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Background
Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.Objective
The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.Methods
A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.Results
Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).Conclusion
Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.3.
Background
Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages.Objective
This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis.Methods
Relevant English-language studies were identified and retrieved from the PubMed search engine (1981–2017) using the following keywords: “Erythropoiesis”, “Catecholamines”, “Nervous system”, and “Cytokines.”Results
Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis.Conclusion
Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells (RBCs) in both chronic and physiological catecholamine activation.4.
Hansa Jain 《生物学前沿》2017,12(2):116-123
Background
Periodontitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides (AMPs) which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, viruses, and parasites, and cancerous cells have been linked to periodontitis. The AMPs even possess the caliber of immunomodulation, and are significantly responsive to innate immuno-stimulation and infections. LL-37 plays a salubrious role by preventing and in treatment of chronic forms of periodontitis.Objective
In the present work we will review the role of antimicrobial peptide LL-37 in periodontitis.Methods
A systematic search was carried out from the beginning till August, 2016 using the Pubmed search engine. The keywords included “LL-37,” “periodontitis,” “Papillon–Lefevre syndrome,” “Morbus Kostmann,” “Haim-Munk syndrome” along with use of Boolean operator “and.”Results
The search resulted in identifying 67 articles which included articles linking LL-37 with periodontitis, articles on Papillon–Lefevre syndrome, Morbus Kostmann, Haim-Munk syndrome, LL-37 and periodontitis and articles on pathogenicity of periodontitis.Conclusion
The literature search concluded that LL-37 plays a pivotal role in preventing and treatment of severe form of periodontitis.5.
Background
Bone marrow mesenchymal stromal cells (BM-MSCs) are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type.Methods
A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used: “cytogenetic,” “leukemia,” “bone marrow,” and “mesenchymal stromal cells.”Results
Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cellsConclusions
Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.6.
Background
Detecting protein complexes in protein-protein interaction (PPI) networks plays an important role in improving our understanding of the dynamic of cellular organisation. However, protein interaction data generated by high-throughput experiments such as yeast-two-hybrid (Y2H) and tandem affinity-purification/mass-spectrometry (TAP-MS) are characterised by the presence of a significant number of false positives and false negatives. In recent years there has been a growing trend to incorporate diverse domain knowledge to support large-scale analysis of PPI networks.Methods
This paper presents a new algorithm, by incorporating Gene Ontology (GO) based semantic similarities, to detect protein complexes from PPI networks generated by TAP-MS. By taking co-complex relations in TAP-MS data into account, TAP-MS PPI networks are modelled as bipartite graph, where bait proteins consist of one set of nodes and prey proteins are on the other. Similarities between pairs of bait proteins are computed by considering both the topological features and GO-driven semantic similarities. Bait proteins are then grouped in to sets of clusters based on their pair-wise similarities to produce a set of 'seed' clusters. An expansion process is applied to each 'seed' cluster to recruit prey proteins which are significantly associated with the same set of bait proteins. Thus, completely identified protein complexes are then obtained.Results
The proposed algorithm has been applied to real TAP-MS PPI networks. Fifteen quality measures have been employed to evaluate the quality of generated protein complexes. Experimental results show that the proposed algorithm has greatly improved the accuracy of identifying complexes and outperformed several state-of-the-art clustering algorithms. Moreover, by incorporating semantic similarity, the proposed algorithm is more robust to noises in the networks.7.
