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Garima Verma, Namita Surolia
The complex life cycle of intracellular parasitic protozoans entails multiple rounds of DNA replication and mitosis followed by cytokinesis to release daughter parasites. To gain insights into mitotic events it is imperative to identify the biomarkers that constitute the chromosome segregation machinery in the parasite. Chromosomal loci called centromeres and their associated proteins play an essential role in accurate chromosome segregation. Although new information on the centromere-kinetochore proteins has been added to the existing pool of knowledge, a paucity of biomarkers for nuclear division prevents a global view of chromosome segregation mechanism in the malaria parasite...
June 22, 2018: IUBMB Life
Elizabeth Story-Roller, Gyanu Lamichhane
β-lactams are the most widely used antibiotics and are effective against a spectrum of pathogenic bacteria. Here, we focus on the state-of-the-art understanding of the molecular underpinnings that determine the overall efficacy of β-lactams against TB and include historical perspectives of this antibiotic class against this ancient disease. We summarize literature that describes why earlier generations of β-lactams are ineffective and the potential promise of newer β-lactams that exhibit improved efficacy against TB...
June 22, 2018: IUBMB Life
Kavitha Sarvepalli, Utpal Nath
Leaves are the most conspicuous planar organs in plants, designed for efficient capture of sunlight and its conversion to energy that is channeled into sustaining the entire biosphere. How a few founder cells derived from the shoot apical meristem give rise to diverse leaf forms has interested naturalists and developmental biologists alike. At the heart of leaf morphogenesis lie two simple cellular processes, division and expansion, that are spatially and temporally segregated in a developing leaf. In leaves of dicot model species, cell division occurs predominantly at the base, concomitant with the expansion and differentiation of cells at the tip of the lamina that drives increase in leaf surface area...
June 22, 2018: IUBMB Life
Parijat Chakraborty, Ajith V Pankajam, Abhishek Dutta, Koodali T Nishant
Diploid organisms undergo meiosis to produce haploid germ cells. Crossover events during meiosis promote genetic diversity and facilitate accurate chromosome segregation. The baker's yeast Saccharomyces cerevisiae is extensively used as a model for analysis of meiotic recombination. Conventional methods for measuring recombination events in S. cerevisiae have been limited by the number and density of genetic markers. Next generation sequencing (NGS)-based analysis of hybrid yeast genomes bearing thousands of heterozygous single nucleotide polymorphism (SNP) markers has revolutionized analysis of meiotic recombination...
June 22, 2018: IUBMB Life
Mehak Zahoor Khan, Prabhjot Kaur, Vinay Kumar Nandicoori
The emergence of increasingly drug-resistant Mycobacterium tuberculosis strains has become a crucial public health concern. In order to effectively treat tuberculosis, it is imperative to find newer drug targets, which are important for the in vivo bacterial survival and persistence. Phosphorylation based signaling cascades modulated by eukaryotic-like serine/threonine protein kinases and phosphatase in M. tuberculosis, transduce extracellular stimuli to a cellular response ensuing pathogen's growth, persistence and pathogenesis...
June 22, 2018: IUBMB Life
Ye Bai, Shuang Qiu, Yan Li, Yong Li, Weijing Zhong, Meijuan Shi, Xiaojuan Zhu, Huiyi Jiang, Yaqin Yu, Yi Cheng, Yawen Liu
Autism spectrum disorder (ASD), as one of early-onset neurodevelopmental disorders, is characterized by the following symptoms, including repetitive and stereotyped behaviors, impairments in social interaction, and dysfunctions in communication. ASD afflicts ∼1.5% of children aged 8 years in America and ∼4.5‰ of children aged 0-6 years in China. Existing studies suggest that SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) is implicated in ASD. However, associations between SNPs in SHANK2 introns and ASD risk have been less investigated...
June 22, 2018: IUBMB Life
Lloyd Tanner, Paolo Denti, Lubbe Wiesner, Digby F Warner
Anti-tuberculosis (TB) drugs possess diverse abilities to penetrate the different host tissues and cell types in which infecting Mycobacterium tuberculosis bacilli are located during active disease. This is important since there is increasing evidence that the respective "lesion-penetrating" properties of the front-line TB drugs appear to correlate well with their specific activity in standard combination therapy. In turn, these observations suggest that rational efforts to discover novel treatment-shortening drugs and drug combinations should incorporate knowledge about the comparative abilities of both existing and experimental anti-TB agents to access bacilli in defined physiological states at different sites of infection, as well as avoid elimination by efflux or inactivation by host or bacterial metabolism...
