Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers.

The airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent, , adheres to ciliated cells of the human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We examined the impact of infection and of adenylate cyclase toxin-hemolysin (CyaA) action on the functional integrity of human bronchial epithelial cells cultured at the air-liquid interface (ALI).

Characterizing indeterminate liver lesions in patients with localized pancreatic cancer at the time of diagnosis.

Background: In patients with newly diagnosed pancreatic cancer, the classification of indeterminate liver lesions is an unanswered clinical dilemma as misclassification of these lesions can impact the assignment of clinical stage and subsequent treatment planning. Our objective was to design a standardized classification system to more accurately define the risk of malignancy in indeterminate liver lesions.

Methods: In this retrospective study, patients with localized, non-metastatic pancreatic cancer were identified and pre-treatment computed tomography (CT) scans were evaluated for the presence or absence of liver lesions.

Pancreatic adenocarcinoma: cross-sectional imaging techniques.

Pancreatic adenocarcinoma is a common malignancy that has a poor prognosis. Imaging is vital in its detection, staging, and management. Although a variety of imaging techniques are available, MDCT is the preferred imaging modality for staging and assessing the resectability of pancreatic adenocarcinoma.

CCR6 signaling inhibits suppressor function of induced-Treg during gut inflammation.

CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3CD4 T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6 Tregs enhanced the expression of RORγt.

A day in the life of a pharmacovigilance case processor.

Pharmacovigilance (PV) has grown significantly in India in the last couple of decades. The etymological roots for the word "pharmacovigilance" are "Pharmakon" (Greek for drug) and "Vigilare" (Latin for to keep watch). It relies on information gathered from the collection of individual case safety reports and other pharmacoepidemiological data.

Is There a Lower Size Limit for Superconductivity?

The ultimate lower size limit for superconducting order to exist is set by the "Anderson criterion"-arising from quantum confinement-that appears to be remarkably accurate and universal. We show that carefully grown, phase-pure, nanocrystalline bcc-Ta remains superconducting (with ordering temperature, T ≈ 0.9 K) down to sizes 40% below the conventional estimate of the Anderson limit of 4.

Loss of inversin decreases transepithelial sodium transport in murine renal cells.

Type II nephronophthisis (NPHP2) is an autosomal recessive renal cystic disorder characterized by mutations in the inversin gene. Humans and mice with mutations in inversin have enlarged cystic kidneys that may be due to fluid accumulation resulting from altered ion transport. To address this, transepithelial ion transport was measured in shRNA-mediated inversin-depleted mouse cortical collecting duct (mCCD) cells.

Endoscopic Myringoplasty Versus Microscopic Myringoplasty in Tubotympanic CSOM: A Comparative Study of 120 Cases.

Myringoplasty is one of the commonest operations performed on the middle ear. Our aim was to compare the results of endoscopic permeatal myringoplasty with that of conventional myringoplasty by post aural approach using operating microscope. A total of 120 patients having central perforation of tympanic membrane were randomly divided into two equal groups of 60 patients each.

Bimaxillary concomitant hypohyperdontia in a 10-year-old child.

Numerical anomalies, either addition or deletion, are quite a common findings in human dentition. However, it is extremely rare to find both hypodontia and hyperdontia simultaneously in the same individual. This condition is referred as concomitant hypohyperdontia (CHH).

IL-1 Receptor-Knockout Mice Develop Epidermal Cysts and Show an Altered Innate Immune Response after Exposure to UVB Radiation.

In this study, we observed that mice lacking the IL-1 receptor (IL-1R) (IL1r) or deficient in IL1-β developed multiple epidermal cysts after chronic UVB exposure. Cysts that developed in IL1r mice were characterized by the presence of the hair follicle marker Sox 9, keratins 10 and 14, and normal melanocyte distribution and retinoid X receptor-α expression. The increased incidence of cysts in IL1r mice was associated with less skin inflammation as characterized by decreased recruitment of macrophages, and their skin also maintained epidermal barrier function compared with wild-type mice.

A receptor dependent-4D QSAR approach to predict the activity of mutated enzymes.

Screening and selection tools to obtain focused libraries play a key role in successfully engineering enzymes of desired qualities. The quality of screening depends on efficient assays; however, a focused library generated with a priori information plays a major role in effectively identifying the right enzyme. As a proof of concept, for the first time, receptor dependent - 4D Quantitative Structure Activity Relationship (RD-4D-QSAR) has been implemented to predict kinetic properties of an enzyme.

Enhanced anticancer efficacy of histone deacetyl inhibitor, suberoylanilide hydroxamic acid, in combination with a phosphodiesterase inhibitor, pentoxifylline, in human cancer cell lines and in-vivo tumor xenografts.

Vorinostat [suberoylanilide hydroxamic acid (SAHA)], a histone deacetylase inhibitor, shows limited clinical activity against solid tumors when used alone. The methyl xanthine drug, pentoxifylline (PENT), has been described to have antitumor properties. The aim of this study was to look for the enhanced anticancer activities of both agents when used in combination at doses lower than their respective efficacy dose when used alone.

