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  • 1.

    【2hr】Oncolytic Newcastle Disease Virus for cancer therapy: old challenges and new directions

    包量

    机译 用于癌症治疗的溶瘤新城疫病毒：旧挑战和新方向
    摘要：
  • 2.

    【2hr】A Coincidence Detector Triggers Botulinum Neurotoxin Translocation

    包量

    机译 巧合检测器触发肉毒杆菌神经毒素易位
    摘要：
  • 3.

    【2hr】Developing insights into the mechanisms of evolution of bacterial pathogens from whole-genome sequences

    包量

    机译 深入了解全基因组序列中细菌病原体进化的机制
    摘要：Evolution of bacterial pathogen populations has been detected in a variety of ways including phenotypic tests, such as metabolic activity, reaction to antisera and drug resistance and genotypic tests that measure variation in chromosome structure, repetitive loci and individual gene sequences. While informative, these methods only capture a small subset of the total variation and, therefore, have limited resolution. Advances in sequencing technologies have made it feasible to capture whole-genome sequence variation for each sample under study, providing the potential to detect all changes at all positions in the genome from single nucleotide changes to large-scale insertions and deletions. In this review, we focus on recent work that has applied this powerful new approach and summarize some of the advances that this has brought in our understanding of the details of how bacterial pathogens evolve.
  • 4.

    【2hr】Host detection of pathogen-induced translational inhibition: a new pathogen-specific branch of the innate immune system?

    包量

    机译 宿主检测病原体诱导的翻译抑制：先天免疫系统的新病原体特异性分支？
    • 作者：Emily Troemel
    • 刊名：Future Microbiology
    • 2012年第10期
    摘要：
  • 5.

    【2hr】Bacteriophage endolysins as novel antimicrobials

    包量

    机译 噬菌体溶菌素作为新型抗菌剂
    摘要：Endolysins are enzymes used by bacteriophages at the end of their replication cycle to degrade the peptidoglycan of the bacterial host from within, resulting in cell lysis and release of progeny virions. Due to the absence of an outer membrane in the Gram-positive bacterial cell wall, endolysins can access the peptidoglycan and destroy these organisms when applied externally, making them interesting antimicrobial candidates, particularly in light of increasing bacterial drug resistance. This article reviews the modular structure of these enzymes, in which cell wall binding and catalytic functions are separated, as well as their mechanism of action, lytic activity and potential as antimicrobials. It particularly focuses on molecular engineering as a means of optimizing endolysins for specific applications, highlights new developments that may render these proteins active against Gram-negative and intracellular pathogens and summarizes the most recent applications of endolysins in the fields of medicine, food safety, agriculture and biotechnology.
  • 6.

    【2hr】Pretreatment HIV-1 drug resistance is strongly associated with virologic failure in HIV-infected patients receiving partly active antiretroviral regimens

    包量

    机译 在接受部分有效抗逆转录病毒治疗的HIV感染患者中，HIV-1的预处理耐药与病毒学衰竭密切相关
    摘要：The scale-up of antiretroviral therapy in sub-Saharan Africa has significantly reduced mortality from AIDS. Hamers et al. explores the impact of pretreatment HIV-1 drug resistance on virologic failure, immunologic response, and acquisition of drug resistance after 1 year of first-line antiretroviral therapy by longitudinally evaluating 2579 participants with pretreatment drug resistance results from the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) cohort. Participants with pretreatment drug resistance who were given a treatment regimen with reduced activity to at least one prescribed drug had a significantly greater risk of virologic failure and acquired drug resistance compared with both participants without pretreatment drug resistance, and participants with pretreatment drug resistance who were prescribed fully active regimens. This paper by Hamers et al. validates the need for at least three fully active antiretroviral drugs to prevent the acquisition of drug resistance and to optimize treatment success in resource limited settings.
  • 7.

    【2hr】Evolutionary and genomic insights into meningococcal biology

    包量

    机译 脑膜炎球菌生物学的进化论和基因组学见解
    摘要：
  • 8.

    【2hr】Optimizing the balance between host and environmental survival skills: lessons learned from Listeria monocytogenes

    包量

    机译 优化宿主和环境生存技能之间的平衡：从单核细胞增生性李斯特菌中吸取的教训
    摘要：Environmental pathogens – organisms that survive in the outside environment but maintain the capacity to cause disease in mammals – navigate the challenges of life in habitats that range from water and soil to the cytosol of host cells. The bacterium Listeria monocytogenes has served for decades as a model organism for studies of host–pathogen interactions and for fundamental paradigms of cell biology. This ubiquitous saprophy te has recently become a model for understanding how an environmental bacterium switches to life within human cells. This review describes how L. monocytogenes balances life in disparate environments with the help of a critical virulence regulator known as PrfA. Understanding L. monocytogenes survival strategies is important for gaining insight into how environmental microbes become pathogens.
  • 9.