June 22, 2018: IUBMB Life
Manikuntala Kundu
Tuberculosis is a global health problem, with a third of the world's population infected with the bacillus, Mycobacterium tuberculosis. The problem is exacerbated by the emergence of multidrug resistant and extensively drug resistant strains. The search for new drug targets is therefore a priority for researchers in the field. The two-component systems (TCSs) are central to the ability of the bacterium to sense and to respond appropriately to its environment. Here we summarize current knowledge on the paired TCSs of M...
June 9, 2018: IUBMB Life
Lei Zhong, Changjun Zheng, Hongjuan Fang, Meng Xu, Bingpeng Chen, Chen Li
In this work, we explored the aberrant expression pattern, clinical association, and functional regulations of microRNA-1270 (miR-1270) in osteosarcoma. Among in vitro osteosarcoma cell lines and in situ tissues of osteosarcoma patients, quantitative real time-PCR was used to examine their endogenous miR-1270 expression. Clinical correlation between endogenous miR-1270 expression and clinicopathological features of osteosarcoma patients, as well as cancer patients' overall survival, was statistically examined...
May 18, 2018: IUBMB Life
Amogh Kulkarni, Ajay Kumar Sharma, Harinath Chakrapani
The emergence of drug resistance has posed a major challenge to treatment of tuberculosis worldwide. The new drug candidates in the pipeline are few and therefore there is an urgent need to develop antimycobacterials with novel mechanisms of action. Maintenance of redox homeostasis is integral to mycobacterial survival and growth. Therefore, perturbation of this equilibrium can result in irreversible stress induction and inhibition of growth. Herein, we review a number of small molecules that have either been designed to induce redox stress or were found to do so after their discovery...
May 14, 2018: IUBMB Life
Rohan Dhiman, Ramandeep Singh
Tuberculosis (TB) is a leading cause of mortality and morbidity with an estimated 1.7 billion people latently infected with the pathogen worldwide. Clinically, TB infection presents itself as an asymptomatic infection, which gradually manifests to life threatening disease. The emergence of various drug resistant strains of Mycobacterium tuberculosis and lengthy duration of chemotherapy are major challenges in the field of TB drug development. Hence, there is an urgent need to develop scaffolds that possess a novel mechanism of action, can shorten the duration of therapy, and are active against both drug resistant and susceptible strains...
May 14, 2018: IUBMB Life
Nisha Singh, Zeeshan Ahmad, Navin Baid, Ashwani Kumar
Infectious diseases are a major challenge in management of human health worldwide. Recent literature suggests that host immune system could be modulated to ameliorate the pathogenesis of infectious disease. Heme oxygenase (HMOX1) is a key regulator of cellular signaling and it could be modulated using pharmacological reagents. HMOX1 is a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO), biliverdin, and molecular iron. CO and biliverdin (or bilirubin derived from it) can restrict the growth of a few pathogens...
May 14, 2018: IUBMB Life
Anuradha Kumari, Dulal Panda
The centrosome executes diverse functions including the nucleation and organization of microtubules. A subset of centrosomal proteins is found to be involved in regulating the nucleation, stability, and dynamics of microtubules. Literature is flooded with reports of centrosomal proteins regulating microtubule nucleation. However, the centrosomal proteins that regulate microtubule stability are underexplored. Here, we review the centrosomal proteins, which either enhance or reduce the stability of microtubules and thereby regulate microtubule dynamics...
May 7, 2018: IUBMB Life
Hong-Ling Jia, Xiao-Qin Zeng, Feng Huang, Ya-Meng Liu, Bi-Shuang Gong, Kai-Zhao Zhang, Jiang-Hui Zeng, Dong-Guang Guo, Zhuo-Ya Wang, Yu-Gu Li
MicroRNAs (miRNAs) play key roles in the regulation of gene expression during multiple physiological processes, including early development, differentiation, and ageing. However, their involvement in age-related thymic involution is not clear. In this study, we profiled the global transcriptome and miRNAome of thymic epithelial cells in 1- and 3-month-old male and female mice, and predicted the possible transcription factors and target genes of the four most significantly differentially expressed miRNAs (DEMs) (miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p) by performing bioinformatics analyses...
