Structural and Functional Analysis of the Gut Microbiome for Toxicologists.

Characterizing the reciprocal interactions between toxicants, the gut microbiota, and the host, holds great promise for improving our mechanistic understanding of toxic endpoints. Advances in culture-independent sequencing analysis (e.g.

Bias-Driven Conductance Increase with Length in Porphyrin Tapes.

A key goal in molecular electronics has been to find molecules that facilitate efficient charge transport over long distances. Normally, molecular wires become less conductive with increasing length. Here, we report a series of fused porphyrin oligomers for which the conductance increases substantially with length by >10-fold at a bias of 0.

Post-Operative Infections: Trends in Distribution, Risk Factors, and Clinical and Economic Burdens.

Background: Post-operative infection (POI) is a serious complication in all surgical disciplines and can derail a patient's treatment and recovery course. In this analysis, we examine national trends, risk factors, and costs associated with POI.

Methods: Using the Nationwide Inpatient Sample (NIS) for the years available for data analysis at the time of this study (2003-2010), we performed a cross-sectional study of adult (≥18 years) inpatients with POI and designated Clinical Classification Software (CCS) procedural class codes for the operations performed.

Unconventional Single-Molecule Conductance Behavior for a New Heterocyclic Anchoring Group: Pyrazolyl.

Electrical conductance across a molecular junction is strongly determined by the anchoring group of the molecule. Here we highlight the unusual behavior of 1,4-bis(1H-pyrazol-4-ylethynyl)benzene that exhibits unconventional junction current versus junction-stretching distance curves, which are peak-shaped and feature two conducting states of 2.3 × 10 G and 3.

Pencil beam scanning versus passively scattered proton therapy for unresectable pancreatic cancer.

Background: With an increasing number of proton centers capable of delivering pencil beam scanning (PBS), understanding the dosimetric differences in PBS compared to passively scattered proton therapy (PSPT) for pancreatic cancer is of interest.

Methods: Optimized PBS plans were retrospectively generated for 11 patients with locally advanced pancreatic cancer previously treated with PSPT to 59.4 Gy on a prospective trial.

Genetic diversity maintained among fragmented populations of a tree undergoing range contraction.

Dwarf birch (Betula nana) has a widespread boreal distribution but has declined significantly in Britain where populations are now highly fragmented. We analyzed the genetic diversity of these fragmented populations using markers that differ in mutation rate: conventional microsatellites markers (PCR-SSRs), RADseq generated transition and transversion SNPs (RAD-SNPs), and microsatellite markers mined from RADseq reads (RAD-SSRs). We estimated the current population sizes by census and indirectly, from the linkage-disequilibrium found in the genetic surveys.

RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers.

Oncogenic alterations in the RAS/RAF/MEK/ERK pathway drive the growth of a wide spectrum of cancers. While BRAF and MEK inhibitors are efficacious against BRAF-driven cancers, effective targeted therapies are lacking for most cancers driven by other pathway alterations, including non-V600E oncogenic BRAF, RAS GTPase-activating protein (GAP) NF1 (neurofibromin 1) loss and oncogenic KRAS. Here, we show that targeting the SHP2 phosphatase (encoded by PTPN11) with RMC-4550, a small-molecule allosteric inhibitor, is effective in human cancer models bearing RAS-GTP-dependent oncogenic BRAF (for example, class 3 BRAF mutants), NF1 loss or nucleotide-cycling oncogenic RAS (for example, KRAS).

Progressive adaptation of whole-limb kinematics after peripheral nerve injury.

The ability to recover purposeful movement soon after debilitating neuromuscular injury is essential to animal survival. Various neural and mechanical mechanisms exist to preserve whole-limb kinematics despite exhibiting long-term deficits of individual joints following peripheral nerve injury. However, it is unclear whether functionally relevant whole-limb movement is acutely conserved following injury.

Towards molecular electronic devices based on 'all-carbon' wires.

Nascent molecular electronic devices based on linear 'all-carbon' wires attached to gold electrodes through robust and reliable C-Au contacts are prepared via efficient in situ sequential cleavage of trimethylsilyl end groups from an oligoyne, MeSi-(C[triple bond, length as m-dash]C)-SiMe (1). In the first stage of the fabrication process, removal of one trimethylsilyl (TMS) group in the presence of a gold substrate, which ultimately serves as the bottom electrode, using a stoichiometric fluoride-driven process gives a highly-ordered monolayer, Au|C[triple bond, length as m-dash]CC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CSiMe (Au|CSiMe). In the second stage, treatment of Au|CSiMe with excess fluoride results in removal of the remaining TMS protecting group to give a modified monolayer Au|C[triple bond, length as m-dash]CC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CH (Au|CH).

Charge transport at a molecular GaAs nanoscale junction.

In recent years, the use of non-metallic electrodes for the fabrication of single-molecule junctions has developed into an elegant way to impart new properties to nanodevices. Integration of molecular junctions in a semiconducting platform would also speed technological deployment, as it would take advantage of established industrial infrastructures. In a previous proof-of-concept paper, we used simple α,ω-dithiol self-assembled monolayers on a gallium arsenide (GaAs) substrate to fabricate molecular Schottky diodes with a STM.

Carbon-contacted single molecule electrical junctions.

