The causes and scope of political egalitarianism during the Last Glacial: a multi-disciplinary perspective

This paper reviews and synthesizes emerging multi-disciplinary evidence toward understanding the development of social and political organization in the Last Glacial. Evidence for the prevalence and scope of political egalitarianism is reviewed and the biological, social, and environmental influences on this mode of human organization are further explored. Viewing social and political organization in the Last Glacial in a much wider, multi-disciplinary context provides the footing for coherent theory building and hypothesis testing by which to further explore human political systems. We aim to overcome the claim that our ancestors’ form of social organization is untestable, as well as counter a degree of exaggeration regarding possibilities for sedentism, population densities, and hierarchical structures prior to the Holocene with crucial advances from disparate disciplines.     

Spontaneous class switch recombination in B cell lymphopoiesis generates aberrant switch junctions and is increased after VDJ rearrangement

Mature B cells replace the mu constant region of the H chain with a downstream isotype in a process of class switch recombination (CSR). Studies suggest that CSR induction is limited to activated mature B cells in the periphery. Recently, we have shown that CSR spontaneously occur in B lymphopoiesis. However, the mechanism and regulation of it have not been defined. In this study, we show that spontaneous CSR occurs at all stages of B cell development and generates aberrant joining of the switch junctions as revealed by: 1) increased load of somatic mutations around the CSR break points, 2) reduced sequence overlaps at the junctions, and 3) excessive switch region deletion. In addition, we found that incidence of spontaneous CSR is increased in cells carrying VDJ rearrangements. Our results reveal major differences between spontaneous CSR in developing B cells and CSR induced in mature B cells upon activation. These differences can be explained by deregulated expression or function of activation-induced cytidine deaminase early in B cell development.     

Modeling regulation mechanisms in the immune system

We develop a mathematical framework for modeling regulatory mechanisms in the immune system. The model describes dynamics of key components of the immune network within two compartments: lymph node and tissue. We demonstrate using numerical simulations that our system can eliminate virus-infected cells, which are characterized by a tendency to increase without control (in absence of an immune response), while tolerating normal cells, which are characterized by a tendency to approach a stable equilibrium population. We experiment with different combinations of T cell reactivities that lead to effective systems and conclude that slightly self-reactive T cells can exist within the immune system and are controlled by regulatory cells. We observe that CD8+ T cell dynamics has two phases. In the first phase, CD8+ cells remain sequestered within the lymph node during a period of proliferation. In the second phase, the CD8+ population emigrates to the tissue and destroys its target population. We also conclude that a self-tolerant system must have a mechanism of central tolerance to ensure that self-reactive T cells are not too self-reactive. Furthermore, the effectiveness of a system depends on a balance between the reactivities of the effector and regulatory T cell populations, where the effectors are slightly more reactive than the regulatory cells.     

Synchronization of cell death in a dinoflagellate population is mediated by an excreted thiol protease

Regulated programmed cell death (PCD) processes have been documented in several phytoplankton species and are hypothesized to play a role in population dynamics. However, the mechanisms leading to the coordinated collapse of phytoplankton blooms are poorly understood. We showed that the collapse of the annual bloom of Peridinium gatunense, an abundant dinoflagellate in Lake Kinneret, Israel, is initiated by CO2 limitation followed by oxidative stress that triggers a PCD-like cascade. We provide evidences that a protease excreted by senescing P. gatunense cells sensitizes younger cells to oxidative stress and may consequently trigger synchronized cell death of the population. Ageing of the P. gatunense cultures was characterized by a remarkable rise in DNA fragmentation and enhanced sensitivity to H2O2. Exposure of logarithmic phase (young) cultures to conditioning media from stationary phase (old) cells sensitized them to H2O2 and led to premature massive cell death. We detected the induction of specific extracellular protease activity, leupeptin-sensitive, in ageing cultures and in lake waters during the succession of the P. gatunense bloom. Partial purification of the conditioned media revealed that this protease activity is responsible for the higher susceptibility of young cells to oxidative stress. Inhibition of the protease activity lowered the sensitivity to oxidative stress, whereas application of papain to logarithmic phase P. gatunense cultures mimicked the effect of the spent media and enhanced cell death. We propose a novel mechanistic framework by which a population of unicellular phytoplankton orchestrates a coordinated response to stress, thereby determine the fate of its individuals.     

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

A special group of mitochondrial outer membrane (MOM) proteins spans the membrane several times via multiple helical segments. Such multispan proteins are synthesized on cytosolic ribosomes before their targeting to mitochondria and insertion into the MOM. Previous work recognized the import receptor Tom70 and the mitochondrial import (MIM) complex, both residents of the MOM, as required for optimal biogenesis of these proteins. However, their involvement is not sufficient to explain either the entire import pathway or its regulation. To identify additional factors that are involved in the biogenesis of MOM multispan proteins, we performed complementary high-throughput visual and growth screens in Saccharomyces cerevisiae. Cardiolipin (CL) synthase (Crd1) appeared as a candidate in both screens. Our results indeed demonstrate lower steady-state levels of the multispan proteins Ugo1, Scm4, and Om14 in mitochondria from crd1Δ cells. Importantly, MOM single-span proteins were not affected by this mutation. Furthermore, organelles lacking Crd1 had a lower in vitro capacity to import newly synthesized Ugo1 and Scm4 molecules. Crd1, which is located in the mitochondrial inner membrane, condenses phosphatidylglycerol together with CDP-diacylglycerol to obtain de novo synthesized CL molecules. Hence, our findings suggest that CL is an important component in the biogenesis of MOM multispan proteins.     

Does the modern urbanized sleeping habitat pose a breast cancer risk?

Due to its disruptive effects on circadian rhythms and sleep deprivation at night, shiftworking is currently recognized as a risk factor for breast cancer (BC). As revealed by the present analysis based on a comparative case-control study of 1679 women, exposure to light-at-night (LAN) in the "sleeping habitat" is significantly associated with BC risk (odds ratio [OR]?=?1.220, 95% confidence interval [CI]?=?1.118-1.311; p?相似文献   

Reconstructing a puzzle: existence of cyanophages containing both photosystem‐I and photosystem‐II gene suites inferred from oceanic metagenomic datasets

Cyanobacteria play a key role in marine photosynthesis, which contributes to the global carbon cycle and to the world oxygen supply. Genes encoding the photosystem‐II (PSII) reaction centre are found in many cyanophage genomes, and it was suggested that the horizontal transfer of these genes might be involved in increasing phage fitness. Recently, evidence for the existence of phages carrying Photosystem‐I (PSI) genes was also reported. Here, using a combination of different marine metagenomic datasets and a unique crossing of the datasets, we now describe the finding of phages that, as in plants and cyanobacteria, contain both PSII and PSI genes. In addition, these phages also contain NADH dehydrogenase genes. The presence of modified PSII and PSI genes in the same viral entities in combination with electron transfer proteins like NAD(P)H dehydrogenase (NDH‐1) strongly points to a role in perturbation of the cyanobacterial host photosynthetic electron flow. We therefore suggest that, depending on the physiological condition of the infected cyanobacterial host, the viruses may use different options to maximize survival. The modified PSI may alternate between functioning with PSII in linear electron transfer and contributing to the production of both NADPH and ATP or functioning independently of PSII in cyclic mode via the NDH‐1 complex and thus producing only ATP.