May 4, 2018: IUBMB Life
Christopher S Ealand, Edith E Machowski, Bavesh D Kana
Disruption of peptidoglycan (PG) biosynthesis in the bacterial cell wall by β-lactam antibiotics has transformed therapeutic options for bacterial infections. These antibiotics target the transpeptidase domains in penicillin binding proteins (PBPs), which can be classified into high and low molecular weight (LMW) counterparts. While the essentiality of the former has been extensively demonstrated, the physiological roles of LMW PBPs remain poorly understood. Herein, we review the function of LMW PBPs, β-lactamases and ld-transpeptidases (Ldts) in pathogens associated with respiratory tract infections...
May 2, 2018: IUBMB Life
Robert B Abramovitch
Reporter strains have proven to be powerful tools to study Mycobacterium tuberculosis (Mtb) physiology. Transcriptional and translational reporter strains are engineered by fusing a readout gene, encoding a fluorescent, luminescent or enzymatic protein, downstream of a promoter or in-frame with a gene of interest. When the reporter is expressed, it generates a signal that acts as a synthetic phenotype, enabling the study of physiologies that might have otherwise been hidden. This review will discuss approaches for generating reporter strains in Mtb and how they can be used as tools for high-throughput genetic and small molecule screening and as biomarkers for examining Mtb responses to drug or immune stresses during animal infections...
April 29, 2018: IUBMB Life
Yanfeng Shen, Feng Xi, Haibin Li, Yin Luo, Cheng Chen, Lei Wang
We aimed to investigate the role of telomerase reverse transcriptase (TERT) in hepatocellular cancer (HCC) cells. R software was used for differential expressed gene analysis. Western blot and quantitative real time polymerase chain reaction (qRT-PCR), respectively, were used to detect protein expression and mRNA level of TERT in tumor cell lines. Real-time quantitative telomeric repeat amplification protocol assay, MTT assay, colony formation assay, and flow cytometry (FCM) assay were used to analyze the telomerase activity, viability, proliferation, cell cycle progression and apoptosis of HCC cells...
April 29, 2018: IUBMB Life
Mashkoor Alam, Abhishek Srivastava, Ankita Dutta, Apurba Kumar Sau
Despite importance of arginine decarboxylase (ADC: EC of Helicobacter pylori (H. pylori) 26695 pathogenic strain for acid adaptation in host, the enzyme has not yet been studied at a molecular level. Using combined approaches that include kinetic assays, site-directed mutagenesis, circular dichroism, heat-induced denaturation, analytical gel-filtration, and homology modeling, we report here a detailed investigation of H. pylori ADC. The pyridoxal 5'-phosphate (PLP)-dependent enzyme exhibits higher catalytic activity in the presence of Mg2+ ions at pH ∼8...
April 23, 2018: IUBMB Life
Amrita Saha, Moumita Basu, Anindita Ukil
Invasion of host cell by pathogens induce various intracellular signalling pathways. The host cell through the initiation of these signalling circuits desperately wants to get rid of the pathogen, whereas the pathogen tries to subvert these defence strategies to create an environment for their successful survival. Leishmania spp. is not an exception. Leishmania have to evolve a range of strategic mechanisms to neutralize macrophage defensive arsenals which enable the parasite to replicate within the phagolysosome of infected host...
April 23, 2018: IUBMB Life
Tao Peng, Wencui Wan, Jingtao Wang, Yu Liu, Zhenqiang Fu, Xingrong Ma, Junmin Li, Guifang Sun, Yangfei Ji, Jingjing Lu, Hong Lu, Yufeng Liu
Endothelial dysfunction is fundamental to ischemic stroke and brain injury. The humanin analogue S14G-humanin (HNG) has been shown to be a cytoprotective derivative. In this study, we investigated the neuroprotective effects of HNG in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, HNG ameliorates cerebral infarction and suppresses the production of TNF-α, IL-1β, IL-6 and MCP-1 cytokines. HNG inhibits the expression of vascular adhesion molecules such as VCAM-1 and ICAM-1 in the cortex tissue...
July 2018: IUBMB Life
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