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Jaimie Dufresne Angelique Florentinus-Mefailoski Juliet Ajambo Ammara Ferwa Peter Bowden John Marshall 《Clinical proteomics》2017,14(1):41
Background
Normal human EDTA plasma samples were collected on ice, processed ice cold, and stored in a freezer at – 80 °C prior to experiments. Plasma test samples from the – 80 °C freezer were thawed on ice or intentionally warmed to room temperature.Methods
Protein content was measured by CBBR binding and the release of alcohol soluble amines by the Cd ninhydrin assay. Plasma peptides released over time were collected over C18 for random and independent sampling by liquid chromatography micro electrospray ionization and tandem mass spectrometry (LC–ESI–MS/MS) and correlated with X!TANDEM.Results
Fully tryptic peptides by X!TANDEM returned a similar set of proteins, but was more computationally efficient, than “no enzyme” correlations. Plasma samples maintained on ice, or ice with a cocktail of protease inhibitors, showed lower background amounts of plasma peptides compared to samples incubated at room temperature. Regression analysis indicated that warming plasma to room temperature, versus ice cold, resulted in a ~ twofold increase in the frequency of peptide identification over hours–days of incubation at room temperature. The type I error rate of the protein identification from the X!TANDEM algorithm combined was estimated to be low compared to a null model of computer generated random MS/MS spectra.Conclusion
The peptides of human plasma were identified and quantified with low error rates by random and independent sampling that revealed 1000s of peptides from hundreds of human plasma proteins from endogenous tryptic peptides.9.
Background
The relatively fast selection of symbiotic bacteria within hosts and the potential transmission of these bacteria across generations of hosts raise the question of whether interactions between host and bacteria support emergent adaptive capabilities beyond those of germ-free hosts.Results
To investigate possibilities for emergent adaptations that may distinguish composite host-microbiome systems from germ-free hosts, we introduce a population genetics model of a host-microbiome system with vertical transmission of bacteria. The host and its bacteria are jointly exposed to a toxic agent, creating a toxic stress that can be alleviated by selection of resistant individuals and by secretion of a detoxification agent (“detox”). We show that toxic exposure in one generation of hosts leads to selection of resistant bacteria, which in turn, increases the toxic tolerance of the host’s offspring. Prolonged exposure to toxin over many host generations promotes anadditional form of emergent adaptation due to selection of hosts based on detox produced by their bacterial community as a whole (as opposed to properties of individual bacteria).Conclusions
These findings show that interactions between pure Darwinian selections of host and its bacteria can give rise to emergent adaptive capabilities, including Lamarckian-like adaptation of the host-microbiome system.Reviewers
This article was reviewed by Eugene Koonin, Yuri Wolf and Philippe Huneman.10.
Background
Recently, growing attention has been directed toward stem cell metabolism, with the key observation that metabolism not only fuels the proper functioning of stem cells but also regulates the fate of these cells. There seems to be a clear link between the self-renewal of pluripotent stem cells (PSCs), in which cells proliferate indefinitely without differentiation, and the activity of specific metabolic pathways. The unique metabolism in PSCs plays an important role in maintaining pluripotency by regulating signaling pathways and resetting the epigenome.Objective
To review the most recent publications concerning the metabolism of pluripotent stem cells and the role of metabolism in PSC self-renewal and differentiation.Methods
A systematic literature search related to the metabolism of PSCs was conducted in databases including Medline, Embase, and Web of Science. The search was performed without language restrictions on all papers published before May 2016. The following keywords were used: “metabolism” combined with either “embryonic stem cell” or “epiblast stem cell.”Results
Hundreds of papers focusing specifically on the metabolism of pluripotent stem cells were uncovered and summarized.Conclusion
Identifying the specific metabolic pathways involved in pluripotency maintenance is crucial for progress in the field of developmental biology and regenerative medicine. Additionally, better understanding of the metabolism in PSCs will facilitate the derivation and maintenance of authentic PSCs from species other than mouse, rat, and human.11.
Hansa Jain 《生物学前沿》2017,12(3):192-198
Background
Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide, fimbriae, capsular polysaccharide, haemagglutinin and cysteine proteases (Arg-gingipains and Lys-gingipain) are considered to be involved in the pathogenesis of periodontitis. Leupeptin is a cysteine protease inhibitor which is specific for Arg gingipains. The present review focuses on action of leupeptin on Arg gingipains.Method
A search was carried out systematically from the start till September, 2016. The search was made in Medline database via PubMed. The keywords enlisted were “leupeptin”; “gingipains”; “periodontitis” using Boolean operator “and.”Results
The result was selection of 58 articles which linked leupeptin to periodontitis and gingipains; pathogenesis of periodontitis, pathogenicity of gingipains and role of leupeptin.Conclusion
It was concluded that leupeptin inhibits and attenuates a number of destructive activities of Arg gingipains including inhibition of platelet aggregation; inhibit degradation of LL-37, which is an antimicrobial peptide; blocking inhibition of monocyte chemoattractant protein; restoring level of interleukin-2; inhibiting degradation of collagen type I and IV to name a few.12.
