The Missing Link of Jewish European Ancestry: Contrasting the Rhineland and the Khazarian Hypotheses

The question of Jewish ancestry has been the subject of controversy for over two centuries and has yet to be resolved. The "Rhineland Hypothesis" proposes that Eastern European Jews emerged from a small group of German Jews who migrated eastward and expanded rapidly. Alternatively, the "Khazarian Hypothesis" suggests that Eastern European descended from Judean tribes who joined the Khazars, an amalgam of Turkic clans that settled the Caucasus in the early centuries CE and converted to Judaism in the 8th century. The Judaized Empire was continuously reinforced with Mesopotamian and Greco-Roman Jews until the 13th century. Following the collapse of their empire, the Judeo-Khazars fled to Eastern Europe. The rise of European Jewry is therefore explained by the contribution of the Judeo-Khazars. Thus far, however, their contribution has been estimated only empirically; the absence of genome-wide data from Caucasus populations precluded testing the Khazarian Hypothesis. Recent sequencing of modern Caucasus populations prompted us to revisit the Khazarian Hypothesis and compare it with the Rhineland Hypothesis. We applied a wide range of population genetic analyses - including principal component, biogeographical origin, admixture, identity by descent, allele sharing distance, and uniparental analyses - to compare these two hypotheses. Our findings support the Khazarian Hypothesis and portray the European Jewish genome as a mosaic of Caucasus, European, and Semitic ancestries, thereby consolidating previous contradictory reports of Jewish ancestry.Comment: 21 pages, 7 figures, 1 table, 7 supplementary figures, 7 supplementary table

Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants

The global burden of neonatal and infant mortality due to infection is staggering, particularly in resource-poor settings. Early childhood vaccination is one of the major interventions that can reduce this burden, but there are specific limitations to inducing effective immunity in early life, including impaired neonatal leukocyte production of Th1-polarizing cytokines to many stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate immune responses in infants may shed light on susceptibility to infection in this vulnerable age group, and provide insights into TLR agonists as candidate adjuvants for improved neonatal vaccines. As little is known about the leukocyte responses of infants in resource-poor settings, we characterized production of Th1-, Th2-, and anti-inflammatory- cytokines in response to agonists of TLRs 1-9 in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12 months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5, and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that also uniquely induced cord blood IFNγ production. For most agonists, TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of age. TLR8 agonists also induced the greatest production of the Th1-polarizing cytokines TNFα and IFNγ throughout the first year of life, although the relative responses to the single TLR8 agonist and the combined TLR7/8 agonist changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most agonists were robust at birth and remained stable through 12 months of age. These observations provide fresh insights into the ontogeny of innate immunity in African children, and may inform development of age-specific adjuvanted vaccine formulations important for global health

Iterative approximation of k-limited polling systems

The present paper deals with the problem of calculating queue length distributions in a polling model with (exhaustive) k-limited service under the assumption of general arrival, service and setup distributions. The interest for this model is fueled by an application in the field of logistics. Knowledge of the queue length distributions is needed to operate the system properly. The multi-queue polling system is decomposed into single-queue vacation systems with k-limited service and state-dependent vacations, for which the vacation distributions are computed in an iterative approximate manner. These vacation models are analyzed via matrix-analytic techniques. The accuracy of the approximation scheme is verified by means of an extensive simulation study. The developed approximation turns out be accurate, robust and computationally efficient

Mitochondrial haplogroup N1a phylogeography, with implication to the origin of European farmers

<p>Abstract</p> <p>Background</p> <p>Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations.</p> <p>Results</p> <p>The geographic origin and expansion of farmer lineages related N1a subclades have been deduced from combined analysis of 19 complete sequences with 166 N1a haplotypes. The phylogeographic analysis revealed that the central European farmer lineages have originated from different sources: from eastern Europe, local central Europe, and from the Near East via southern Europe.</p> <p>Conclusions</p> <p>The results obtained emphasize that the arrival of central European farmer lineages did not occur via a single demic diffusion event from the Near East at the onset of the Neolithic spread of agriculture into Europe. Indeed these results indicate that the Neolithic transition process was more complex in central Europe and possibly the farmer N1a lineages were a result of a 'leapfrog' colonization process.</p

Controlled mobility in stochastic and dynamic wireless networks

We consider the use of controlled mobility in wireless networks where messages arriving randomly in time and space are collected by mobile receivers (collectors). The collectors are responsible for receiving these messages via wireless transmission by dynamically adjusting their position in the network. Our goal is to utilize a combination of wireless transmission and controlled mobility to improve the throughput and delay performance in such networks. First, we consider a system with a single collector. We show that the necessary and sufficient stability condition for such a system is given by ρ<1 where ρ is the expected system load. We derive lower bounds for the expected message waiting time in the system and develop policies that are stable for all loads ρ<1 and have asymptotically optimal delay scaling. We show that the combination of mobility and wireless transmission results in a delay scaling of Θ([1 over 1−ρ]) with the system load ρ, in contrast to the Θ([1 over (1−ρ)[superscript 2]]) delay scaling in the corresponding system without wireless transmission, where the collector visits each message location. Next, we consider the system with multiple collectors. In the case where simultaneous transmissions to different collectors do not interfere with each other, we show that both the stability condition and the delay scaling extend from the single collector case. In the case where simultaneous transmissions to different collectors interfere with each other, we characterize the stability region of the system and show that a frame-based version of the well-known Max-Weight policy stabilizes the system asymptotically in the frame length.National Science Foundation (U.S.) (Grant CNS-0915988)United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-08-1-0238

Update on the hyper immunoglobulin M syndromes

The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination (CSR), with or without defects of somatic hypermutation (SHM). They can be classified as defects of signalling through CD40 causing both a humoral immunodeficiency and a susceptibility to opportunistic infections, or intrinsic defects in B cells of the mechanism of CSR resulting in a pure humoral immunodeficiency. A HIGM picture can also be seen as part of generalized defects of DNA repair and in antibody deficiency syndromes, such as common variable immunodeficiency. CD40 signalling defects may require corrective therapy with bone marrow transplantation. Gene therapy, a potential curative approach in the future, currently remains a distant prospect. Those with a defective CSR mechanism generally do well on immunologoblulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy

Neuroanatomical Circuitry Associated with Exploratory Eye Movement in Schizophrenia: A Voxel-Based Morphometric Study

Schizophrenic patients present abnormalities in a variety of eye movement tasks. Exploratory eye movement (EEM) dysfunction appears to be particularly specific to schizophrenia. However, the underlying mechanisms of EEM dysfunction in schizophrenia are not clearly understood. To assess the potential neuroanatomical substrates of EEM, we recorded EEM performance and conducted a voxel-based morphometric analysis of gray matter in 33 schizophrenic patients and 29 well matched healthy controls. In schizophrenic patients, decreased responsive search score (RSS) and widespread gray matter density (GMD) reductions were observed. Moreover, the RSS was positively correlated with GMD in distributed brain regions in schizophrenic patients. Furthermore, in schizophrenic patients, some brain regions with neuroanatomical deficits overlapped with some ones associated with RSS. These brain regions constituted an occipito-tempro-frontal circuitry involved in visual information processing and eye movement control, including the left calcarine cortex [Brodmann area (BA) 17], the left cuneus (BA 18), the left superior occipital cortex (BA 18/19), the left superior frontal gyrus (BA 6), the left cerebellum, the right lingual cortex (BA 17/18), the right middle occipital cortex (BA19), the right inferior temporal cortex (BA 37), the right dorsolateral prefrontal cortex (BA 46) and bilateral precentral gyri (BA 6) extending to the frontal eye fields (FEF, BA 8). To our knowledge, we firstly reported empirical evidence that gray matter loss in the occipito-tempro-frontal neuroanatomical circuitry of visual processing system was associated with EEM performance in schizophrenia, which may be helpful for the future effort to reveal the underlying neural mechanisms for EEM disturbances in schizophrenia