Neuron Navigator 1 (Nav1) regulates the response to cocaine in mice.

Genetic variation accounts for much of the risk for developing a substance use disorder, but the underlying genetic factors and their genetic effector mechanisms are mostly unknown. Inbred mouse strains exhibit substantial and heritable differences in the extent of voluntary cocaine self-administration. Computational genetic analysis of cocaine self-administration data obtained from twenty-one inbred strains identified Nav1, a member of the neuron navigator family that regulates dendrite formation and axonal guidance, as a candidate gene. To test this genetic hypothesis, we generated and characterized Nav1 knockout mice. Consistent with the genetic prediction, Nav1 knockout mice exhibited increased voluntary cocaine intake and had increased motivation for cocaine consumption. Immunohistochemistry, electrophysiology, and transcriptomic studies were performed as a starting point for investigating the mechanism for the Nav1 knockout effect. Nav1 knockout mice had a reduced inhibitory synapse density in their cortex, increased excitatory synaptic transmission in their cortex and hippocampus, and increased excitatory neurons in a deep cortical layer. Collectively, our results indicate that Nav1 regulates the response to cocaine, and we identified Nav1 knockout induced changes in the excitatory and inhibitory synaptic balance in the cortex and hippocampus that could contribute to this effect.

A review of anti-surge control systems of compressors and advanced fault-tolerant control techniques for integration perspective.

In this review paper, the anti-surge control (ASC) of the compressors and fault-tolerant control (FTC) systems are described from the perspective of integration for reliability enhancement against faults in the system components. It explains the phenomenon of a surge in the compressors, surge precursors, and the potential damage caused by this surge. The explanation of surge avoidance methods in compressors incorporated with modern surge control systems is described along with their applications. The sizing of the system components and valves, particularly methodologies for appropriately estimating acceptable upstream pipe sizes, are elaborated. The existing surge protection techniques for compressors are analyzed to highlight the advantages and disadvantages and from a future perspective, new approaches for detecting system changes and surges, are included. In the end, the concept of fault tolerance and its advanced applications concerning the anti-surge control for compressors are explained. This study contributes to the young researchers in the field of anti-surge control systems for compressors with the integration of fault tolerance to increase the reliability of the system.

Analysis of structural variation among inbred mouse strains.

BACKGROUND: 'Long read' sequencing methods have been used to identify previously uncharacterized structural variants that cause human genetic diseases. Therefore, we investigated whether long read sequencing could facilitate genetic analysis of murine models for human diseases. RESULTS: The genomes of six inbred strains (BTBR T + Itpr3tf/J, 129Sv1/J, C57BL/6/J, Balb/c/J, A/J, SJL/J) were analyzed using long read sequencing. Our results revealed that (i) Structural variants are very abundant within the genome of inbred strains (4.8 per gene) and (ii) that we cannot accurately infer whether structural variants are present using conventional short read genomic sequence data, even when nearby SNP alleles are known. The advantage of having a more complete map was demonstrated by analyzing the genomic sequence of BTBR mice. Based upon this analysis, knockin mice were generated and used to characterize a BTBR-unique 8-bp deletion within Draxin that contributes to the BTBR neuroanatomic abnormalities, which resemble human autism spectrum disorder. CONCLUSION: A more complete map of the pattern of genetic variation among inbred strains, which is produced by long read genomic sequencing of the genomes of additional inbred strains, could facilitate genetic discovery when murine models of human diseases are analyzed.

Clinical studies investigating the role of mesenchymal stem cells in healing of fracture non-unions: a systematic review.

Objectives: To identify and evaluate the effectiveness of mesenchymal stem cells (MSCs) in augmenting healing in fracture non-unions. METHODS: A focused literature search was performed on the PubMed/MEDLINE index using the keywords: "non-union", "mesenchymal stem cells", "bone healing", "MSC", "stem cells", and their MeSH terms. The search was reiterated until the 10th of August 2022. Clinical studies were included that assessed the effect of MSCs on fracture non-unions. RESULTS: Thirteen human clinical trials, studying a total of 318 participants were identified and studied. MSCs with and without biological or synthetic scaffolds were found to be effective in healing of non-unions. CONCLUSIONS: MSCs has been demonstrated to have promising outcomes in the treatment of bone non-union and tissue engineering methods utilizing MSCs may well prove to be valuable in accelerating the process of bone union. However, clinical application of MSCs as a standard method in achieving union in fracture non-unions requires larger clinical trials with a standardised approach to analyzing outcomes.