Hao Chen Xiao Zheng Justine Nicholas Sara T. Humes Julia C. Loeb Sarah E. Robinson Joseph H. BisesiJr Dipesh Das Navid B. Saleh William L. Castleman John A. Lednicky Tara Sabo-Attwood 《Virology journal》2017,14(1):242
Background
Numerous toxicological studies have focused on injury caused by exposure to single types of nanoparticles, but few have investigated how such exposures impact a host’s immune response to pathogen challenge. Few studies have shown that nanoparticles can alter a host’s response to pathogens (chiefly bacteria) but there is even less knowledge of the impact of such particles on viral infections. In this study, we performed experiments to investigate if exposure of mice to single-walled carbon nanotubes (SWCNT) alters immune mechanisms and viral titers following subsequent influenza A virus (IAV) infection.Methods
Male C57BL/6 mice were exposed to 20 μg of SWCNT or control vehicle by intratracheal instillation followed by intranasal exposure to 3.2?×?104 TCID50 IAV or PBS after 3 days. On day 7 mice were euthanized and near-infrared fluorescence (NIRF) imaging was used to track SWCNT in lung tissues. Viral titers, histopathology, and mRNA expression of antiviral and inflammatory genes were measured in lung tissue. Differential cell counts and cytokine levels were quantified in bronchoalveolar lavage fluid (BALF).Results
Viral titers showed a 63-fold increase in IAV in SWCNT + IAV exposed lungs compared to the IAV only exposure. Quantitation of immune cells in BALF indicated an increase of neutrophils in the IAV group and a mixed profile of lymphocytes and neutrophils in SWCNT + IAV treated mice. NIRF indicated SWCNT remained in the lung throughout the experiment and localized in the junctions of terminal bronchioles, alveolar ducts, and surrounding alveoli. The dual exposure exacerbated pulmonary inflammation and tissue lesions compared to SWCNT or IAV single exposures. IAV exposure increased several cytokine and chemokine levels in BALF, but greater levels of IL-4, IL-12 (P70), IP-10, MIP-1, MIP-1α, MIP-1β, and RANTES were evident in the SWCNT?+?IAV group. The expression of tlr3, ifnβ1, rantes, ifit2, ifit3, and il8 was induced by IAV alone but several anti-viral targets showed a repressed trend (ifits) with pre-exposure to SWCNT.Conclusions
These findings reveal a pronounced effect of SWCNT on IAV infection in vivo as evidenced by exacerbated lung injury, increased viral titers and several cytokines/chemokines levels, and reduction of anti-viral gene expression. These results imply that SWCNT can increase susceptibility to respiratory viral infections as a novel mechanism of toxicity.13.
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Background
The influenza matrix protein (M1) layer under the viral membrane plays multiple roles in virus assembly and infection. N-domain and C-domain are connected by a loop region, which consists of conserved RQMV motif.Methods
The function of the highly conserve RQMV motif in the influenza virus life cycle was investigated by site-directed mutagenesis and by rescuing mutant viruses by reverse genetics. Co-localization of M1 with nucleoprotein (NP), clustered mitochondria homolog protein (CLUH), chromosome region maintenance 1 protein (CRM1), or plasma membrane were studied by confocal microscopy.Results
Mutant viruses containing an alanine substitution of R163, Q164 and V166 result in the production of the virus indistinguishable from the wild type phenotype. Single M165A substitution was lethal for rescuing infection virus and had a striking effect on the distribution of M1 and NP proteins. We have observed statistically significant reduction in distribution of both M165A (p?0,05) and NP (p?0,001) proteins to the nucleus in the cells transfected with the reverse –genetic system with mutated M1. M165A protein was co-localized with CLUH protein in the cytoplasm and around the nucleus but transport of M165-CLUH complex through the nuclear membrane was restricted.Conclusions
Our finding suggest that methionine 165 is essential for virus replication and RQMV motif is involved in the nuclear import of viral proteins.15.
