scholarly journals Deep genome annotation of the opportunistic human pathogenStreptococcus pneumoniaeD39

2018 ◽  
Author(s):  
Jelle Slager ◽  
Rieza Aprianto ◽  
Jan-Willem Veening
Keyword(s):  
Single Molecule ◽  
Genome Annotation ◽  
Antigenic Variation ◽  
Current Knowledge ◽  
Bacterial Genome ◽  
Treatment Strategies ◽  
Human Pathogens ◽  
Genome Data ◽  
Manual Curation ◽  
Automated Tools

ABSTRACTA precise understanding of the genomic organization into transcriptional units and their regulation is essential for our comprehension of opportunistic human pathogens and how they cause disease. Using single-molecule real-time (PacBio) sequencing we unambiguously determined the genome sequence ofStreptococcus pneumoniaestrain D39 and revealed several inversions previously undetected by short-read sequencing. Significantly, a chromosomal inversion results in antigenic variation of PhtD, an important surface-exposed virulence factor. We generated a new genome annotation using automated tools, followed by manual curation, reflecting the current knowledge in the field. By combining sequence-driven terminator prediction, deep paired-end transcriptome sequencing and enrichment of primary transcripts by Cappable-Seq, we mapped 1,015 transcriptional start sites and 748 termination sites. Using this new genomic map, we identified several new small RNAs (sRNAs), riboswitches (including twelve previously misidentified as sRNAs), and antisense RNAs. In total, we annotated 92 new protein-encoding genes, 39 sRNAs and 165 pseudogenes, bringing theS. pneumoniaeD39 repertoire to 2,151 genetic elements. We report operon structures and observed that 9% of operons lack a 5’-UTR. The genome data is accessible in an online resource called PneumoBrowse (https://veeninglab.com/pneumobrowse) providing one of the most complete inventories of a bacterial genome to date. PneumoBrowse will accelerate pneumococcal research and the development of new prevention and treatment strategies.

scholarly journals Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1392
Author(s):  
Hidaya A. Kader ◽  
Muhammad Azeem ◽  
Suhib A. Jwayed ◽  
Aaesha Al-Shehhi ◽  
Attia Tabassum ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Food Allergies ◽  
Th2 Response ◽  
Therapeutic Outcomes ◽  
Environmental Agents ◽  
Novel Treatment Strategies

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.

scholarly journals Campylobacter and helicobacter in the etiology of gastrointestinal diseases

2012 ◽  
Vol 64 (4) ◽  
pp. 1389-1404 ◽  
Author(s):  
Biljana Miljkovic-Selimovic ◽  
Branislava Kocic ◽  
Tatjana Babic
Keyword(s):  
Bacterial Genome ◽  
Optimal Growth ◽  
The Elderly ◽  
Distinct Species ◽  
Gastrointestinal Diseases ◽  
Human Pathogens ◽  
Endotoxin Activity ◽  
Clinical Presentations ◽  
Human Disorders ◽  
H Pylori

The order Campylobacterales comprises two genera: Campylobacter and Helicobacter, with a widespread distribution in both humans and animals. They are Gram-negative, spiral, helical and microaerophilic bacteria, with an optimal growth temperature of 37?C for H. pylori and 42?C for C. jejuni strains. While Helicobacter pylori are restricted to humans, other helicobacter species can be found in different mammals and occasionally in humans. Several Campylobacter species are recognized as human pathogens, while distinct species are pathogenic only occasionally, in children, the elderly and immunocompromised patients. Campylobacters and helicobacters are well adapted to the living conditions inside the gastrointestinal tract, where they can cause diseases as a consequence of inflammation. In addition, they are related to certain extraintestinal diseases, post-infectious sequels, malignancy and autoimmunity. Different clinical presentations of human disorders may be the consequences of the diversity in host immune response, bacterial genome, endotoxin activity as well as specific bacterial virulence factors.

scholarly journals Systematizing Genome Privacy Research: A Privacy-Enhancing Technologies Perspective

2019 ◽  
Vol 2019 (1) ◽  
pp. 87-107 ◽  
Author(s):  
Alexandros Mittos ◽  
Bradley Malin ◽  
Emiliano De Cristofaro
Keyword(s):  
Data Privacy ◽  
Online Survey ◽  
Current Knowledge ◽  
Genomic Data ◽  
Well Being ◽  
Security And Privacy ◽  
Genome Data ◽  
Privacy Enhancing Technologies ◽  
Cost Efficient ◽  
New Research

Abstract Rapid advances in human genomics are enabling researchers to gain a better understanding of the role of the genome in our health and well-being, stimulating hope for more effective and cost efficient healthcare. However, this also prompts a number of security and privacy concerns stemming from the distinctive characteristics of genomic data. To address them, a new research community has emerged and produced a large number of publications and initiatives. In this paper, we rely on a structured methodology to contextualize and provide a critical analysis of the current knowledge on privacy-enhancing technologies used for testing, storing, and sharing genomic data, using a representative sample of the work published in the past decade. We identify and discuss limitations, technical challenges, and issues faced by the community, focusing in particular on those that are inherently tied to the nature of the problem and are harder for the community alone to address. Finally, we report on the importance and difficulty of the identified challenges based on an online survey of genome data privacy experts.