Role of stem cells in the treatment of osteoarthritis- a review of literature.

The purpose of this review was to identify and assess the effectiveness of stem cells in the form of injectables in the treatment of joint osteoarthritis as published in the literature. Studies were searched from multiple databases like Pubmed, Embase and Cochrane Library until June 2022 using multiple keywords. Randomized controlled trials of patients with osteoarthritis (OA) were included which compared the pain and functional outcomes for those getting Mesenchymal Stem Cells (MSCs) injectables as compared to those who received no MSCs injection. Twelve randomized controlled trials, assessing a total of 486 participants were identified and studied. Overall, stem cells injection has no significant effect on pain along with physical function. Stem cells injection could be effective in reducing pain and might also help in improving functional outcome in patients with OA. However, the findings are not yet significant and further clinical trials with larger samples are needed to come to a positive conclusion.

A case-control study to assess the association of Alopecia areata with thyroid dysfunction and thyroid Autoimmunity.

BACKGROUND: Several previous studies have suggested a positive association between Alopecia Areata and thyroid disorders. However, there is a paucity of such studies in our country. Our study aimed to know the frequency of thyroid dysfunction and thyroid autoimmunity in patients reporting to Dermatology Outdoors with Alopecia Areata (AA) and to compare it with normal controls. METHODS: This was a Case-Control study conducted at the Dermatology outpatient of a tertiary care hospital in Pakistan. 102 patients with AA and 102 age and sex-matched controls were enrolled. The age of onset of the disease, the involved sites and the presence of other associated diseases were noted. Venous blood samples were taken from patients and controls for Thyroid function tests and Anti- Thyroid peroxidase antibodies (Anti-TPO Ab). The data was analyzed using Statistical Package for Social Sciences (SPSS) version 23. RESULTS: The mean age of onset of the disease was 30.37±12.53. 91.2% of patients had the classic patch type of AA. The most commonly involved site was Scalp. Associated diseases were found in eight (7.8%) patients. Thyroid dysfunction was found in two patients and none of the Controls. Both the patients had Subclinical thyroid disease. The p-value was 0.157, which was not statistically significant. Thyroid autoimmunity (raised Anti-TPO Ab titre) was detected in five (4.90%) patients and none of the Controls. The p-value was 0.024, which was statistically significant. CONCLUSIONS: AA is significantly associated with Thyroid autoimmunity but there is no significant association between AA and clinical or subclinical thyroid disease.

Design of Active Fault-Tolerant Control System for Air-Fuel Ratio control of Internal Combustion engine using nonlinear regression-based observer model.

Internal Combustion (IC) engines are prevalent in the process sector, and maintaining sufficient Air-Fuel Ratio (AFR) regulation in their fuel system is crucial for enhanced engine performance, fuel economy, and environmental safety. Faults in the AFR system's sensors cause the engine to shut down, hence, fault tolerance is essential. In order to avoid engine shutdown, this paper offers a novel Active Fault-Tolerant Control System (AFTCS) for air-fuel ratio control of an Internal Combustion (IC) engine in a process plant. In the Fault Detection and Isolation (FDI) unit, the proposed AFTCS uses a nonlinear regression-based observer model for analytical redundancy. The suggested system was simulated in the MATLAB / Simulink environment. The proposed system was tested at two different speeds (300 r/min and 600 r/min) and the results show that the system's response is within the acceptable bound without compromising the stability. The findings also demonstrate the higher fault tolerance capability for sensor defects of the AFR control system, particularly for the MAP sensor (at 300 r/min) in terms of reduced oscillatory response in comparison to the current literature. Compared to the linear regression-based and Genetic Algorithm (GA) based model, the nonlinear regression-based model results in a more accurate estimation of the faulty sensors. The proposed model is also efficient in terms of computation power and response time.

Acceptance of COVID-19 Vaccine Booster Doses Using the Health Belief Model: A Cross-Sectional Study in Low-Middle- and High-Income Countries of the East Mediterranean Region.

Coronavirus disease (COVID-19) booster doses decrease infection transmission and disease severity. This study aimed to assess the acceptance of COVID-19 vaccine booster doses in low, middle, and high-income countries of the East Mediterranean Region (EMR) and its determinants using the health belief model (HBM). In addition, we aimed to identify the causes of booster dose rejection and the main source of information about vaccination. Using the snowball and convince sampling technique, a bilingual, self-administered, anonymous questionnaire was used to collect the data from 14 EMR countries through different social media platforms. Logistic regression analysis was used to estimate the key determinants that predict vaccination acceptance among respondents. Overall, 2327 participants responded to the questionnaire. In total, 1468 received compulsory doses of vaccination. Of them, 739 (50.3%) received booster doses and 387 (26.4%) were willing to get the COVID-19 vaccine booster doses. Vaccine booster dose acceptance rates in low, middle, and high-income countries were 73.4%, 67.9%, and 83.0%, respectively (p < 0.001). Participants who reported reliance on information about the COVID-19 vaccination from the Ministry of Health websites were more willing to accept booster doses (79.3% vs. 66.6%, p < 0.001). The leading causes behind booster dose rejection were the beliefs that booster doses have no benefit (48.35%) and have severe side effects (25.6%). Determinants of booster dose acceptance were age (odds ratio (OR) = 1.02, 95% confidence interval (CI): 1.01-1.03, p = 0.002), information provided by the Ministry of Health (OR = 3.40, 95% CI: 1.79-6.49, p = 0.015), perceived susceptibility to COVID-19 infection (OR = 1.88, 95% CI: 1.21-2.93, p = 0.005), perceived severity of COVID-19 (OR = 2.08, 95% CI: 137-3.16, p = 0.001), and perceived risk of side effects (OR = 0.25, 95% CI: 0.19-0.34, p < 0.001). Booster dose acceptance in EMR is relatively high. Interventions based on HBM may provide useful directions for policymakers to enhance the population's acceptance of booster vaccination.

Compendious survey of protein tandem repeats in inbred mouse strains.

Short tandem repeats (STRs) play a crucial role in genetic diseases. However, classic disease models such as inbred mice lack such genome wide data in public domain. The examination of STR alleles present in the protein coding regions (are known as protein tandem repeats or PTR) can provide additional functional layer of phenotype regulars. Motivated with this, we analysed the whole genome sequencing data from 71 different mouse strains and identified STR alleles present within the coding regions of 562 genes. Taking advantage of recently formulated protein models, we also showed that the presence of these alleles within protein 3-dimensional space, could impact the protein folding. Overall, we identified novel alleles from a large number of mouse strains and demonstrated that these alleles are of interest considering protein structure integrity and functionality within the mouse genomes. We conclude that PTR alleles have potential to influence protein functions through impacting protein structural folding and integrity.

A comprehensive review of fault diagnosis and fault-tolerant control techniques for modular multi-level converters.

BACKGROUND: Many faults occur in the modular multi-level converters (MMCs), including unbalancing capacitor voltage, lower and upper arm unbalancing, the line to line voltage unbalancing, sensors and actuators fault, system fault, and sub-modules fault in high as well as medium voltage applications. INTRODUCTION: Several fault-tolerant approaches are presented to overcome these problems, such as active fault-tolerant control system (AFTCS), passive fault-tolerant control system (PFTCS), hybrid fault-tolerant control system (HFTCS), redundant system technique, special power circuit with the controller, and zero sequence voltage methods, which we will explain extensively in this article. METHODOLOGY: This review emphasizes the types of faults in the MMCs and discusses the protection methods under failure conditions. The MMC is more popular in high voltage applications because it not only improves the quality of the grid but also has good harmonic performance in high power transmission. There is no need for any isolated dc sources to operate it. When faults are removed, the efficiency and reliability of the system will be increased. RESULTS: This extensive explanation of the current literature on MMC fault diagnosis and control techniques will conclude which methods provide a more valuable solution. Finally, this paper discusses the best approach to reduce MMC faults and provides a future research direction to the readers.

Advanced Fault-Tolerant Anti-Surge Control System of Centrifugal Compressors for Sensor and Actuator Faults.

Faults frequently occur in the sensors and actuators of process machines to cause shutdown and process interruption, thereby creating costly production loss. centrifugal compressors (CCs) are the most used equipment in process industries such as oil and gas, petrochemicals, and fertilizers. A compressor control system called an anti-surge control (ASC) system based on many critical sensors and actuators is used for the safe operation of CCs. In this paper, an advanced active fault-tolerant control system (AFTCS) has been proposed for sensor and actuator faults of the anti-surge control system of a centrifugal compressor. The AFTCS has been built with a dedicated fault detection and isolation (FDI) unit to detect and isolate the faulty part as well as replace the faulty value with the virtual redundant value from the observer model running in parallel with the other healthy sensors. The analytical redundancy is developed from the mathematical modeling of the sensors to provide estimated values to the controller in case the actual sensor fails. Dual hardware redundancy has been proposed for the anti-surge valve (ASV). The simulation results of the proposed Fault-tolerant control (FTC) for the ASC system in the experimentally validated CC HYSYS model reveal that the system continued to operate in the event of faults in the sensors and actuators maintaining system stability. The proposed FTC for the ASC system is novel in the literature and significant for the process industries to design a highly reliable compressor control system that would continue operation despite faults in the sensors and actuators, hence preventing costly production loss.