    【2hr】Oxidative stress resistance in Porphyromonas gingivalis

    包量

    机译 牙龈卟啉单胞菌的抗氧化应激
    摘要：Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets.
  • 10.

    【2hr】Defense at the border: the blood–brain barrier versus bacterial foreigners

    包量

    机译 边境防御：血脑屏障与细菌外国人
    摘要：Bacterial meningitis is among the top ten causes of infectious disease-related deaths worldwide, with up to half of the survivors left with permanent neurological sequelae. The blood–brain barrier (BBB), composed mainly of specialized brain microvascular endothelial cells, maintains biochemical homeostasis in the CNS by regulating the passage of nutrients, molecules and cells from the blood to the brain. Despite its highly restrictive nature, certain bacterial pathogens are able to gain entry into the CNS resulting in serious disease. In recent years, important advances have been made in understanding the molecular and cellular events that are involved in the development of bacterial meningitis. In this review, we summarize the progress made in elucidating the molecular mechanisms of bacterial BBB-crossing, highlighting common themes of host–pathogen interaction, and the potential role of the BBB in innate defense during infection.
  • 11.

    【2hr】Bacterial Type IV Secretion Systems: Versatile Virulence Machines

    包量

    机译 细菌IV型分泌系统：多功能毒力机
    摘要：Many bacterial pathogens employ multicomponent protein complexes to deliver macromolecules directly into their eukaryotic host cell to promote infection. Some Gram-negative pathogens use a versatile type IV secretion system (T4SS) that can translocate DNA or proteins into host cells. T4SSs represent major bacterial virulence determinants and have recently been the focus of intense research efforts designed to better understand and combat infectious diseases. Interestingly, although the two major classes of T4SSs function in a similar manner to secrete proteins, the translocated “effectors” vary substantially from one organism to another. In fact, differing effector repertoires likely contribute to organism-specific host cell interactions and disease outcomes. In this review, we discuss the current state of T4SS research, with an emphasis on intracellular bacterial pathogens of humans and the diverse array of translocated effectors used to manipulate host cells.
  • 12.

    【2hr】Microcin C: biosynthesis and mechanisms of bacterial resistance

    包量

    机译 Microcin C：细菌抗性的生物合成及其机理
    摘要：Nonhydrolyzable aminoacyl-adenylates that inhibit protein synthesis provide a promising route towards the development of novel antibiotics whose mechanism of action limits the appearance of bacterial drug resistance. The ‘Trojan horse’ antibiotic microcin C (McC) consists of a nonhydrolyzable aspartyl–adenylate that is efficiently imported into bacterial cells owing to a covalently attached peptide carrier. Once inside the cell, the carrier is removed by proteolytic processing to release a potent aspartyl tRNA synthetase inhibitor. The focus of this article is on the mechanism of biosynthesis of McC. We also examine the strategies utilized by McC-producing strains to overcome toxicity due to unwanted, premature processing of the drug. This article will discuss how McC biosynthesis can be systematically manipulated for the development of derivatives that will target the entire battery of aminoacyl tRNA synthetases in various bacteria.
  • 13.

    【2hr】Future perspective on host-pathogen interactions during bacterial biofilm formation within the nasopharynx

    包量

    机译 鼻咽内细菌生物膜形成过程中宿主-病原体相互作用的未来展望
    摘要：Nasopharyngeal colonization provides bacteria with a place of residence, a platform for person-to-person transmission and for many opportunistic pathogens it is a prerequisite event towards the development of invasive disease. Therefore, how host factors within the nasopharynx contribute to, inhibit or otherwise shape biofilm formation, the primary mode of existence for colonizing bacteria, and how biofilm bacteria subvert the acute inflammatory response that facilitates clearance, are important topics for future microbiological research. This review proposes the examination of host components as bridging molecules for bacterial interactions during biofilm formation, altered virulence determinant production and cell wall modification as a mechanism for immunoquiescence, and the role of host factors as signals and co-opted mechanisms for bacterial dissemination, together providing an opportunity for disease.
  • 14.

