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Contemporary Israel
Since its formation in 1948, and particularly since the assassination of Prime Minister Yitzak Rabin in 1995, Israel has experienced turbulent political change and numerous ongoing security challenges, including major party splits, collapsed peace talks with the Palestinians and Syria, nuclear threats from Iran, and even the specter of civil war as Israel withdrew from Gaza. This essential survey brings together Israeli and American scholars to provide a much-needed balanced introduction to Israel?s domestic politics and foreign policy. Experts tackle this difficult subject in three parts: domestic politics, foreign policy challenges, and strategic challenges. Domestic topics include the Israeli Right and Left; religious, Russian, and Arab parties; the Supreme Court; and the economy. Part two discusses Israel?s complicated and often fractious relationships with the Palestinians and the Arab world, as well as its improved relations with Turkey and India and continuing close relationship with the United States. The Israel-Hizbollah War of 2006 and existential threats to Israel, including the threat from Iran, are detailed in part three. This compelling and authoritative coverage provides students with the necessary framework to understand Israel?s political past and present, as well as the direction Israel is likely to take in the future.Contents1. Introduction (Robert O. Freedman)Part One: Israeli Domestic Politics 2. The Israeli Right (Ilan Peleg) 3. The Israeli Zionist Left (Mark Rosenblum) 4. Israel?s Religious Parties (Shmuel Sander and Aaron Kampinsky) 5. Israel?s Russian Parties (Vladimir Ze?ev Khanin) 6. Israel?s Arab Parties (Hillel Frisch) 7. Israel?s Supreme Court (Pnina Lahav) 8. Israel?s Economy (Ofira Seliktar)Part Two: Israel?s Foreign Policy Challenges 9. Israel and the Palestinians (Barry Rubin) 10. Israel and the Arab World (David Lesch) 11. Israel?s Strategic Relations with Turkey and India (Efraim Inbar) 12. Israel and the United States (Robert O. Freedman)Part Three: Israel?s Strategic Challenges 13. Existential Threats to Israel (Steven David) 14. Israel?s Second Lebanon War (Elli Lieberman)
eBook
Israel and the United States
This unique volume intensively studies the nature and extent of US - Israeli relations, from 1948 through the Bush and Obama administrations. Leading experts in the field (including Israeli and North American scholars from a variety of political perspectives) contribute original essays on the principal political, religious, ethnic, military, economic, and juridical connections between the United States and Israel. Specific topics covered in this new book include: the pro-Israel lobby in the United States; the US Jewish community and its relations to Israel; evangelical Christians and Israel; military and economic ties between the United States and Israel; the threat of a nuclear Iran for both countries; and the impact of American jurisprudence on Israel. Section introductions from the editor effectively contextualize the issues and provide students with an in-depth understanding of the past, present, and future of the US - Israel relationship.
eBook
Male fetus susceptibility to maternal inflammation: C-reactive protein and brain development
Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.
Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.
Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.
The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.
Journal Article
Ketamine and ECT in Depression — Risks and Rewards
Investigators from five referral clinics for electroconvulsive therapy (ECT) report in the
Journal
the results of an open-label, randomized, noninferiority trial of ECT or ketamine infusion in patients with moderately severe depression.
1
After randomization, 365 patients (170 in the ECT group and 195 in the ketamine group) were included in the primary analysis. At the conclusion of the 3-week, randomized, active-treatment phase, 41% of the patients in the ECT group and 55% of those in the ketamine group reported a 50% or greater reduction in symptoms, findings that are consistent with moderate-to-excellent responses to treatment.
2
Patients who had a response . . .
Journal Article
A VNTR Regulates miR-137 Expression Through Novel Alternative Splicing and Contributes to Risk for Schizophrenia
The
MIR137HG
gene encoding microRNA-137 (miR-137) is genome-wide associated with schizophrenia (SZ), however, the underlying molecular mechanisms remain unknown. Through cloning and sequencing of individual transcripts from fetal and adult human brain tissues we describe novel pri-miR-137 splice variants which exclude the mature miR-137 sequence termed ‘del-miR-137’ that would function to down-regulate miR-137 expression. Sequencing results demonstrate a significant positive association between del-miR-137 transcripts and the length of a proximal variable number tandem repeat (VNTR) element. Additionally, a significantly higher proportion of sequenced transcripts from fetal brain were del-miR-137 transcripts indicating neurodevelopmental splicing regulation.
