Severe hurricanes increase recruitment and gene flow in the clonal sponge Aplysina cauliformis.

Upright branching sponges, such as Aplysina cauliformis, provide critical three-dimensional habitat for other organisms and assist in stabilizing coral reef substrata, but are highly susceptible to breakage during storms. Breakage can increase sponge fragmentation, contributing to population clonality and inbreeding. Conversely, storms could provide opportunities for new genotypes to enter populations via larval recruitment, resulting in greater genetic diversity in locations with frequent storms. The unprecedented occurrence of two Category 5 hurricanes in close succession during 2017 in the U.S. Virgin Islands (USVI) provided a unique opportunity to evaluate whether recolonization of newly available substrata on coral reefs was due to local (e.g. re-growth of remnants, fragmentation, larval recruitment) or remote (e.g. larval transport and immigration) sponge genotypes. We sampled A. cauliformis adults and juveniles from four reefs around St. Thomas and two in St. Croix (USVI). Using a 2bRAD protocol, all samples were genotyped for single-nucleotide polymorphisms (SNPs). Results showed that these major storm events favoured sponge larval recruitment but did not increase the genetic diversity of A. cauliformis populations. Recolonization of substratum post-storms via clonality was lower (15%) than expected and instead was mainly due to sexual reproduction (85%) via local larval recruitment. Storms did enhance gene flow among and within reef sites located south of St. Thomas and north of St. Croix. Therefore, populations of clonal marine species with low pelagic dispersion, such as A. cauliformis, may benefit from increased frequency and magnitude of hurricanes for the maintenance of genetic diversity and to combat inbreeding, enhancing the resilience of Caribbean sponge communities to extreme storm events.

Investigating the interactive effects of temperature, pH, and salinity on Naegleria fowleri persistence.

Naegleria fowleri causes primary amoebic meningoencephalitis, a deadly infection that occurs when free-living amoebae enter the nose via freshwater and travel to the brain. N. fowleri naturally thrives in freshwater and soil and is thought to be associated with elevated water temperatures. While environmental and laboratory studies have sought to identify what environmental factors influence its presence, many questions remain. This study investigated the interactive effects of temperature, pH, and salinity on N. fowleri in deionized and environmental waters. Three temperatures (15, 25, 35°C), pH values (6.5, 7.5, 8.5), and salinity concentrations (0.5%, 1.5%, 2.5% NaCl) were used to evaluate the growth of N. fowleri via ATP luminescent assays. Results indicated N. fowleri grew best at 25°C, and multiple interactive effects occurred between abiotic factors. Interactions varied slightly by water type but were largely driven by temperature and salinity. Lower temperature increased N. fowleri persistence at higher salinity levels, while low salinity (0.5% NaCl) supported N. fowleri growth at all temperatures. This research provided an experimental approach to assess interactive effects influencing the persistence of N. fowleri. As climate change impacts water temperatures and conditions, understanding the microbial ecology of N. fowleri will be needed minimize pathogen exposure.

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2.

BACKGROUND: Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2. METHODS: Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62). RESULTS: PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients. CONCLUSIONS: Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.

Recovery From Dialysis in Patients With Primary Hyperoxaluria Type 1 Treated With Pyridoxine: A Report of 3 Cases.

Primary hyperoxaluria type 1 (PH1) is a genetic disorder characterized by overproduction of oxalate and eventual kidney failure. Kidney failure is usually irreversible in PH1. However, in patients with PH1 homozygous for the G170R mutation (in which the glycine at amino acid 170 is replaced by an arginine), pyridoxine is an enzyme cofactor and decreases urinary oxalate excretion by reducing hepatic oxalate production. We report recovery from dialysis in 3 patients with PH1 homozygous for the G170R mutation in response to pharmacologic-dose pyridoxine treatment. Median age at initiation or resumption of pyridoxine treatment was 37 (range, 20-53) years, and median daily pyridoxine dose was 8.8 (range, 6.8-14.0) mg per kilogram of body weight. Duration of hemodialysis before recovery of kidney function was 10 (range, 5-19) months. Plasma oxalate concentration improved after recovery of kidney function. At a median of 3 (range, 2-46) months following discontinuation of hemodialysis, estimated glomerular filtration rate was 34 (range, 23-52) mL/min/1.73m2, plasma oxalate concentration was 8.8 (range, 4.6-11.3) µmol/L, and urinary oxalate excretion was 0.93 (range, 0.47-1.03) mmol/d. Kidney function was maintained during a median of 3.2 (range, 1.3-3.8) years of follow-up. These observations suggest that kidney failure may be reversible in a subset of patients with PH1 homozygous for the G170R mutation treated with pharmacologic-dose pyridoxine.