    【2hr】The latency-associated nuclear antigen, a multifunctional protein central to Kaposi’s sarcoma-associated herpesvirus latency

    包量

    机译 潜伏期相关的核抗原，一种多功能蛋白，是卡波济氏肉瘤相关疱疹病毒潜伏期的关键
    摘要：Latency-associated nuclear antigen (LANA) is encoded by the Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) open reading frame 73. LANA is expressed during latent KSHV infection of cells, including tumor cells, such as primary effusion lymphoma, KS and multicentric Castleman’s disease. Latently infected cells have multiple extrachromosomal copies of covalently closed circular KSHV genomes (episomes) that are stably maintained in proliferating cells. LANA’s best characterized function is that of mediating episome persistence. It does so by binding terminal repeat sequences to the chromosomal matrix, thus ensuring episome replication with each cell division and efficient DNA segregation to daughter nuclei after mitosis. To achieve these functions, LANA associates with different host cell proteins, including chromatin-associated proteins and proteins involved in DNA replication. In addition to episome maintenance, LANA has transcriptional regulatory effects and affects cell growth. LANA exerts these functions through interactions with different cell proteins.
  • 15.

    【2hr】Progress in the experimental therapy of severe arenaviral infections

    包量

    机译 严重沙眼病毒感染的实验治疗进展
    摘要：
  • 16.

    【2hr】Vesicular transport systems in fungi

    包量

    机译 真菌中的水泡运输系统
    摘要：Canonical and unconventional mechanisms of secretion in many eukaryotic cells are relatively well known. In contrast to the situation in animal cells, mechanisms of secretion in fungi must include the capacity for trans-cell wall passage of macromolecules to the extracellular space. Although these mechanisms remain somewhat elusive, several studies in recent years have suggested that vesicular transport is required for trans-cell wall secretion of large molecules. Several fungal molecules, including proteins, lipids, polysaccharides and pigments, are released to the extracellular space in vesicles. In pathogenic fungi, a number of these vesicular components are associated with fungal virulence. Indeed, extracellular vesicles produced by fungi can interfere with the immunomodulatory activity of host cells. Fungal vesicles share many functional aspects with mammalian exosomes and extracellular vesicles produced by bacteria, plants and protozoa, but their cellular origin remains unknown. Here, we discuss the involvement of vesicular transport systems in fungal physiology and pathogenesis, making parallels with the mammalian, bacterial, protozoan and plant cell literature.
  • 17.

    【2hr】Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?

    包量

    机译 溃疡分枝杆菌病（Buruli溃疡）的治疗：从手术到抗生素，药丸比小刀强吗？
    摘要：Until 2004, the skin disease known as Buruli ulcer, caused by Mycobacterium ulcerans, could only be treated by surgery and skin grafting. Although this worked reasonably well on early lesions typically found in patients in Australia, the strategy was usually impractical on large lesions resulting from diagnostic delay in patients in rural West Africa. Based on promising preclinical studies, treatment trials in West Africa have shown that a combination of rifampin and streptomycin administered daily for 8 weeks can kill M. ulcerans bacilli, arrest the disease, and promote healing without relapse or reduce the extent of surgical excision. Improved treatment options are the focus of research that has increased tremendously since the WHO began its Global Buruli Ulcer Initiative in 1998.
  • 18.

    【2hr】The modulation of Staphylococcus aureus mRNA turnover

    包量

    机译 金黄色葡萄球菌mRNA更新的调节
    摘要：Staphylococcus aureus is a Gram-positive pathogen capable of causing a wide array of infections owing, in large part, to the coordinated expression of an extensive repertoire of virulence factors. Our laboratory and others have shown that the expression of these factors can occur post-transcriptionally at the level of mRNA turnover and is mediated by ribonucleases, RNA-binding proteins, and regulatory RNA molecules. Moreover, S. aureus harbors the ability to alter the stability of its mRNA titers in response to physiological stresses, including antibiotic exposure. Although ongoing studies are attempting to identify the molecular components that modulate S. aureus mRNA turnover, innovative approaches to target these essential processes have established a novel group of targets for therapeutic development against staphylococcal infections.
  • 19.

    【2hr】Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts

    包量

    机译 人乳头瘤病毒和宫颈癌：生物标记物可提高预防效果
    摘要：While organized screening programs in industrialized countries have significantly reduced cervical cancer incidence, cytology-based screening has several limitations. Equivocal or mildly abnormal Pap tests require costly retesting or diagnostic work-up by colposcopy and biopsy. In low-resource countries, it has been difficult to establish and sustain cytology-based programs. Advances in understanding human papillomavirus biology and the natural history of human papillomavirus-related precancers and cancers have led to the discovery of a range of novel biomarkers in the past decade. In this article, we will discuss the potential role of new biomarkers for primary screening, triage and diagnosis in high-resource countries and their promise for prevention efforts in resource constrained settings.
  • 20.

    【2hr】Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

    包量

    机译 单纯性眼疱疹病毒：潜伏期，再激活，复发性疾病和治疗之间有何关系？
    摘要：Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases.
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