Predicting Seasonal and Spatial Onset of cHABs in Polymictic Reservoirs

Cyanobacterial Harmful Algal Blooms (cHABS) are a naturally occurring but increasingly common phenomenon due to anthropogenic activities and climate change. cHABs reduce water quality by forming unsightly surface scums and sometimes producing algal matts on the surface of water bodies, reduce water quality, and in high densities can produce cyanotoxins that can harm humans, pets, and wildlife. Ecological forecasting of cHABs has proved elusive in part because the in-situ fluorometric methods currently employed for detecting cyanobacteria cells are subject to varied interference as water quality and the biotic community changes. In this study we seek to develop an ecological forecasting capability that overcomes both temporally and spatially derived in-situ fluorometric interferences. We obtained water samples at 26 polymictic reservoirs over a two-day period and at five polymictic reservoirs weekly during the summer of 2019. Collected water samples are being used for quantitative analysis of cyanobacterial cell densities by means of qPCR. We plan a data reduction technique (e.g. PCA, VIF screening, elastic-net regression as appropriate) followed by multivariate predictive model (e.g. multiple regression, ordination, discriminant analysis as appropriate)

Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF

Approximately 75% of the human genome is transcribed, the majority of which does not encode protein. However, many noncoding RNAs (ncRNAs) are rapidly degraded after transcription, and relatively few have established functions, questioning the significance of this observation. Here we show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of ncRNAs from approximately 57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells (ESCs). We show that esBAF functions to both keep NDRs nucleosome-free and promote elevated nucleosome occupancy adjacent to NDRs. Reduction of adjacent nucleosome occupancy upon esBAF depletion is strongly correlated with ncRNA expression, suggesting that flanking nucleosomes form a barrier to pervasive transcription. Upon forcing nucleosome occupancy near two NDRs using a nucleosome-positioning sequence, we found that esBAF is no longer required to silence transcription. Therefore, esBAF\u27s function to enforce nucleosome occupancy adjacent to NDRs, and not its function to maintain NDRs in a nucleosome-free state, is necessary for silencing transcription over ncDNA. Finally, we show that the ability of a strongly positioned nucleosome to repress ncRNA depends on its translational positioning. These data reveal a novel role for esBAF in suppressing pervasive transcription from open chromatin regions in ESCs

NPC1 deficiency impairs cerebellar postnatal development of microglia and climbing fiber refinement in a mouse model of Niemann-Pick disease type C.

Little is known about the effects of NPC1 deficiency in brain development and whether these effects contribute to neurodegeneration in Niemann-Pick disease type C (NPC). Degeneration of cerebellar Purkinje cells occurs at an earlier stage and to a greater extent in NPC; therefore, we analyzed the effect of NPC1 deficiency on microglia and on climbing fiber synaptic refinement during cerebellar postnatal development using th

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model

Translating dosage compensation to trisomy 21

Down syndrome is the leading genetic cause of intellectual disabilities, occurring in 1 out of 700 live births. Given that Down syndrome is caused by an extra copy of chromosome 21 that involves over-expression of 400 genes across a whole chromosome, it precludes any possibility of a genetic therapy. Our lab has long studied the natural dosage compensation mechanism for X chromosome inactivation. To “dosage compensate” X-linked genes between females and males, the X-linked XIST gene produces a large non-coding RNA that silences one of the two X chromosomes in female cells. The initial motivation of this study was to translate the natural mechanisms of X chromosome inactivation into chromosome therapy for Down syndrome. Using genome editing with zinc finger nucleases, we have successfully inserted a large XIST transgene into Chromosome 21 in Down syndrome iPS cells, which results in chromosome-wide transcriptional silencing of the extra Chromosome 21. Remarkably, deficits in proliferation and neural growth are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro surmounts the major first step towards potential development of “chromosome therapy” for Down syndrome. The human iPSC-based trisomy correction system we established opens a unique opportunity to identify therapeutic targets and study transplantation therapies for Down syndrome

Light dark matter versus astrophysical constraints

Hints of direct dark matter detection coming from the DAMA, CoGeNT experiments point toward light dark matter with isospin-violating and possibly inelastic couplings. However an array of astrophysical constraints are rapidly closing the window on light dark matter. We point out that if the relic density is determined by annihilation into invisible states, these constraints can be evaded. As an example we present a model of quasi-Dirac dark matter, interacting via two U(1) gauge bosons, one of which couples to baryon number and the other which kinetically mixes with the photon. Annihilation is primarily into "dark neutrinos" that do not mix with the SM, but which could provide a small component of dark radiation. The model could soon be tested by several experiments searching for such light gauge bosons, and we predict that both could be detected. The model also requires a fourth generation of quarks, whose existence might increase the production cross section of Higgs bosons at the Tevatron and LHC.Comment: 11 pages, two figures; references added, published versio

Genomic imprinting of IGF2 in marsupials is methylation dependent

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