Microorganisms constitute two third of the Earth's biological diversity. As many as 99% of the microorganisms present in certain environments cannot be cultured by standard techniques. Culture-independent methods are required to understand the genetic diversity, population structure and ecological roles of the majority of organisms. Metagenomics is the genomic analysis of microorganisms by direct extraction and cloning of DNA from their natural environment. Protocols have been developed to capture unexplored microbial diversity to overcome the existing barriers in estimation of diversity. New screening methods have been designed to select specific functional genes within metagenomic libraries to detect novel biocatalysts as well as bioactive molecules applicable to mankind. To study the complete gene or operon clusters, various vectors including cosmid, fosmid or bacterial artificial chromosomes are being developed. Bioinformatics tools and databases have added much to the study of microbial diversity. This review describes the various methodologies and tools developed to understand the biology of uncultured microbes including bacteria, archaea and viruses through metagenomic analysis.
Tuberculosis (TB) is a slow growing,
potentially debilitating disease
that has plagued humanity for centuries and has claimed numerous lives
across the globe. Concerted efforts by researchers have culminated
in the development of various strategies to combat this malady. This
review aims to raise awareness of the rapidly increasing incidences
of multidrug-resistant (MDR) and extensively drug-resistant (XDR)
tuberculosis, highlighting the significant modifications that were
introduced in the TB treatment regimen over the past decade. A description
of the role of pathogen–host immune mechanisms together with
strategies for prevention of the disease is discussed. The struggle
to develop novel drug therapies has continued in an effort to reduce
the treatment duration, improve patient compliance and outcomes, and
circumvent TB resistance mechanisms. Herein, we give an overview of
the extensive medicinal chemistry efforts made during the past decade
toward the discovery of new chemotypes, which are potentially active
against TB-resistant strains.
The integrity of the blood–brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.
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