Mapping Human Immunity and the Education of Waldeyer\u27s Ring

The development and deployment of single-cell genomic technologies have driven a resolution revolution in our understanding of the immune system, providing unprecedented insight into the diversity of immune cells present throughout the body and their function in health and disease. Waldeyer\u27s ring is the collective name for the lymphoid tissue aggregations of the upper aerodigestive tract, comprising the palatine, pharyngeal (adenoids), lingual, and tubal tonsils. These tonsils are the first immune sentinels encountered by ingested and inhaled antigens and are responsible for mounting the first wave of adaptive immune response. An effective mucosal immune response is critical to neutralizing infection in the upper airway and preventing systemic spread, and dysfunctional immune responses can result in ear, nose, and throat pathologies. This review uses Waldeyer\u27s ring to demonstrate how single-cell technologies are being applied to advance our understanding of the immune system and highlight directions for future research

Catchment changes in response to tectonics and climate: using river terraces and DEM data in the southern High Atlas Mountains (Morocco)

Tectonics and climate drive the generation and transport of sediment in mountain rivers as these evolve over time. On a glacial-interglacial scale, in particular catchment reorganisation and catchment incision dynamics control these processes, and affect fan deposition in sedimentary basins. The Atlas Mountains in Morocco exhibit ongoing catchment reorganisation and an abundance of river terraces recording glacial fluvial aggradation and interglacial-glacial incisional periods, opening up insight into the processes behind catchment evolution over geological timescales. Topography and river profiles across drainage divides are similar in a stable divide, and if they are unequal they indicate active catchment reorganisation. When reorganisation occurs, it results in irregularities in river long profiles and changes in river valley erosion. River strath terraces are formed by transition between valley widening and downcutting of terraces in response to local divergence of sediment-transport capacity 3. Consequently, they record changes in catchments due to river capture, climate and tectonics. The presence of river terraces enables catchment processes over time to be investigated. A combination of remote sensing and field mapping and logging was completed in May 2018. River terraces have been mapped with newly released high resolution DEM data in the southern High Atlas in Morocco, and additional surveying was done in the field. Geomorphological indices suggest river catchment capture is a key control on the development of drainage networks. River long profiles suggest tectonic controls have also influenced landscape development over the last few million years. Logging of terrace sediments together with high-resolution sampling for OSL dating enables these catchment-wide effects to be compared with paleo-hydrological and sediment transport characteristics of the fluvial system. The combination of geomorphological DEM and sedimentological field data enables us to explore drivers of catchment change, and will contribute to the wider understanding of fluvial system response to climate and tectonic controls, and to its transport into the sedimentary record

Rock strength and structural controls on fluvial erodibility: Implications for drainage divide mobility in a collisional mountain belt

Numerical model simulations and experiments have suggested that when migration of the main drainage divide occurs in a mountain belt, it can lead to the rearrangement of river catchments, rejuvenation of topography, and changes in erosion rates and sediment flux. We assess the progressive mobility of the drainage divide in three lithologically and structurally distinct groups of bedrock in the High Atlas (NW Africa). The geological age of bedrock and its associated tectonic architecture in the mountain belt increases from east to west in the study area, allowing us to track both variations in rock strength and structural configuration which influence drainage mobility during erosion through an exhuming mountain belt. Collection of field derived measurements of rock strength using a Schmidt hammer and computer based extraction of river channel steepness permit estimations of contrasts in fluvial erodibilities of rock types. The resulting difference in fluvial erodibility between the weakest and the strongest lithological unit is up to two orders of magnitude. Published evidence of geomorphic mobility of the drainage divide indicates that such a range in erodibilities in horizontal stratigraphy of the sedimentary cover may lead to changes in erosion rates as rivers erode through strata, leading to drainage divide migration. In contrast, we show that the faulted and folded metamorphic sedimentary rocks in the centre of the mountain belt coincide with a stable drainage divide. Finally, where the strong igneous rocks of the crystalline basement are exposed after erosion of the covering meta-sediments, there is a decrease in fluvial erodibility of up to a factor of three, where the drainage divide is mobile towards the centre of the exposed crystalline basement. The mobility of the drainage divide in response to erosion through rock-types and their structural configuration in a mountain belt has implications for the perception of autogenic dynamism of drainage networks and fluvial erosion in mountain belts, and the interpretation of the geomorphology and downstream stratigraphy.</p

