Meridiani Planum and the global hydrology of Mars

The Opportunity Mars Exploration Rover found evidence for groundwater activity in the Meridiani Planum region of Mars in the form of aeolian and fluvial sediments composed of sulphate-rich grains. These sediments appear to have experienced diagenetic modification in the presence of a fluctuating water table. In addition to the extensive secondary aqueous alteration, the primary grains themselves probably derive from earlier playa evaporites. Little is known, however, about the hydrologic processes responsible for this environmental history-particularly how such extensive evaporite deposits formed in the absence of a topographic basin. Here we investigate the origin of these deposits, in the context of the global hydrology of early Mars, using numerical simulations, and demonstrate that Meridiani is one of the few regions of currently exposed ancient crust predicted to have experienced significant groundwater upwelling and evaporation. The global groundwater flow would have been driven primarily by precipitation-induced recharge and evaporative loss, with the formation of the Tharsis volcanic rise possibly playing a role through the burial of aquifers and induced global deformation. These results suggest that the deposits formed as a result of sustained groundwater upwelling and evaporation, rather than ponding within an enclosed basin. The evaporite formation coincided with a transition to more arid conditions that increased the relative impact of a deep-seated, global-scale hydrology on the surface evolution.     

Effect of niobium alloying level on the oxidation behavior of titanium aluminides at 850°C

This work addresses the alloying of titanium aluminides used in aircraft engine applications and automobiles. The oxidation resistance behavior of two titanium aluminides of α₂ + γ(Ti₃Al + TiAl) and orthorhombic Ti₂NbAl, recognized as candidates for high-temperature applications, was investigated by exposure of the alloys for 100 h in air. Thus, oxidation resistance was expressed as the mass gain rate, whereas surface aspects were analyzed using scanning electron microscopy in conjunction with energy-dispersive X-ray spectroscopy, and the type of oxidation products was analyzed by X-ray diffraction and Raman spectroscopy. The orthorhombic Ti₂NbAl alloy was embrittled, and pores and microcracks were formed as a result of oxygen diffusion through the external oxide layer formed during thermal oxidation for 100 h.     

Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIV(MAC251) challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1.     

Genetic diversity of rhizobial populations recovered from three Lotus species cultivated in the infra-arid Tunisian soils

Eighty-three bacterial strains isolated from root nodules of Lotus creticus, L. pusillus, and L. arabicus grown in infra-arid Tunisian soils were characterized using a polyphasic approach including phenotypic analysis, rep-PCR and PCR-RFLP analyses of the 16S rRNA gene. Phenotypically, all isolates are fast growers the majority of which grow at a pH of between 5.5 and 9. Most of the tested isolates tolerate NaCl concentrations from 1.39% to 3.48%. By rep-PCR fingerprinting, the genomic similarity varied from 30% to 98%. All tested isolates were clustered into 32 rep-PCR clusters at the similarity level of 80%. The genomic divergence of strains revealed by rep/PCR analysis appeared to be very important since a molecular polymorphism delimiting symbionts for each species of Lotus was identified. With the high-resolution of rep-PCR profiles of the isolates obtained using Pearson’s/UPGMA analysis, the isolates were resolved into 60 different profiling groups to undergo 16S ARDRA analyses. The analysis of all restriction fragments from each strain based on the UPGMA algorithm from the combined patterns showed that Lotus isolates are very diverse and that they were affiliated to Sinorhizobium, Rhizobium, and Mesorhizobium genera.     

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.     

Sustained translational repression by eIF2α-P mediates prion neurodegeneration

The mechanisms leading to neuronal death in neurodegenerative disease are poorly understood. Many of these disorders, including Alzheimer's, Parkinson's and prion diseases, are associated with the accumulation of misfolded disease-specific proteins. The unfolded protein response is a protective cellular mechanism triggered by rising levels of misfolded proteins. One arm of this pathway results in the transient shutdown of protein translation, through phosphorylation of the α-subunit of eukaryotic translation initiation factor, eIF2. Activation of the unfolded protein response and/or increased eIF2α-P levels are seen in patients with Alzheimer's, Parkinson's and prion diseases, but how this links to neurodegeneration is unknown. Here we show that accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis by eIF2α-P, associated with synaptic failure and neuronal loss in prion-diseased mice. Further, we show that promoting translational recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression of GADD34, a specific eIF2α-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA interference, reduced eIF2α-P levels. As a result, both approaches restored vital translation rates during prion disease, rescuing synaptic deficits and neuronal loss, thereby significantly increasing survival. In contrast, salubrinal, an inhibitor of eIF2α-P dephosphorylation, increased eIF2α-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice. Given the prevalence of protein misfolding and activation of the unfolded protein response in several neurodegenerative diseases, our results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders.     

Migration in later life: evidence from the British Household Panel Study

This article uses data from the British Household Panel Study over the period 1991 - 2007 to examine the factors associated with residential mobility among people aged 50 and over. In line with earlier research, the likelihood of migrating, that is, changing address, is found to vary according to the demographic and socio-economic characteristics of the older person. Those in late middle age (50-59) and the oldest-old (90 and over) were most likely to move. Migration was also strongly associated with changes in partnership, health and economic status during the last 12 months, highlighting the importance of seeing migration within a life course context with certain life course events such as divorce, widowhood or retirement being important triggers for prompting a move. As divorce and remarriage become more common in later life, 'relationship driven migration' is likely to become more important, adding a new category to the classical typology of later life migration.     

The changing demography of mid-life, from the 1980s to the 2000s

This article examines changes between 1984 and 2007 in the demographic and socio-economic circumstances of British men and women in mid-life. Changing living arrangements in mid-life reflect historical changes in the occurrence and timing of life events such as marriage and parenthood, as well as increased longevity. In order to place mid-life in this wider demographic context, the article first reviews changes over time in kin availability across the adult life course using the British Household Panel Survey (2001) and Understanding Society (2009). The article goes on to use data from the General Household Survey (1984-2007) to document shifts over time in living arrangements for those aged 20- 79. In the final part of the article we focus specifically on those aged between 45 and 64 and examine how their characteristics in terms of marital status, educational attainment, activity status and housing tenure have changed over the past quarter century.