Transitions in microbial communities along a 1600 km freshwater trophic gradient

This study examined vertically-resolved patterns in microbial community structure across a freshwater trophic gradient extending 1600 km from the oligotrophic waters of Lake Superior to the eutrophic waters of Lake Erie, the most anthropogenically influenced of the Laurentian Great Lakes system. Planktonic bacterial communities clustered by Principal Coordinates Analysis (PCoA) on UniFrac distance matrices into four groups representing the epilimnion and hypolimnion of the upper Great Lakes (Lakes Superior and Huron), Lake Superior\u27s northern bays (Nipigon and Black bays), and Lake Erie. The microbes within the upper Great Lakes hypolimnion were the most divergent of these groups with elevated abundance of Planctomycetes and Chloroflexi compared to the surface mixed layer. Statistical tests of the correlation between distance matrices identified temperature and sample depth as the most influential community structuring parameters, reflecting the strong UniFrac clustering separating mixed-layer and hypolimnetic samples. Analyzing mixed-layer samples alone showed clustering patterns were correlated with nutrient concentrations. Operational taxonomic units (OTU) which were differentially distributed among these conditions often accounted for a large portion of the reads returned. While limited in coverage of temporal variability, this study contributes a detailed description of community variability that can be related to other large freshwater systems characterized by changing trophic state

An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism

Acute myeloid leukemia (AML) is an aggressive blood cancer with an overall survival of 30%. One form of AML, acute promyelocytic leukemia (APL) has become more than 90% curable with differentiation therapy, consisting of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Application of differentiation therapy to other AML subtypes would be a major treatment advance. Recent studies have indicated that autophagy plays a key role in the differentiation of ATRA-responsive APL cells. In this study, we have investigated whether differentiation could be enhanced in ATRA resistant cells by promoting autophagy induction with valproic acid (VPA). ATRA sensitive (NB4) and resistant leukemia cells (NB4R and THP-1) were co-treated with ATRA and valproic acid, followed by assessment of autophagy and differentiation. The combination of VPA and ATRA induced autophagic flux and promoted differentiation in ATRA-sensitive and -resistant cell lines. shRNA knockdown of ATG7 and TFEB autophagy regulators impaired both autophagy and differentiation, demonstrating the importance of autophagy in the combination treatment. These data suggest that ATRA combined with valproic acid can promote differentiation in myeloid leukemia cells by mechanism involving autophagy

Connections of climate change and variability to large and extreme forest fires in southeast Australia

The 2019/20 Black Summer bushfire disaster in southeast Australia was unprecedented: the extensive area of forest burnt, the radiative power of the fires, and the extraordinary number of fires that developed into extreme pyroconvective events were all unmatched in the historical record. Australia’s hottest and driest year on record, 2019, was characterised by exceptionally dry fuel loads that primed the landscape to burn when exposed to dangerous fire weather and ignition. The combination of climate variability and long-term climate trends generated the climate extremes experienced in 2019, and the compounding effects of two or more modes of climate variability in their fire-promoting phases (as occurred in 2019) has historically increased the chances of large forest fires occurring in southeast Australia. Palaeoclimate evidence also demonstrates that fire-promoting phases of tropical Pacific and Indian ocean variability are now unusually frequent compared with natural variability in preindustrial times. Indicators of forest fire danger in southeast Australia have already emerged outside of the range of historical experience, suggesting that projections made more than a decade ago that increases in climate-driven fire risk would be detectable by 2020, have indeed eventuated. The multiple climate change contributors to fire risk in southeast Australia, as well as the observed non-linear escalation of fire extent and intensity, raise the likelihood that fire events may continue to rapidly intensify in the future. Improving local and national adaptation measures while also pursuing ambitious global climate change mitigation efforts would provide the best strategy for limiting further increases in fire risk in southeast Australia

Children’s imaginaries in the city: on things and materials

The article is an exploration of urban imaginaries emerging through a play with materials. Starting from a complex activist exercise for reimagining the space of a park in decay, whose protagonists are children, we propose a reflection on the productivity and resilience of matter. We argue that a new materialist sociology is one that takes disappearances seriously. Capitalism renders space abstract not only through flow and circulation, but also through stillness. We follow the curious disappearances and reappearances of the park in question, tracing the mutations of urban planning, of the juridical domain, and of the everyday use of space. Finally, we analyse the making of a maquette of the park by a group of children and their alliances with activists. The maquette is a political “thing”: it leads us away from an urban imaginary populated by discrete objects to an urban imaginary of depth and it reconcretises space

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Beyond Environmental Regulatory Fragmentation: Signs of Integration in the Case of the Great Lakes Basin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72007/1/j.1468-0491.1995.tb00197.x.pd

Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that <it>NAT1 </it>and/or <it>NAT2 </it>polymorphisms contribute to the increased cancer evident in IBD.</p> <p>Methods</p> <p>A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. <it>NAT1 </it>and <it>NAT2 </it>genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs) were characterized for <it>NAT1 </it>and 7 SNPs for <it>NAT2</it>. Haplotype frequencies were estimated using an Expectation-Maximization (EM) method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of <it>NAT1 </it>and <it>NAT2 </it>haplotypes and deduced NAT2 phenotypes.</p> <p>Results</p> <p>No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the <it>NAT1 </it>SNPs and the <it>NAT2 </it>SNPs.</p> <p>Conclusion</p> <p>This study did not demonstrate an association between <it>NAT1 </it>and <it>NAT2 </it>polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.</p

Nutritional Asymmetries Are Related to Division of Labor in a Queenless Ant

Eusocial species exhibit pronounced division of labor, most notably between reproductive and non-reproductive castes, but also within non-reproductive castes via morphological specialization and temporal polyethism. For species with distinct worker and queen castes, age-related differences in behavior among workers (e.g. within-nest tasks versus foraging) appear to result from physiological changes such as decreased lipid content. However, we know little about how labor is divided among individuals in species that lack a distinct queen caste. In this study, we investigated how fat storage varied among individuals in a species of ant (Dinoponera australis) that lacks a distinct queen caste and in which all individuals are morphologically similar and capable of reproduction (totipotent at birth). We distinguish between two hypotheses, 1) all individuals are physiologically similar, consistent with the possibility that any non-reproductive may eventually become reproductive, and 2) non-reproductive individuals vary in stored fat, similar to highly eusocial species, where depletion is associated with foraging and non-reproductives have lower lipid stores than reproducing individuals. Our data support the latter hypothesis. Location in the nest, the probability of foraging, and foraging effort, were all associated with decreased fat storage