Large subglacial lakes in East Antarctica at the onset of fast-flowing ice streams

Water plays a crucial role in ice-sheet stability and the onset of ice streams. Subglacial lake water moves between lakes and rapidly drains, causing catastrophic floods. The exact mechanisms by which subglacial lakes influence ice-sheet dynamics are unknown, however, and large subglacial lakes have not been closely associated with rapidly flowing ice streams. Here we use satellite imagery and ice-surface elevations to identify a region of subglacial lakes, similar in total area to Lake Vostok, at the onset region of the Recovery Glacier ice stream in East Antarctica and predicted by ice-sheet models. We define four lakes through extensive, flat, featureless regions of ice surface bounded by upstream troughs and downstream ridges. Using ice velocities determined using interferometric synthetic aperture radar (InSAR), we find the onset of rapid flow (moving at 20 to 30 m yr(-1)) of the tributaries to the Recovery Glacier ice stream in a 280-km-wide segment at the downslope margins of these four subglacial lakes. We conclude that the subglacial lakes initiate and maintain rapid ice flow through either active modification of the basal thermal regime of the ice sheet by lake accretion or through scouring bedrock channels in periodic drainage events. We suggest that the role of subglacial lakes needs to be considered in ice-sheet mass balance assessments.     

Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells

Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth.     

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

A latent ability to persist: differentiation in <Emphasis Type="Italic">Toxoplasma gondii</Emphasis>

A critical factor in the transmission and pathogenesis of Toxoplasma gondii is the ability to convert from an acute disease-causing, proliferative stage (tachyzoite), to a chronic, dormant stage (bradyzoite). The conversion of the tachyzoite-containing parasitophorous vacuole membrane into the less permeable bradyzoite cyst wall allows the parasite to persist for years within the host to maximize transmissibility to both primary (felids) and secondary (virtually all other warm-blooded vertebrates) hosts. This review presents our current understanding of the latent stage, including the factors that are important in bradyzoite induction and maintenance. Also discussed are the recent studies that have begun to unravel the mechanisms behind stage switching.     

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.