Subtracting the background by reducing cell-free DNA's confounding effects on Mycobacterium tuberculosis quantitation and the sputum microbiome.

DNA characterisation in people with tuberculosis (TB) is critical for diagnostic and microbiome evaluations. However, extracellular DNA, more frequent in people on chemotherapy, confounds results. We evaluated whether nucleic acid dyes [propidium monoazide (PMA), PEMAX] and DNaseI could reduce this.

Erratum to "Bifunctional Tumor-Targeted Bioprobe for Phototheranosis".

[This corrects the article DOI: 10.34133/bmr.0002.

Brazilian Portuguese Translation and Validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA revised.

Introduction And Hypothesis: Condition-specific sexual questionnaires are important patient-reported outcome measures. The aim of this study was to translate and validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association Revised (PISQ-IR) into Brazilian Portuguese and to clinically validate it in a Brazilian Portuguese-speaking population.

Methods: Translation and validation of the PISQ-IR was performed according to the International Urogynecological Association-recommended process and guidelines.

Bifunctional Tumor-Targeted Bioprobe for Phototheranosis.

Near-infrared (NIR) phototheranostics provide promising noninvasive imaging and treatment for head and neck squamous cell carcinoma (HNSCC), capitalizing on its adjacency to skin or mucosal surfaces. Activated by laser irradiation, targeted NIR fluorophores can selectively eradicate cancer cells, harnessing the power of synergistic photodynamic therapy and photothermal therapy. However, there is a paucity of NIR bioprobes showing tumor-specific targeting and effective phototheranosis without hurting surrounding healthy tissues.

Novel technologies to characterize and engineer the microbiome in inflammatory bowel disease.

We present an overview of recent experimental and computational advances in technology used to characterize the microbiome, with a focus on how these developments improve our understanding of inflammatory bowel disease (IBD). Specifically, we present studies that make use of flow cytometry and metabolomics assays to provide a functional characterization of microbial communities. We also describe computational methods for strain-level resolution, temporal series, mycobiome and virome data, co-occurrence networks, and compositional data analysis.

Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer.

Fluorescence-guided surgery (FGS) aids surgeons with real-time visualization of small cancer foci and borders, which improves surgical and prognostic efficacy of cancer. Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH-sensitive near-infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported.

Quickly evolving near-infrared photoimmunotherapy provides multifaceted approach to modern cancer treatment.

Among modalities of cancer immunotherapy, near-infrared photoimmunotherapy (NIR-PIT) has reached significant preclinical and clinical stages and quickly evolved over the last 5 years. NIR-PIT uses deep-penetrable NIR light to induce physicochemical changes in the antibody-photosensitizer conjugate (APC), leading to resultant necrosis and immunogenic cell death (ICD) of the cancer cells. Alternatively, other types of photomedicine use photosensitizers to convert absorbed light energy either into reactive oxygen species for photodynamic therapy (PDT) or into heat for photothermal therapy (PTT).

Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores.

The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near-infrared (NIR) fluorescence-guided surgery is actively utilized for tumor localization and complete resection during surgery. However, currently available contrast-enhancing agents display low on-target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use.

Spatial-temporal dynamics of a microbial cooperative behavior resistant to cheating.

Much of our understanding of bacterial behavior stems from studies in liquid culture. In nature, however, bacteria frequently live in densely packed spatially-structured communities. How does spatial structure affect bacterial cooperative behaviors? In this work, we examine rhamnolipid production-a cooperative and virulent behavior of Pseudomonas aeruginosa.

Structure and properties of the giant reed (Arundo donax) lectin (ADL).

Arundo donax lectin (ADL) is a 170 amino acid protein that can be purified from the rhizomes of the giant reed or giant cane by exploiting its selective binding to chitin followed by elution with N-acetylglucosamine. The lectin is listed in the UniProt server, the largest protein sequence database, as an uncharacterized protein with chitin-binding domains (A0A0A9P802). This paper reports the purification, structure and ligand-binding properties of ADL.

Structure and properties of the oyster mushroom (Pleurotus ostreatus) lectin.

Pleurotus ostreatus Lectin (POL) is a 353 amino acid chain lectin that can be purified from the fruiting bodies of the very well-known and widely diffused edible oyster mushrooms (P. ostreatus). The lectin has been partially characterized by different groups and, although it was crystallized about 20 years ago, its 3D structure and the details of its interactions with carbohydrates are still unknown.

The Ultimate Guide to Bacterial Swarming: An Experimental Model to Study the Evolution of Cooperative Behavior.

Cooperation has fascinated biologists since Darwin. How did cooperative behaviors evolve despite the fitness cost to the cooperator? Bacteria have cooperative behaviors that make excellent models to take on this age-old problem from both proximate (molecular) and ultimate (evolutionary) angles. We delve into swarming, a phenomenon where billions of bacteria move cooperatively across distances of centimeters in a matter of a few hours.

Going beyond Structure: Nickel-Substituted Rubredoxin as a Mechanistic Model for the [NiFe] Hydrogenases.

Well-defined molecular systems for catalytic hydrogen production that are robust, easily generated, and active under mild aqueous conditions remain underdeveloped. Nickel-substituted rubredoxin (NiRd) is one such system, featuring a tetrathiolate coordination environment around the nickel center that is identical to the native [NiFe] hydrogenases and demonstrating hydrogenase-like proton reduction activity. However, until now, the catalytic mechanism has remained elusive.