Hydroxyproline Metabolism and Oxalate Synthesis in Primary Hyperoxaluria.

Background Endogenous oxalate synthesis contributes to calcium oxalate stone disease and is markedly increased in the inherited primary hyperoxaluria (PH) disorders. The incomplete knowledge regarding oxalate synthesis complicates discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the formation of oxalate and glycolate. However, the relative contribution of Hyp metabolism to endogenous oxalate and glycolate synthesis is not known.Methods To define this contribution, we performed primed, continuous, intravenous infusions of the stable isotope [15N,13C5]-Hyp in nine healthy subjects and 19 individuals with PH and quantified the levels of urinary 13C2-oxalate and 13C2-glycolate formed using ion chromatography coupled to mass detection.Results The total urinary oxalate-to-creatinine ratio during the infusion was 73.1, 70.8, 47.0, and 10.6 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3 and controls, respectively. Hyp metabolism accounted for 12.8, 32.9, and 14.8 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3, respectively, compared with 1.6 mg oxalate/g creatinine in controls. The contribution of Hyp to urinary oxalate was 15% in controls and 18%, 47%, and 33% in subjects with PH1, PH2, and PH3, respectively. The contribution of Hyp to urinary glycolate was 57% in controls, 30% in subjects with PH1, and <13% in subjects with PH2 or PH3.Conclusions Hyp metabolism differs among PH types and is a major source of oxalate synthesis in individuals with PH2 and PH3. In patients with PH1, who have the highest urinary excretion of oxalate, the major sources of oxalate remain to be identified.

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) are stone-forming diseases that may result in the formation of calcium (Ca) oxalate (Ox) stones, nephrocalcinosis, and progressive chronic kidney disease (CKD). Poorer clinical outcome in PH1 is segregated by the highest urine (Ur)-Ox (UrOx), while IHC outcomes are not predictable by UrCa. We hypothesized that differences would be found in selected Ur-protein (PRO) patterns in PH1 and IHC, compared to healthy intra-familial sibling controls (C) of PH1 patients. We also hypothesized that the PRO patterns associated with higher UrOx levels would reflect injury, inflammation, biomineralization, and abnormal tissue repair processes in PH1. METHODS: Twenty four-hour Ur samples were obtained from 3 cohorts: PH1 (n = 47); IHC (n = 35) and C (n = 13) and were analyzed using targeted platform-based multi-analyte profile immunoassays and for UrOx and UrCa by biochemical measurements. RESULTS: Known stone matrix constituents, osteopontin, calbindin, and vitronectin were lowest in PH1 (C > IHC > PH1; p < 0.05). Ur-interleukin-10; chromogranin A; epidermal growth factor (EGF); insulin-like growth factor-1 (IGF-1), and macrophage inflammatory PRO-1α (MIP-1α) were higher in PH1 > C (p = 0.03 to p < 0.05). Fetuin A; IGF-1, MIP-1α, and vascular cell adhesion molecule-1 were highest in PH1 > IHC (p < 0.001 to p = 0.005). CONCLUSION: PH1 Ur-PROs reflected overt inflammation, chemotaxis, oxidative stress, growth factors (including EGF), and pro-angiogenic and calcification regulation/inhibition compared to the C and IHC cohorts. Many of the up- and downregulated PH1-PROs found in this study are also found in CKD, acute kidney injury, stone formers, and/or stone matrices. Further data analyses may provide evidence for PH1 unique PROs or demonstrate a poorer clinical outcome.

