Salivary alpha amylase-cortisol asymmetry in maltreated youth

BACKGROUND: Maltreatment represents a major stressor in the lives of many youth. Given the known effects of stress exposure on subsequent functioning of biological stress response systems, researchers have been interested in the effects of maltreatment on the functioning of these systems. Experimental studies reveal that previous exposure to stress affects the symmetry between components of the physiological stress response to subsequent stress. The present study examined asymmetry between salivary alpha amylase (sAA), a sympathetic indicator, and cortisol reactivity to a social stressor among maltreated and comparison youth age 9 to 14 years. Consistent with earlier studies suggesting that stress leads to asymmetry between hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity, we expected that maltreated youth would exhibit greater sAA-cortisol asymmetry than would comparison youth. METHODS: Forty-seven maltreated and 37 comparison youth visited the laboratory and engaged in a social stress protocol. We collected 2 saliva samples before the stressor and 4 after, at 0 min post-stress and every 10 min for 30 min. RESULTS: Maltreatment status moderated the relation between sAA and cortisol activity in response to the stressor. Comparison youth showed significant links between the sAA and cortisol responses; maltreated youth had no significant associations between responses in the two biomarkers. CONCLUSION: The data were consistent with sAA-cortisol asymmetry among maltreated youth. Further research should seek to replicate this finding and investigate its implication for developmental trajectories.     

Quality of pharmaceutical industry press releases based on original research

Background

Press releases are a popular vehicle to disseminate health information to the lay media. While the quality of press releases issued by scientific conferences and medical journals has been questioned, no efforts to assess pharmaceutical industry press releases have been made. Therefore, we sought to systematically examine pharmaceutical company press releases about original research for measures of quality.

Methodolgy/Principal Findings

Press releases issued by the ten top selling, international pharmaceutical companies in the year 2005 were selected for evaluation. A total of 1028 electronic press releases were issued and 235 were based on original research. More than half (59%) reported results presented at a scientific meeting. Twenty-one percent of releases were not explicit about the source of original data. While harms or adverse events were commonly cited (76%), study limitations were rarely noted (6%). Almost one-third (29%) of releases did not quantify study results. Studies presented in abstract form were subsequently published within at least 20 months in 53% of cases.

Conclusions

Pharmaceutical company press releases frequently report basic study details. However, readers should be cautioned by the preliminary nature of the data and lack of identified limitations. Methods to improve the reporting and interpretation of drug company press releases are desirable to prevent misleading media coverage.     

Conserved sequence elements associated with exon skipping

One of the major forms of alternative splicing, which generates multiple mRNA isoforms differing in the precise combinations of their exon sequences, is exon skipping. While in constitutive splicing all exons are included, in the skipped pattern(s) one or more exons are skipped. The regulation of this process is still not well understood; so far, cis- regulatory elements (such as exonic splicing enhancers) were identified in individual cases. We therefore set to investigate the possibility that exon skipping is controlled by sequences in the adjacent introns. We employed a computer analysis on 54 sequences documented as undergoing exon skipping, and identified two motifs both in the upstream and downstream introns of the skipped exons. One motif is highly enriched in pyrimidines (mostly C residues), and the other motif is highly enriched in purines (mostly G residues). The two motifs differ from the known cis-elements present at the 5′ and 3′ splice site. Interestingly, the two motifs are complementary, and their relative positional order is conserved in the flanking introns. These suggest that base pairing interactions can underlie a mechanism that involves secondary structure to regulate exon skipping. Remarkably, the two motifs are conserved in mouse orthologous genes that undergo exon skipping.     

Pepitope: epitope mapping from affinity-selected peptides

Identifying the epitope to which an antibody binds is central for many immunological applications such as drug design and vaccine development. The Pepitope server is a web-based tool that aims at predicting discontinuous epitopes based on a set of peptides that were affinity-selected against a monoclonal antibody of interest. The server implements three different algorithms for epitope mapping: PepSurf, Mapitope, and a combination of the two. The rationale behind these algorithms is that the set of peptides mimics the genuine epitope in terms of physicochemical properties and spatial organization. When the three-dimensional (3D) structure of the antigen is known, the information in these peptides can be used to computationally infer the corresponding epitope. A user-friendly web interface and a graphical tool that allows viewing the predicted epitopes were developed. Pepitope can also be applied for inferring other types of protein-protein interactions beyond the immunological context, and as a general tool for aligning linear sequences to a 3D structure. AVAILABILITY: http://pepitope.tau.ac.il/     

Deletion Mutagenesis within the Dimerization Initiation Site of Human Immunodeficiency Virus Type 1 Results in Delayed Processing of the p2 Peptide from Precursor Proteins

Previous work has shown that deletions of genomic segments at nucleotide (nt) positions +238 to +253, i.e., construct BH10-LD3, or nt positions +261 to +274, i.e., construct BH10-LD4, within the human immunodeficiency virus type 1 (HIV-1) dimerization initiation site (DIS) destroyed DIS secondary structure and dramatically reduced viral replication capacity. Surprisingly, two point mutations located within the viral peptide 2 (p2) and nucleocapsid (NC) protein termed MP2 and MNC, respectively, were able to compensate for this defect. Since the MP2 mutation involves an amino acid substitution near the cleavage site between p2 and NC, we investigated the effects of the above-mentioned deletions on the processing of Gag proteins. Immunoprecipitation assays performed with monoclonal antibodies against viral capsid (CA) (p24) protein showed that p2 was cleaved from CA with less efficiency in viruses that contained the LD3 and LD4 deletions than in wild-type viruses. The presence of the two compensatory mutations, MP2 and MNC, increased the efficiency of the cleavage of p2 from CA, but neither mutation alone had this effect or was sufficient to compensate for the observed impairment in infectiousness. A virus that contained both of the above-mentioned deletions within the DIS was also impaired in regard to processing and infectiousness, and it could likewise be compensated by the MP2 and MNC point mutations. These results suggest that the DIS region of HIV-1 RNA plays an important role in the processing of Gag proteins.     

