River outgassing has proven to be an integral part of the carbon cycle. In Southeast Asia, river outgassing quantities are uncertain due to lack of measured data. Here we investigate six rivers in Indonesia and Malaysia, during five expeditions. CO2 fluxes from Southeast Asian rivers amount to 66.9 ± 15.7 Tg C per year, of which Indonesia releases 53.9 ± 12.4 Tg C per year. Malaysian rivers emit 6.2 ± 1.6 Tg C per year. These moderate values show that Southeast Asia is not the river outgassing hotspot as would be expected from the carbon-enriched peat soils. This is due to the relatively short residence time of dissolved organic carbon (DOC) in the river, as the peatlands, being the primary source of DOC, are located near the coast. Limitation of bacterial production, due to low pH, oxygen depletion or the refractory nature of DOC, potentially also contributes to moderate CO2 fluxes as this decelerates decomposition.
The small ubiquitin-like modifier (SUMO) is implicated in various cellular activities, including transcriptional regulation. We previously showed that the yeast activator Gcn4 becomes sumoylated during activation, facilitating its eventual promoter eviction and transcriptional shut off. Here we show that the corepressor Tup1 is sumoylated, at two specific lysines, under various stress conditions. Mutation of these sites has no effect on Tup1 recruitment or RNAP II promoter occupancy immediately following induction. However, Tup1 levels subsequently decrease, while RNAP II and transcription increase in Tup1 mutant cells. Consistent with this, a Tup1 mutant displaying increased sumoylation led to reduced transcription. We also show that coordinated sumoylation of Gcn4 and Tup1 enhances Gcn4 promoter eviction and that multiple Tup1-interacting proteins become sumoylated after stress. Together, our studies provide evidence that coordinated sumoylation of Gcn4, Tup1 and likely other factors dampens activated transcription by stabilizing Tup1 binding and stimulating Gcn4 and RNAP II removal.
Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.
GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
Oil palm, a plantation crop of major economic importance in Southeast Asia, is the predominant source of edible oil worldwide. We report the identification of the virescens (VIR) gene, which controls fruit exocarp colour and is an indicator of ripeness. VIR is a R2R3-MYB transcription factor with homology to Lilium LhMYB12 and similarity to Arabidopsis production of anthocyanin pigment1 (PAP1). We identify five independent mutant alleles of VIR in over 400 accessions from sub-Saharan Africa that account for the dominant-negative virescens phenotype. Each mutation results in premature termination of the carboxy-terminal domain of VIR, resembling McClintock's C1-I allele in maize. The abundance of alleles likely reflects cultural practices, by which fruits were venerated for magical and medicinal properties. The identification of VIR will allow selection of the trait at the seed or early-nursery stage, 3-6 years before fruits are produced, greatly advancing introgression into elite breeding material.
Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.
Defaunation is causing declines of large-seeded animal-dispersed trees in tropical forests worldwide, but whether and how these declines will affect carbon storage across this biome is unclear. Here we show, using a pan-tropical data set, that simulated declines of large-seeded animal-dispersed trees have contrasting effects on aboveground carbon stocks across Earth's tropical forests. In our simulations, African, American and South Asian forests, which have high proportions of animal-dispersed species, consistently show carbon losses (2-12%), but Southeast Asian and Australian forests, where there are more abiotically dispersed species, show little to no carbon losses or marginal gains (±1%). These patterns result primarily from changes in wood volume, and are underlain by consistent relationships in our empirical data (∼2,100 species), wherein, large-seeded animal-dispersed species are larger as adults than small-seeded animal-dispersed species, but are smaller than abiotically dispersed species. Thus, floristic differences and distinct dispersal mode-seed size-adult size combinations can drive contrasting regional responses to defaunation.
To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.
