Implications of Thermal Events on Thrust Emplacement Sequence in the Appalachian Fold and Thrust Belt: Some New Vitrinite Reflectance Data

Interpretation of existing geothermometry data combined with new vitrinite reflectance data, within the framework of a detailed composite tectonic setting, elucidates the evolution of structural sequencing of thrust sheets during the Alleghanian event in the Valley and Ridge Province in Virginia. That the Pulaski thrust sheet preceded the Saltville thrust sheet in the emplacement sequence, and that both reached thermal maxima prior to, or during, respective emplacement may be inferred from vitrinite and other geothermometry data. In contrast, the Narrows and St. Clair thrust sheets probably each attained their thermal maximum after emplacement. New vitrinite reflectance data are consistent with CAI and other temperature-sensitive information heretofore ascertained in the Valley and Ridge Province and support previously established maximum temperatures of ca. 200°C for strata of the Saltville thrust sheet as young as Mississippian. Rmax values from Mississippian coals in the Price Formation of the Saltville sheet, beneath but near the Pulaski thrust, range from 1.61% to 2.60%. At the structural front of the fold and thrust belt, a single Mississippian coal sample from the Bluefield Formation yields an Rmax value of 1.35%. Those coals showing highest Rmax values are more intensely fractured with secondary minerals filling the fractures. Warm fluids introduced during tectonic events may have played at least as important a role as that of combined stratigraphic and tectonic burial

Lung cancer::a new frontier for microbiome research and clinical translation

The lung microbiome has been shown to reflect a range of pulmonary diseases—for example: asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Studies have now begun to show microbiological changes in the lung that correlate with lung cancer (LC) which could provide new insights into lung carcinogenesis and new biomarkers for disease screening. Clinical studies have suggested that infections with tuberculosis or pneumonia increased the risk of LC possibly through inflammatory or immunological changes. These have now been superseded by genomic-based microbiome sequencing studies based on bronchoalveolar lavage, sputum or saliva samples. Although some discrepancies exist, many have suggested changes in particular bacterial genera in LC samples particularly, Granulicatella, Streptococcus and Veillonella. Granulicatella is of particular interest, as it appeared to show LC stage-specific increases in abundance. We propose that these microbial community changes are likely to reflect biochemical changes in the LC lung, linked to an increase in anaerobic environmental niches and altered pyridoxal/polyamine/nitrogenous metabolism to which Granulicatella could be particularly responsive. These are clearly preliminary observations and many more expansive studies are required to develop our understanding of the LC microbiome

The Connectedness of Ivory Towers and Inner Cities - Conversations About Us and Them

Also PCMA Working Paper #46.http://deepblue.lib.umich.edu/bitstream/2027.42/51291/1/527.pd

A pilot study using metagenomic sequencing of the sputum microbiome suggests potential bacterial biomarkers for lung cancer

BBSRC (UK) support (BBS/E/W/10964A01A)Lung cancer (LC) is the most prevalent cancer worldwide, and responsible for over 1.3 million deaths each year. Currently, LC has a low five year survival rates relative to other cancers, and thus, novel methods to screen for and diagnose malignancies are necessary to improve patient outcomes. Here, we report on a pilot-sized study to evaluate the potential of the sputum microbiome as a source of non-invasive bacterial biomarkers for lung cancer status and stage. Spontaneous sputum samples were collected from ten patients referred with possible LC, of which four were eventually diagnosed with LC (LC+), and six had no LC after one year (LC-). Of the seven bacterial species found in all samples, Streptococcus viridans was significantly higher in LC+ samples. Seven further bacterial species were found only in LC-, and 16 were found only in samples from LC+. Additional taxonomic differences were identified in regards to significant fold changes between LC+ and LC-cases, with five species having significantly higher abundances in LC+, with Granulicatella adiacens showing the highest level of abundance change. Functional differences, evident through significant fold changes, included polyamine metabolism and iron siderophore receptors. G. adiacens abundance was correlated with six other bacterial species, namely Enterococcus sp. 130, Streptococcus intermedius, Escherichia coli, S. viridans, Acinetobacter junii, and Streptococcus sp. 6, in LC+ samples only, which could also be related to LC stage. Spontaneous sputum appears to be a viable source of bacterial biomarkers which may have utility as biomarkers for LC status and stagepublishersversionPeer reviewe

Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity

Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease. The bacterial metagenomes within sputum samples from eight COPD patients and ten 'healthy' smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus. The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations. Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism. This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity

Rapid alteration in circulating free thyroxine modulates pituitary type II 5\u27 deiodinase and basal thyrotropin secretion in the rat

TSH secretion is decreased by both T4 and T3. This negative feedback control of TSH secretion has been correlated with an increase in pituitary nuclear T3 content, and it is not clear whether T4 exerts its effect directly on the thyrotroph or after its deiodination to T3. However, levels of the pituitary enzyme catalyzing T4 to T3 conversion, 5\u27D-II, are decreased in the presence of an increased amount of T4. Thus, it is unclear why the thyrotroph would have a mechanism for modulating the production of T3, if T3 is, in fact, the sole bioactive signal providing negative feedback inhibition. To examine this apparent paradox, we administered EMD 21388, a compound which inhibits the binding of T4 to transthyretin resulting in a rapid increase in circulating free T4 levels, to rats pretreated with radiolabeled T4 and T3. We observed increases in pituitary and liver T4 content of greater than 150%, without increases in the respective tissue T3 contents. The EMD 21388-treated rats also exhibited a 25% decrease in pituitary 5\u27D-II activity (103.8 +/- 15.8 fmol 125I released.mg protein-1.h-1, vs. control, 137.4 +/- 15.9, mean +/- SE), as did rats treated with sodium salicylate, another compound that inhibits T4-TTR binding (100.8 +/- 7.1). TSH levels significantly decreased 2 h after the administration of EMD 21388. These data demonstrate that despite a T4-mediated decrease in pituitary 5\u27D-II activity, an increase in T4 independently decreases TSH secretion

Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

BackgroundTo characterize acoustic features of an infant's cry and use machine learning to provide an objective measurement of behavioral state in a cry-translator. To apply the cry-translation algorithm to colic hypothesizing that these cries sound painful.MethodsAssessment of 1000 cries in a mobile app (ChatterBabyTM). Training a cry-translation algorithm by evaluating >6000 acoustic features to predict whether infant cry was due to a pain (vaccinations, ear-piercings), fussy, or hunger states. Using the algorithm to predict the behavioral state of infants with reported colic.ResultsThe cry-translation algorithm was 90.7% accurate for identifying pain cries, and achieved 71.5% accuracy in discriminating cries from fussiness, hunger, or pain. The ChatterBaby cry-translation algorithm overwhelmingly predicted that colic cries were most likely from pain, compared to fussy and hungry states. Colic cries had average pain ratings of 73%, significantly greater than the pain measurements found in fussiness and hunger (p < 0.001, 2-sample t test). Colic cries outranked pain cries by measures of acoustic intensity, including energy, length of voiced periods, and fundamental frequency/pitch, while fussy and hungry cries showed reduced intensity measures compared to pain and colic.ConclusionsAcoustic features of cries are consistent across a diverse infant population and can be utilized as objective markers of pain, hunger, and fussiness. The ChatterBaby algorithm detected significant acoustic similarities between colic and painful cries, suggesting that they may share a neuronal pathway

Dopaminergic Control of Striatal Cholinergic Interneurons Underlies Cocaine-Induced Psychostimulation

Cocaine drastically elevates dopamine (DA) levels in the striatum, a brain region that is critical to the psychomotor and rewarding properties of the drug. DA signaling regulates intrastriatal circuits connecting medium spiny neurons (MSNs) with afferent fibers and interneurons. While the cocaine-mediated increase in DA signaling on MSNs is well documented, that on cholinergic interneurons (ChIs) has been more difficult to assess. Using combined pharmacological, chemogenetic, and cell-specific ablation approaches, we reveal that the D2R-dependent inhibition of acetylcholine (ACh) signaling is fundamental to cocaine-induced changes in behavior and the striatal genomic response. We show that the D2R-dependent control of striatal ChIs enables the motor, sensitized, and reinforcing properties of cocaine. This study highlights the importance of the DA- and D2R-mediated inhibitory control of ChIs activity in the normal functioning of striatal networks

Inclusive teaching circles : mechanisms for creating welcoming classrooms.

This essay examines the Inclusive Teaching Circle (ITC) as a mechanism for faculty development in creating instructional tools that embrace an inclusive pedagogy reflecting diversity, cultural competence and social justice. We describe one group’s year-long participation in an ITC at a large, metropolitan research university in the south. Next, we share several members’ strategies for promoting more inclusive and equitable learning for students in our classrooms. Finally, we consider the implications of ITCs for its group participants and the professorate at large

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity