Biology subjects

Rosenthal, A.

Publications and source records attributed to Rosenthal, A..

3 recordsLinked to original sources

bioRxiv2019

Microhomology-mediated end joining drives complex rearrangements and over expression of MYC and PVT1 in multiple myeloma

MYC is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. MYC is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that MYC rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1267). Rearrangements were complex and associated with increased expression of MYC and PVT1, but not other genes at 8q24. The highest effect on gene expression was detected in cases where the MYC locus is juxtaposed next to super-enhancers associated with genes such as IGH, IGK, IGL, TXNDC5/BMP6, FAM46C and FOXO3. We identified three hotspots of recombination at 8q24, one of which is enriched for IGH-MYC translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the IGH locus occur through non-homologous end joining, whereas secondary MYC rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates MYC rearrangements. Rearrangements resulted in over-expression of key genes and ChIP-seq identified that HK2, a member of the glucose metabolism pathway, is directly over-expressed through binding of MYC at its promoter.

cancer biology↗

bioRxiv2018

Comammox Nitrospira are the dominant ammonia oxidizers in a mainstream low dissolved oxygen nitrification reactor

Recent findings show that a subset of bacteria affiliated with Nitrospira, a genus known for its importance in nitrite oxidation for biological nutrient removal applications, are capable of complete ammonia oxidation (comammox) to nitrate. Early reports suggested that they were absent or present in low abundance in most activated sludge processes, and thus likely functionally irrelevant. Here we show the accumulation of comammox Nitrospira in a nitrifying sequencing batch reactor operated at low dissolved oxygen (DO) concentrations. Actual mainstream wastewater was used as influent after primary settling and an upstream pre-treatment process for carbon and phosphorus removal. The ammonia removal rate was stable and exceeded that of the treatment plants parallel full-scale high DO nitrifying activated sludge reactor. 16S rRNA sequencing showed a steady accumulation of Nitrospira to 53% total abundance and a decline in conventional ammonia oxidizing bacteria to <1% total abundance over 400+ days of operation. After ruling out other known ammonia oxidizers, qPCR confirmed the accumulation of comammox Nitrospira beginning around day 200, to eventually comprise 94% of all detected amoA and 4% of total bacteria by day 407. Quantitative fluorescence in-situ hybridization confirmed the increasing trend and high relative abundance of Nitrospira. These results demonstrate that comammox can be metabolically relevant to nitrogen transformation in wastewater treatment, and can even dominate the ammonia oxidizing community. Our results suggest that comammox may be an important functional group in energy efficient nitrification systems designed to operate at low DO levels.

bioengineering↗

bioRxiv2018

Biomass segregation between biofilm and flocs improves the control of nitrite-oxidizing bacteria in mainstream partial nitritation and anammox processes

The control of nitrite-oxidizing bacteria (NOB) challenges the implementation of partial nitritation and anammox (PN/A) processes under mainstream conditions. The aim of the present study was to understand how operating conditions impact microbial competition and the control of NOB in hybrid PN/A systems, where biofilm and flocs coexist. A hybrid PN/A moving-bed biofilm reactor (MBBR; also referred to as integrated fixed film activated sludge or IFAS) was operated at 15 {degrees}C on aerobically pre-treated municipal wastewater (23 mgNH4-N{middle dot}L-1). Ammonium-oxidizing bacteria (AOB) and NOB were enriched primarily in the flocs, and anammox bacteria (AMX) in the biofilm. After decreasing the dissolved oxygen concentration (DO) from 1.2 to 0.17 mgO2{middle dot}L-1 - with all other operating conditions unchanged - washout of NOB from the flocs was observed. The activity of the minor NOB fraction remaining in the biofilm was suppressed at low DO. As a result, low effluent NO3- concentrations (0.5 mgN{middle dot}L-1) were consistently achieved at aerobic nitrogen removal rates (80 mgN{middle dot}L-1{middle dot}d-1) comparable to those of conventional treatment plants. A simple dynamic mathematical model, assuming perfect biomass segregation with AOB and NOB in the flocs and AMX in the biofilm, was able to qualitatively reproduce the selective washout of NOB from the flocs in response to the decrease in DO-setpoint. Similarly, numerical simulations indicated that flocs removal is an effective operational strategy to achieve the selective washout of NOB. The direct competition for NO2- between NOB and AMX - the latter retained in the biofilm and acting as a \"NO2-sink\" - was identified by the model as key mechanism leading to a difference in the actual growth rates of AOB and NOB (i.e., NOB < AOB in flocs) and allowing for the selective NOB washout. Experimental results and model predictions demonstrate the increased operational flexibility, in terms of variables that can be easily controlled by operators, offered by hybrid systems as compared to solely biofilm systems for the control of NOB in mainstream PN/A applications.\n\nHighlightsO_LIHybrid PN/A systems provide increased operational flexibility for NOB control\nC_LIO_LIAOB and NOB enrich primarily in the flocs, and AMX in the biofilm (\"NO2-sink\")\nC_LIO_LIAMX use NO2- allowing to differentiate AOB and NOB growth rates\nC_LIO_LIA decrease in DO or an increase in floc removal leads to selective NOB washout from flocs\nC_LIO_LIThe activity of the minor NOB fraction in the biofilm is suppressed at limiting DO\nC_LI\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=63 SRC=\"FIGDIR/small/480780v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (21K):\norg.highwire.dtl.DTLVardef@cad5deorg.highwire.dtl.DTLVardef@9efef3org.highwire.dtl.DTLVardef@7409feorg.highwire.dtl.DTLVardef@3c1043_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