Design of active fault-tolerant control system for Air-fuel ratio control of internal combustion engines using fuzzy logic controller.

BACKGROUND: Fault-Tolerant Control Systems (FTCS) are used in critical and safety applications to improve performance and stability despite failure modes. As a result, costly production losses related to unusual and unplanned shutdowns can be prevented by incorporating these systems in the critical process plant machines. The Internal Combustion (IC) engines are highly used process plant machines and faults in their sensors will cause their shutdown instigating the need to install FTCS in them. INTRODUCTION: In this paper, an Active Fault-Tolerant Control System (AFTCS) based on a Fuzzy Logic Controller (FLC) is suggested to improve the reliability of the Air-Fuel Ratio (AFR) control system of an IC engine. METHODOLOGY: For analytical redundancy, a nonlinear Fuzzy Logic (FL) based observer is implemented in the proposed system for the Fault Detection and Isolation (FDI) unit for nonlinear sensors of the AFR system. Lyapunov stability analysis was used for designing a stable system in both faulty and normal conditions. To evaluate its performance, this system was developed in the MATLAB/Simulink platform. RESULTS: The simulation results show that the developed system is robust under sensor fault conditions, retaining stability with a minimum decrease of AFR. This study's comparison with the existing literature demonstrates that the proposed system is effective for maintaining the AFR in IC engines during sensor faulty conditions thus reducing shutdown of engine and production loss for increased profits.

Molecular detection of blaOXA-23 gene and blaOXA-51 gene in carbapenem resistant strains of Acinetobacter baumannii in patients with ventilator associated pneumonia at tertiary care hospitals.

OBJECTIVE: To evaluate carbapenem resistance and to detect blaOXA-23 and blaOXA-51 genes in carbapenem-resistant Acinetobacter baumanii isolates recovered from patients having pneumonia secondary to ventilation. METHODS: The cross-sectional study was conducted from July 2017 to June 2018 at the Department of Microbiology, University of Health Sciences, Lahore, Pakistan, and comprised endotracheal aspirates / tracheobroncheal lavage samples from patients irrespective of age and gender who developed pneumonia after being on the ventilator for 48 hrs at the Combined Military Hospital, and Jinnah Hospital, Lahore. The samples were inoculated on MacConkey and blood agar and aerobically incubated at a temperature of 370C for 18-24 hours. The isolated organisms were further assessed by standard morphological, cultural and biochemical profile. Antibiotic susceptibility was done by Kirby-Bauer disc diffusion method. Carbapenem-resistant Acinetobacter baumannii were checked for carbapenemase production using Modified Hodge Test. Conventional polymerase chain reaction and agarose gel electrophoresis were performed to detect blaOXA-23 and blaOXA-51 genes. Data was analysed using SPSS 17. RESULTS: Out of 157 samples, 92(58.6%) yielded growth of bacteria, and, among them, 39(42.4%) were identified as Acinetobacter baumannii. All (100%) Acinetobacter baumannii cases showed resistance to carbapenem, were producing carbapenemase enzyme, and were positive for blaOXA-51 gene. The blaOXA-23 gene was amplified in 38(97.4%) isolates. CONCLUSIONS: BlaOXA-23 gene appeared to be the major cause of carbapenem resistance.

An international virtual hackathon to build tools for the analysis of structural variants within species ranging from coronaviruses to vertebrates.

In October 2020, 62 scientists from nine nations worked together remotely in the Second Baylor College of Medicine & DNAnexus hackathon, focusing on different related topics on Structural Variation, Pan-genomes, and SARS-CoV-2 related research.   The overarching focus was to assess the current status of the field and identify the remaining challenges. Furthermore, how to combine the strengths of the different interests to drive research and method development forward. Over the four days, eight groups each designed and developed new open-source methods to improve the identification and analysis of variations among species, including humans and SARS-CoV-2. These included improvements in SV calling, genotyping, annotations and filtering. Together with advancements in benchmarking existing methods. Furthermore, groups focused on the diversity of SARS-CoV-2. Daily discussion summary and methods are available publicly at  https://github.com/collaborativebioinformatics provides valuable insights for both participants and the research community.

