ResearchPad - minireview https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Protein Assays on Organic Electronics: Rational Device and Material Designs for Organic Transistor‐Based Sensors]]> https://www.researchpad.co/article/elastic_article_8330 OFETs go next: Organic field‐effect transistors (OFETs) functionalized with artificial receptors offer simple methods for the sensitive and selective detection of proteins and their chemical information, such as post‐translational modifications. Thus, the OFETs will be new caididates for the next‐generation electronic devices for healthcare applications.

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<![CDATA[Late‐Stage Diversification of Tryptophan‐Derived Biomolecules]]> https://www.researchpad.co/article/elastic_article_8325 Pd‐mediated reactions have emerged as a powerful tool for the site‐selective and bioorthogonal late‐stage diversification of amino acids, peptides and related compounds. Halotryptophans are accessible by biocatalytic approaches opening the application of a variety of cross‐coupling reactions for late‐stage modification of halotryptophan containing biomolecules.

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<![CDATA[Development of Glucose Transporter (GLUT) Inhibitors]]> https://www.researchpad.co/article/elastic_article_8235 Potent glucose transporter (GLUT) inhibitors have been developed over the last years. This Minireview serves as an overview of the origin (natural products, natural product‐inspired, non‐natural compounds, and virtual screening) of these molecules.John Wiley & Sons, Ltd.

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<![CDATA[Maturation of the mammalian secretome]]> https://www.researchpad.co/article/5b7c8abb463d7e1cbb579986

What methodology will define the complete secretome?

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<![CDATA[Tumor microenvironments, the immune system and cancer survival]]> https://www.researchpad.co/article/5b7a0c9f463d7e2d43cfb8f5

Recent microarray analyses of lymphomas suggest that the prognosis of cancer patients is related to an interplay between cancer cells and their microenvironment, including the immune response.

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<![CDATA[2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission]]> https://www.researchpad.co/article/N0248b252-038b-460d-82a9-c3e3547a9e91

With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms.

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<![CDATA[The gut microbiota and its interactions with cardiovascular disease]]> https://www.researchpad.co/article/N12abbdda-fc24-4fb4-a7fc-1f5ca76b6266

Summary

The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

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<![CDATA[Ultrasound‐mediated therapies for the treatment of biofilms in chronic wounds: a review of present knowledge]]> https://www.researchpad.co/article/N44c0d2f4-067a-411c-b16e-08a8345ec14d

Summary

Bacterial biofilms are an ever‐growing concern for public health, featuring both inherited genetic resistance and a conferred innate tolerance to traditional antibiotic therapies. Consequently, there is a growing interest in novel methods of drug delivery, in order to increase the efficacy of antimicrobial agents. One such method is the use of acoustically activated microbubbles, which undergo volumetric oscillations and collapse upon exposure to an ultrasound field. This facilitates physical perturbation of the biofilm and provides the means to control drug delivery both temporally and spatially. In line with current literature in this area, this review offers a rounded argument for why ultrasound‐responsive agents could be an integral part of advancing wound care. To achieve this, we will outline the development and clinical significance of biofilms in the context of chronic infections. We will then discuss current practices used in combating biofilms in chronic wounds and then critically evaluate the use of acoustically activated gas microbubbles as an emerging treatment modality. Moreover, we will introduce the novel concept of microbubbles carrying biologically active gases that may facilitate biofilm dispersal.

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<![CDATA[Bioengineered Escherichia coli Nissle 1917 for tumour‐targeting therapy]]> https://www.researchpad.co/article/N2a92b180-411e-4877-913f-e3d30721d4d1

Summary

Bacterial vectors, as microscopic living ‘robotic factories’, can be reprogrammed into microscopic living ‘robotic factories’, using a top‐down bioengineering approach to produce and deliver anticancer agents. Most of the current research has focused on bacterial species such as Salmonella typhimurium or Clostridium novyi. However, Escherichia coli Nissle 1917 (EcN) is another promising candidate with probiotic properties. EcN offers increased applicability for cancer treatment with the development of new molecular biology and complete genome sequencing techniques. In this review, we discuss the genetics and physical properties of EcN. We also summarize and analyse recent studies regarding tumour therapy mediated by EcN. Many challenges remain in the development of more promising strategies for combatting cancer with EcN.