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria.

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.

Oxalate quantification in hemodialysate to assess dialysis adequacy for primary hyperoxaluria.

BACKGROUND: Patients with primary hyperoxaluria (PH) overproduce oxalate which is eliminated via the kidneys. If end-stage kidney disease develops they are at high risk for systemic oxalosis, unless adequate oxalate is removed during hemodialysis (HD) to equal or exceed ongoing oxalate production. The purpose of this study was to validate a method to measure oxalate removal in this unique group of dialysis patients. METHODS: Fourteen stable patients with a confirmed diagnosis of PH on HD were included in the study. Oxalate was measured serially in hemodialysate and plasma samples in order to calculate rates of oxalate removal. HD regimens were adjusted according to a given patient's historical oxalate production, amount of oxalate removal at dialysis, residual renal clearance of oxalate, and plasma oxalate levels. RESULTS: After a typical session of HD, plasma oxalate was reduced by 78.4 ± 7.7%. Eight patients performed HD 6 times/week, 2 patients 5 times/week, and 3 patients 3 times/week. Combined oxalate removal by HD and the kidneys was sufficient to match or exceed endogenous oxalate production. After a median period of 9 months, pre-dialysis plasma oxalate was significantly lower than initially (75.1 ± 33.4 vs. 54.8 ± 46.6 mmol/l, p = 0.02). CONCLUSION: This methodology can be used to individualize the dialysis prescription of PH patients to prevent oxalosis during the time they are maintained on HD and to reduce risk of oxalate injury to a transplanted kidney.

Trade-offs in defensive metabolite production but not ecological function in healthy and diseased sponges.

Diseases of marine organisms, and sponges in particular, are increasingly reported worldwide. Prior research indicates that the survival of sponges on reefs is due largely to their production of biologically active secondary metabolites that provide protection from a diversity of stressors. Aplysina Red Band Syndrome (ARBS) is an emerging disease affecting Caribbean rope sponges (Aplysina spp.), but it is not known whether secondary metabolites play a role in disease susceptibility and resistance. To investigate whether differences in secondary metabolites may explain variability in susceptibility to ARBS in Aplysina cauliformis, we used high performance liquid chromatography (HPLC) to generate chemical profiles from healthy tissue in both healthy and diseased sponges, and quantified peak areas for 15 metabolites. Analyses of healthy and diseased sponges revealed qualitative and quantitative differences in their chemical profiles. Aplysamine-1 and fistularin-3 were produced in significantly higher concentrations by healthy sponges, whereas aerothionin and 11-oxoaerothionin were found only in diseased sponges. At natural concentrations, extracts from both healthy and diseased sponges deterred feeding by an omnivorous reef fish. Fistularin-3 deterred feeding at concentrations found in healthy sponges, but not at concentrations found in diseased sponges. Aerothionin deterred feeding at concentrations found in diseased sponges, and may at least partially replace the loss of fistularin-3 as a feeding deterrent compound following pathogenesis, suggesting a trade-off in the production of feeding deterrent compounds. Extracts from healthy and diseased sponges inhibited bacterial growth, and both aplysamine-1 and fistularin-3 displayed selective antibacterial activity. Despite differences in secondary metabolite production between healthy and diseased sponges, the stress associated with ARBS does not appear to compromise the ability of A. cauliformis to maintain defenses against some of its natural enemies.

Transmission studies and the composition of prokaryotic communities associated with healthy and diseased Aplysina cauliformis sponges suggest that Aplysina Red Band Syndrome is a prokaryotic polymicrobial disease.