Dengue and Chikungunya virus co-infection in major metropolitan cities of provinces of Punjab and Khyber Pakhtunkhwa: A multi-center study.

Dengue has become endemic in Pakistan with annual recurrence. A sudden increase in the dengue cases was reported from Rawalpindi in 2016, while an outbreak occurred for the first time in Peshawar in 2017. Therefore, a multi-center study was carried out to determine the circulating dengue virus (DENV) serotypes and Chikungunya virus (CHIKV) co-infection in Lahore, Rawalpindi, and Peshawar cities in 2016-18. A hospital-based cross-sectional study was carried out in Lahore and Rawalpindi in 2016-18, while a community-based study was carried out in Peshawar in 2017. The study participants were tested for dengue NS1 antigen using an immunochromatographic device while anti-dengue IgM/IgG antibodies were detected by indirect ELISA. All NS1 positive samples were used for DENV serotyping using multiplex real-time PCR assay. Additionally, dengue samples were tested for CHIKV co-infection using IgM/IgG ELISA. A total of 6291 samples were collected among which 8.11% were NS1 positive while 2.5% were PCR positive. DENV-2 was the most common serotype (75.5%) detected, followed by DENV-1 in 16.1%, DENV-3 in 3.9% and DENV-4 in 0.7% while DENV-1 and DENV-4 concurrent infections were detected in 3.9% samples. DENV-1 was the predominant serotype (62.5%) detected from Lahore and Rawalpindi, while DENV-2 was the only serotype detected from Peshawar. Comorbidities resulted in a significant increase (p-value<0.001) in the duration of hospital stay of the patients. Type 2 diabetes mellitus substantially (p-value = 0.004) contributed to the severity of the disease. Among a total of 590 dengue positive samples, 11.8% were also positive for CHIKV co-infection. Co-circulation of multiple DENV serotypes and CHIKV infection in Pakistan is a worrisome situation demanding the urgent attention of the public health experts to strengthen vector surveillance.

Integrated Multi-Omics Analysis of Mechanisms Underlying Yeast Ethanol Tolerance.

For yeast cells, tolerance to high levels of ethanol is vital both in their natural environment and in industrially relevant conditions. We recently genotyped experimentally evolved yeast strains adapted to high levels of ethanol and identified mutations linked to ethanol tolerance. In this study, by integrating genomic sequencing data with quantitative proteomics profiles from six evolved strains (data set identifier PXD006631) and construction of protein interaction networks, we elucidate exactly how the genotype and phenotype are related at the molecular level. Our multi-omics approach points to the rewiring of numerous metabolic pathways affected by genomic and proteomic level changes, from energy-producing and lipid pathways to differential regulation of transposons and proteins involved in cell cycle progression. One of the key differences is found in the energy-producing metabolism, where the ancestral yeast strain responds to ethanol by switching to respiration and employing the mitochondrial electron transport chain. In contrast, the ethanol-adapted strains appear to have returned back to energy production mainly via glycolysis and ethanol fermentation, as supported by genomic and proteomic level changes. This work is relevant for synthetic biology where systems need to function under stressful conditions, as well as for industry and in cancer biology, where it is important to understand how the genotype relates to the phenotype.

Detection of active mycobacterium tuberculosis at 6th month exit among declared successfully treated cases in Pakistan.

OBJECTIVES: Tuberculosis (TB) is a significant public health concern, and the basis of successful anti-tuberculosis treatment (ATT) rests on the complete eradication of live bacilli from a patient. This study was conducted to detect the live TB bacilli in Lowenstein Jensen culture media among exit cases of TB who were declared successfully treated, either cured or treatment completed. METHODS: This cross-sectional study was conducted across Pakistan. Fifty-eight active TB DOTS centers were selected. The sample size of 3355 TB cases were equally distributed in all DOTS facilities. A detailed questionnaire was developed to record the information from TB DOTS and patients. After successful treatment, the sputum was taken from TB cases and examined to detect live bacilli on L-J culture. RESULTS: A total of 3355 TB cases were enrolled in the study. The male to female proportion was 1704(50.9%) and 1651(49.2%). Initially, 1993(59.4%) cases were cured, and 1362(40.6%) were declared as treatment completed cases. At exit, 324(9.65%) cases were again ZN smear-positive, and 328(9.77%) were positive on L-J culture, after being declared successfully treated for TB. CONCLUSIONS: To eradicate live TB bacilli, all TB cases should be subjected to L-J culture at the end of ATT.

