The microstratigraphy and depositional environments of Lida Ajer and Ngalau Gupin, two fossil-bearing tropical limestone caves of west Sumatra.

Lida Ajer and Ngalau Gupin are karstic caves situated in the Padang Highlands, western Sumatra, Indonesia. Lida Ajer is best known for yielding fossil evidence that places the arrival of Homo sapiens in Southeast Asia during Marine Isotope Stage 4, one of the earliest records for the region. Ngalau Gupin recently produced the first record of hippopotamid Hexaprotodon on the island, representing the only globally extinct taxon in Pleistocene deposits from Sumatra.

An arginase 2 promoter transgenic line illuminates immune cell polarisation in zebrafish.

Innate immune responses to inflammation and infection are complex and represent major challenges for developing much needed new treatments for chronic inflammatory diseases and drug-resistant infections. To be ultimately successful, the immune response must be balanced to allow pathogen clearance without excess tissue damage, processes controlled by pro- and anti-inflammatory signals. The roles of anti-inflammatory signalling in raising an appropriate immune response are underappreciated, representing overlooked potential drug targets.

Functional Characterization of Rare Genetic Variants in the N-Terminus of Complement Factor H in aHUS, C3G, and AMD.

Membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), atypical haemolytic uraemic syndrome (aHUS) and age-related macular degeneration (AMD) have all been strongly linked with dysfunction of the alternative pathway (AP) of complement. A significant proportion of individuals with MPGN, C3G, aHUS and AMD carry rare genetic variants in the gene that cause functional or quantitative deficiencies in the factor H (FH) protein, an important regulator of the AP. analysis of the deleteriousness of rare genetic variants in is not reliable and careful biochemical assessment remains the gold standard.

A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H-Related 3 Gene in Atypical Hemolytic Uremic Syndrome.

The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H-related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination.

Characterization of a factor H mutation that perturbs the alternative pathway of complement in a family with membranoproliferative GN.

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN.

Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.

To define the role of rare variants in advanced age-related macular degeneration (AMD) risk, we sequenced the exons of 681 genes within all reported AMD loci and related pathways in 2,493 cases and controls. We first tested each gene for increased or decreased burden of rare variants in cases compared to controls. We found that 7.

Interpretation of genetic variants of uncertain significance in atypical hemolytic uremic syndrome.

Mutations in complement proteins predispose to atypical hemolytic uremic syndrome (aHUS). Mutation screening in aHUS is challenging, because most of the disease-associated mutations are individually rare, and a significant proportion of variants consist of missense mutations of unknown significance. The definitive interpretation of a variant of unknown significance (VUS) is often dependent on a reliable functional assay too time-consuming to be used in a diagnostic screening service.

Silencing mediated by the Schizosaccharomyces pombe HIRA complex is dependent upon the Hpc2-like protein, Hip4.

Background: HIRA (or Hir) proteins are conserved histone chaperones that function in multi-subunit complexes to mediate replication-independent nucleosome assembly. We have previously demonstrated that the Schizosaccharomyces pombe HIRA proteins, Hip1 and Slm9, form a complex with a TPR repeat protein called Hip3. Here we have identified a new subunit of this complex.

The fission yeast HIRA histone chaperone is required for promoter silencing and the suppression of cryptic antisense transcripts.

The assembly of nucleosomes by histone chaperones is an important component of transcriptional regulation. Here, we have assessed the global roles of the HIRA histone chaperone in Schizosaccharomyces pombe. Microarray analysis indicates that inactivation of the HIRA complex results in increased expression of at least 4% of fission yeast genes.