A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not placodal lineage EGFP expression in a transgenic animal.

Under physiological conditions, the voltage-gated sodium channel Nav1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Nav1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Nav1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 μm). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (∼10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Nav1.8 transcript (95%), Nav1.8-immunoreactivity (70%), and TTX-R INa (100%), although not all Nav1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Nav1.8-immunoreactivity confirmed Nav1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R INa recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Nav1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Nav1.8 expression pattern in neural crest-derived sensory neurons.This work was supported by the Intramural program at the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholis

Alfvén waves in the near-PSBL lobe: Cluster observations

Electromagnetic low-frequency waves in the magnetotail lobe close to the PSBL (Plasma Sheet Boundary Layer) are studied using the Cluster spacecraft. The lobe waves show Alfvénic properties and transport their wave energy (Poynting flux) on average toward the Earth along magnetic field lines. Most of the wave events are rich with oxygen (O+) ion plasma. The rich O+ plasma can serve to enhance the magnetic field fluctuations, resulting in a greater likelihood of observation, but it does not appear to be necessary for the generation of the waves. Taking into account the fact that all events are associated with auroral electrojet enhancements, the source of the lobe waves might be a substorm-associated instability, i.e. some instability near the reconnection site, or an ion beam-related instability in the PSBL

Catastrophic senescence and semelparity in the Penna aging model

The catastrophic senescence of the Pacific salmon is among the initial tests used to validate the Penna aging model. Based on the mutation accumulation theory, the sudden decrease in fitness following reproduction may be solely attributed to the semelparity of the species. In this work, we report other consequences of mutation accumulation. Contrary to earlier findings, such dramatic manifestation of aging depends not only on the choice of breeding strategy but also on the value of the reproduction age, R, and the mutation threshold, T. Senescence is catastrophic when $T \leq R$. As the organism's tolerance for harmful genetic mutations increases, the aging process becomes more gradual. We observe senescence that is threshold dependent whenever T>R. That is, the sudden drop in survival rate occurs at age equal to the mutation threshold value

Human GPR42 is a transcribed multisite variant that exhibits copy number polymorphism and is functional when heterologously expressed.

FFAR3 (GPR41) is a G-protein coupled receptor for which short-chain fatty acids serve as endogenous ligands. The receptor is found on gut enteroendocrine L-cells, pancreatic β-cells, and sympathetic neurons, and is implicated in obesity, diabetes, allergic airway disease, and altered immune function. In primates, FFAR3 is segmentally duplicated resulting in GPR42, a gene currently classified as a suspected pseudogene. In this study, we sequenced FFAR3 and GPR42 open reading frames from 56 individuals and found an unexpectedly high frequency of polymorphisms contributing to several complex haplotypes. We also identified a frequent (18.8%) structural variation that results in GPR42 copy number polymorphism. Finally, sequencing revealed that 50.6% of GPR42 haplotypes differed from FFAR3 by only a single non-synonymous substitution and that the GPR42 reference sequence matched only 4.4% of the alleles. Sequencing of cDNA from human sympathetic ganglia and colon revealed processed transcripts matching the GPR42 genotype. Expression of several GPR42 haplotypes in rat sympathetic neurons revealed diverse pharmacological phenotypes that differed in potency and efficacy. Our data suggest that GPR42 be reclassified as a functioning gene and that recognition of sequence and copy number polymorphism of the FFAR3/GPR42 complex be considered during genetic and pharmacological investigation of these receptors

Obesity and Undiagnosed Diabetes in the U.S.

OBJECTIVE—To study whether obese individuals, who are at higher risk for diabetes and disparities in care than nonobese individuals, are more likely to have undiagnosed diabetes

Responses to gestational weight management guidance: a thematic analysis of comments made by women in online parenting forums

Background: The National Institute for Health and Clinical Excellence (NICE) published guidance on weight management in pregnancy in July 2010[1], and this received considerable press coverage across a range of media. This offered an opportunity to examine how gestational weight management guidance was received by UK women. Methods: A thematic analysis was conducted of 400 posts made in UK-based parenting internet forums in the week following the publication of the NICE guidance. This allowed us to examine the naturally occurring comments from 202 women who posted about the guidance on public forums. Results: Three main themes were identified and explored: i) Perceived control/responsibility ii) Risk perception iii) Confused messages. Conclusions: Women differed in their perceptions of the level of control that they had over being overweight with some feeling responsible and motivated to maintain a healthy lifestyle. Others felt there were multiple factors influencing their weight issues beyond their control. There were reports of feeling guilty about the impact of weight on the growing baby and experiencing significant obesity stigma from the public and health professionals. Information about the risks of overweight and obesity in pregnancy were difficult messages for women to hear, and for health professionals to deliver. Women reported being confused by the messages that they received. Health messages need to be delivered sensitively to women, and health professionals need support and training to do this. Risk information should always be accompanied with clear advice and support to help women to manage their weight in pregnancy. Keywords: internet-mediated research, gestational weight gain, parenting forums, NICE, women, views, risk perception</p

Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia.

Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology

Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia.

Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology