Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism.

The FtsZ protein is a central component of the bacterial cell division machinery. It polymerizes at mid-cell and recruits more than 30 proteins to assemble into a macromolecular complex to direct cell wall constriction. FtsZ polymers exhibit treadmilling dynamics, driving the processive movement of enzymes that synthesize septal peptidoglycan (sPG). Here, we combine theoretical modelling with single-molecule imaging of live bacterial cells to show that FtsZ's treadmilling drives the directional movement of sPG enzymes via a Brownian ratchet mechanism. The processivity of the directional movement depends on the binding potential between FtsZ and the sPG enzyme, and on a balance between the enzyme's diffusion and FtsZ's treadmilling speed. We propose that this interplay may provide a mechanism to control the spatiotemporal distribution of active sPG enzymes, explaining the distinct roles of FtsZ treadmilling in modulating cell wall constriction rate observed in different bacteria

Accelerated and Improved Quantification of Lymphocytic Choriomeningitis Virus (LCMV) Titers by Flow Cytometry

Lymphocytic choriomeningitis virus (LCMV), a natural murine pathogen, is a member of the Arenavirus family, may cause atypical meningitis in humans, and has been utilized extensively as a model pathogen for the study of virus-induced disease and immune responses. Historically, viral titers have been quantified by a standard plaque assay, but for non-cytopathic viruses including LCMV this requires lengthy incubation, so results cannot be obtained rapidly. Additionally, due to specific technical constraints of the plaque assay including the visual detection format, it has an element of subjectivity along with limited sensitivity. In this study, we describe the development of a FACS-based assay that utilizes detection of LCMV nucleoprotein (NP) expression in infected cells to determine viral titers, and that exhibits several advantages over the standard plaque assay. We show that the LCMV-NP FACS assay is an objective and reproducible detection method that requires smaller sample volumes, exhibits a ∼20-fold increase in sensitivity to and produces results three times faster than the plaque assay. Importantly, when applied to models of acute and chronic LCMV infection, the LCMV-NP FACS assay revealed the presence of infectious virus in samples that were determined to be negative by plaque assay. Therefore, this technique represents an accelerated, enhanced and objective alternative method for detection of infectious LCMV that is amenable to adaptation for other viral infections as well as high throughput diagnostic platforms

IL-21 and IL-6 Are Critical for Different Aspects of B Cell Immunity and Redundantly Induce Optimal Follicular Helper CD4 T Cell (Tfh) Differentiation

Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of B cell immunity in vivo. C57BL/6 or IL-21−/− mice were treated with a neutralizing monoclonal antibody against IL-6 throughout the course of an acute viral infection (lymphocytic choriomeningitis virus, LCMV). The combined absence of IL-6 and IL-21 resulted in reduced Tfh differentiation and reduced Bcl6 protein expression. In addition, we observed that these cytokines had a large impact on antigen-specific B cell responses. IL-6 and IL-21 collaborate in the acute T-dependent antiviral antibody response (90% loss of circulating antiviral IgG in the absence of both cytokines). In contrast, we observed reduced germinal center formation only in the absence of IL-21. Absence of IL-6 had no impact on germinal centers, and combined absence of both IL-21 and IL-6 revealed no synergistic effect on germinal center B cell development. Studying CD4 T cells in vitro, we found that high IL-21 production was not associated with high Bcl6 or CXCR5 expression. TCR stimulation of purified naïve CD4 T cells in the presence of IL-6 also did not result in Tfh differentiation, as determined by Bcl6 or CXCR5 protein expression. Cumulatively, our data indicates that optimal Tfh formation requires IL-21 and IL-6, and that cytokines alone are insufficient to drive Tfh differentiation

Tertiary Lymphoid Organs in Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects the joints, with inflammation of the synovial membrane, characterized by hyperplasia, neo-angiogenesis, and immune cell infiltration that drives local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous. In particular, in about 40% of patients with RA, synovitis is characterized by a dense lymphocytic infiltrate that can acquire the features of fully functional tertiary lymphoid organs (TLO). These structures amplify autoimmunity and inflammation locally associated with worse prognosis and potential implications for treatment response. Here, we will review the current knowledge on TLO in RA, with a focus on their pathogenetic and clinical relevance

Natural hazards in Goma and the surrounding villages, East African Rift System

The city of Goma and its surrounding villages (Democratic Republic of the Congo, DRC) are among the world's most densely populated regions strongly affected by volcanic hazards. In 2002, Nyiragongo volcano erupted destroying 10-15% of Goma and forced a mass evacuation of the population. Hence, the 1.5 million inhabitants of Goma and Gisenyi (Rwanda) continue to live with the threat of new lava flows and other eruptive hazards from this volcano. The current network of fractures extends from Nyiragongo summit to Goma and continues beneath Lake Kivu, which gives rise to the fear that an eruption could even produce an active vent within the center of Goma or within the lake. A sub-lacustrine volcanic eruption with vents in the floor of the main basin and/or Kabuno Bay of Lake Kivu could potentially release about 300 km(3) of carbon dioxide (CO2) and 60 km(3) of methane (CH4) dissolved in its deep waters that would be catastrophic to populations ( 2.5 million people) along the lake shores. For the time being, ongoing hazards related to Nyiragongo and Nyamulagira volcanoes silently kill people and animals, slowly destroy the environment, and seriously harm the health of the population. They include mazuku (CO2-rich locations where people often die of asphyxiation), the highly fluoridated surface and ground waters, and other locally neglected hazards. The volcanic gas plume causes poor air quality and acid rain, which is commonly used for drinking water. Given the large number of people at risk and the continued movement of people to Goma and the surrounding villages, there is an urgent need for a thorough natural hazards assessment in the region. This paper presents a general view of natural hazards in the region around Goma based on field investigations, CO2 measurements in mazuku, and chemistry data for Lake Kivu, rivers and rainwater. The field investigations and the datasets are used in conjunction with extremely rich-historical (1897-2000) and recently published information about Nyiragongo and Nyamulagira volcanoes and Lake Kivu. We also present maps of mazuku and fractures in Goma, describe the volcanic eruption history with hazard assessment and mitigation implications, and consider social realities useful for an integrated risk management strategy

New paleomagnetic data from Late Neoproterozoic sedimentary successions in Southern Urals, Russia: implications for the Late Neoproterozoic paleogeography of the Iapetan realm

We present the results of paleomagnetic study of Ediacaran sedimentary successions from the Southern Urals. The analysis of the sedimentary rocks of the Krivaya Luka, Kurgashlya and Bakeevo Formations reveal stable mid-temperature and high-temperature remanence components.Mid-temperature components were acquired during Devonian (Bakeevo Formation) and Late Carboniferous–Early Permian remagnetization events. The high-temperature components in Kurgashlya and Bakeevo Formations are interpreted to be primar , because they are supported by a positive conglomerate test (Bakeevo Formation) and magnetostratigraphic pattern (Kurgashlya Formation). Thehigh-temperature component in the Krivaya Luka Formation is interpreted to be a Late Ediacaran overprint. Our new paleomagnetic poles together with some previously published Ediacaran poles from Baltica and Laurentia are used herein to produce a series of paleogeographic reconstructions of the opening of the Iapetus Ocean