Aplysina cauliformis, the Caribbean purple rope sponge, is commonly affected by Aplysina Red Band Syndrome (ARBS). This transmissible disease manifests as circular lesions with red margins and results in bare spongin fibers. Leptolyngbya spp. appear to be responsible for the characteristic red coloration but transmission studies with a sponge-derived isolate failed to establish disease, leaving the etiology of ARBS unknown. To investigate the cause of ARBS, contact transmission experiments were performed between healthy and diseased sponges separated by filters with varying pore sizes. Transmission occurred when sponges were separated by filters with pore sizes ≥ 2.5 µm, suggesting a prokaryotic pathogen(s) but not completely eliminating eukaryotic pathogen(s). Using 16S rRNA gene sequencing methods, 38 prokaryotic taxa were significantly enriched in diseased sponges, including Leptolyngbya, whereas seven taxa were only found in some, but not all, of the ARBS-affected sponges. These results do not implicate a single taxon, but rather a suite of taxa that changed in relative abundance with disease, suggesting a polymicrobial etiology as well as dysbiosis. As a better understanding of dysbiosis is gained, changes in the composition of associated prokaryotic communities may have increasing importance for evaluating and maintaining the health of individuals and imperiled coral reef ecosystems.

Streptomyces scopuliridis sp. nov., a bacteriocin-producing soil streptomycete.

Actinomycete strain RB72(T) was isolated from woodland bluff soil in northern Alabama, USA, and shown to produce a broad spectrum bacteriocin. Based on morphological and chemotaxonomic characteristics, the strain was determined to belong to the genus Streptomyces. Phylogenetic analysis of the near-complete 16S rRNA gene sequence indicated that it differed from those of the described streptomycetes available in public databases. The distinctive white aerial hyphae and lack of sporulation suggest a deficiency in the whi pathway of the organism. A combination of substrate utilization patterns, morphological and chemotaxonomic characteristics and DNA-DNA hybridization results supported the affiliation of strain RB72(T) to the genus Streptomyces and enabled the genotypic and phenotypic differentiation of strain RB72(T) from closely related reference strains. Strain RB72(T) therefore represents a novel species of the genus Streptomyces, for which the name Streptomyces scopuliridis sp. nov. is proposed. The type strain is RB72(T) ( = DSM 41917(T)  = NRRL B-24574(T)).

Natural History of Clinical, Laboratory, and Echocardiographic Parameters of a Primary Hyperoxaluria Cohort on Long Term Hemodialysis.

Background: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT. Methods: Patients with PH1 enrolled in the Rare Kidney Stone Consortium PH Registry who progressed to require RRT, had ≥2 plasma oxalate (pOx) measurements 3-36 months after start of RRT, and at least one pair of pOx measurements between 6 and 18 months apart were retrospectively analyzed. Clinical, echocardiographic, and laboratory results were obtained from the Registry. Results: The 17 PH1 patients in our cohort had a mean total HD hours/week of 17.4 (SD 7.9; range 7.5-36) and a range of age of RRT start of 0.2-75.9 years. The average change in plasma oxalate (pOx) over time on RRT was -0.74 [-2.9, 1.4] µmol/L/month with the mean pOx never declining below 50 µmol/L. Over time on RRT, oxalosis progressively developed in multiple organ systems. Echocardiography performed on 13 subjects showed worsening of left ventricular global longitudinal strain correlated with pOx (p < 0.05). Conclusions: Even when a cohort of PH1 patients were treated with intensified RRT, their predialysis pOx remained above target and they developed increasing evidence of oxalosis. Echocardiographic data suggest that cardiac dysfunction could be related to elevated pOx and may worsen over time.

Environmental abiotic and biotic factors affecting the distribution and abundance of Naegleria fowleri.