scholarly journals Challenges and opportunities to understanding genetics of fungal diseases: towards a functional genomics approach

2021 ◽  
Author(s):  
Mariolina Bruno ◽  
Vasiliki Matzaraki ◽  
Frank L van de Veerdonk ◽  
Vinod Kumar ◽  
Mihai G. Netea
Keyword(s):  
Infectious Diseases ◽  
Fungal Infections ◽  
Critical Role ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Fungal Diseases ◽  
Human Pathogens ◽  
Challenges And Opportunities ◽  
Patients At Risk ◽  
Immune Related Genes

Infectious diseases are a leading cause of morbidity and mortality worldwide and human pathogens have long been recognized as one of the main sources of evolutionary pressure, resulting in a high variable genetic background in immune-related genes. The study of the genetic contribution to infectious diseases has undergone tremendous advances over the last decades. Here, focusing on genetic predisposition to fungal diseases, we provide an overview of the available approaches for studying human genetic susceptibility to infections, reviewing current methodological and practical limitations. We describe how the classical methods available, such as family-based studies and candidate-gene studies, have contributed to the discovery of crucial susceptibility factors for fungal infections. We will also discuss the contribution of novel unbiased approaches to the field, highlighting their success but also their limitations for the fungal immunology field. Finally, we show how a systems genomics approach can overcome those limitations and can lead to efficient prioritization and identification of genes and pathways with a critical role in susceptibility to fungal diseases. This knowledge will help stratify patients at risk groups and, subsequently, develop early appropriate prophylactic and treatment strategies.

Diagnosis and Treatment of Smoke Inhalation

1995 ◽  
Vol 10 (3) ◽  
pp. 117-127 ◽  
Author(s):  
Basil A. Pruitt ◽  
William G. Cioffi
Keyword(s):  
Current Knowledge ◽  
Treatment Strategies ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Diagnosis And Treatment ◽  
Laboratory Research ◽  
Individualization Of Therapy ◽  
Injured Patients

Inhalation remains the most frequent and serious comorbid event that occurs in thermally injured patients. A thorough understanding of the pathophysiology enables individualization of therapy and appropriate triage of patients. We summarize our current knowledge of the pathophysiology, diagnosis, and treatment of inhalation injury, with a focus on newer treatment strategies that are evolving secondary to laboratory research.

Monogenic Epilepsies: Disease Mechanisms, Clinical Phenotypes, and Targeted Therapies

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012744
Author(s):  
Renzo Guerrini ◽  
Simona Balestrini ◽  
Elaine C. Wirrell ◽  
Matthew C. Walker
Keyword(s):  
Observational Studies ◽  
Current Knowledge ◽  
Functional Characterization ◽  
Treatment Strategies ◽  
Controlled Trials ◽  
Epileptogenic Zone ◽  
Missense Mutations ◽  
Number Of Patients ◽  
Functional Consequences ◽  
Genetic Epilepsies

A monogenic aetiology can be identified in up to 40% of people with severe epilepsy. To address earlier and more appropriate treatment strategies, clinicians are required to know the implications that specific genetic causes might have on pathophysiology, natural history, comorbidities and treatment choices. In this narrative review, we summarise concepts on the genetic epilepsies based on the underlying pathophysiological mechanisms and present the current knowledge on treatment options based on evidence provided by controlled trials or studies with lower classification of evidence. Overall, evidence robust enough to guide antiseizure medication (ASM) choices in genetic epilepsies remains limited to the more frequent conditions for which controlled trials and observational studies have been possible. Most monogenic disorders are very rare and ASM choices for them are still based on inferences drawn from observational studies and early, often anecdotal, experiences with precision therapies. Precision medicine remains applicable to only a narrow number of patients with monogenic epilepsies and may target only part of the actual functional defects. Phenotypic heterogeneity is remarkable, and some genetic mutations activate epileptogenesis through their developmental effects, which may not be reversed postnatally. Other genes seem to have pure functional consequences on excitability, acting through either loss- or gain-of-function effects, and these may have opposite treatment implications. In addition, the functional consequences of missense mutations may be difficult to predict, making precision treatment approaches considerably more complex than estimated by deterministic interpretations. Knowledge of genetic aetiologies can influence the approach to surgical treatment of focal epilepsies. Identification of germline mutations in specific genes contraindicates surgery while mutations in other genes do not. Identification, quantification and functional characterization of specific somatic mutations before surgery using cerebrospinal fluid liquid biopsy or after surgery in brain specimens, will likely be integrated in planning surgical strategies and re-intervention after a first unsuccessful surgery as initial evidence suggests that mutational load may correlate with the epileptogenic zone. Promising future directions include gene manipulation by DNA or mRNA targeting; although most are still far from clinical use, some are in early phase clinical development.

Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Epigenetic Regulator ◽  
Novel Treatment Strategies

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

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