Exposure to female pheromones stimulates a specific type of neuronal population in the male but not female magnocellular division of the medial preoptic nucleus (MPN mag) of the Syrian hamster

The magnocellular division of the medial preoptic area (MPN mag) integrates pheromonal and hormonal signals to play a critical role in the expression of male typical sex behavior. The MPN mag contains two morphologically distinct neuronal populations; the percentage of each type within the nucleus is sex specific. Males have more neurons with a single nucleolus whereas females have more with multiple nucleoli. To determine which neuronal subtype mediates pheromonal induction of copulation, tissue from male and female hamsters exposed to female pheromones was immunolabeled for the immediate early protein (EGR-1). Subsequently the tissue was counterstained and the number of ERG-1 neurons with one or two nuclei was determined. The results indicate that pheromones stimulate neurons with single nucleoli in males but fail to stimulate either neuronal subtype in females suggesting that synaptic input to the MPN mag is sexually differentiated.     

Tangles of neurogenetics, neuroethics, and culture

Neurogenetics promises rich insights into how the mind works. Researchers investigating the range of topics from normal brain functioning to pathological states are increasingly looking to genetics for clues on human variability and disease etiology. Is it fair to assume this interest in neurogenetics is universal? How should researchers and clinicians approach ideas of consent to research or prediction of disease when a subject or patient understands the mind with concepts or language incompatible with neurogenetics? In this paper we consider how non-Western philosophies bring complexity to ideas of individual and community consent and confidentiality in the context of neurogenetics.     

Splice-variant changes of the CaV3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development

Low voltage-activated T-type calcium (Ca) channels contribute to the normal development of the heart and are also implicated in pathophysiological states such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can be generated by alternative splicing from each of three different T-type genes (Ca_V3.1, Ca_V3.2, Ca_V3.3), although it remains to be described whether specific splice variants are associated with developmental states and pathological conditions. We aimed to identify and functionally characterize Ca_V3.2 T-type Ca channel alternatively spliced variants from newborn animals and to compare with adult normotensive and spontaneously hypertensive rats (SHR). DNA sequence analysis of full-length Ca_V3.2 cDNA generated from newborn heart tissue identified ten major regions of alternative splicing, the more common variants of which were analyzed by quantitative real-time PCR (qRT-PCR) and also subject to functional examination by whole-cell patch clamp. The main findings are that: (1) cardiac Ca_V3.2 T-type Ca channels are subject to considerable alternative splicing, (2) there is preferential expression of Ca_V3.2(−25) splice variant channels in newborn rat heart with a developmental shift in adult heart that results in approximately equal levels of expression of both (+25) and (−25) exon variants, (3) in the adult stage of hypertensive rats there is both an increase in overall Ca_V3.2 expression and a shift towards expression of Ca_V3.2(+25) containing channels as the predominant form and (4) alternative splicing confers a variant-specific voltage-dependent facilitation of Ca_V3.2 channels. We conclude that Ca_V3.2 alternative splicing generates significant T-type Ca channel structural and functional diversity with potential implications relevant to cardiac developmental and pathophysiological states.Key words: voltage-dependent facilitation, alternative splicing, T-type calcium channel, hypertension, cardiac hypertrophy     

A survey of UK public interest in internet-based personal genome testing

Background

In view of the increasing availability of commercial internet-based Personal Genome Testing (PGT), this study aimed to explore the reasons why people would consider taking such a test and how they would use the genetic risk information provided.

Methodology/Principal Findings

A self-completion questionnaire assessing public awareness and interest in PGT and motivational reasons for undergoing PGT was completed by 4,050 unselected adult volunteers from the UK-based TwinsUK register, aged 17 to 91 (response rate 62%). Only 13% of respondents were aware of the existence of PGT. After reading a brief summary about PGT, one in twenty participants (5%) were potentially interested at current prices (£250), however this proportion rose to half (50%) if the test was free of charge. Nearly all respondents who were interested in free PGT reported they would take the test to encourage them to adopt a healthier lifestyle if found to be at high genetic risk of a disease (93%). Around 4 in 5 respondents would have the test to convey genetic risk information to their children and a similar proportion felt that having a PGT would enable their doctor to monitor their health more closely. A TwinsUK research focus group also indicated that consumers would consult their GP to help interpret results of PGT.

Conclusions/Significance

This hypothetical study suggests that increasing publicity and decreasing costs of PGT may lead to increased uptake, driven in part by the general public''s desire to monitor and improve their health. Although the future extent of the clinical utility of PGT is currently unknown, it is crucial that consumers are well informed about the current limitations of PGT. Our results suggest that health professionals will inevitably be required to respond to individuals who have undergone PGT. This has implications for health service providers regarding both cost and time.