Naegleria fowleri is a free-living protozoan that resides in soil and freshwater. Human intranasal amoebae exposure through water or potentially dust particles can culminate in primary amoebic meningoencephalitis, which generally causes death. While many questions remain regarding pathogenesis, the microbial ecology of N. fowleri is even less understood. This review outlines current knowledge of the environmental abiotic and biotic factors that affect the distribution and abundance of N. fowleri. Although the impacts of some abiotic factors remain poorly investigated or inconclusive, N. fowleri appears to have a wide pH range, low salinity tolerance and thermophilic preference. From what is known about biotic factors, the amoebae preferentially feed upon bacteria and are preyed upon by other free-living amoebae. Additional laboratory and environmental studies are needed to fill in knowledge gaps, which are crucial for surveillance and management of N. fowleri in freshwaters. As surface water temperatures increase with climate change, it is likely that this amoeba will pose a greater threat to human health, suggesting that identifying its abiotic and biotic preferences is critical to mitigating this risk.

Molecular comparison of bacterial communities within iron-containing flocculent mats associated with submarine volcanoes along the Kermadec Arc.

Iron oxide sheaths and filaments are commonly found in hydrothermal environments and have been shown to have a biogenic origin. These structures were seen in the flocculent material associated with two submarine volcanoes along the Kermadec Arc north of New Zealand. Molecular characterization of the bacterial communities associated with the flocculent samples indicated that no known Fe-oxidizing bacteria dominated the recovered clone libraries. However, clones related to the recently described Fe-oxidizing bacterium Mariprofundus ferrooxydans were obtained from both the iron-containing flocculent (Fe-floc) and sediment samples, and peaks corresponding to Mariprofundus ferrooxydans, as well as the related clones, were observed in several of our terminal restriction fragment length polymorphism profiles. A large group of epsilonproteobacterial sequences, for which there is no cultured representative, dominated clones from the Fe-floc libraries and were less prevalent in the sediment sample. Phylogenetic analyses indicated that several operational taxonomic units appeared to be site specific, and statistical analyses of the clone libraries found that all samples were significantly different from each other. Thus, the bacterial communities in the Fe-floc samples were not more closely related to each other than to the sediment communities.

Phenotypic and functional analysis of human SLC26A6 variants in patients with familial hyperoxaluria and calcium oxalate nephrolithiasis.

BACKGROUND: Urinary oxalate is a major risk factor for calcium oxalate stones. Marked hyperoxaluria arises from mutations in 2 separate loci, AGXT and GRHPR, the causes of primary hyperoxaluria (PH) types 1 (PH1) and 2 (PH2), respectively. Studies of null Slc26a6(-/-) mice have shown a phenotype of hyperoxaluria, hyperoxalemia, and calcium oxalate urolithiasis, leading to the hypothesis that SLC26A6 mutations may cause or modify hyperoxaluria in humans. STUDY DESIGN: Cross-sectional case-control. SETTING & PARTICIPANTS: Cases were recruited from the International Primary Hyperoxaluria Registry. Control DNA samples were from a pool of adult subjects who identified themselves as being in good health. PREDICTOR: PH1, PH2, and non-PH1/PH2 genotypes in cases. OUTCOMES & MEASURES: Homozygosity or compound heterozygosity for SLC26A6 variants. Functional expression of oxalate transport in Xenopus laevis oocytes. RESULTS: 80 PH1, 6 PH2, 8 non-PH1/PH2, and 96 control samples were available for SLC26A6 screening. A rare variant, c.487C-->T (p.Pro163Ser), was detected solely in 1 non-PH1/PH2 pedigree, but this variant failed to segregate with hyperoxaluria, and functional studies of oxalate transport in Xenopus oocytes showed no transport defect. No other rare variant was identified specifically in non-PH1/PH2. Six additional missense variants were detected in controls and cases. Of these, c.616G-->A (p.Val206Met) was most common (11%) and showed a 30% reduction in oxalate transport. To test p.Val206Met as a potential modifier of hyperoxaluria, we extended screening to PH1 and PH2. Heterozygosity for this variant did not affect plasma or urine oxalate levels in this population. LIMITATIONS: We did not have a sufficient number of cases to determine whether homozygosity for p.Val206Met might significantly affect urine oxalate. CONCLUSIONS: SLC26A6 was effectively ruled out as the disease gene in this non-PH1/PH2 cohort. Taken together, our studies are the first to identify and characterize SLC26A6 variants in patients with hyperoxaluria. Phenotypic and functional analysis excluded a significant effect of identified variants on oxalate excretion.