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<![CDATA[Do antimicrobial mass medications work? A systematic review and meta-analysis of randomised clinical trials investigating antimicrobial prophylaxis or metaphylaxis against naturally occurring bovine respiratory disease]]> https://www.researchpad.co/article/N008e9581-de49-4414-b2b1-a68877c88182

Abstract

A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications (prophylaxis, metaphylaxis) to healthy individuals. The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease (i.e. morbidity) and/or die (i.e. mortality). Bovine respiratory disease (BRD) represents the major indication for cattle antimicrobials worldwide. The objectives were to perform a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality. In total, 58 publications met the inclusion criteria summarizing 169 individual RCTs, spanning 50 years (1966–2016). Antimicrobial prophylaxis and metaphylaxis demonstrated moderate, yet highly variable relative risk reductions in BRD morbidity. These were dependent on the antimicrobial classes used, dependent on metaphylaxis definition, BRD attack rates and duration of the RCTs. Best relative risk reductions were from broad-spectrum critically important antimicrobials, or combinations. BRD prophylaxis/metaphylaxis represents major antimicrobial consumption for highly variable short-term gains in absolute risk reduction of morbidity/mortality. Despite widespread use of prevention products, the need for antimicrobial mass medications should be re-evaluated since the underlying problem is more likely the segmented infrastructure of the feedlot and veal calf industries compared to the disease itself.

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<![CDATA[Emerging zoonotic viral infections of occupational health importance]]> https://www.researchpad.co/article/N0de96b38-9420-4d27-9c47-0e920af638bf

ABSTRACT

Emerging viral infections represent a public health risk pointed out by the spreading of pathogens with potential zoonotic risk. Moreover, the risk of zoonosis has probably been underestimated in occupational settings. A literature review between 2007 and 2018 was performed to identify evidences concerning the epidemiological associations between some emerging viruses and occupational diseases. Observational studies and case-reports were selected and analyzed. West Nile Virus (WNV) disease, Crimean-Congo Hemorrhagic Fever (CCHF) disease and Hepatitis E virus (HEV) infection were included in the review for their potential zoonotic transmission. The most important risk factor for acquiring WNV infection and CCHF infection is the exposure to infected mosquitoes and ticks, respectively; therefore, outdoor workers are at risk of infection. HEV is responsible for epidemics and endemics of acute hepatitis in humans, that can become infected through waterborne, foodborne and zoonotic transmission routes. A total of 10, 34 and 45 eligible studies for WNV, CCHF virus (CCFHV) and HEV, respectively, were analyzed by year, country, study design, risk group and outcomes. The occupational risk groups mainly included farm and agricultural workers, veterinarians, slaughterers, animal handlers, healthcare workers and soldiers. These findings support the need to develop effective interventions to prevent transmission of emerging viruses.

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<![CDATA[The role of the IKK complex in viral infections]]> https://www.researchpad.co/article/N4fd48691-fb0e-43d1-8e9d-4e1db54d60fa

Abstract

The NF‐κB signal transduction pathway is a critical regulator of multiple cellular functions that ultimately shift the balance between cell survival and death. The cascade is activated by many intrinsic and extrinsic stimuli, which is transduced via adaptor proteins to phosphorylate the IκB kinase (IKK) complex, which in turn phosphorylates the inhibitory IκBα protein to undergo proteasomal degradation and sets in motion nuclear events in response to the initial stimulus. Viruses are important modulators of the NF‐κB cascade and have evolved multiple mechanisms to activate or inhibit this pathway in a manner conducive to viral multiplication and establishment of a productive infectious cycle. This is a subject of extensive research by multiple laboratories whereby unraveling the interactions between specific viral components and members of the NF‐κB signal transduction cascade can shed unique perspectives on infection associated pathogenesis and novel therapeutic targets. In this review, we highlight the interactions between components of the IKK complex and multiple RNA and DNA viruses with the emphasis on mechanisms by which the interaction feeds the infection. Understanding these interactions will shed light on the exploitative capabilities of viruses to maintain an environment favorable for a productive infection.

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<![CDATA[ Escherichia coli, cattle and the propagation of disease]]> https://www.researchpad.co/article/N6efceab8-318a-4427-831e-f54eaf4c9be4

Abstract

Several early models describing host–pathogen interaction have assumed that each individual host has approximately the same likelihood of becoming infected or of infecting others. More recently, a concept that has been increasingly emphasized in many studies is that for many infectious diseases, transmission is not homogeneous but highly skewed at the level of populations. In what became known as the ‘20/80 rule’, about 20% of the hosts in a population were found to contribute to about 80% of the transmission potential. These heterogeneities have been described for the interaction between many microorganisms and their human or animal hosts. Several epidemiological studies have reported transmission heterogeneities for Escherichia coli by cattle, a phenomenon with far-reaching agricultural, medical and public health implications. Focusing on E. coli as a case study, this paper will describe super-spreading and super-shedding by cattle, review the main factors that shape these transmission heterogeneities and examine the interface with human health. Escherichia coli super-shedding and super-spreading by cattle are shaped by microorganism-specific, cattle-specific and environmental factors. Understanding the factors that shape heterogeneities in E. coli dispersion by cattle and the implications for human health represent key components that are critical for targeted infection control initiatives.

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<![CDATA[Mini‐transposons in microbial ecology and environmental biotechnology]]> https://www.researchpad.co/article/N547ba651-eefd-4058-8ec7-b4303bb2d9c5

Abstract

Mini‐transposon is the generic name given to the members of a collection of genetic assets derived from transposons Tn10 and Tn5, in which the naturally occurring functional segments of DNA have been rearranged artificially to originate shorter mobile elements. In the most widespread design (that known as the pUT system), any heterologous DNA segment can be conveniently cloned within the boundaries of a mini‐Tn5 vector and finally inserted into the chromosome of target Gram‐negative bacteria after a few simple genetic manipulations. The large variety of antibiotic, non‐antibiotic and excisable selection markers available has been combined at ease with DNA fragments encoding one or more phenotypes of interest for ecological or biotechnological applications. These include the tagging of specific strains in a community with selectable and/or optical marker genes, the production of stable gene fusions for monitoring transcriptional regulation in single cells, the metabolic engineering of strains destined for bioremediation, the non‐disruptive monitoring of gene transfer and the assembly of gene containment and strain containment circuits for genetically manipulated microorganisms.

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<![CDATA[Interaction of viral proteins with metal ions: role in maintaining the structure and functions of viruses]]> https://www.researchpad.co/article/N1d29969b-6425-46d4-8c01-98ed93227980

Abstract

Metal ions are integral part of some viral proteins and play an important role in their survival and pathogenesis. Zinc, magnesium and copper are the commonest metal ion that binds with viral proteins. Metal ions participate in maturation of genomic RNA, activation and catalytic mechanisms, reverse transcription, initial integration process and protection of newly synthesized DNA, inhibition of proton translocation (M2 protein), minus‐ and plus‐strand transfer, enhance nucleic acid annealing, activation of transcription, integration of viral DNA into specific sites and act as a chaperone of nucleic acid. Metal ions are also required for nucleocapsid protein‐transactivation response (TAR)–RNA interactions. In certain situations more than one metal ion is required e.g. RNA cleavage by RNase H. This review underscores the importance of metal ions in the survival and pathogenesis of a large group of viruses and studies on structural basis for metal binding should prove useful in the early design and development of viral inhibitors.