Monoanionic, Bis(pyrazolyl)methylborate [(PhB)CH(3,5-(CH)Pz))] as a Supporting Ligand for Copper(I)-ethylene, cis-2-Butene, and Carbonyl Complexes.

The monoanionic bidentate ligand [(PhB)CH(3,5-(CH)Pz))] has been prepared from lithium bis(pyrazolyl)methanide and triphenylborane. This useful new ligand is closely related to the well-established bis(pyrazolyl)borate and bis(pyrazolyl)methane ligands but has key differences to both analogues as well. The ethylene, cis-2-butene, and carbon monoxide adducts [(PhB)CH(3,5-(CH)Pz)]Cu(L) (where L = CH, cis-CHHC═CHCH, and CO) have been prepared from [(PhB)CH(3,5-(CH)Pz))]Li(THF), copper(I) triflate, and the corresponding coligand.

Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection.

The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand the host factors that influence its control. Previously, the complement system has been shown to provide protection during the seasonal influenza virus infection, however, the role of individual complement pathways is not yet clear. Here, we have dissected the role of intact complement as well as of its individual activation pathways during the pandemic influenza virus infection using mouse strains deficient in various complement components.

Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling.

In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours.

Intratumoral natural killer cells show reduced effector and cytolytic properties and control the differentiation of effector Th1 cells.

Natural killer (NK) cells are known to have effector and cytolytic properties to kill virus infected or tumor cells spontaneously. Due to these properties, NK cells have been used as an adoptive cellular therapy to control tumor growth in various clinical trials but have shown limited clinical benefits. This indicates that our knowledge about phenotypic and functional differences in NK cells within the tumor microenvironment and secondary lymphoid tissues is incomplete.

His-Bundle Pacing for Identifying Optimal Ablation Sites in Patients Undergoing Atrioventricular Junction Ablation: Teaching an Old Dog a New Trick.

Background: Atrioventricular (AV) junction (AVJ) ablation is conventionally performed by localizing the His-bundle electrogram (HBE). Identification of HBE in the presence of atrial fibrillation (AF) can be difficult, and can make this simple procedure challenging. In this study, we describe our experience with an alternative approach to localize optimal ablation sites using His-bundle pacing (HBP).

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance.

The intestinal epithelial lining is a very dynamic interface, where multiple interactions occur with the external world. The intestinal epithelial barrier is continuously exposed to a huge load of commensal microorganisms, food-borne antigens, as well as invading enteropathogens. Intestinal epithelial cells (IECs) and underlying immune cells are the main players in maintaining the delicate balance between gut tolerance and inflammation.

The silver(I) complex [HB{3-(CF),5-(CH)Pz}]AgNCCH supported by a partially fluorinated scorpionate ligand.

Tris(pyrazolyl)borates are used extensively in metal coordination chemistry and belong to a class of ligands generally referred to as scorpionates. The steric and electronic properties of these ligands can be modified quite easily by varying the substituents on the 3-, 4-, and 5-positions of the pyrazolyl moieties on the B atom. Fluorinated tris(pyrazolyl)borates are useful in the stabilization of rare silver(I) complexes.

Imaging for Oncologic Response Assessment in Lymphoma.

Objective: The purpose of this article is to examine the role of different imaging biomarkers, focusing in particular on the use of updated CT and PET response criteria for the assessment of oncologic treatment effectiveness in patients with lymphoma but also discussing other potential functional imaging methods and their limitations.

Conclusion: Lymph nodes are commonly involved by metastatic solid tumors as well as by lymphoma. Evolving changes in cancer therapy for lymphoma and metastases have led to improved clinical outcomes.

Structural and biophysical properties of h-FANCI ARM repeat protein.

Fanconi anemia complementation groups - I (FANCI) protein facilitates DNA ICL (Inter-Cross-link) repair and plays a crucial role in genomic integrity. FANCI is a 1328 amino acids protein which contains armadillo (ARM) repeats and EDGE motif at the C-terminus. ARM repeats are functionally diverse and evolutionarily conserved domain that plays a pivotal role in protein-protein and protein-DNA interactions.

Rationale for a Minimum Number of Lymph Nodes Removed with Non-Small Cell Lung Cancer Resection: Correlating the Number of Nodes Removed with Survival in 98,970 Patients.

Background: The benefit of thoracic lymphadenectomy in the treatment of resectable non-small cell lung cancer (NSCLC) continues to be debated. We hypothesized that the number of lymph nodes (LNs) removed for patients with pathologic node-negative NSCLC would correlate with survival.

Methods: The National Cancer Data Base (NCDB) was queried for resected, node-negative, NSCLC patients treated between 2004 and 2014.

Conformational Response of Influenza A M2 Transmembrane Domain to Amantadine Drug Binding at Low pH (pH 5.5).

The M2 protein from influenza A plays important roles in its viral cycle. It contains a single transmembrane helix, which oligomerizes into a homotetrameric proton channel that conducts in the low-pH environment of the host-cell endosome and Golgi apparatus, leading to virion uncoating at an early stage of infection. We studied conformational rearrangements that occur in the M2 core transmembrane domain residing on the lipid bilayer, flanked by juxtamembrane residues (M2TMD21-49 fragment), upon its interaction with amantadine drug at pH 5.