The sponge microbiome project.

Marine sponges (phylum Porifera) are a diverse, phylogenetically deep-branching clade known for forming intimate partnerships with complex communities of microorganisms. To date, 16S rRNA gene sequencing studies have largely utilised different extraction and amplification methodologies to target the microbial communities of a limited number of sponge species, severely limiting comparative analyses of sponge microbial diversity and structure. Here, we provide an extensive and standardised dataset that will facilitate sponge microbiome comparisons across large spatial, temporal, and environmental scales. Samples from marine sponges (n = 3569 specimens), seawater (n = 370), marine sediments (n = 65) and other environments (n = 29) were collected from different locations across the globe. This dataset incorporates at least 268 different sponge species, including several yet unidentified taxa. The V4 region of the 16S rRNA gene was amplified and sequenced from extracted DNA using standardised procedures. Raw sequences (total of 1.1 billion sequences) were processed and clustered with (i) a standard protocol using QIIME closed-reference picking resulting in 39 543 operational taxonomic units (OTU) at 97% sequence identity, (ii) a de novo clustering using Mothur resulting in 518 246 OTUs, and (iii) a new high-resolution Deblur protocol resulting in 83 908 unique bacterial sequences. Abundance tables, representative sequences, taxonomic classifications, and metadata are provided. This dataset represents a comprehensive resource of sponge-associated microbial communities based on 16S rRNA gene sequences that can be used to address overarching hypotheses regarding host-associated prokaryotes, including host specificity, convergent evolution, environmental drivers of microbiome structure, and the sponge-associated rare biosphere.

Colony versus population variation in susceptibility and resistance to dark spot syndrome in the Caribbean coral Siderastrea siderea.

Scleractinian corals appear to be increasingly susceptible to pathogenic diseases, yet it is poorly understood why certain individuals, populations or species are more susceptible to diseases than others. Clearly an understanding of mechanisms of disease resistance in corals is essential to our understanding of patterns of disease incidence and virulence; this work must begin by examining the colony and population levels of organization. The Caribbean coral Siderastrea siderea exhibits variability in susceptibility to dark spot syndrome (DSS), a disease of unknown origin that can result in tissue necrosis. On the reef scale, variability in DSS prevalence in S. siderea occurred through time, but was not correlated with site, seawater temperature or depth. We monitored colonies of S. siderea affected by DSS, as well as their nearest neighbor controls, for 2 years in the Bahamas and found a marked decline in extent of DSS infection in October of both years. A preliminary survey of antimicrobial activity in S. siderea indicated selective activity against certain ecologically relevant bacteria. To assess whether changes in chemical defenses were responsible for the observed temporal variability in DSS prevalence, we sampled S. siderea for qualitative and quantitative analysis of chemical variability between resistant and susceptible colonies of S. siderea. These data suggest that phenotypic plasticity in antimicrobial activity may impact microbial settlement and/or survival.

The Prevalence and Distribution of Neurodegenerative Compound-Producing Soil Streptomyces spp.

Recent work from our labs demonstrated that a metabolite(s) from the soil bacterium Streptomyces venezuelae caused dopaminergic neurodegeneration in Caenorhabditis elegans and human neuroblastoma cells. To evaluate the capacity for metabolite production by naturally occurring streptomycetes in Alabama soils, Streptomyces were isolated from soils under different land uses (agriculture, undeveloped, and urban). More isolates were obtained from agricultural than undeveloped soils; there was no significant difference in the number of isolates from urban soils. The genomic diversity of the isolates was extremely high, with only 112 of the 1509 isolates considered clones. A subset was examined for dopaminergic neurodegeneration in the previously established C. elegans model; 28.3% of the tested Streptomyces spp. caused dopaminergic neurons to degenerate. Notably, the Streptomyces spp. isolates from agricultural soils showed more individual neuron damage than isolates from undeveloped or urban soils. These results suggest a common environmental toxicant(s) within the Streptomyces genus that causes dopaminergic neurodegeneration. It could also provide a possible explanation for diseases such as Parkinson's disease (PD), which is widely accepted to have both genetic and environmental factors.

