A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates

The development of a safe and effective mucosal adjuvant is a crucial step toward a mucosal HIV/AIDS vaccine. This study seeks to determine the promise of a nontoxic mutant of cholera toxin (mCT; E112K) as a mucosal adjuvant in nonhuman primates. HIV-1 gp120 was nasally administered together with mCT E112K or native CT (nCT) as adjuvant on five to six occasions over a 6- to 8-wk period to groups of four rhesus macaques and alone to two monkeys that acted as controls. Macaques given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG and IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues and of IL-4-producing Th2-type CD4-positive (CD4(+)) T cells than did controls. Even though significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal damage was observed only in the nCT-treated, but not in the control or mCT E112K-treated groups. These results clearly show that mCT E112K is an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.     

A survey on bacteria inhabiting the sea surface microlayer of coastal ecosystems

Bacterial populations inhabiting the sea surface microlayer from two contrasted Mediterranean coastal stations (polluted vs. oligotrophic) were examined by culturing and genetic fingerprinting methods and were compared with those of underlying waters (50 cm depth), for a period of two years. More than 30 samples were examined and 487 strains were isolated and screened. Proteobacteria were consistently more abundant in the collection from the pristine environment whereas Gram-positive bacteria (i.e., Actinobacteria and Firmicutes) were more abundant in the polluted site. Cythophaga-Flavobacter-Bacteroides (CFB) ranged from 8% to 16% of total strains. Overall, 22.5% of the strains showed a 16S rRNA gene sequence similarity only at the genus level with previously reported bacterial species and around 10.5% of the strains showed similarities in 16S rRNA sequence below 93% with reported species. The CFB group contained the highest proportion of unknown species, but these also included Alpha- and Gammaproteobacteria. Such low similarity values showed that we were able to culture new marine genera and possibly new families, indicating that the sea-surface layer is a poorly understood microbial environment and may represent a natural source of new microorganisms. Genetic fingerprinting showed, however, no consistent differences between the predominant bacterial assemblages from surface microlayer and underlying waters, suggesting that the presence of a stable and abundant neustonic bacterial community is not a common trait of coastal marine environments.     

Role of the immune system in chronic pain

During the past two decades, an important focus of pain research has been the study of chronic pain mechanisms, particularly the processes that lead to the abnormal sensitivity - spontaneous pain and hyperalgesia - that is associated with these states. For some time it has been recognized that inflammatory mediators released from immune cells can contribute to these persistent pain states. However, it has only recently become clear that immune cell products might have a crucial role not just in inflammatory pain, but also in neuropathic pain caused by damage to peripheral nerves or to the CNS.     

Building a protein name dictionary from full text: a machine learning term extraction approach

Background  

The majority of information in the biological literature resides in full text articles, instead of abstracts. Yet, abstracts remain the focus of many publicly available literature data mining tools. Most literature mining tools rely on pre-existing lexicons of biological names, often extracted from curated gene or protein databases. This is a limitation, because such databases have low coverage of the many name variants which are used to refer to biological entities in the literature.     

Tail loss, body condition and swimming performances in tiger snakes, Notechis ater occidentalis

In limbless tetrapods such as snakes, propulsive forces are generated by lateral undulations of the body and of the tail. In a large population of tiger snakes from Western Australia, tail loss was extremely common (58% of the individuals) and often very severe (more than two-thirds of the tail was missing in 14% of the cases, and in some instances, the tail was totally lost). Tail loss was not however correlated with body size, mass or body condition of wild individuals, and hence did not influence their abilities to acquire resources. These large venomous snakes exhibit marked aquatic habits. Locomotor tests in controlled conditions revealed that tail loss had a significant negative influence on burst swimming performances. However, no effect was found on routine swimming speed and total distance travelled over 5 min. These results suggest that a long and slender tail, although important for maximal speed, is not necessarily relevant for the locomotor abilities required for successful hunting. Tail-damaged individuals outnumbered intact snakes, suggesting that tail loss did not severely compromise survival. Overall, in this species, a slight deterioration of maximal speed due to severe tail loss probably has a low (undetectable) ecological impact, at least for adults.     

Genome replication,virion secretion,and e antigen expression of naturally occurring hepatitis B virus core promoter mutants

The core promoter mutants of hepatitis B virus (HBV) emerge as the dominant viral population at the late HBeAg and the anti-HBe stages of HBV infection, with the A1762T/G1764A substitutions as the hotspot mutations. The double core promoter mutations were found by many investigators to moderately enhance viral genome replication and reduce hepatitis B e antigen (HBeAg) expression. A much higher replication capacity was reported for a naturally occurring core promoter mutant implicated in the outbreak of fulminant hepatitis, which was caused by the neighboring C1766T/T1768A mutations instead. To systemically study the biological properties of naturally occurring core promoter mutants, we amplified full-length HBV genomes by PCR from sera of HBeAg(+) individuals infected with genotype A. All 12 HBV genomes derived from highly viremic sera (5 x 10(9) to 5.7 x 10(9) copies of viral genome/ml) harbored wild-type core promoter sequence, whereas 37 of 43 clones from low-viremia samples (0.2 x 10(7) to 4.6 x 10(7) copies/ml) were core promoter mutants. Of the 11 wild-type genomes and 14 core promoter mutants analyzed by transfection experiments in human hepatoma cell lines, 6 core promoter mutants but none of the wild-type genomes replicated at high levels. All had 1762/1764 mutations and an additional substitution at position 1753 (T to C), at position 1766 (C to T), or both. Moreover, these HBV clones varied greatly in their ability to secrete enveloped viral particles irrespective of the presence of core promoter mutations. High-replication clones with 1762/1764/1766 or 1753/1762/1764/1766 mutations expressed very low levels of HBeAg, whereas high-replication clones with 1753/1762/1764 triple mutations expressed high levels of HBeAg. Experiments with site-directed mutants revealed that both 1762/1764/1766 and 1753/1762/1764/1766 mutations conferred significantly higher viral replication and lower HBeAg expression than 1762/1764 mutations alone, whereas the 1753/1762/1764 triple mutant displayed only mild reduction in HBeAg expression similar to the 1762/1764 mutant. Thus, core promoter mutations other than those at positions 1762 and 1764 can have major impact on viral DNA replication and HBeAg expression.     

Store-operated Ca2+ current in prostate cancer epithelial cells. Role of endogenous Ca2+ transporter type 1

Ca(2+) influx via store-operated channels (SOCs) following stimulation of the plasma membrane receptors is the key event controlling numerous processes in nonexcitable cells. The human transient receptor potential vanilloid type 6 channel, originally termed Ca(2+) transporter type 1 (CaT1) protein, is one of the promising candidates for the role of endogenous SOC, although investigations of its functions have generated considerable controversy. In order to assess the role of CaT1 in generating endogenous store-operated Ca(2+) current (I(SOC)) in the lymph node carcinoma of the prostate (LNCaP) human prostate cancer epithelial cell line, we manipulated its endogenous levels by means of antisense hybrid depletion or pharmacological up-regulation (antiandrogen treatment) combined with functional evaluation of I(SOC). Antisense hybrid depletion of CaT1 decreased I(SOC) in LNCaP cells by approximately 50%, whereas enhancement of CaT1 levels by 60% in response to Casodex treatment potentiated I(SOC) by 30%. The functional characteristics of I(SOC) in LNCaP cells were similar in many respects to those reported for heterologously expressed CaT1, although 2-aminoethoxydiphenyl borate sensitivity and lack of constitutive current highlighted notable departures. Our results suggest that CaT1 is definitely involved in I(SOC), but it may constitute only a part of the endogenous SOC, which in general may be a heteromultimeric channel composed of homologous CaT1 and other transient receptor potential subunits.     

Basal and physiological Ca(2+) leak from the endoplasmic reticulum of pancreatic acinar cells. Second messenger-activated channels and translocons

We have studied the Ca(2+) leak pathways in the endoplasmic reticulum of pancreatic acinar cells by directly measuring Ca(2+) in the endoplasmic reticulum ([Ca(2+)](ER)). Cytosolic Ca(2+) ([Ca(2+)](C)) was clamped to the resting level by a BAPTA-Ca(2+) mixture. Administration of cholecystokinin within the physiological concentration range caused a graded decrease of [Ca(2+)](ER), and the rate of Ca(2+) release generated by 10 pm cholecystokinin is at least 3x as fast as the basal Ca(2+) leak revealed by inhibition of the endoplasmic reticulum Ca(2+)-ATPase. Acetylcholine also evokes a dose-dependent decrease of [Ca(2+)](ER), with an EC(50) of 0.98 +/- 0.06 microm. Inhibition of receptors for inositol 1,4,5-trisphosphate (IP(3)) by heparin or flunarizine blocks the effect of acetylcholine but only partly blocks the effect of cholecystokinin. 8-NH(2) cyclic ADP-ribose (20 microm) inhibits the action of cholecystokinin, but not of acetylcholine(.) The basal Ca(2+) leak from the endoplasmic reticulum is not blocked by antagonists of the IP(3) receptor, the ryanodine receptor, or the receptor for nicotinic acid adenine dinucleotide phosphate. However, treatment with puromycin (0.1-1 mm) to remove nascent polypeptides from ribosomes increases Ca(2+) leak from the endoplasmic reticulum by a mechanism independent of the endoplasmic reticulum Ca(2+) pumps and of the receptors for IP(3) or ryanodine.     

Sleep and motor skill learning

The improvement of a perceptual or motor skill continues after training has ended. The central question is whether this improvement is just a function of time or whether sleep, a certain circadian phase, or their interaction (sleep occurring in a particular circadian phase) is favorable to the reprocessing of recent memory traces. In this issue of Neuron, provide behavioral evidence that most of the improvement of a motor skill depends on nocturnal sleep.