Combining Relative Chronology and AMS 14C Dating to Contextualize ‘Megasites’, Serial Migrations and Diachronic Expressions of Material Culture in the Western Tripolye Culture, Ukraine

Scholarship regarding the Eneolithic Cucuteni-Tripolye cultural complex of Romania, Moldova and Ukraine has recently focused on ‘megasites’ of the Western Tripolye culture (WTC) in Central Ukraine. However, in order to properly contextualize such unusual phenomena, we must explore the broader typo-chronology of the WTC, which is suggestive of a high degree of mobility and technological transfer between regions. We report 28 new AMS 14C dates from sites representing diagnostic types and propose a high-resolution chronological sequence for the WTC’s development. Our results support the relative chronology and offer an opportunity to propose a new chronological synthesis for the WTC

Quantitative Organization of GABAergic Synapses in the Molecular Layer of the Mouse Cerebellar Cortex

In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells) provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary subtractive strategies to quantitatively assess the ratio of GABAergic synapses on Purkinje cell dendrites versus those on interneurons. We generated a mouse model in which the GABAA receptor α1 subunit (GABAARα1) was selectively removed from Purkinje cells using the Cre/loxP system. Deletion of the α1 subunit resulted in a complete loss of GABAAR aggregates from Purkinje cells, allowing us to determine the density of GABAAR clusters in interneurons. In a complementary approach, we determined the density of GABA synapses impinging on Purkinje cells using α-dystroglycan as a specific marker of inhibitory postsynaptic sites. Combining these inverse approaches, we found that synapses received by interneurons represent approximately 40% of all GABAergic synapses in the molecular layer. Notably, this proportion was stable during postnatal development, indicating synchronized synaptogenesis. Based on the pure quantity of GABAergic synapses onto interneurons, we propose that mutual inhibition must play an important, yet largely neglected, computational role in the cerebellar cortex

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar purkinje cells

Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABA(A) receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABA(A) receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABA(A) receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABA(A) receptors and is abolished by preventing CaMKII phosphorylation of GABA(A) receptors. Our results reveal a novel GABA(A) receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe

Urban Youth Workers' Use of “Personal Knowledge” in Resolving Complex Dilemmas of Practice

Using narrative inquiry to analyze accounts of how two experienced youth workers handled the potential for gun violence in their organizations, this article argues that youth worker expertise in part is based on personal knowledge derived from childhood neighborhood-based peer groups and participation in youth programs. Expert youth workers draw on personal and professional craft knowledge and move between the rules of youth organizations and the rules of the streets to read people and situations and address the potential for serious violence. Implications for youth worker professional development are raised. © 2013 Taylor and Francis Group, LLC

Individual and Contextual Effects of School Adjustment on Adolescent Alcohol Use

This paper examines the effect of a student’s own school adjustment as well as the contextual level of school adjustment (the normative level of school adjustment among students in a school) on students’ self-reported use of alcohol. Using a dataset of 43,465 male and female 8th grade students from 349 schools across the contiguous United States who participated in a national study of substance use in rural communities between 1996 and 2000, multilevel latent covariate models were utilized to disentangle the individual-level and contextual effects of three school adjustment variables (i.e., school bonding, behavior at school, and friend’s school bonding) on alcohol use. All three school adjustment factors were significant predictors of alcohol use both within and between schools. Furthermore, this study demonstrated a strong contextual effect: Students who attended schools where the overall level of school adjustment was higher reported lower levels of alcohol use even after taking their own school adjustment into account. The results demonstrate the importance of both a student’s own level of school adjustment and the normative level of school adjustment among students in the school on an adolescent’s use of alcohol. Differences in school adjustment across schools were quite strongly related to an adolescent’s own alcohol use, indicating that school adjustment is an important aspect of school climate. Initiatives aimed at improving school climate may have beneficial effects on students’ alcohol use