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Bacterial and fungal pathogens face various microenvironmental conditions during infection. In addition to acidosis, nutrient consumption, and hypercapnia, pathogen infections are associated with hypoxia, which is induced by bacterial and fungal respiration during the formation of foci of infection or biofilms. Consequently, the in vivo interaction between host immune cells and pathogens is anticipated to occur mainly under low-oxygen conditions. Various infectious disease models have reported that pathogens benefit from hypoxia, which dampens the oxygen-dependent antimicrobial activities of macrophages and neutrophils, such as the production of reactive oxygen species (ROS). Due to their dual respiration capacity (aerobic and anaerobic) or phenotypical adaptation (e.g., dormancy), pathogens have the capacity to survive and disseminate in the absence of oxygen. In addition, hypoxia modulates various mechanisms of pathogen virulence, promoting the dissemination of pathogens. Further investigations are still required to evaluate the relative importance of oxygen on the capacity of pathogens to invade and colonize host organs and to better understand alternative strategies developed by immune cells to circumvent pathogen dissemination in the absence of oxygen. Addressing this important and fundamental question in various models of infection may direct the development of innovative therapeutic strategies.

The last deglaciation is the most recent interval of large-scale climate change that drove the Greenland ice sheet from continental shelf to within its present extent. Here, we use a database of 645 published 10Be ages from Greenland to document the spatial and temporal patterns of retreat of the Greenland ice sheet during the last deglaciation. Following initial retreat of its marine margins, most land-based deglaciation occurred in Greenland following the end of the Younger Dryas cold period (12.9–11.7 ka). However, deglaciation in east Greenland peaked significantly earlier (13.0–11.5 ka) than that in south Greenland (11.0–10 ka) or west Greenland (10.5–7.0 ka). The terrestrial deglaciation of east and south Greenland coincide with adjacent ocean warming. 14C ages and a recent ice-sheet model reconstruction do not capture this progression of terrestrial deglacial ages from east to west Greenland, showing deglaciation occurring later than observed in 10Be ages. This model-data misfit likely reflects the absence of realistic ice-ocean interactions. We suggest that oceanic changes may have played an important role in driving the spatial-temporal ice-retreat pattern evident in the 10Be data.

Erratum in Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection. [Cell Host Microbe. 2019]; International audience; Intestinal epithelial cells are constantly exposed to pathogens and mechanical forces. However, the impact of mechanical forces on infections leading to diarrheal diseases remains largely unknown. Here, we addressed whether flow and peristalsis impact the infectivity of the human pathogen Shigella within a 3D colonic epithelium using Intestine-Chip technology. Strikingly, infection is significantly increased and minimal bacterial loads are sufficient to invade enterocytes from the apical side and trigger loss of barrier integrity, thereby shifting the paradigm about early stage Shigella invasion. Shigella quickly colonizes epithelial crypt-like invaginations and demonstrates the essential role of the microenvironment. Furthermore, by modulating the mechanical forces of the microenvironment, we find that peristalsis impacts Shigella invasion. Collectively, our results reveal that Shigella leverages the intestinal microenvironment by taking advantage of the microarchitecture and mechanical forces to efficiently invade the intestine. This approach will enable molecular and mechanistic interrogation of human-restricted enteric pathogens.

Ice core records were recently used to infer elevation changes of the Greenland ice sheet throughout the Holocene. The inferred elevation changes show a significantly greater elevation reduction than those output from numerical models, bringing into question the accuracy of the model-based reconstructions and, to some extent, the estimated elevation histories. A key component of the ice core analysis involved removing the influence of vertical surface motion on the δ 18 O signal measured from the Agassiz and Renland ice caps. We re-visit the original analysis with the intent to determine if the use of more accurate land uplift curves can account for some of the above noted discrepancy. To improve on the original analysis, we apply a geophysical model of glacial isostatic adjustment calibrated to sea-level records from the Queen Elizabeth Islands and Greenland to calculate the influence of land height changes on the δ 18 O signal from the two ice cores. This procedure is complicated by the fact that δ 18 O contained in Agassiz ice is influenced by land height changes distant from the ice cap and so selecting a single location at which to compute the land height signal is not possible. Uncertainty in this selection is further complicated by the possible influence of Innuitian ice during the early Holocene (12–8 ka BP). Our results indicate that a more accurate treatment of the uplift correction leads to elevation histories that are, in general, shifted down relative to the original curves at GRIP, NGRIP, DYE-3 and Camp Century. In addition, compared to the original analysis, the 1-σ uncertainty is considerably larger at GRIP and NGRIP. These changes reduce the data-model discrepancy reported by Vinther et al. (2009) at GRIP, NGRIP, DYE-3 and Camp Century. A more accurate treatment of isostasy and surface loading also acts to improve the data-model fits such that the residuals at all four sites for the period 8 ka BP to present are significantly reduced compared to the original analysis. Prior to 8 ka BP, the possible influence of Innuitian ice on the inferred elevation histories prevents a meaningful comparison.

Introduction: Shigella spp. are the leading cause of bacillary dysentery, and a serious public health problem in developing countries. There are approximately 150 million episodes of shigellosis each year, with the burden falling mainly on children in less wealthy countries. Shigella can successfully invade into non-phagocytic human cells. This invasive capacity is a pre-requisite for virulence and is entirely dependent on a multi-protein molecular syringe, a type three secretion system (T3SS), which enables the bacterium to inject toxin effector molecules directly into the host cell. Although all enteric pathogens must survive in the anaerobic environment of the large intestine, little is known about the impact of low oxygen on the behaviour of enteric pathogens. Results: We found that an S. flexneri strain lacking the transcription factor FNR mutant is avirulent in rabbit intestinal loop model. FNR controls the metabolic adaptation of bacteria to anaerobiosis. Therefore, we investigated the impact of low oxygen tension on the invasive capacity of S. flexneri. Strikingly, the invasion of Shigella was increased by an order of magnitude in anaerobic conditions, and this was dependent on FNR. We demonstrated that there are distinct alterations in the structure and function of the T3SS in the absence of oxygen with: i) a reduction of secretion through the T3SS with retention of effectors in the bacterium, and ii) an increase of the length of the needles. Both changes are meditated by FNR. Thus anaerobiasis induces a ‘primed state’ in Shigella that promotes invasion of host cells and virulence. Discussion: The ‘primed state’ results from FNR controlling the expression of virulence genes that are necessary for the synthesis of the T3SS. S. flexneri employs a regulator of bacterial metabolism to sense the host environment and enhance its virulence. HIV AWARENESS IN WOMEN ATTENDING A COMMUNITY BASED FAMILY PLANNING AND ANTENATAL CLINIC IN A RURAL KENYAN COMMUNITY Olubanke Davies, Pippa Oakeshott St George’s, University of London, London, United Kingdom Abstract Introduction: This study was done to describe HIV awareness in young women attending a community based family planning and antenatal clinic in rural Kenya. Method: A questionnaire was administered to consecutive women aged 18 to 32, attending a family planning and antenatal clinic in Kwenikabilet local community, Kenya. It asked about demographics such as age and level of education; and assessed the extent of knowledge of transmission and prevention of HIV.