The Josephson effect describes the generic appearance of a supercurrent in a weak link between two superconductors. Its exact physical nature deeply influences the properties of the supercurrent. In recent years, considerable efforts have focused on the coupling of superconductors to the surface states of a three-dimensional topological insulator. In such a material, an unconventional induced p-wave superconductivity should occur, with a doublet of topologically protected gapless Andreev bound states, whose energies vary 4π-periodically with the superconducting phase difference across the junction. In this article, we report the observation of an anomalous response to rf irradiation in a Josephson junction made of a HgTe weak link. The response is understood as due to a 4π-periodic contribution to the supercurrent, and its amplitude is compatible with the expected contribution of a gapless Andreev doublet. Our work opens the way to more elaborate experiments to investigate the induced superconductivity in a three-dimensional insulator.
Understanding fluid dynamics under extreme confinement, where device and intrinsic fluid length scales become comparable, is essential to successfully develop the coming generations of fluidic devices. Here we report measurements of advancing fluid fronts in such a regime, which we dub superconfinement. We find that the strong coupling between contact-line friction and geometric confinement gives rise to a new stability regime where the maximum speed for a stable moving front exhibits a distinctive response to changes in the bounding geometry. Unstable fronts develop into drop-emitting jets controlled by thermal fluctuations. Numerical simulations reveal that the dynamics in superconfined systems is dominated by interfacial forces. Henceforth, we present a theory that quantifies our experiments in terms of the relevant interfacial length scale, which in our system is the intrinsic contact-line slip length. Our findings show that length-scale overlap can be used as a new fluid-control mechanism in strongly confined systems.
Balancing economic development with international commitments to protect biodiversity is a global challenge. Achieving this balance requires an understanding of the possible consequences of alternative future scenarios for a range of stakeholders. We employ an integrated economic and environmental planning approach to evaluate four alternative futures for the mega-diverse island of Borneo. We show what could be achieved if the three national jurisdictions of Borneo coordinate efforts to achieve their public policy targets and allow a partial reallocation of planned land uses. We reveal the potential for Borneo to simultaneously retain ∼50% of its land as forests, protect adequate habitat for the Bornean orangutan (Pongo pygmaeus) and Bornean elephant (Elephas maximus borneensis), and achieve an opportunity cost saving of over US$43 billion. Such coordination would depend on enhanced information sharing and reforms to land-use planning, which could be supported by the increasingly international nature of economies and conservation efforts.
Invertebrates are dominant species in primary tropical rainforests, where their abundance and diversity contributes to the functioning and resilience of these globally important ecosystems. However, more than one-third of tropical forests have been logged, with dramatic impacts on rainforest biodiversity that may disrupt key ecosystem processes. We find that the contribution of invertebrates to three ecosystem processes operating at three trophic levels (litter decomposition, seed predation and removal, and invertebrate predation) is reduced by up to one-half following logging. These changes are associated with decreased abundance of key functional groups of termites, ants, beetles and earthworms, and an increase in the abundance of small mammals, amphibians and insectivorous birds in logged relative to primary forest. Our results suggest that ecosystem processes themselves have considerable resilience to logging, but the consistent decline of invertebrate functional importance is indicative of a human-induced shift in how these ecological processes operate in tropical rainforests.
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
Modern mangroves are among the most carbon-rich biomes on Earth, but their long-term (≥106 years) impact on the global carbon cycle is unknown. The extent, productivity and preservation of mangroves are controlled by the interplay of tectonics, global sea level and sedimentation, including tide, wave and fluvial processes. The impact of these processes on mangrove-bearing successions in the Oligo-Miocene of the South China Sea (SCS) is evaluated herein. Palaeogeographic reconstructions, palaeotidal modelling and facies analysis suggest that elevated tidal range and bed shear stress optimized mangrove development along tide-influenced tropical coastlines. Preservation of mangrove organic carbon (OC) was promoted by high tectonic subsidence and fluvial sediment supply. Lithospheric storage of OC in peripheral SCS basins potentially exceeded 4,000 Gt (equivalent to 2,000 p.p.m. of atmospheric CO2). These results highlight the crucial impact of tectonic and oceanographic processes on mangrove OC sequestration within the global carbon cycle on geological timescales.
