Traffic Congestion and Efficient Ways to Deal with It in Tbilisi, Georgia

Traffic Congestion has become a new version of plague for urbanized areas. Massive breakthroughs in technology, increasing in production of motorized cars, global reduction in prices for automobiles and the rapid population growth in Tbilisi, Georgia has led to the urgence of complete rearrangement of transportation system in the city. As a post-Soviet Union country, Georgia has had rudiments like “Marshrutkas” (privately owned minibuses) as a primary mode of transportation. Serious research and actions started in 2019 when sustainable urban mobility plan was introduced in Tbilisi; which favors public transport and pedestrians. In the course of this project one of the main avenues was converted into complete street model and hourly parking was introduced in the city centers. However, the problem regarding traffic jams still stands. This paper contributes to analyzing current situation in Tbilisi and suggesting suitable solutions. It will cover how reversible lanes, road pricing, signalized Intersections, reserved bus lanes and parking can be adapted to Tbilisi in order to reduce traffic jams.

Functional interaction between the RNA exosome and the sirtuin deacetylase Hst3 maintains transcriptional homeostasis

Eukaryotic cells maintain an optimal level of mRNAs through unknown mechanisms that balance RNA synthesis and degradation. We found that inactivation of the RNA exosome leads to global reduction of nascent mRNA transcripts, and that this defect is accentuated by loss of deposition of histone variant H2A.Z. We identify the mRNA for the sirtuin deacetylase Hst3 as a key target for the RNA exosome that mediates communication between RNA degradation and transcription machineries. These findings reveal how the RNA exosome and H2A.Z function together to control a deacetylase, ensuring proper levels of transcription in response to changes in RNA degradation.

Transcription feedback dynamics in the wake of cytoplasmic degradation shutdown

In the last decade, multiple studies have shown that cells maintain a balance of mRNA production and degradation in different settings, but the mechanisms by which cells implement this balance remain poorly understood. Here, we monitored cells’ mRNA and nascent mRNA profiles immediately following an acute depletion of Xrn1 - the main 5’-3’ mRNA exonuclease - that was previously implicated in balancing mRNA levels. We captured the detailed dynamics of the cells’ adaptation to rapid degradation of Xrn1 and observed a significant accumulation of mRNA, followed by global reduction in nascent transcription and a return to baseline mRNA levels. We present evidence that this transcriptional response is linked to cell cycle progression, and that it is not unique to Xrn1 depletion; rather, it is induced earlier when upstream factors in the 5’-3’ degradation pathway are perturbed. Using the detailed dynamic measurements we hypothesize a cell-cycle-linked feedback mechanism that monitors the accumulation of inputs to the 5’-3’ exonucleolytic pathway rather than its outputs.

G6b-B regulates an essential step in megakaryocyte maturation

G6b-B is a megakaryocyte lineage-specific immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor, essential for platelet homeostasis. Mice with a genomic deletion of the entire Mpig6b locus develop severe macrothrombocytopenia and myelofibrosis, which is reflected in humans with null-mutations in MPIG6B. The current model proposes that megakaryocytes lacking G6b-B develop normally, while proplatelet release is hampered, but the underlying molecular mechanism remains unclear. Here, we report on a spontaneous recessive single nucleotide mutation in C57BL/6 mice, localized within the intronic region of the Mpig6b locus that abolishes G6b-B expression and reproduces macrothrombocytopenia, myelofibrosis and osteosclerosis. As the mutation is based on a single nucleotide exchange, Mpig6bmut mice represent an ideal model to study the role of G6b-B. Megakaryocytes from these mice were smaller in size, displayed a less developed demarcation membrane system and reduced expression of receptors. RNA sequencing revealed a striking global reduction in the level of megakaryocyte specific transcripts, in conjunction with decreased protein levels of the transcription factor GATA-1, and impaired thrombopoietin signaling. The reduced number of mature MKs in the bone marrow was corroborated on a newly developed Mpig6b null mouse strain. Our findings highlight an unexpected essential role of G6b-B in the early differentiation within the megakaryocytic lineage.

Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk.Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings.Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD + ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons.Conclusion: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD + ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.

What sub-Saharan African countries can learn from malaria elimination in China

Malaria is one of the most devastating diseases plaguing the sub-Saharan African region since time immemorial. In spite of a global reduction in mortality rates, a significant proportion of deaths due to malaria is still accounted for in the region. China recently joined the 40 countries declared malaria free by the World Health Organization and became the first country in the WHO Western Pacific Region to be awarded the certification. We commented on the strategies employed by China to eliminate malaria, address challenges facing malaria control in sub-Saharan Africa, and derive lessons that could be learned in the sub-Saharan African context.

Stent-Save a Life international survey on the practice of primary coronary angioplasty during the COVID-19 pandemic

Aims To evaluate the impact of the COVID-19 pandemic on patient admissions with acute coronary syndromes (ACS) and primary coronary angioplasty (PPCI) in countries participating in the Stent-Save a Life (SSL) global initiative. Methods and results We conducted a multicenter, observational survey to collect data on patient admissions for ACS, STEMI and PPCI in the SSL participating countries throughout a period during the COVID-19 outbreak (March and April 2020) compared with the equivalent period in 2019. From the 32 member countries of the SSL global initiative, 17 accepted to participate in the survey (3 from Africa, 5 from Asia, 6 from Europe and 3 from Latin America (LATAM)). We observed a global reduction of 27,5% and 20,0% in admissions with ACS and STEMI respectively. The decrease in PPCI was 26,7% (Figure 1). This trend was observed in all countries except two. In these two countries, the pandemic peaked later than in the other countries. Conclusions This survey shows that the COVID-19 outbreak was associated with a significant reduction of hospital admissions for ACS and STEMI as well as a reduction of PPCI, which can be explained by both patient and system related factors. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility.

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk. Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings. Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD +ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons. Conclusions: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD +ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.

A STUDY ON ACTIVATION OF THE CARBON CONCENTRATING MECHANISM BY CARBON DI-OXIDE DEPRIVATION OVERLAPS WITH MASSIVE TRANSCRIPTIONAL REARRANGEMENT IN CHLAMYDOMONAS REINHARDTII

A CO2-concentrating mechanism (CCM) is essential for the growth of most eukaryotic algae under ambient (392 ppm) and very low (<100 ppm) CO2 concentrations. In this study, we used replicated deep mRNAsequencing and regulatory network reconstruction to capture a remarkable scope of changes in gene expression that occurs when Chlamydomonas reinhardtii cells are shifted from high to very low levels of CO2 (≤100 ppm). CCM induction 30 to 180 min post-CO2 deprivation coincides with statistically signicant changes in the expression of an astonishing 38% (5884) of the 15,501 nonoverlapping C. reinhardtii genes. Of these genes, 1088 genes were induced and 3828 genes were downregulated by a log2 factor of 2. The latter indicate a global reduction in photosynthesis, protein synthesis, and energy-related biochemical pathways. The magnitude of transcriptional rearrangement and its major patterns are robust as analyzed by three different statistical methods. De novo DNA motif discovery revealed new putative binding sites for Myeloid oncogene family transcription factors potentially involved in activating low CO2–induced genes. The (CA)n repeat (9 ≤ n ≤ 25) is present in 29% of upregulated genes but almost absent from promoters of downregulated genes. These discoveries open many avenues for new research.

SARS-CoV-2 Restructures the Host Chromatin Architecture

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.