Yinjie Gao Bingqing Yu Jiangfeng Mao Xi Wang Min Nie Xueyan Wu 《BMC endocrine disorders》2018,18(1):85
Background
After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility.Methods
To determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials.Clinical trials were systematically searched in Medline, Embase, and the Cochrane central register of controlled trials databases. The keywords and major terms covered “hypogonadotropic hypogonadism”, “kallmann syndrome”, “assisted reproductive techniques”, “intrauterine insemination”, “intracytoplasmic sperm injection”, “testicular sperm extraction”, “in vitro fertilization”, “embryo transplantation” and “intra-Fallopian transfer”.Results
A total of 388 pregnancies occurred among 709 CHH patients who received ART (effectiveness 46, 95% confidence interval 0.39 to 0.53) in the 20 studies we included. The I2 in trials assessing overall pregnancy rate (PR) per embryo transfer (ET) cycle was 73.06%. Similar results were observed in subgroup analysis by different gender. Regression indicates pregnancy rate decreases with increasing age. Fertilization, implantation and live birth rates (72, 36 and 40%) showed no significant differences as compared to infertility due to other causes.Conclusions
Despite CHH patients usually being difficult to generate gametes, their actual chances of fertility are similar to subjects with other non-obstructive infertility. ART is a suitable option for CHH patients who do not conceive after long-term gonadotropin treatment.16.
Objectives
To develop a site-specific integration strategy for CAR-T engineering by using a non-viral vector dependent on adeno-associated viral (AAV) genome, which tends to be integrated into AAVS1 site with the help of its Rep proteins.Results
AAV-dependent vectors were produced in Sf9 cells. Structural analyses revealed the vector as covalently close-ended, linear duplex molecules, which was termed “CELiD” DNA. A plasmid CMV-Rep was constructed to express the integrases Rep78 and Rep68. Jurkat cells were co-electroporated with “CELiD” DNA and plasmid CMV-Rep in order to specifically integrate CAR gene into AAVS1 site. We examined 71 stably transfected Jurkat clones by nested PCR, sequencing and southern blotting, of which 30 clones bore CAR gene within AAVS1 site. The site-specific integration efficiency was nearly 42.2 %.Conclusions
The AAV-dependent vector preferentially integrated CAR into AAVS1 site, which could be further used in human T cell modification and enhance the security of CAR-T therapy.17.
BACKGROUND
Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions.OBJECTIVE
In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns.METHODS
We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations: “interneuron”, “somatosensory”, “development”, “activity”, “network patterns”, “thalamocortical”, “NMDA receptor”, “plasticity”. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab.RESULTS
We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and patterns of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016.CONCLUSION
Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.18.
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Background
Protein synthetic lethal genetic interactions are useful to define functional relationships between proteins and pathways. However, the molecular mechanism of synthetic lethal genetic interactions remains unclear.Results
In this study we used the clusters of short polypeptide sequences, which are typically shorter than the classically defined protein domains, to characterize the functionalities of proteins. We developed a framework to identify significant short polypeptide clusters from yeast protein sequences, and then used these short polypeptide clusters as features to predict yeast synthetic lethal genetic interactions. The short polypeptide clusters based approach provides much higher coverage for predicting yeast synthetic lethal genetic interactions. Evaluation using experimental data sets showed that the short polypeptide clusters based approach is superior to the previous protein domain based one.Conclusion
We were able to achieve higher performance in yeast synthetic lethal genetic interactions prediction using short polypeptide clusters as features. Our study suggests that the short polypeptide cluster may help better understand the functionalities of proteins.20.
Nicholas W. Burman Joel Croft Shaun Engelbrecht A. O. Ladenika O. S. MacGregor Mpho Maepa Michael Oluwatosin Bodunrin Kevin G. Harding 《The International Journal of Life Cycle Assessment》2018,23(8):1693-1700