Review of \u3ci\u3eThe Chosen Folks: Jews on the Frontiers of Texas\u3c/i\u3e by Bryan Edward Stone

Bryan Stone\u27s The Chosen Folks deserves widespread appeal. Those interested in Jewish studies, Texas history, and immigration will certainly find it a useful analysis. What\u27s more, those concerned with the frontier-where Jewish, Texan, immigrant, and other identities intertwine, influence, and define each other-will especially benefit. Stone aptly applies the modern reconceptualization of the frontier to describe the experiences of Jews- the quintessential frontierspeople -in Texas, a quintessential frontier. Throughout the book Stone uses the frontier to organize and interpret the Texas Jewish experience. For example, the Republic of Texas\u27s location on a geographic frontier allowed Jews to develop an interior frontier wherein they could express or hide their Jewishness in accord with their circumstances. Furthermore, the geographic frontier enhanced Jews\u27 sense of being both insiders and outsiders in the newly formed state. Living great distances from centers of Jewish life, they identified with the dominant Anglo culture. Their Jewish heritage, however, distinguished them to some extent from the Anglo majority

A Giant Sample of Giant Pulses from the Crab Pulsar

We observed the Crab pulsar with the 43-m telescope in Green Bank, WV over a timespan of 15 months. In total we obtained 100 hours of data at 1.2 GHz and seven hours at 330 MHz, resulting in a sample of about 95000 giant pulses (GPs). This is the largest sample, to date, of GPs from the Crab pulsar taken with the same telescope and backend and analyzed as one data set. We calculated power-law fits to amplitude distributions for main pulse (MP) and interpulse (IP) GPs, resulting in indices in the range of 2.1-3.1 for MP GPs at 1.2 GHz and in the range of 2.5-3.0 and 2.4-3.1 for MP and IP GPs at 330 MHz. We also correlated the GPs at 1.2 GHz with GPs from the Robert C. Byrd Green Bank Telescope (GBT), which were obtained simultaneously at a higher frequency (8.9 GHz) over a span of 26 hours. In total, 7933 GPs from the 43-m telescope at 1.2 GHz and 39900 GPs from the GBT were recorded during these contemporaneous observations. At 1.2 GHz, 236 (3%) MP GPs and 23 (5%) IP GPs were detected at 8.9 GHz, both with zero chance probability. Another 15 (4%) low-frequency IP GPs were detected within one spin period of high-frequency IP GPs, with a chance probability of 9%. This indicates that the emission processes at high and low radio frequencies are related, despite significant pulse profile shape differences. The 43-m GPs were also correlated with Fermi gamma-ray photons to see if increased pair production in the magnetosphere is the mechanism responsible for GP emission. A total of 92022 GPs and 393 gamma-ray photons were used in this correlation analysis. No significant correlations were found between GPs and gamma-ray photons. This indicates that increased pair production in the magnetosphere is likely not the dominant cause of GPs. Possible methods of GP production may be increased coherence of synchrotron emission or changes in beaming direction.Comment: 33 pages, 10 figures, 6 tables, accepted for publication in Ap

Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk.MethodsIn June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD.ResultsWe describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs.ConclusionsPD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders

The unstructured C-terminus of the τ subunit of Escherichia coli DNA polymerase III holoenzyme is the site of interaction with the α subunit

The τ subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the α subunit through its C-terminal Domain V, τC16. We show that the extreme C-terminal region of τC16 constitutes the site of interaction with α. The τC16 domain, but not a derivative of it with a C-terminal deletion of seven residues (τC16Δ7), forms an isolable complex with α. Surface plasmon resonance measurements were used to determine the dissociation constant (KD) of the α−τC16 complex to be ∼260 pM. Competition with immobilized τC16 by τC16 derivatives for binding to α gave values of KD of 7 μM for the α−τC16Δ7 complex. Low-level expression of the genes encoding τC16 and τC16▵7, but not τC16Δ11, is lethal to E. coli. Suppression of this lethal phenotype enabled selection of mutations in the 3′ end of the τC16 gene, that led to defects in α binding. The data suggest that the unstructured C-terminus of τ becomes folded into a helix–loop–helix in its complex with α. An N-terminally extended construct, τC24, was found to bind DNA in a salt-sensitive manner while no binding was observed for τC16, suggesting that the processivity switch of the replisome functionally involves Domain IV of τ

AMI observations of northern supernova remnants at 14-18 GHz

We present observations between 14.2 and 17.9 GHz of 12 reported supernova remnants (SNRs) made with the Arcminute Microkelvin Imager Small Array (AMI SA). In conjunction with data from the literature at lower radio frequencies, we determine spectra of these objects. For well-studied SNRs (Cas A, Tycho's SNR, 3C58 and the Crab Nebula), the results are in good agreement with spectra based on previous results. For the less well-studied remnants the AMI SA observations provide higher-frequency radio observations than previously available, and better constrain their radio spectra. The AMI SA results confirm a spectral turnover at ~11 GHz for the filled-centre remnant G74.9+1.2. We also see a possible steepening of the spectrum of the filled-centre remnant G54.1+0.3 within the AMI SA frequency band compared with lower frequencies. We confirm that G84.9+0.5, which had previously been identified as a SNR, is rather an HII region and has a flat radio spectrum.Comment: 12 pages, 24 figures, accepted MNRA

The impact of herpes zoster and post-herpetic neuralgia on quality-of-life

International audienceBACKGROUND: The potentially serious nature of herpes zoster (HZ) and the long-term complication post-herpetic neuralgia (PHN) are often underestimated. One in four people will contract herpes zoster in their lifetime, with this risk rising markedly after the age of 50 years, and affecting one in two in elderly individuals. Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients. In the acute phase, pain is usually moderate or severe, with patients ranking HZ pain as more intense than post-surgical or labour pains. Up to 20% of patients with HZ develop PHN, which is moderate-to-severe chronic pain persisting for months or years after the acute phase. We review the available data on the effect of HZ and PHN on patients' quality-of-life. DISCUSSION: Findings show that HZ, and particularly PHN, have a major impact on patients' lives across all four health domains--physical, psychological, functional and social. There is a clear correlation between increasing severity of pain and greater interference with daily activities. Non-pain complications such as HZ ophthalmicus can increase the risk of permanent physical impairment. Some elderly individuals may experience a permanent loss of independence after an acute episode of HZ. Current challenges in the management of HZ and PHN are highlighted, including the difficulty in administering antiviral agents before pain becomes established and the limited efficacy of pain treatments in many patients. We discuss the clinical rationale for the HZ vaccine and evidence demonstrating that the vaccine reduces the burden of the disease. The Shingles Prevention Study, conducted among >38,000 people aged >or=60 years old, showed that the HZ vaccine significantly reduces the burden of illness and the incidence of both HZ and PHN. In the entire study population, zoster vaccination reduced the severity of interference of HZ and PHN with activities of daily living by two-thirds, as measured by two questionnaires specific to HZ. SUMMARY: A vaccination scheme may positively impact the incidence and course of HZ disease, thereby improving patients' quality-of-life

Genetic Dissection of Acute Ethanol Responsive Gene Networks in Prefrontal Cortex: Functional and Mechanistic Implications

Background Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol. Results Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol\u27s effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b,Gria1, Sncb and Nell2. Conclusions The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol response of gene networks could have important implications for future studies regarding the mechanisms and treatment of alcohol use disorders

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.

OBJECTIVE: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. METHODS: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. RESULTS: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset. INTERPRETATION: This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV