Spatial scales of bacterial diversity in cold-water coral reef ecosystems

Background

Cold-water coral reef ecosystems are recognized as biodiversity hotspots in the deep sea, but insights into their associated bacterial communities are still limited. Deciphering principle patterns of bacterial community variation over multiple spatial scales may however prove critical for a better understanding of factors contributing to cold-water coral reef stability and functioning.

Methodology/Principal Findings

Bacterial community structure, as determined by Automated Ribosomal Intergenic Spacer Analysis (ARISA), was investigated with respect to (i) microbial habitat type and (ii) coral species and color, as well as the three spatial components (iii) geomorphologic reef zoning, (iv) reef boundary, and (v) reef location. Communities revealed fundamental differences between coral-generated (branch surface, mucus) and ambient microbial habitats (seawater, sediments). This habitat specificity appeared pivotal for determining bacterial community shifts over all other study levels investigated. Coral-derived surfaces showed species-specific patterns, differing significantly between Lophelia pertusa and Madrepora oculata, but not between L. pertusa color types. Within the reef center, no community distinction corresponded to geomorphologic reef zoning for both coral-generated and ambient microbial habitats. Beyond the reef center, however, bacterial communities varied considerably from local to regional scales, with marked shifts toward the reef periphery as well as between different in- and offshore reef sites, suggesting significant biogeographic imprinting but weak microbe-host specificity.

Conclusions/Significance

This study presents the first multi-scale survey of bacterial diversity in cold-water coral reefs, spanning a total of five observational levels including three spatial scales. It demonstrates that bacterial communities in cold-water coral reefs are structured by multiple factors acting at different spatial scales, which has fundamental implications for the monitoring of microbial diversity and function in those ecosystems.     

The Plasmodium vivax Merozoite Surface Protein 3β Sequence Reveals Contrasting Parasite Populations in Southern and Northwestern Thailand

Background

Malaria control efforts have a significant impact on the epidemiology and parasite population dynamics. In countries aiming for malaria elimination, malaria transmission may be restricted to limited transmission hot spots, where parasite populations may be isolated from each other and experience different selection forces. Here we aim to examine the Plasmodium vivax population divergence in geographically isolated transmission zones in Thailand.

Methodology

We employed the P. vivax merozoite surface protein 3β (PvMSP3β) as a molecular marker for characterizing P. vivax populations based on the extensive diversity of this gene in Southeast Asian parasite populations. To examine two parasite populations with different transmission levels in Thailand, we obtained 45 P. vivax isolates from Tak Province, northwestern Thailand, where the annual parasite incidence (API) was more than 2%, and 28 isolates from Yala and Narathiwat Provinces, southern Thailand, where the API was less than 0.02%. We sequenced the PvMSP3β gene and examined its genetic diversity and molecular evolution between the parasite populations.

Principal Findings

Of 58 isolates containing single PvMSP3β alleles, 31 sequence types were identified. The overall haplotype diversity was 0.77±0.06 and nucleotide diversity 0.0877±0.0054. The northwestern vivax malaria population exhibited extensive haplotype diversity (HD) of PvMSP3β (HD = 1.0). In contrast, the southern parasite population displayed a single PvMSP3β allele (HD = 0), suggesting a clonal population expansion. This result revealed that the extent of allelic diversity in P. vivax populations in Thailand varies among endemic areas.

Conclusion

Malaria parasite populations in a given region may vary significantly in genetic diversity, which may be the result of control and influenced by the magnitude of malaria transmission intensity. This is an issue that should be taken into account for the implementation of P. vivax control measures such as drug policy and vaccine development.     

Spatial and Temporal Variation of Archaeal,Bacterial and Fungal Communities in Agricultural Soils

Background

Soil microbial communities are in constant change at many different temporal and spatial scales. However, the importance of these changes to the turnover of the soil microbial communities has been rarely studied simultaneously in space and time.

Methodology/Principal Findings

In this study, we explored the temporal and spatial responses of soil bacterial, archaeal and fungal β-diversities to abiotic parameters. Taking into account data from a 3-year sampling period, we analyzed the abundances and community structures of Archaea, Bacteria and Fungi along with key soil chemical parameters. We questioned how these abiotic variables influence the turnover of bacterial, archaeal and fungal communities and how they impact the long-term patterns of changes of the aforementioned soil communities. Interestingly, we found that the bacterial and fungal β-diversities are quite stable over time, whereas archaeal diversity showed significantly higher fluctuations. These fluctuations were reflected in temporal turnover caused by soil management through addition of N-fertilizers.

Conclusions

Our study showed that management practices applied to agricultural soils might not significantly affect the bacterial and fungal communities, but cause slow and long-term changes in the abundance and structure of the archaeal community. Moreover, the results suggest that, to different extents, abiotic and biotic factors determine the community assembly of archaeal, bacterial and fungal communities.     

Identification of lipocalin-2 as a PKCδ phosphorylation substrate in neutrophils

Background

PKCδ expressed in neutrophils is implicated in promoting reperfusion injury after ischemic stroke. To understand the molecular and cellular actions of PKCδ, we employed a chemical-genetics approach to identify PKCδ substrates in neutrophils.

Results

We recently generated knock-in mice endogenously expressing analog-specific PKCδ (AS-PKCδ) that can utilize ATP analogs as phosphate donors. Using neutrophils isolated from the knock-in mice, we identified several PKCδ substrates, one of which was lipocalin-2 (LCN2), which is an iron-binding protein that can trigger apoptosis by reducing intracellular iron concentrations. We found that PKCδ phosphorylated LCN2 at T115 and this phosphorylation was reduced in Prkcd^−/− mice. PKCδ colocalized with LCN2 in resting and stimulated neutrophils. LCN2 release from neutrophils after cerebral ischemia was reduced in PKCδ null mice.

Conclusions

These findings suggest that PKCδ phosphorylates LCN2 and mediates its release from neutrophils during ischemia-reperfusion injury.     

Additive Partitioning of Coral Reef Fish Diversity across Hierarchical Spatial Scales throughout the Caribbean

There is an increasing need to examine regional patterns of diversity in coral-reef systems since their biodiversity is declining globally. In this sense, additive partitioning might be useful since it quantifies the contribution of alpha and beta to total diversity across different scales. We applied this approach using an unbalanced design across four hierarchical scales (80 sites, 22 subregions, six ecoregions, and the Caribbean basin). Reef-fish species were compiled from the Reef Environmental Education Foundation (REEF) database and distributions were confirmed with published data. Permutation tests were used to compare observed values to those expected by chance. The primary objective was to identify patterns of reef-fish diversity across multiple spatial scales under different scenarios, examining factors such as fisheries and demographic connectivity. Total diversity at the Caribbean scale was attributed to β-diversity (nearly 62% of the species), with the highest β-diversity at the site scale. α¯-diversity was higher than expected by chance in all scenarios and at all studied scales. This suggests that fish assemblages are more homogenous than expected, particularly at the ecoregion scale. Within each ecoregion, diversity was mainly attributed to alpha, except for the Southern ecoregion where there was a greater difference in species among sites. β-components were lower than expected in all ecoregions, indicating that fishes within each ecoregion are a subsample of the same species pool. The scenario involving the effects of fisheries showed a shift in dominance for β-diversity from regions to subregions, with no major changes to the diversity patterns. In contrast, demographic connectivity partially explained the diversity pattern. β-components were low within connectivity regions and higher than expected by chance when comparing between them. Our results highlight the importance of ecoregions as a spatial scale to conserve local and regional coral reef-fish diversity.     

Loss of Hepatocyte-Nuclear-Factor-1α Impacts on Adult Mouse Intestinal Epithelial Cell Growth and Cell Lineages Differentiation

Background and Aims

Although Hnf1α is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions.

Methodology/Principal Findings

An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway.

Conclusions/Significance

Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages.     

Psychometrics of the Short Form 36 Health Survey Version 2 (SF-36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese Mainland Patients with Methadone Maintenance Treatment

Objective

To test psychometrics of the Short Form 36 Health Survey version 2 (SF-36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese mainland patients with methadone maintenance treatment (MMT).

Methods

A total of 1,212 patients were recruited from two MMT clinics in Xi’an, China. Reliability was estimated with Cronbach’s α and intra-class correlation (ICC). Convergent and discriminant validity was assessed using multitrait-multimethod correlation matrix. Sensitivity was measured with ANOVA and relative efficiency. Responsiveness was evaluated by pre-post paired-samples t-test and standardized response mean based on the patients’ health status changes following 6-month period.

Results

Cronbach’s α of the SF-36v2 physical and mental summary components were 0.80 and 0.86 (eight scales range 0.73–0.92) and the QOL-DAv2.0 was 0.96 (four scales range: 0.80–0.93). ICC of the SF-36v2 two components were 0.86 and 0.85 (eight scales range: 0.72–0.87) and the QOL-DAv2.0 was 0.94 (four scales range: 0.88–0.92). Convergent validity was lower between the two instruments (γ <0.70) while discriminant validity was acceptable within each instrument. Sensitivity was satisfied in self-evaluated health status (both instruments) and average daily methadone dose (SF-36v2 physical functioning and vitality scales; QOL-DAv2.0 except psychology scale). Responsiveness was acceptable in the improved health status change (SF-36v2 except vitality scale; QOL-DAv2.0 except psychology and symptoms scales) and deteriorated health status change (SF-36v2 except vitality, social functioning and mental health scales; QOL-DAv2.0 except society scale).

Conclusions

The SF-36v2 and the QOL-DAv2.0 are valid tools and can be used independently or complementary according to different emphases of health-related quality of life evaluation in patients with MMT.     

Renal Water Molecular Diffusion Characteristics in Healthy Native Kidneys: Assessment with Diffusion Tensor MR Imaging

Background

To explore the characteristics of diffusion tensor imaging (DTI) and magnetic resonance (MR) imaging in healthy native kidneys.

Methods

Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI) sequences accompanied by an array spatial sensitivity encoding technique (ASSET). Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD), fractional anisotropy (FA) and primary, secondary and tertiary eigenvalues (λ₁, λ₂, λ₃) were analysed in both kidneys and in different genders.

Results

Cortical MD, λ₂, λ₃, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ₁ and RD values in the left kidney were lower than in the right kidney. Medullary λ₂, and λ₃ values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002) and λ₁ (r = 0.277, P = 0.018) positively correlated with eGFR. Medullary FA (r = −0.25, P = 0.033) negatively correlated with age.

Conclusions

Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue.     

Unprecedented Mass Bleaching and Loss of Coral across 12° of Latitude in Western Australia in 2010–11

Background

Globally, coral bleaching has been responsible for a significant decline in both coral cover and diversity over the past two decades. During the summer of 2010–11, anomalous large-scale ocean warming induced unprecedented levels of coral bleaching accompanied by substantial storminess across more than 12° of latitude and 1200 kilometers of coastline in Western Australia (WA).

Methodology/Principal Findings

Extreme La-Niña conditions caused extensive warming of waters and drove considerable storminess and cyclonic activity across WA from October 2010 to May 2011. Satellite-derived sea surface temperature measurements recorded anomalies of up to 5°C above long-term averages. Benthic surveys quantified the extent of bleaching at 10 locations across four regions from tropical to temperate waters. Bleaching was recorded in all locations across regions and ranged between 17% (±5.5) in the temperate Perth region, to 95% (±3.5) in the Exmouth Gulf of the tropical Ningaloo region. Coincident with high levels of bleaching, three cyclones passed in close proximity to study locations around the time of peak temperatures. Follow-up surveys revealed spatial heterogeneity in coral cover change with four of ten locations recording significant loss of coral cover. Relative decreases ranged between 22%–83.9% of total coral cover, with the greatest losses in the Exmouth Gulf.

Conclusions/Significance

The anomalous thermal stress of 2010–11 induced mass bleaching of corals along central and southern WA coral reefs. Significant coral bleaching was observed at multiple locations across the tropical-temperate divide spanning more than 1200 km of coastline. Resultant spatially patchy loss of coral cover under widespread and high levels of bleaching and cyclonic activity, suggests a degree of resilience for WA coral communities. However, the spatial extent of bleaching casts some doubt over hypotheses suggesting that future impacts to coral reefs under forecast warming regimes may in part be mitigated by southern thermal refugia.     

Impact of Herbivore Identity on Algal Succession and Coral Growth on a Caribbean Reef

Background

Herbivory is an important top-down force on coral reefs that regulates macroalgal abundance, mediates competitive interactions between macroalgae and corals, and provides resilience following disturbances such as hurricanes and coral bleaching. However, reductions in herbivore diversity and abundance via disease or over-fishing may harm corals directly and may indirectly increase coral susceptibility to other disturbances.

Methodology and Principal Findings

In two experiments over two years, we enclosed equivalent densities and masses of either single-species or mixed-species of herbivorous fishes in replicate, 4 m² cages at a depth of 17 m on a reef in the Florida Keys, USA to evaluate the effects of herbivore identity and species richness on colonization and development of macroalgal communities and the cascading effects of algae on coral growth. In Year 1, we used the redband parrotfish (Sparisoma aurofrenatum) and the ocean surgeonfish (Acanthurus bahianus); in Year 2, we used the redband parrotfish and the princess parrotfish (Scarus taeniopterus). On new substrates, rapid grazing by ocean surgeonfish and princess parrotfish kept communities in an early successional stage dominated by short, filamentous algae and crustose coralline algae that did not suppress coral growth. In contrast, feeding by redband parrotfish allowed an accumulation of tall filaments and later successional macroalgae that suppressed coral growth. These patterns contrast with patterns from established communities not undergoing primary succession; on established substrates redband parrotfish significantly reduced upright macroalgal cover while ocean surgeonfish and princess parrotfish allowed significant increases in late successional macroalgae.

Significance

This study further highlights the importance of biodiversity in affecting ecosystem function in that different species of herbivorous fishes had very different impacts on reef communities depending on the developmental stage of the community. The species-specific effects of herbivorous fishes suggest that a species-rich herbivore fauna can be critical in providing the resilience that reefs need for recovery from common disturbances such as coral bleaching and storm damage.     

Coverage,Diversity, and Functionality of a High-Latitude Coral Community (Tatsukushi,Shikoku Island,Japan)

Background

Seawater temperature is the main factor restricting shallow-water zooxanthellate coral reefs to low latitudes. As temperatures increase, coral species and perhaps reefs may move into higher-latitude waters, increasing the chances of coral reef ecosystems surviving despite global warming. However, there is a growing need to understand the structure of these high-latitude coral communities in order to analyze their future dynamics and to detect any potential changes.

Methodology/Principal Findings

The high-latitude (32.75°N) community surveyed was located at Tatsukushi, Shikoku Island, Japan. Coral cover was 60±2% and was composed of 73 scleractinian species partitioned into 7 functional groups. Although only 6% of species belonged to the ‘plate-like’ functional group, it was the major contributor to species coverage. This was explained by the dominance of plate-like species such as Acropora hyacinthus and A. solitaryensis. Comparison with historical data suggests a relatively recent colonization/development of A. hyacinthus in this region and a potential increase in coral diversity over the last century. Low coverage of macroalgae (2% of the benthic cover) contrasted with the low abundance of herbivorous fishes, but may be reasonably explained by the high density of sea urchins (12.9±3.3 individuals m⁻²).

Conclusions/Significance

The structure and composition of this benthic community are relatively remarkable for a site where winter temperature can durably fall below the accepted limit for coral reef development. Despite limited functionalities and functional redundancy, the current benthic structure might provide a base upon which a reef could eventually develop, as characterized by opportunistic and pioneer frame-building species. In addition to increasing seawater temperatures, on-going management actions and sea urchin density might also explain the observed state of this community. A focus on such ‘marginal’ communities should be a priority, as they can provide important insights into how tropical corals might cope with environmental changes.     

Spatial and Temporal Patterns in Macrofaunal Diversity Components Relative to Sea Floor Landscape Structure

We examined temporal changes in macrofaunal α- and β-diversity over several spatial scales (within patches, among patches, across landscapes and across regions) in Long Island Sound on the northeast USA coast. Regional ε-diversity was estimated at 144 taxa, however γ-diversity fluctuated over time as did α- and β-diversity components. Based on additive partitioning, patch- and region-scale β-diversity components generally had the highest contributions to γ-diversity; lower percentages were found at within-patch and landscape scales. Multiplicative diversity partitioning indicated highest species turnover at within- and among patch scales. For all partition results, within-patch and patch-scale β-diversity increased sharply when hypoxia impacted benthic communities. Spatial variation in diversity components can be attributed to the collection of different patch types at varying spatial scales and their associated habitats across the benthic landscapes, as well as gradients in depth and other estuarine-scale characteristics. Temporal variation in diversity components across spatial scales may be related to seasonal changes in habitat heterogeneity, species population dynamics, and seasonal disturbances. Rare species were significant and temporally consistent components of macrofaunal diversity patterns over different spatial scales. Our findings agree with other marine and terrestrial studies that show diversity components vary significantly over different spatial scales and the importance of habitat/landscape heterogeneity in supporting diversity. However, our results indicate that the relative contributions of scale-specific β-diversity components can also change significantly over time. Thus, studies of diversity patterns across patches and landscapes based on data collected at one time, or assembled into a single data set from different times, may not capture the full suite of diversity patterns that occur over varying spatial scales and any time-specific determinants of those patterns. Many factors that shape and maintain sedimentary communities vary temporally, and appear to play an important role in determining and maintaining macrofaunal diversity over different spatial scales.     

Different Relationships between Temporal Phylogenetic Turnover and Phylogenetic Similarity and in Two Forests Were Detected by a New Null Model

Background

Ecologists have been monitoring community dynamics with the purpose of understanding the rates and causes of community change. However, there is a lack of monitoring of community dynamics from the perspective of phylogeny.

Methods/Principle Findings

We attempted to understand temporal phylogenetic turnover in a 50 ha tropical forest (Barro Colorado Island, BCI) and a 20 ha subtropical forest (Dinghushan in southern China, DHS). To obtain temporal phylogenetic turnover under random conditions, two null models were used. The first shuffled names of species that are widely used in community phylogenetic analyses. The second simulated demographic processes with careful consideration on the variation in dispersal ability among species and the variations in mortality both among species and among size classes. With the two models, we tested the relationships between temporal phylogenetic turnover and phylogenetic similarity at different spatial scales in the two forests. Results were more consistent with previous findings using the second null model suggesting that the second null model is more appropriate for our purposes. With the second null model, a significantly positive relationship was detected between phylogenetic turnover and phylogenetic similarity in BCI at a 10 m×10 m scale, potentially indicating phylogenetic density dependence. This relationship in DHS was significantly negative at three of five spatial scales. This could indicate abiotic filtering processes for community assembly. Using variation partitioning, we found phylogenetic similarity contributed to variation in temporal phylogenetic turnover in the DHS plot but not in BCI plot.

Conclusions/Significance

The mechanisms for community assembly in BCI and DHS vary from phylogenetic perspective. Only the second null model detected this difference indicating the importance of choosing a proper null model.     

Significant Association of Glutathione S-Transferase T1 Null Genotype with Prostate Cancer Risk: A Meta-Analysis of 26,393 Subjects

Background

Recent studies on the association between Glutathione S-transferase T1 (GSTT1) polymorphism and risk of prostate cancer showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies.

Methods

Data were collected from the following electronic databases: Pubmed, Embase, and Chinese Biomedical Database (CBM). The odds ratio (OR) and its 95% confidence interval (95%CI) was used to assess the strength of the association. We summarized the data on the association between GSTT1 null genotype and risk of prostate cancer in the overall population, and performed subgroup analyses by ethnicity, adjusted ORs, and types of controls.

Results

Ultimately, a total of 43 studies with a total of 26,393 subjects (9,934 cases and 16,459 controls) were eligible for meta-analysis. Overall, there was a significant association between GSTT1 null genotype and increased risk of prostate cancer (OR = 1.14, 95%CI 1.01–1.29, P = 0.034). Meta-analysis of adjusted ORs also showed a significant association between GSTT1 null genotype and increased risk of prostate cancer (OR = 1.34, 95%CI 1.09–1.64, P = 0.006). Similar results were found in the subgroup analyses by ethnicity and types of controls.

Conclusion

This meta-analysis demonstrates that GSTT1 null genotype is associated with prostate cancer susceptibility, and GSTT1 null genotype contributes to increased risk of prostate cancer.     

A molecular census of early‐life stage scleractinian corals in shallow and mesophotic zones

The decline of coral reefs has fueled interest in determining whether mesophotic reefs can shield against disturbances and help replenish deteriorated shallower reefs. In this study, we characterized spatial (horizontal and vertical) and seasonal patterns of diversity in coral recruits from Dabaisha and Guiwan reefs at Ludao, Taiwan. Concrete blocks supporting terra‐cotta tiles were placed at shallow (15m) and mesophotic (40m) depths, during 2016–2018. Half of the tiles were retrieved and replaced biannually over three 6‐month surveys (short‐term); the remainder retrieved at the end of the 18‐month (long‐term) survey. 451 recruits were located using fluorescent censusing and identified by DNA barcoding. Barcoding the mitochondrial cytochrome oxidase I (COI) gene resulted in 17 molecular operational taxonomic units (MOTUs). To obtain taxonomic resolution to the generic level, Pocillopora were phylotyped using the mitochondrial open reading frame (ORF), resolving eight MOTUs. Acropora, Isopora, and Montipora recruits were identified by the nuclear PaxC intron, yielding ten MOTUs. Overall, 35 MOTUs were generated and were comprised primarily of Pocillopora and, in fewer numbers, Acropora, Isopora, Pavona, Montipora, Stylophora, among others. 40% of MOTUs recruited solely within mesophotic reefs while 20% were shared by both depth zones. MOTUs recruiting across a broad depth distribution appear consistent with the hypothesis of mesophotic reefs acting as a refuge for shallow‐water coral reefs. In contrast, Acropora and Isopora MOTUs were structured across depth zones representing an exception to this hypothesis. This research provides an imperative assessment of coral recruitment in understudied mesophotic reefs and imparts insight into the refuge hypothesis.     

γδ T Cells Are Involved in Acute HIV Infection and Associated with AIDS Progression

Background

Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described.

Methods

Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79) were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21) at month 0, 6, 12 and 18.

Results

In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027) with Vδ2 population reduced (P = 0.002). Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively), while proportion of terminal γδ T cells increased (P = 0.002). γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008), and IFN-γ-producing cells were unaffected (P = 0.115). Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001), which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes.

Conclusions

γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression.     

ADH1B and ADH1C Genotype,Alcohol Consumption and Biomarkers of Liver Function: Findings from a Mendelian Randomization Study in 58,313 European Origin Danes

Background

The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol.

Methods

We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), γ-glutamyl-transferase (γ-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56).

Results

In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (−4.5, 11.9) from genetic-IV analyses] and γ-GT [8.2% (7.8, 8.5) and 6.8% (−2.8, 16.5)]. The point estimates from the two methods were very similar and statistically the results from the two methods were consistent with each other for effects with ALT and γ-GT (both p_diff>0.3). Results from the multivariable analyses suggested a weak inverse association of alcohol with ALP [−1.5% (−1.7, −1.3)], which differed from the strong positive effect found in genetic-IV analyses [11.6% (6.8, 16.4)] (p_diff<0.0001). In both multivariable and genetic-IV analyses associations with bilirubin and protrombin action were weak and close to the null.

Conclusions

Our results suggest that greater consumption of alcohol is related to poorer liver function as indicated by higher ALT, γ-GT and ALP, but not to clotting or bilirubin.     

Characterization of Drosophila GDNF Receptor-Like and Evidence for Its Evolutionarily Conserved Interaction with Neural Cell Adhesion Molecule (NCAM)/FasII

Background

Glial cell line-derived neurotrophic factor (GDNF) family ligands are secreted growth factors distantly related to the TGF-β superfamily. In mammals, they bind to the GDNF family receptor α (Gfrα) and signal through the Ret receptor tyrosine kinase. In order to gain insight into the evolution of the Ret-Gfr-Gdnf signaling system, we have cloned and characterized the first invertebrate Gfr-like cDNA (DmGfrl) from Drosophila melanogaster and generated a DmGfrl mutant allele.

Results

We found that DmGfrl encodes a large GPI-anchored membrane protein with four GFR-like domains. In line with the fact that insects lack GDNF ligands, DmGfrl mediated neither Drosophila Ret phosphorylation nor mammalian RET phosphorylation. In situ hybridization analysis revealed that DmGfrl is expressed in the central and peripheral nervous systems throughout Drosophila development, but, surprisingly, DmGfrl and DmRet expression patterns were largely non-overlapping. We generated a DmGfrl null allele by genomic FLP deletion and found that both DmGfrl null females and males are viable but display fertility defects. The female fertility defect manifested as dorsal appendage malformation, small size and reduced viability of eggs laid by mutant females. In male flies DmGfrl interacted genetically with the Drosophila Ncam (neural cell adhesion molecule) homolog FasII to regulate fertility.

Conclusion

Our results suggest that Ret and Gfrl did not function as an in cis receptor-coreceptor pair before the emergence of GDNF family ligands, and that the Ncam-Gfr interaction predated the in cis Ret-Gfr interaction in evolution. The fertility defects that we describe in DmGfrl null flies suggest that GDNF receptor-like has an evolutionarily ancient role in regulating male fertility and a previously unrecognized role in regulating oogenesis.

Significance

These results shed light on the evolutionary aspects of the structure, expression and function of Ret-Gfrα and Ncam-Gfrα signaling complexes.