Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones

Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing and fork directionality profiles obtained by RNA-seq, Repli-seq and OK-seq. ORC and MCM are significantly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early- than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms specifying when and where replication initiates in human cells.

Human ORC/MCM density is low in active genes and correlates with replication time but does not solely define replication initiation zones

Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing and fork directionality profiles obtained by RNA-seq, Repli-seq and OK-seq. ORC and MCM are strongly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early-than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms that specify when and where replication initiates in human cells.

Lsr2 is a nucleoid-associated protein that exerts pleiotropic effects on mycobacterial cellular processes

Lsr2 is involved in maintaining chromosome structure in asymmetrically dividing mycobacteria and is essential in the tubercle bacillus (M. tuberculosis) during infection. Here, we report that a lack of Lsr2 profoundly impacts the mycobacterial cell morphology and the properties of the cell envelope resulting in the formation of smooth, short and antibiotics sensitive cells. Lsr2 forms large and dynamic nucleoprotein complexes in vivo and deletion of lsr2 gene exerts a profound effect on the replication time and replisome dynamics. We suggest that the Lsr2 nucleoprotein complexes may contribute to maintaining the proper organization of the newly synthesized DNA. Moreover, we demonstrate that the N-terminal oligomerization domain of Lsr2 is indispensable for the formation of nucleoprotein complexes in vivo. Collectively, our results indicate that Lsr2 exerts a pleiotropic effect on cellular processes and appears to be an attractive target for the development of a novel antitubercular drugs.

A Distributed File-Based Storage System for Improving High Availability of Space Weather Data

In space science research, the Indonesia National Institute of Aeronautics and Space (LAPAN) is concerned with the development of a system that provides actual information and predictions called the Space Weather Information and Forecast Services (SWIFtS). SWIFtS is supported by a data storage system that serves data, implementing a centralized storage model. This has some problems that impact to researchers as the primary users. The single point of failure and also the delay in data updating on the server is a significant issue when researchers need the latest data, but the server is unable to provide it. To overcome these problems, we proposed a new system that utilized a decentralized model for storing data, leveraging the InterPlanetary File System (IPFS) file system. Our proposed method focused on the automated background process, and its scheme would increase the data availability and throughput by spreading it into nodes through a peer-to-peer connection. Moreover, we also included system monitoring for real-time data flow from each node and information of node status that combines active and passive approaches. For system evaluation, the experiment was performed to determine the performance of the proposed system compared to the existing system by calculating mean replication time and the mean throughput of a node. As expected, performance evaluations showed that our proposed scheme had faster file replication time and supported high throughput.

Implementasi Sistem Database Terdistribusi Dengan Metode Multi-Master Database Replication

Databases are the main need for every computer application to store, process and modify data. One important problem faced in databases is the availability of adequate information technology infrastructure in managing and securing data contained in the database. Data stored on the database must have protection against threats and disturbances. Threats and disruptions can result from a variety of things, such as maintenance, data damage, and natural disasters. To anticipate data loss and damage, replication of the database system needs to be done. The replication mechanism used by researchers is multi-master replication. The replication technique is able to form a database cluster with replication time of fewer than 0.2 seconds.

Hidden Markov Models Lead to Higher Resolution Maps of Mutation Signature Activity in Cancer

Knowing the activity of the mutational processes shaping a cancer genome may provide insight into tumorigenesis and personalized therapy. It is thus important to uncover the characteristic signatures of active mutational processes in patients from their patterns of single base substitutions. However, mutational processes do not act uniformly on the genome and are biased by factors such as the genome’s chromatin structure or replication origins. These factors may lead to statistical dependencies among neighboring mutations, calling for modeling approaches that can account for such dependencies to better estimate mutational process activities.Here we develop the first sequence-dependent models for mutation signatures. We apply these models to characterize genomic and other factors that influence the activity of previously validated mutation signatures in breast cancer. We find that our tool, SigMa, can accurately assign genomic mutations to mutation signatures, yielding assignments that are of higher likelihood than those obtained with models that assume independence between signatures and align better with current biological knowledge. Our analysis resolves a controversy related to the dependency of APOBEC signatures on replication time and links Signatures 18 and 30 to oxidative damage.Modeling the sequential dependencies of mutation signatures leads to improved estimates of mutation signature activity both at the tumor-level and within specific genomic regions, yielding higher resolution maps of mutation signature activity in cancer.

The effect of nitrogen and sodium chloride stress in the productivity of some fatty acids in Chlorococcum humicola green alga

Algae have been considered a sources task of biofuels, which is a future alternative to fossil fuels, and this lead the environmental studies concerned with the lifting of curves or growth rates and time of replication of different kinds of algae, as well as algae cells in response to different environmental conditions, whether chemical or physical, to assess their impact on the composition of these cells and the extent of affected components that make up the living, especially fatty acid ,total fats, proteins and carbohydrates, Gbrha. Green Chlorococcum humicola showed a different response when treated with an average of agriculture Chu-10 and Chu-13 which used as control media,Compared with the degree of its response when exposed to environmental stress when remove of N or adding different concentrations of NaCl for both mentioned media, That represents a different quality and quantity of fatty acids produced inside. When Ch-10 treatment with NaCl fatty acids Palmetic, ?-liolenic and Oleic recorded marking increase as for Stearic, Linoleic and Arachidic recorded a decrease in there rates, there for In Ch-13 the acids Palmetic, Linoleic and ?-liolenic recorded significantly increase while, decreased value of Stearic acid only. When N remove from the two media, Ch-10 scored a remarkable increase in the rates of all acids except stearic acid which recorded larger decrease. Ch-13 has recorded an increase in acid values Palmetic, Linoleic and, ?-liolenic, there for stearic, oleic and Arachidic recorded less than all values in (control.) The results also showed a presence difference in curves, growth rates and replication time when the transactions mentioned