The phosphatidylethanolamine biosynthesis pathway provides a new target for cancer chemotherapy.

BACKGROUND & AIMS: Since human induced pluripotent stem cells (iPSCs) develop into hepatic organoids through stages that resemble human embryonic liver development, they can be used to study developmental processes and disease pathology. Therefore, we examined the early stages of hepatic organoid formation to identify key pathways affecting early liver development. METHODS: Single-cell RNA-sequencing and metabolomic analysis was performed on developing organoid cultures at the iPSC, hepatoblast (day 9) and mature organoid stage. The importance of the phosphatidylethanolamine biosynthesis pathway to early liver development was examined in developing organoid cultures using iPSC with a CRISPR-mediated gene knockout and an over the counter medication (meclizine) that inhibits the rate-limiting enzyme in this pathway. Meclizine's effect on the growth of a human hepatocarcinoma cell line in a xenotransplantation model and on the growth of acute myeloid leukemia cells in vitro was also examined. RESULTS: Transcriptomic and metabolomic analysis of organoid development indicated that the phosphatidylethanolamine biosynthesis pathway is essential for early liver development. Unexpectedly, early hepatoblasts were selectively sensitive to the cytotoxic effect of meclizine. We demonstrate that meclizine could be repurposed for use in a new synergistic combination therapy for primary liver cancer: a glycolysis inhibitor reprograms cancer cell metabolism to make it susceptible to the cytotoxic effect of meclizine. This combination inhibited the growth of a human liver carcinoma cell line in vitro and in a xenotransplantation model, without causing significant side effects. This drug combination was also highly active against acute myeloid leukemia cells. CONCLUSION: Our data indicate that phosphatidylethanolamine biosynthesis is a targetable pathway for cancer; meclizine may have clinical efficacy as a repurposed anti-cancer drug when used as part of a new combination therapy. LAY SUMMARY: The early stages of human liver development were modeled using human hepatic organoids. We identified a pathway that was essential for early liver development. Based upon this finding, a novel combination drug therapy was identified that could be used to treat primary liver cancer and possibly other types of cancer.

yMap: an automated method to map yeast variants to protein modifications and functional regions.

Summary: Recent advances in sequence technology result in large datasets of sequence variants. For the human genome, several tools are available to predict the impact of these variants on gene and protein functions. However, for model organisms such as yeast such tools are lacking, specifically to predict the effect of protein sequence altering variants on the protein level. We present a python framework that enables users to map in a fully automated fashion large set of variants to protein functional regions and post-translationally modified residues. Furthermore, we provide the user with the possibility to retrieve predicted functional information on modified residues from other resources for example that are predicted to play a role in protein-protein interactions. The results are complemented by statistical tests to highlight the significance of underlying functions and pathways affected by mutations. We show the application of this package on a yeast dataset derived from a recent evolutionary experiment on adaptation to ethanol. Availability and Implementation: The package is available from https://github.com/CSB-KUL/yMap and is implemented in Python. Contact: vera.vannoort@biw.kuleuven.be. Supplementary information: Supplementary data are available at Bioinformatics online.

Evolutionary conservation of Ebola virus proteins predicts important functions at residue level.

MOTIVATION: The recent outbreak of Ebola virus disease (EVD) resulted in a large number of human deaths. Due to this devastation, the Ebola virus has attracted renewed interest as model for virus evolution. Recent literature on Ebola virus (EBOV) has contributed substantially to our understanding of the underlying genetics and its scope with reference to the 2014 outbreak. But no study yet, has focused on the conservation patterns of EBOV proteins. RESULTS: We analyzed the evolution of functional regions of EBOV and highlight the function of conserved residues in protein activities. We apply an array of computational tools to dissect the functions of EBOV proteins in detail: (i) protein sequence conservation, (ii) protein-protein interactome analysis, (iii) structural modeling and (iv) kinase prediction. Our results suggest the presence of novel post-translational modifications in EBOV proteins and their role in the modulation of protein functions and protein interactions. Moreover, on the basis of the presence of ATM recognition motifs in all EBOV proteins we postulate a role of DNA damage response pathways and ATM kinase in EVD. The ATM kinase is put forward, for further evaluation, as novel potential therapeutic target. AVAILABILITY AND IMPLEMENTATION: http://www.biw.kuleuven.be/CSB/EBOV-PTMs CONTACT: vera.vannoort@biw.kuleuven.beSupplementary information: Supplementary data are available at Bioinformatics online.