Biophysical suitability, economic pressure and land-cover change: a global probabilistic approach and insights for REDD+

There has been a concerted effort by the international scientific community to understand the multiple causes and patterns of land-cover change to support sustainable land management. Here, we examined biophysical suitability, and a novel integrated index of “Economic Pressure on Land” (EPL) to explain land cover in the year 2000, and estimated the likelihood of future land-cover change through 2050, including protected area effectiveness. Biophysical suitability and EPL explained almost half of the global pattern of land cover (R 2 = 0.45), increasing to almost two-thirds in areas where a long-term equilibrium is likely to have been reached (e.g. R 2 = 0.64 in Europe). We identify a high likelihood of future land-cover change in vast areas with relatively lower current and past deforestation (e.g. the Congo Basin). Further, we simulated emissions arising from a “business as usual” and two reducing emissions from deforestation and forest degradation (REDD) scenarios by incorporating data on biomass carbon. As our model incorporates all biome types, it highlights a crucial aspect of the ongoing REDD + debate: if restricted to forests, “cross-biome leakage” would severely reduce REDD + effectiveness for climate change mitigation. If forests were protected from deforestation yet without measures to tackle the drivers of land-cover change, REDD + would only reduce 30 % of total emissions from land-cover change. Fifty-five percent of emissions reductions from forests would be compensated by increased emissions in other biomes. These results suggest that, although REDD + remains a very promising mitigation tool, implementation of complementary measures to reduce land demand is necessary to prevent this leakage

UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection

Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection

Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites

Peer reviewedPublisher PD

Identification of Novel Proteins in Neospora caninum Using an Organelle Purification and Monoclonal Antibody Approach

Neospora caninum is an important veterinary pathogen that causes abortion in cattle and neuromuscular disease in dogs. Neospora has also generated substantial interest because it is an extremely close relative of the human pathogen Toxoplasma gondii, yet does not appear to infect humans. While for Toxoplasma there are a wide array of molecular tools and reagents available for experimental investigation, relatively few reagents exist for Neospora. To investigate the unique biological features of this parasite and exploit the recent sequencing of its genome, we have used an organelle isolation and monoclonal antibody approach to identify novel organellar proteins and develop a wide array of probes for subcellular localization. We raised a panel of forty-six monoclonal antibodies that detect proteins from the rhoptries, micronemes, dense granules, inner membrane complex, apicoplast, mitochondrion and parasite surface. A subset of the proteins was identified by immunoprecipitation and mass spectrometry and reveal that we have identified and localized many of the key proteins involved in invasion and host interaction in Neospora. In addition, we identified novel secretory proteins not previously studied in any apicomplexan parasite. Thus, this organellar monoclonal antibody approach not only greatly enhances the tools available for Neospora cell biology, but also identifies novel components of the unique biological characteristics of this important veterinary pathogen

Identification of Attractive Drug Targets in Neglected-Disease Pathogens Using an In Silico Approach

In cell-based drug development, researchers attempt to create drugs that kill a pathogen without necessarily understanding the details of how the drugs work. In contrast, target-based drug development entails the search for compounds that act on a specific intracellular target—often a protein known or suspected to be required for survival of the pathogen. The latter approach to drug development has been facilitated greatly by the sequencing of many pathogen genomes and the incorporation of genome data into user-friendly databases. The present paper shows how the database TDRtargets.org can identify proteins that might be considered good drug targets for diseases such as African sleeping sickness, Chagas disease, parasitic worm infections, tuberculosis, and malaria. These proteins may score highly in searches of the database because they are dissimilar to human proteins, are structurally similar to other “druggable” proteins, have functions that are easy to measure, and/or fulfill other criteria. Researchers can use the lists of high-scoring proteins as a basis for deciding which potential drug targets to pursue experimentally