Authigenic Clays used as Terrestrial Climate Proxies: Locality 80, Olduvai Gorge, Tanzania

Authigenic clays are potential proxies for paleoclimate change when formed under saline conditions. Between 1.9 -1.7 mya, Olduvai was a closed-hydrologic basin into which Al- and Fe- rich detrital clays were transported from surrounding soils. Authigenic Mg-rich smectite formed within the basin due to chemical alteration in alkaline and saline conditions. 40 samples were chosen from a stratigraphic section in the center of the paleolake and analyzed to characterize the geochemical facies of the material using XRD, EMPA, and FTIR. ~70% of samples were Mg-rich with clay d060 XRD peaks between 1.506-1.523Å. EMPA indicated (Al2O3 + Fe2O3)/MgO ratios ranged from 0.2-4.8, 21 had ratios \u3e1.0, indicating higher (Al2O3 + Fe2O3) content. These clay data correlated with bulk XRF data, indicating diagenetic controls on bulk composition. Therefore, bulk geochemistry can potentially indicate paleoclimate change when influenced by Mg-rich phyllosilicate formation

Viral Vectors in Gene Therapy and Clinical Applications

Developments in gene therapy, coupled with advances in genome sequencing and a greater understanding of DNA sequences, have given rise to an exciting area of research. The use of viral vectors in gene therapy has become a very promising and fast-emerging technology over the past few decades. Despite previous setbacks, the approval of viral vector therapies worldwide, with many in late-stage clinical trials has led to a significant increase in research in this area of gene therapy. Retroviral, adenoviral, adeno-associated viral, and lentiviral vectors are all key vectors currently being researched and used in clinical trials. There are many challenges with the use of viral vectors that are yet to be overcome including cost of production, the immune response, and the ability to precisely regulate the expression of the transgene. However, with increased numbers of clinical trials showing efficacy, safety, and growing financial investment, the future use of viral vectors in gene therapy is increasingly promising

Clostridioides difficile binary toxin binding component (cdtb) increases virulence in a hamster model

Background Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection. Methods To determine the contribution of the separate components of CDT during infection, we developed strains of C difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness. Results Although expression of CDTb without CDTa did not induce significant disease in a mouse model of C difficile infection, we found that complementation of a CDT-deficient C difficile strain with CDTb alone restored virulence in a hamster model of C difficile infection. Conclusions Overall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection

A global model of the response of tropical and sub-tropical forest biodiversity to anthropogenic pressures

Habitat loss and degradation, driven largely by agricultural expansion and intensification, present the greatest immediate threat to biodiversity. Tropical forests harbour among the highest levels of terrestrial species diversity and are likely to experience rapid land-use change in the coming decades. Synthetic analyses of observed responses of species are useful for quantifying how land use affects biodiversity and for predicting outcomes under land-use scenarios. Previous applications of this approach have typically focused on individual taxonomic groups, analysing the average response of the whole community to changes in land use. Here, we incorporate quantitative remotely sensed data about habitats in, to our knowledge, the first worldwide synthetic analysis of how individual species in four major taxonomic groups—invertebrates, ‘herptiles’ (reptiles and amphibians), mammals and birds—respond to multiple human pressures in tropical and sub-tropical forests. We show significant independent impacts of land use, human vegetation offtake, forest cover and human population density on both occurrence and abundance of species, highlighting the value of analysing multiple explanatory variables simultaneously. Responses differ among the four groups considered, and—within birds and mammals—between habitat specialists and habitat generalists and between narrow-ranged and wide-ranged species

Genetic Evidence for a Mitochondriate Ancestry in the ‘Amitochondriate’ Flagellate Trimastix pyriformis

Most modern eukaryotes diverged from a common ancestor that contained the α-proteobacterial endosymbiont that gave rise to mitochondria. The ‘amitochondriate’ anaerobic protist parasites that have been studied to date, such as Giardia and Trichomonas harbor mitochondrion-related organelles, such as mitosomes or hydrogenosomes. Yet there is one remaining group of mitochondrion-lacking flagellates known as the Preaxostyla that could represent a primitive ‘pre-mitochondrial’ lineage of eukaryotes. To test this hypothesis, we conducted an expressed sequence tag (EST) survey on the preaxostylid flagellate Trimastix pyriformis, a poorly-studied free-living anaerobe. Among the ESTs we detected 19 proteins that, in other eukaryotes, typically function in mitochondria, hydrogenosomes or mitosomes, 12 of which are found exclusively within these organelles. Interestingly, one of the proteins, aconitase, functions in the tricarboxylic acid cycle typical of aerobic mitochondria, whereas others, such as pyruvate:ferredoxin oxidoreductase and [FeFe] hydrogenase, are characteristic of anaerobic hydrogenosomes. Since Trimastix retains genetic evidence of a mitochondriate ancestry, we can now say definitively that all known living eukaryote lineages descend from a common ancestor that had mitochondria

Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions

Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases

Vascular β-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAβ mice

Cerebrovascular lesions related to congophilic amyloid angiopathy (CAA) often accompany deposition of β-amyloid (Aβ) in Alzheimer’s disease (AD), leading to disturbed cerebral blood flow and cognitive dysfunction, posing the question how cerebrovascular pathology contributes to the pathology of AD. To address this question, we characterised the morphology, biochemistry and functionality of brain blood vessels in transgenic arctic β-amyloid (arcAβ) mice expressing human amyloid precursor protein (APP) with both the familial AD-causing Swedish and Arctic mutations; these mice are characterised by strong CAA pathology. Mice were analysed at early, mid and late-stage pathology. Expression of the glucose transporter GLUT1 at the blood–brain barrier (BBB) was significantly decreased and paralleled by impaired in vivo blood-to-brain glucose transport and reduced cerebral lactate release during neuronal activation from mid-stage pathology onwards. Reductions in astrocytic GLUT1 and lactate transporters, as well as retraction of astrocyte endfeet and swelling consistent with neurovascular uncoupling, preceded wide-spread β-amyloid plaque pathology. We show that CAA at later disease stages is accompanied by severe morphological alterations of brain blood vessels including stenoses, BBB leakages and the loss of vascular smooth muscle cells (SMCs). Together, our data establish that cerebrovascular and astrocytic pathology are paralleled by impaired cerebral metabolism in arcAβ mice, and that astrocyte alterations occur already at premature stages of pathology, suggesting that astrocyte dysfunction can contribute to early behavioural and cognitive impairments seen in these mice