In
-
silico
results predict an independent regulatory function for del-miR-137 transcripts through competitive endogenous RNA function. A case-control haplotype analysis (n = 998) in SZ implicates short VNTR length in risk, with longer lengths imparting a protective effect. Rare high risk haplotypes were also observed indicating multiple risk variants within the region. A second haplotype analysis was performed to evaluate recombination effects excluding the VNTR and results indicate that recombination of the region was found to independently contribute to risk. Evaluation of the evolutionary conservation of the VNTR reveals a human lineage specific expansion. These findings shed further light on the risk architecture of the miR-137 region and provide a novel regulatory mechanism through VNTR length and alternative
MIR137HG
transcripts which contribute to risk for SZ.
Journal Article
Prospects for improving future mental health of children through prenatal maternal micronutrient supplementation in China
Prenatal micronutrients in pregnant women’s diets, including supplements, have an essential role in fetal brain development and may reduce the risk of mental disorders in offspring. Folic acid, vitamin D, omega‐3 fatty acids, and choline have been investigated for this purpose. Folic acid supplementation throughout pregnancy has well‐established positive effects. Vitamin D, administered to the mother before birth or to the newborn, has also been shown to reduce the risk of neurodevelopmental disorders. Omega‐3 fatty acids during pregnancy have a more uncertain role, with recent trials questioning a beneficial effect on cognition and attention deficit disorder, despite positive effects on prematurity and neonatal wheezing prevention. Choline supplementation is associated with positive effects on cognition and behavior, including early behaviors associated with the development of autism and schizophrenia. There is no experience yet with COVID‐19, but adverse effects on fetal brain development of most common coronaviruses are mitigated by higher choline levels. Maternal dietary supplementation of nutrients is a benign and inexpensive intervention in pregnancy to prevent life‐long disability from mental illness. Use of dietary supplements in poorer, rural areas of China is below recommendations. Physicians, midwives, and public health officials in China can promote prenatal nutrient supplementation to reduce the future burden of mental illnesses that might be prevented before birth.
Journal Article
Protein Disulfide-Isomerase Interacts with a Substrate Protein at All Stages along Its Folding Pathway
In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10(-5) M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding - differential affinity, rapid ligand exchange and conformational flexibility.
Journal Article
Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia
Auditory sensory gating, a biological measurement of the ability to suppress the evoked response to the second of two auditory stimuli, is diminished in people with schizophrenia. Deficits in sensory gating are associated with attentional impairment, and may contribute to cognitive symptoms and perceptual disturbances. This inhibitory process, which involves the alpha(7) nicotinic receptor mediated release of gamma-aminobutyric acid (GABA) by hippocampal interneurons, represents a potential new target for therapeutic intervention in schizophrenia.
This paper will review several lines of evidence implicating the nicotinic-cholinergic, and specifically, the alpha(7) nicotinic receptor system in the pathology of schizophrenia and the evidence that alpha(7) nicotinic receptor agonists may ameliorate some of these deficits.
Impaired auditory sensory gating has been linked to the alpha(7) nicotinic receptor gene on the chromosome 15q14 locus. Single nucleotide polymorphisms of the promoter region of this gene are more frequent in people with schizophrenia. Although nicotine can acutely reverse diminished auditory sensory gating in people with schizophrenia, this effect is lost on a chronic basis due to receptor desensitization. Clozapine is able to reverse auditory sensory gating impairment, probably through an alpha(7) nicotinic receptor mechanism, in both humans and animal models with repeated dosing. The alpha(7) nicotinic agonist 3-2,4 dimethoxybenzylidene anabaseine (DMXBA) can also enhance auditory sensory gating in animal models. DMXBA is well tolerated in humans and improves several cognitive measures.
Alpha-7 nicotinic receptor agonists appear to be reasonable candidates for the treatment of cognitive and perceptual disturbances in schizophrenia.
Conference Proceeding
Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry
Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.
Journal Article