mediate specific island responses to drivers of change.     

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.     

Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion

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Independent and combined cytotoxicity and genotoxicity of triethylene glycol dimethacrylate and urethane dimethacrylate

Dental composite materials contain polymers of methacrylates, which, due to mechanical abrasion and enzymatic action of saliva, may release their monomers into oral cavity and the pulp. Moreover, polymerization is always incomplete and leaves usually considerable fraction of free monomers. Mechanisms of the genotoxicity of methacrylate monomers have been rarely explored. As the polymerization of a monomer is catalyzed by a co-monomer, their combined action should be considered. In the present work, we investigated cytotoxic and genotoxic effects of urethane dimethacrylate (UDMA), often used as a monomer, at 1 mM, and triethylene glycol dimethacrylate (TEGDMA), a typical co-monomer, at 5 mM singly and in combination. Experiments were conducted on Chinese hamster ovary cells. Cell viability, apoptosis and cell cycle were assessed by flow cytometry, whereas DNA damage was evaluated by plasmid conformation test and comet assay. Both compounds decreased the viability of the cells, but did not induce strand breaks in an isolated plasmid DNA. However, both substances, either singly or in combination, damaged DNA in CHO cells as evaluated by comet assay. Both compounds induced apoptosis, but a combined action of them led to a decrease in the number of apoptotic cells. The combined action of UDMA and TEGDMA in the disturbance of cell cycle was lesser compared to the action of each compound individually. Individually, though UDMA and TEGDMA may induce cytotoxic and genotoxic, however, a combination of both does not produce a significant increase in these effects.