Coral reefs can provide significant coastal protection benefits to people and property. Here we show that the annual expected damages from flooding would double, and costs from frequent storms would triple without reefs. For 100-year storm events, flood damages would increase by 91% to $US 272 billion without reefs. The countries with the most to gain from reef management are Indonesia, Philippines, Malaysia, Mexico, and Cuba; annual expected flood savings exceed $400 M for each of these nations. Sea-level rise will increase flood risk, but substantial impacts could happen from reef loss alone without better near-term management. We provide a global, process-based valuation of an ecosystem service across an entire marine biome at (sub)national levels. These spatially explicit benefits inform critical risk and environmental management decisions, and the expected benefits can be directly considered by governments (e.g., national accounts, recovery plans) and businesses (e.g., insurance).
The continuing development of improved capture-recapture (CR) modeling techniques used to study apex predators has also limited robust temporal and cross-site analyses due to different methods employed. We develop an approach to standardize older non-spatial CR and newer spatial CR density estimates and examine trends for critically endangered Sumatran tigers (Panthera tigris sumatrae) using a meta-regression of 17 existing densities and new estimates from our own fieldwork. We find that tiger densities were 47% higher in primary versus degraded forests and, unexpectedly, increased 4.9% per yr from 1996 to 2014, likely indicating a recovery from earlier poaching. However, while tiger numbers may have temporarily risen, the total potential island-wide population declined by 16.6% from 2000 to 2012 due to forest loss and degradation and subpopulations are significantly more fragmented. Thus, despite increasing densities in smaller parks, we conclude that there are only two robust populations left with >30 breeding females, indicating Sumatran tigers still face a high risk of extinction unless deforestation can be controlled.
Satellite imagery reveals flowstripes on Foundation Ice Stream parallel to ice flow, and meandering features on the ice-shelf that cross-cut ice flow and are thought to be formed by water exiting a well-organised subglacial system. Here, ice-penetrating radar data show flow-parallel hard-bed landforms beneath the grounded ice, and channels incised upwards into the ice shelf beneath meandering surface channels. As the ice transitions to flotation, the ice shelf incorporates a corrugation resulting from the landforms. Radar reveals the presence of subglacial water alongside the landforms, indicating a well-organised drainage system in which water exits the ice sheet as a point source, mixes with cavity water and incises upwards into a corrugation peak, accentuating the corrugation downstream. Hard-bedded landforms influence both subglacial hydrology and ice-shelf structure and, as they are known to be widespread on formerly glaciated terrain, their influence on the ice-sheet-shelf transition could be more widespread than thought previously.
Woody (lignocellulosic) plant biomass is an abundant renewable feedstock, rich in polysaccharides that are bound into an insoluble fiber composite with lignin. Marine crustacean woodborers of the genus Limnoria are among the few animals that can survive on a diet of this recalcitrant material without relying on gut resident microbiota. Analysis of fecal pellets revealed that Limnoria targets hexose-containing polysaccharides (mainly cellulose, and also glucomannans), corresponding with the abundance of cellulases in their digestive system, but xylans and lignin are largely unconsumed. We show that the limnoriid respiratory protein, hemocyanin, is abundant in the hindgut where wood is digested, that incubation of wood with hemocyanin markedly enhances its digestibility by cellulases, and that it modifies lignin. We propose that this activity of hemocyanins is instrumental to the ability of Limnoria to feed on wood in the absence of gut symbionts. These findings may hold potential for innovations in lignocellulose biorefining.
Multi-layer structure of functional materials often involves the integration of different crystalline phases. The film growth orientation thus frequently exhibits a transformation, owing to multiple possibilities caused by incompatible in-plane structural symmetry. Nevertheless, the detailed mechanism of the transformation has not yet been fully explored. Here we thoroughly probe the heteroepitaxially grown hexagonal zinc oxide (ZnO) films on cubic (001)-magnesium oxide (MgO) substrates using advanced scanning transition electron microscopy, X-ray diffraction and first principles calculations, revealing two distinct interface models of (001) ZnO/(001) MgO and (100) ZnO/(001) MgO. We have found that the structure alternatives are controlled thermodynamically by the nucleation, while kinetically by the enhanced Zn adsorption and O diffusion upon the phase transformation. This work not only provides a guideline for the interface fabrication with distinct crystalline phases but also shows how polar and non-polar hexagonal ZnO films might be manipulated on the same cubic substrate.