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<![CDATA[Structural studies on the Ebola virus matrix protein VP40 indicate that matrix proteins of enveloped RNA viruses are analogues but not homologues]]> https://www.researchpad.co/article/N70237d3b-c89f-4f5d-9fdb-8a4a3ef262a4

Abstract

Matrix proteins are the driving force of assembly of enveloped viruses. Their main function is to interact with and polymerize at cellular membranes and link other viral components to the matrix–membrane complex resulting in individual particle shapes and ensuring the integrity of the viral particle. Although matrix proteins of different virus families show functional analogy, they share no sequence or structural homology. Their diversity is also evident in that they use a variety of late domain motifs to commit the cellular vacuolar protein sorting machinery to virus budding. Here, we discuss the structural and functional aspects of the filovirus matrix protein VP40 and compare them to other known matrix protein structures from vesicular stomatitis virus, influenza virus and retroviral matrix proteins.

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<![CDATA[Proteomic strategies for the discovery of novel diagnostic and therapeutic targets for infectious diseases]]> https://www.researchpad.co/article/N0e8d66ca-a00c-4e45-ab67-45918e276d8f

Abstract

Viruses have developed numerous and elegant strategies to manipulate the host cell machinery to establish a productive infectious cycle. The interaction of viral proteins with host proteins plays an important role in infection and pathogenesis, often bypassing traditional host defenses such as the interferon response and apoptosis. Host–viral protein interactions can be studied using a variety of proteomic approaches ranging from genetic and biochemical to large‐scale high‐throughput technologies. Protein interactions between host and viral proteins are greatly influenced by host signal transduction pathways. In this review, we will focus on comparing proteomic information obtained through differing technologies and how their integration can be used to determine the functional aspect of the host response to infection. We will briefly review and evaluate techniques employed to elucidate viral–host interactions with a primary focus on Protein Microarrays (PMA) and Mass Spectrometry (MS) as potential tools in the discovery of novel therapeutic targets. As many potential molecular markers and targets are proteins, proteomic profiling is expected to yield both clearer and more direct answers to functional and pharmacologic questions.

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<![CDATA[When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico]]> https://www.researchpad.co/article/N1e0eb4c1-a3b1-41f7-8f37-58f542647e67

Abstract

During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty‐one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re‐evaluation of historical data suggests that approximately 60–70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.

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<![CDATA[Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium]]> https://www.researchpad.co/article/Nd648dcab-06b7-4a97-878a-9c9fb11262e1

Abstract

Influenza is an acute infection of the respiratory tract, which affects each year millions of people. Influenza virus infection is initiated by the surface glycoprotein hemagglutinin (HA) through receptor binding and fusion of viral and endosomal membranes. HA is synthesized as a precursor protein and requires cleavage by host cell proteases to gain its fusion capacity. Although cleavage of HA is crucial for virus infectivity, little was known about relevant proteases in the human airways for a long time. Recent progress in the identification and characterization of HA‐activating host cell proteases has been considerable however and supports the idea of targeting HA cleavage as a novel approach for influenza treatment. Interestingly, certain bacteria have been demonstrated to support HA activation either by secreting proteases that cleave HA or due to activation of cellular proteases and thereby may contribute to virus spread and enhanced pathogenicity. In this review, we give an overview on activation of influenza viruses by proteases from host cells and bacteria with the main focus on recent progress on HA cleavage by proteases HAT and TMPRSS2 in the human airway epithelium. In addition, we outline investigations of HA‐activating proteases as potential drug targets for influenza treatment.

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<![CDATA[Cellular and molecular mechanisms of viral infection in the human placenta]]> https://www.researchpad.co/article/N3181cf93-188b-4957-bf94-45299ccc83c0

Abstract

The placenta is a highly specialized organ that is formed during human gestation for conferring protection and generating an optimal microenvironment to maintain the equilibrium between immunological and biochemical factors for fetal development. Diverse pathogens, including viruses, can infect several cellular components of the placenta, such as trophoblasts, syncytiotrophoblasts and other hematopoietic cells. Viral infections during pregnancy have been associated with fetal malformation and pregnancy complications such as preterm labor. In this minireview, we describe the most recent findings regarding virus–host interactions at the placental interface and investigate the mechanisms through which viruses may access trophoblasts and the pathogenic processes involved in viral dissemination at the maternal–fetal interface.

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