Conformational Dynamics of Influenza A Virus Ribonucleoprotein Complexes during RNA Synthesis.

Viral ribonucleoproteins (vRNPs) are the cornerstones of viral proliferation, as they form the macromolecular complexes that are responsible for the transcription and replication of most single-stranded RNA viruses. The influenza A virus (IAV) polymerase catalyzes RNA synthesis within the context of vRNPs where genomic viral RNA (vRNA) is packaged by the viral nucleoprotein (NP). We used high-speed atomic force microscopy and electron microscopy to study the conformational dynamics of individual IAV recombinant RNPs (rRNPs) during RNA synthesis.

DNA replication machineries: Structural insights from crystallography and electron microscopy.

Since the discovery of DNA as the genetic material, scientists have been investigating how the information contained in this biological polymer is transmitted from generation to generation. X-ray crystallography, and more recently, cryo-electron microscopy techniques have been instrumental in providing essential information about the structure, functions and interactions of the DNA and the protein machinery (replisome) responsible for its replication. In this chapter, we highlight several works that describe the structure and structure-function relationships of the core components of the prokaryotic and eukaryotic replisomes.

Brazilian Society of Surgical Oncology consensus on fertility-sparing surgery for cervical cancer.

Objective: Several controversies remain on conservative management of cervical cancer. Our aim was to develop a consensus recommendation on important and novel topics of fertility-sparing treatment of cervical cancer.

Methods: The consensus was sponsored by the Brazilian Society of Surgical Oncology (BSSO) from March 2020 to September 2020 and included a multidisciplinary team of 55 specialists.

Cancer risk-reducing surgery: Brazilian Society of Surgical Oncology Guideline Part 2 (Gastrointestinal and thyroid).

Background: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population.

Objectives: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations.

Development of colorimetric sensors based on gold nanoparticles for SARS-CoV-2 RdRp, E and S genes detection.

We present a fast, reliable and easy to scale-up colorimetric sensor based on gold nanoparticles (AuNPs) to detect the sequences coding for the RdRp, E, and S proteins of SARS-CoV-2. The optimization of the system (so-called "the sensor") includes the evaluation of different sizes of nanoparticles, sequences of oligonucleotides and buffers. It is stable for months without any noticeable decrease in its activity, allowing the detection of SARS-CoV-2 sequences by the naked eye in 15 min.

In vitro single-molecule manipulation studies of viral DNA replication.

Faithfull replication of genomic information relies on the coordinated activity of the multi-protein machinery known as the replisome. Several constituents of the replisome operate as molecular motors that couple thermal and chemical energy to a mechanical task. Over the last few decades, in vitro single-molecule manipulation techniques have been used to monitor and manipulate mechanically the activities of individual molecular motors involved in DNA replication with nanometer, millisecond, and picoNewton resolutions.

DNA replication machinery: Insights from single-molecule approaches.

The replisome is the multiprotein molecular machinery that replicates DNA. The replisome components work in precise coordination to unwind the double helix of the DNA and replicate the two strands simultaneously. The study of DNA replication using single-molecule approaches provides a novel quantitative understanding of the dynamics and mechanical principles that govern the operation of the replisome and its components.

Proposal for a provisional protocol for the care and identification of dental transmission routes of COVID-19 in Latin America: A Literature review.

Background: The new coronavirus called COVID-19 originated in the city of Wuhan, China and has currently spread to different continents, leading the World Health Organization (WHO) to declare a "pandemic". Therefore, the aim of this review was to present a new proposal for a care protocol in Peruvian Dentistry: Provisional review of the diagnosis, treatment, epidemiological characteristics, routes of transmission and recommendations of COVID-19.

Material And Methods: A search of digital scientific literature was made in the databases: Science Direct, Pubmed and Google Scholar.

Knowledge and Awareness of Effective Recycling of Dental Materials and Waste Management among Peruvian Undergraduate Students of Dentistry: A Logistic Regression Analysis.

Objective: Biomedical waste management and recycling is a very important topic today to preserve the environment, especially at the university level where future specialists in the health sciences are trained. So, the aim of this study was to evaluate the knowledge and awareness about recycling of dental materials and waste management among Peruvian undergraduate students of dentistry.

Materials And Methods: This cross-sectional study evaluated 254 Peruvian undergraduate dentistry students from October 2019 to January 2020, at the National University of San Marcos.

Understanding the paradoxical mechanical response of in-phase A-tracts at different force regimes.

A-tracts are A:T rich DNA sequences that exhibit unique structural and mechanical properties associated with several functions in vivo. The crystallographic structure of A-tracts has been well characterized. However, the mechanical properties of these sequences is controversial and their response to force remains unexplored.

Brazilian Society of Surgical Oncology guidelines for surgical treatment of endometrial cancer in regions with limited resources.

Background: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines.

Objectives: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers.

Dynamic constriction and fission of endoplasmic reticulum membranes by reticulon.

The endoplasmic reticulum (ER) is a continuous cell-wide membrane network. Network formation has been associated with proteins producing membrane curvature and fusion, such as reticulons and atlastin. Regulated network fragmentation, occurring in different physiological contexts, is less understood.

Permeability modes in fluctuating lipid membranes with DNA-translocating pores.

Membrane pores can significantly alter not only the permeation dynamics of biological membranes but also their elasticity. Large membrane pores able to transport macromolecular contents represent an interesting model to test theoretical predictions that assign active-like (non-equilibrium) behavior to the permeability contributions to the enhanced membrane fluctuations existing in permeable membranes [Maneville et al. Phys.

Effect of Antifungal Treatment in a Diet-Based Murine Model of Disseminated Candidiasis Acquired via the Gastrointestinal Tract.

Candida albicans, normally found as a commensal in the gut, is a major human fungal pathogen responsible for both mucosal and systemic infections in a wide variety of immunocompromised individuals, including cancer patients and organ transplant recipients. The gastrointestinal tract represents a major portal of entry for the establishment of disseminated candidiasis in many of these individuals. Here we report the development of a diet-based mouse model for disseminated candidiasis acquired via the gastrointestinal tract.

Isavuconazole Is Effective for the Treatment of Experimental Cryptococcal Meningitis.

We evaluated the efficacy of isavuconazole against cryptococcal meningitis. Treatment with either oral isavuconazole (120 mg/kg and 240 mg/kg twice a day [BID]) or fluconazole as the positive control significantly improved survival in mice infected intracranially with either Cryptococcus neoformans USC1597 or H99 and significantly reduced brain fungal burdens for both isolates. Concentrations of isavuconazole in plasma and brain tissue also demonstrated that the greatest improvements in survival and fungal burden were associated with elevated exposures.

The novel arylamidine T-2307 demonstrates in vitro and in vivo activity against echinocandin-resistant Candida glabrata.

Objectives: Candida species are major causes of invasive mycoses in immunocompetent and immunocompromised hosts. Treatment options are limited in the setting of antifungal resistance and increased rates of echinocandin-resistant Candida glabrata have been reported. The novel arylamidine T-2307 demonstrates potent in vitro antifungal activity against Candida species.

Characterization of the initial steps in the T7 DNA ejection process.

A specialized complex, the tail, is the most common strategy employed by bacterial viruses to deliver their genome without disrupting cell integrity. T7 has a short, non-contractile tail formed by a tubular structure surrounded by fibers. Recent studies showed that incubation of the virus with lipopolysaccharides (LPS) resulted in complete delivery of the viral genome, demonstrating for the first time that LPS are the T7 receptor.

Efficacy of the investigational echinocandin ASP9726 in a guinea pig model of invasive pulmonary aspergillosis.

ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.

Conformational changes leading to T7 DNA delivery upon interaction with the bacterial receptor.

The majority of bacteriophages protect their genetic material by packaging the nucleic acid in concentric layers to an almost crystalline concentration inside protein shells (capsid). This highly condensed genome also has to be efficiently injected into the host bacterium in a process named ejection. Most phages use a specialized complex (often a tail) to deliver the genome without disrupting cell integrity.

Biophysical analysis of the MHR motif in folding and domain swapping of the HIV capsid protein C-terminal domain.

Infection by human immunodeficiency virus (HIV) depends on the function, in virion morphogenesis and other stages of the viral cycle, of a highly conserved structural element, the major homology region (MHR), within the carboxyterminal domain (CTD) of the capsid protein. In a modified CTD dimer, MHR is swapped between monomers. While no evidence for MHR swapping has been provided by structural models of retroviral capsids, it is unknown whether it may occur transiently along the virus assembly pathway.

The novel arylamidine T-2307 maintains in vitro and in vivo activity against echinocandin-resistant Candida albicans.

We evaluated the in vitro and in vivo activities of the investigational arylamidine T-2307 against echinocandin-resistant Candida albicans. T-2307 demonstrated potent in vitro activity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain.

The investigational agent E1210 is effective in treatment of experimental invasive candidiasis caused by resistant Candida albicans.

The in vitro and in vivo activity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistant Candida albicans. E1210 demonstrated potent in vitro activity, and in mice with invasive candidiasis caused by echinocandin-resistant C. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day).

Mechanical unfolding of long human telomeric RNA (TERRA).

We report the first single molecule investigation of TERRA molecules. By using optical-tweezers and other biophysical techniques, we have found that long RNA constructions of up to 25 GGGUUA repeats form higher order structures comprised of single parallel G-quadruplex blocks, which unfold at lower forces than their DNA counterparts.

Association equilibrium of the HIV-1 capsid protein in a crowded medium reveals that hexamerization during capsid assembly requires a functional C-domain dimerization interface.

Polymerization of the intact capsid protein (CA) of HIV-1 into mature capsidlike particles at physiological ionic strength in vitro requires macromolecularly crowded conditions that approach those inside the virion, where the mature capsid is assembled in vivo. The capsid is organized as a hexameric lattice. CA subunits in each hexamer are connected through interfaces that involve the CA N-terminal domain (NTD); pairs of CA subunits belonging to different hexamers are connected through a different interface that involves the C-terminal domain (CTD).

Interlaboratory and interstudy reproducibility of a novel lateral-flow device and influence of antifungal therapy on detection of invasive pulmonary aspergillosis.

Interest in lateral-flow devices (LFDs) as potential point-of-care assays for the diagnosis of infectious diseases has increased. Our objective was to evaluate the interlaboratory and interstudy reproducibility and the effects of antifungal therapy on an LFD developed for invasive pulmonary aspergillosis (IPA) detection. An established neutropenic guinea pig model of IPA caused by Aspergillus fumigatus was used.