Associations between Self-Reported Gastrointestinal Illness and Water System Characteristics in Community Water Supplies in Rural Alabama: A Cross-Sectional Study.

BACKGROUND: Community water supplies in underserved areas of the United States may be associated with increased microbiological contamination and risk of gastrointestinal disease. Microbial and health risks affecting such systems have not been systematically characterized outside outbreak investigations. The objective of the study was to evaluate associations between self-reported gastrointestinal illnesses (GII) and household-level water supply characteristics. METHODS: We conducted a cross-sectional study of water quality, water supply characteristics, and GII in 906 households served by 14 small and medium-sized community water supplies in Alabama's underserved Black Belt region. RESULTS: We identified associations between respondent-reported water supply interruption and any symptoms of GII (adjusted odds ratio (aOR): 3.01, 95% confidence interval (CI) = 1.65-5.49), as well as low water pressure and any symptoms of GII (aOR: 4.51, 95% CI = 2.55-7.97). We also identified associations between measured water quality such as lack of total chlorine and any symptoms of GII (aOR: 5.73, 95% CI = 1.09-30.1), and detection of E. coli in water samples and increased reports of vomiting (aOR: 5.01, 95% CI = 1.62-15.52) or diarrhea (aOR: 7.75, 95% CI = 2.06-29.15). CONCLUSIONS: Increased self-reported GII was associated with key water system characteristics as measured at the point of sampling in a cross-sectional study of small and medium water systems in rural Alabama in 2012 suggesting that these water supplies can contribute to endemic gastro-intestinal disease risks. Future studies should focus on further characterizing and managing microbial risks in systems facing similar challenges.

Predictors of Incident ESRD among Patients with Primary Hyperoxaluria Presenting Prior to Kidney Failure.

BACKGROUND AND OBJECTIVES: Overproduction of oxalate in patients with primary hyperoxaluria (PH) leads to calcium oxalate deposition in the kidney and ESRD in a substantial number of cases. However, the key determinants for renal outcome remain unclear. Thus, we performed a retrospective analysis to identify predictors for renal outcome among patients with PH participating in the Rare Kidney Stone Consortium (RKSC) PH Registry. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We characterized clinical and laboratory features of patients enrolled in the RKSC PH Registry. We assessed correlation between urinary measures and eGFR at diagnosis by Spearman rank correlation and estimated renal survival using the Kaplan-Meier method. We determined factors associated with renal survival by Cox proportional hazard models. RESULTS: Of 409 patients enrolled in the RKSC Registry as of March 2014, we excluded 112 patients who had ESRD at PH diagnosis from analysis. Among the remaining 297 patients, 65% had PH type 1, 12% had type 2, 13% had type 3, and 11% had unclassified PH. Median (25th, 75th percentile) age at PH diagnosis was 8.1 (4.0, 18.2) years with an eGFR of 73.0 (56.4, 97.5) ml/min per 1.73 m(2) and urinary oxalate excretion rate of 1.64 (1.11, 2.44) mmol/1.73 m(2) per 24 hours. During a median follow-up of 3.9 (1.0, 12.8) years, 59 (20%) patients developed ESRD. Urinary oxalate excretion at diagnosis stratified by quartile was strongly associated with incident ESRD (hazard ratio [HR], 3.4; 95% confidence interval [95% CI], 1.4 to 7.9). During follow-up there was a significant association between urinary oxalate quartile (Q) and incident ESRD (Q4 versus Q1: HR, 3.3; 95% CI, 1.2 to 9.3). This association remained even when adjusted for sex, age, and baseline eGFR (HR, 4.2; 95% CI, 1.6 to 10.8). CONCLUSIONS: Among patients with PH, higher urinary oxalate excretion is predictive of poor renal outcome.