A fully metal-free molecular junction (MJ) has been built by using an electrochemically etched carbon fibre STM tip as the top electrode and graphene as the bottom electrode. The corresponding conductance values for 1,n-alkanediamine and 1,n-alkanedithiol (n = 2, 4, 6, 8 and 10) have been measured using the STM-I(s) technique. The tunnelling decay constant of the alkanediamine and alkanedithiol junctions with these carbon contacts is much lower than the corresponding metal contacted junctions of 0.

Conductance of 'bare-bones' tripodal molecular wires.

Controlling the orientation of molecular conductors on the electrode surfaces is a critical factor in the development of single-molecule conductors. In the current study, we used the scanning tunnelling microscopy-based break junction (STM-BJ) technique to explore 'bare-bones' tripodal molecular wires, employing different anchor groups (AGs) at the 'top' and 'bottom' of the tripod. The triarylphosphine tris(4-(methylthio)phenyl)phosphine and its corresponding phosphine sulfide showed only a single high conductance feature in the resulting 1- and 2-dimensional conductance histograms, whereas analogous molecules with fewer than three thiomethyl AGs did not show clear conductance features.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

Purpose/background: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes.

Methods/procedures: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d).

Rationale and early outcomes for the management of thymoma with proton therapy.

Background: Radiotherapy for thymic malignancies is technically challenging due to their close proximity to the heart, lungs, esophagus, and breasts, raising concerns about significant acute and late toxicities from conventional photon radiotherapy. Proton therapy (PT) may reduce the radiation dose to these vital organs, leading to less toxicity. We reviewed the dosimetry and outcomes among patients treated with PT for thymic malignancies at our institution.

A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.

Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease.

Minimizing polymerase biases in metabarcoding.

DNA metabarcoding is an increasingly popular method to characterize and quantify biodiversity in environmental samples. Metabarcoding approaches simultaneously amplify a short, variable genomic region, or "barcode," from a broad taxonomic group via the polymerase chain reaction (PCR), using universal primers that anneal to flanking conserved regions. Results of these experiments are reported as occurrence data, which provide a list of taxa amplified from the sample, or relative abundance data, which measure the relative contribution of each taxon to the overall composition of amplified product.

Fast and straightforward analysis approach of charge transport data in single molecule junctions.

In this study, we introduce an efficient data sorting algorithm, including filters for noisy signals, conductance mapping for analyzing the most dominant conductance group and sub-population groups. The capacity of our data analysis process has also been corroborated on real experimental data sets of Au-1,6-hexanedithiol-Au and Au-1,8-octanedithiol-Au molecular junctions. The fully automated and unsupervised program requires less than one minute on a standard PC to sort the data and generate histograms.

Rectal Culture and Sensitivity Analysis for Reducing Sepsis Risk After Fiducial Marker Placement.

Purpose: Placement of fiducial markers for prostate radiotherapy (RT) is associated with a 2% to 3% risk of bacterial urinary tract infection (UTI) that may progress to sepsis necessitating hospitalization. These bacterial UTIs are primarily due to flouroquinolone (FQ) resistant Escherichia coli (E. coli).

RNA-Seq transcriptome analysis of Amaranthus palmeri with differential tolerance to glufosinate herbicide.

Amaranthus palmeri (Amaranthaceae) is a noxious weed in several agroecosystems and in some cases seriously threatens the sustainability of crop production in North America. Glyphosate-resistant Amaranthus species are widespread, prompting the use of alternatives to glyphosate such as glufosinate, in conjunction with glufosinate-resistant crop cultivars, to help control glyphosate-resistant weeds. An experiment was conducted to analyze the transcriptome of A.

Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice.

Objective: Limited attention has been given to ocular injuries associated with traumatic brain injury (TBI). The retina is an extension of the central nervous system and evaluation of ocular damage may offer a less-invasive approach to gauge TBI severity and response to treatment. We aim to characterize acute changes in the mouse eye after exposure to two different models of TBI to assess the utility of eye damage as a surrogate to brain injury.

Evaluating the Feasibility and Acceptability of a Telehealth Program in a Rural Palliative Care Population: TapCloud for Palliative Care.

Context: The impact of telehealth and remote patient monitoring has not been well established in palliative care populations in rural communities.

Objectives: The objectives of this study were to 1) describe a telehealth palliative care program using the TapCloud remote patient monitoring application and videoconferencing; 2) evaluate the feasibility, usability, and acceptability of a telehealth system in palliative care; and 3) use a quality data assessment collection tool in addition to TapCloud ratings of symptom burden and hospice transitions.

Methods: A mixed-methods approach was used to assess feasibility, usability, and acceptability.

JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory.

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JNK-interacting protein 1 (JIP1) scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the gene that selectively blocks JIP1-mediated JNK activation.

The aryl hydrocarbon receptor as a moderator of host-microbiota communication.

The aryl hydrocarbon receptor (AHR) is an important component of the host-microbiota communication network. Comparisons of wild-type and -null mice as well as from exposure studies with potent AHR ligands (e.g.

P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity.

Autosomal-dominant, missense mutations in the leucine-rich repeat protein kinase 2 () gene are the most common genetic predisposition to develop Parkinson's disease (PD). LRRK2 kinase activity is increased in several pathogenic mutations (N1437H, R1441C/G/H, Y1699C, G2019S), implicating hyperphosphorylation of a substrate in the pathogenesis of the disease. Identification of the downstream targets of LRRK2 is a crucial endeavor in the field to understand LRRK2 pathway dysfunction in the disease.