High resolution crystal structure data of human plasma retinol-binding protein (RBP4) bound to retinol and fatty acids.

Retinol is transported in vertebrate plasma bound to a protein called retinol-binding protein (RBP4) so far believed to be specific for the vitamin. When the protein is saturated with retinol it binds tightly to another plasma protein, transthyretin while when not saturated with retinol it does not bind to TTR (Goodman, 1984). The X-ray structures of human RBP4, holo and devoid of retinol in its binding site are known to resolutions of 2.

Human plasma retinol-binding protein (RBP4) is also a fatty acid-binding protein.

RBP4 (plasma retinol-binding protein) is the 21 kDa transporter of all-trans retinol that circulates in plasma as a moderately tight 1:1 molar complex of the vitamin with the protein. RBP4 is primarily synthesized in the liver but is also produced by adipose tissue and circulates bound to a larger protein, transthyretin, TTR, that serves to increase its molecular mass and thus avoid its elimination by glomerular filtration. This paper reports the high resolution three-dimensional structures of human RBP4 naturally lacking bound retinol purified from plasma, urine and amniotic fluid.

The long variant of human ileal bile acid-binding protein associated with colorectal cancer exhibits sub-cellular localization and lipid binding behaviour distinct from those of the common isoform.

Background: Ileal bile acid-binding protein, IBABP, participates in the intracellular trafficking of bile salts and influences their signaling activities. The recently discovered variant, IBABP-L, bearing an N-terminal 49-amino acid extension, was found to be associated with colorectal cancer and to protect cancer cells from the cytotoxic effects of deoxycholate. However, the precise function and the molecular properties of this variant are currently unknown.

Metabolism and the Evolution of Social Behavior.

How does metabolism influence social behavior? This fundamental question at the interface of molecular biology and social evolution is hard to address with experiments in animals, and therefore, we turned to a simple microbial system: swarming in the bacterium Pseudomonas aeruginosa. Using genetic engineering, we excised a locus encoding a key metabolic regulator and disrupted P. aeruginosa's metabolic prudence, the regulatory mechanism that controls expression of swarming public goods and protects this social behavior from exploitation by cheaters.

Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications.

For targeted brain delivery, nanoparticles (NPs) should bypass the blood-brain barrier (BBB). Novel functionalization strategies, based on low-density lipoprotein receptor (LDLR) binding domain, have been here tested to increase the brain targeting efficacy of poly d,l-lactic-co-glycolic acid (PLGA) NPs, biodegradable and suited for biomedical applications. Custom-made PLGA NPs were functionalized with an apolipoprotein E modified peptide (pep-apoE) responsible for LDLR binding, or with lipocalin-type prostaglandin-d-synthase (L-PGDS), highly expressed in the brain.

Predictive value of clinical history compared with urodynamic study in 1,179 women.

Objective: to determine the positive predictive value of clinical history in comparison with urodynamic study for the diagnosis of urinary incontinence.

Methods: retrospective analysis comparing clinical history and urodynamic evaluation of 1,179 women with urinary incontinence. The urodynamic study was considered the gold standard, whereas the clinical history was the new test to be assessed.

Single Amino Acid Polymorphisms of Pertussis Toxin Subunit S2 (PtxB) Affect Protein Function.

Whooping cough due to Bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. Polymorphisms in the pertussis toxin, ptxA and ptxB genes, and the pertactin, prn genes of clinical isolates of Bordetella pertussis collected in Cincinnati from 1989 through 2005 were examined. While the ptxA and prn genotypes were variable, all 48 strains had the ptxB2 genotype; ptxB1 encodes glycine at amino acid 18 of the S2 subunit of pertussis toxin, while ptxB2 encodes serine.

All-Purpose Containers? Lipid-Binding Protein - Drug Interactions.

The combined use of in vitro (19F-NMR) and in silico (molecular docking) procedures demonstrates the affinity of a number of human calycins (lipid-binding proteins from ileum, liver, heart, adipose tissue and epidermis, and retinol-binding protein from intestine) for different drugs (mainly steroids and vastatins). Comparative evaluations on the complexes outline some of the features relevant for interaction (non-polar character of the drugs; amino acids and water molecules in the protein calyx most often involved in binding). Dissociation constants (Ki) for drugs typically lie in the same range as Ki for natural ligands; in most instances (different proteins and docking conditions), vastatins are the strongest interactors, with atorvastatin ranking top in half of the cases.

Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait.

Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa.

Three-dimensional structure and ligand-binding site of carp fishelectin (FEL).

Carp FEL (fishelectin or fish-egg lectin) is a 238-amino-acid lectin that can be purified from fish eggs by exploiting its selective binding to Sepharose followed by elution with N-acetylglucosamine. Its amino-acid sequence and other biochemical properties have previously been reported. The glycoprotein has four disulfide bridges and the structure of the oligosaccharides linked to Asn27 has been described.

High-resolution structures of mutants of residues that affect access to the ligand-binding cavity of human lipocalin-type prostaglandin D synthase.

Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the isomerization of the 9,11-endoperoxide group of PGH2 (prostaglandin H2) to produce PGD2 (prostaglandin D2) with 9-hydroxy and 11-keto groups. The product of the reaction, PGD2, is the precursor of several metabolites involved in many regulatory events. L-PGDS, the first member of the important lipocalin family to be recognized as an enzyme, is also able to bind and transport small hydrophobic molecules and was formerly known as β-trace protein, the second most abundant protein in human cerebrospinal fluid.