The potassic sedimentary rocks in Gale Crater, Mars, as seen by ChemCam on board Curiosity

The Mars Science Laboratory rover Curiosity encountered potassium-rich clastic sedimentary rocks at two sites in Gale Crater, the waypoints Cooperstown and Kimberley. These rocks include several distinct meters thick sedimentary outcrops ranging from fine sandstone to conglomerate, interpreted to record an ancient fluvial or fluvio-deltaic depositional system. From ChemCam Laser-Induced Breakdown Spectroscopy (LIBS) chemical analyses, this suite of sedimentary rocks has an overall mean K2O abundance that is more than 5 times higher than that of the average Martian crust. The combined analysis of ChemCam data with stratigraphic and geographic locations reveals that the mean K2O abundance increases upward through the stratigraphic section. Chemical analyses across each unit can be represented as mixtures of several distinct chemical components, i.e., mineral phases, including K-bearing minerals, mafic silicates, Fe-oxides, and Fe-hydroxide/oxyhydroxides. Possible K-bearing minerals include alkali feldspar (including anorthoclase and sanidine) and K-bearing phyllosilicate such as illite. Mixtures of different source rocks, including a potassium-rich rock located on the rim and walls of Gale Crater, are the likely origin of observed chemical variations within each unit. Physical sorting may have also played a role in the enrichment in K in the Kimberley formation. The occurrence of these potassic sedimentary rocks provides additional evidence for the chemical diversity of the crust exposed at Gale Crater

Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods

Comparing orbiter and rover image-based mapping of an ancient sedimentary environment, Aeolis Palus, Gale crater, Mars

This study provides the first systematic comparison of orbital facies maps with detailed ground-based geology observations from the Mars Science Laboratory (MSL) Curiosity rover to examine the validity of geologic interpretations derived from orbital image data. Orbital facies maps were constructed for the Darwin, Cooperstown, and Kimberley waypoints visited by the Curiosity rover using High Resolution Imaging Science Experiment (HiRISE) images. These maps, which represent the most detailed orbital analysis of these areas to date, were compared with rover image-based geologic maps and stratigraphic columns derived from Curiosity's Mast Camera (Mastcam) and Mars Hand Lens Imager (MAHLI). Results show that bedrock outcrops can generally be distinguished from unconsolidated surficial deposits in high-resolution orbital images and that orbital facies mapping can be used to recognize geologic contacts between well-exposed bedrock units. However, process-based interpretations derived from orbital image mapping are difficult to infer without known regional context or observable paleogeomorphic indicators, and layer-cake models of stratigraphy derived from orbital maps oversimplify depositional relationships as revealed from a rover perspective. This study also shows that fine-scale orbital image-based mapping of current and future Mars landing sites is essential for optimizing the efficiency and science return of rover surface operations

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

Evidence for plunging river plume deposits in the Pahrump Hills member of the Murray formation, Gale crater, Mars

Recent robotic missions to Mars have offered new insights into the extent, diversity and habitability of the Martian sedimentary rock record. Since the Curiosity rover landed in Gale crater in August 2012, the Mars Science Laboratory Science Team has explored the origins and habitability of ancient fluvial, deltaic, lacustrine and aeolian deposits preserved within the crater. This study describes the sedimentology of a ca 13 m thick succession named the Pahrump Hills member of the Murray formation, the first thick fine‐grained deposit discovered in situ on Mars. This work evaluates the depositional processes responsible for its formation and reconstructs its palaeoenvironmental setting. The Pahrump Hills succession can be sub‐divided into four distinct sedimentary facies: (i) thinly laminated mudstone; (ii) low‐angle cross‐stratified mudstone; (iii) cross‐stratified sandstone; and (iv) thickly laminated mudstone–sandstone. The very fine grain size of the mudstone facies and abundant millimetre‐scale and sub‐millimetre‐scale laminations exhibiting quasi‐uniform thickness throughout the Pahrump Hills succession are most consistent with lacustrine deposition. Low‐angle geometric discordances in the mudstone facies are interpreted as ‘scour and drape’ structures and suggest the action of currents, such as those associated with hyperpycnal river‐generated plumes plunging into a lake. Observation of an overall upward coarsening in grain size and thickening of laminae throughout the Pahrump Hills succession is consistent with deposition from basinward progradation of a fluvial‐deltaic system derived from the northern crater rim into the Gale crater lake. Palaeohydraulic modelling constrains the salinity of the ancient lake in Gale crater: assuming river sediment concentrations typical of floods on Earth, plunging river plumes and sedimentary structures like those observed at Pahrump Hills would have required lake densities near freshwater to form. The depositional model for the Pahrump Hills member presented here implies the presence of an ancient sustained, habitable freshwater lake in Gale crater for at least ca 103 to 107 Earth years

Efficacy of Fumaric Acid Esters in the R6/2 and YAC128 Models of Huntington's Disease

Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disease. The exact sequel of events finally resulting in neurodegeneration is only partially understood and there is no established protective treatment so far. Some lines of evidence speak for the contribution of oxidative stress to neuronal tissue damage. The fumaric acid ester dimethylfumarate (DMF) is a new disease modifying therapy currently in phase III studies for relapsing-remitting multiple sclerosis. DMF potentially exerts neuroprotective effects via induction of the transcription factor “nuclear factor E2-related factor 2” (Nrf2) and detoxification pathways. Thus, we investigated here the therapeutic efficacy of DMF in R6/2 and YAC128 HD transgenic mice which mimic many aspects of HD and are characterized by an enhanced generation of free radicals in neurons. Treatment with DMF significantly prevented weight loss in R6/2 mice between postnatal days 80–90. At the same time, DMF treatment led to an attenuated motor impairment as measured by the clasping score. Average survival in the DMF group was 100.5 days vs. 94.0 days in the placebo group. In the histological analysis on day 80, DMF treatment resulted in a significant preservation of morphologically intact neurons in the striatum as well as in the motor cortex. DMF treatment resulted in an increased Nrf2 immunoreactivity in neuronal subpopulations, but not in astrocytes. These beneficial effects were corroborated in YAC128 mice which, after one year of DMF treatment, also displayed reduced dyskinesia as well as a preservation of neurons. In conclusion, DMF may exert beneficial effects in mouse models of HD. Given its excellent side effect profile, further studies with DMF as new therapeutic approach in HD and other neurodegenerative diseases are warranted

Laminin γ1 chain peptide, C-16 (KAFDITYVRLKF), promotes migration, MMP-9 secretion, and pulmonary metastasis of B16–F10 mouse melanoma cells

Laminin-1, a heterotrimer of α1, β1, and γ1 chains specific to basement membrane, promotes cell adhesion and migration, proteinase secretion and metastases of tumour cells. Several active sites on the α1 chain have been found to promote B16–F10 melanoma lung colonisation and here we have determined whether additional tumour promoting sites exist on the β1 and γ1 chains. Recently, we have identified novel cell adhesive peptides derived from laminin β1 and γ1 chains by systematic screening of synthetic peptides. Nine β1 peptides and seven γ1 peptides active for cell adhesion were tested for their effects on experimental pulmonary metastases of B16–F10 mouse melanoma cells in vivo. The most active adhesive peptide derived from the γ1 chain globular domain, C-16 (KAFDITYVRLKF), significantly enhanced pulmonary metastases of B16–F10 cells, whereas no other peptides showed enhancement. C-16 also stimulated migration of B16–F10 cells in the Boyden chamber assay in vitro. Furthermore, C-16 significantly induced the production of MMP-9 from B16–F10 cells. These results suggest that this specific laminin γ1 chain peptide has a metastasis-promoting activity and might be a new molecular target of anti-cancer treatment

Stunned Silence: Gene Expression Programs in Human Cells Infected with Monkeypox or Vaccinia Virus

Poxviruses use an arsenal of molecular weapons to evade detection and disarm host immune responses. We used DNA microarrays to investigate the gene expression responses to infection by monkeypox virus (MPV), an emerging human pathogen, and Vaccinia virus (VAC), a widely used model and vaccine organism, in primary human macrophages, primary human fibroblasts and HeLa cells. Even as the overwhelmingly infected cells approached their demise, with extensive cytopathic changes, their gene expression programs appeared almost oblivious to poxvirus infection. Although killed (gamma-irradiated) MPV potently induced a transcriptional program characteristic of the interferon response, no such response was observed during infection with either live MPV or VAC. Moreover, while the gene expression response of infected cells to stimulation with ionomycin plus phorbol 12-myristate 13-acetate (PMA), or poly (I-C) was largely unimpaired by infection with MPV, a cluster of pro-inflammatory genes were a notable exception. Poly(I-C) induction of genes involved in alerting the innate immune system to the infectious threat, including TNF-alpha, IL-1 alpha and beta, CCL5 and IL-6, were suppressed by infection with live MPV. Thus, MPV selectively inhibits expression of genes with critical roles in cell-signaling pathways that activate innate immune responses, as part of its strategy for stealthy infection

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of huntington's disease

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI), as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. © 2013 Rattray et al

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni

Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem. More than 200 million people are infected. Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies (i.e., vaccines, drugs). Schistosomes feed on host blood, and a number of proteolytic enzymes (proteases) contribute to this process. We have identified and characterized a new protease, SmCL3 (for Schistosoma mansoni cathepsin L3), that is found within the gut tissue of the parasite. We have employed various biochemical and molecular biological methods and sequence similarity analyses to characterize SmCL3 and obtain insights into its possible functions in the parasite, as well as its evolutionary position among cathepsin L proteases in general. SmCL3 hydrolyzes major host blood proteins (serum albumin and hemoglobin) and is expressed in parasite life stages infecting the mammalian host. Enzyme substrate specificity detected by positional scanning-synthetic combinatorial library was confirmed by molecular modeling. A sequence analysis placed SmCL3 to the cluster of other cathepsins L in accordance with previous phylogenetic analyses