bluuebunny/crossref_metadata_2025 huggingface dataset:
Campylobacter jejuni Motility Is Required for Infection of the Flagellotropic Bacteriophage F341
Authors: Baldvinsson Signe Berg , Sørensen Martine C. Holst , Vegge Christina S. , Clokie Martha R. J. , Brøndsted Lone
Published: September 2014

Previous studies have identified a specific modification of the capsular polysaccharide as receptor for phages that infect
Campylobacter jejuni
. Using acapsular
kpsM
mutants of
C. jejuni
strains NCTC11168 and NCTC12658, we found that bacteriophage F341 infects
C. jejuni
independently of the capsule. In contrast, phage F341 does not infect
C. jejuni
NCTC11168 mutants that either lack the flagellar filaments (Δ
flaAB
) or that have paralyzed, i.e., nonrotating, flagella (Δ
motA
and Δ
flgP
). Complementing
flgP
confirmed that phage F341 requires rotating flagella for successful infection. Furthermore, adsorption assays demonstrated that phage F341 does not adsorb to these nonmotile
C. jejuni
NCTC11168 mutants. Taken together, we propose that phage F341 uses the flagellum as a receptor. Phage-host interactions were investigated using fluorescence confocal and transmission electron microscopy. These data demonstrate that F341 binds to the flagellum by perpendicular attachment with visible phage tail fibers interacting directly with the flagellum. Our data are consistent with the movement of the
C. jejuni
flagellum being required for F341 to travel along the filament to reach the basal body of the bacterium. The initial binding to the flagellum may cause a conformational change of the phage tail that enables DNA injection after binding to a secondary receptor.
A Highly Diastereoselective Oxidant Contributes to Ligninolysis by the White Rot Basidiomycete Ceriporiopsis subvermispora
Authors: Yelle Daniel J. , Kapich Alexander N. , Houtman Carl J. , Lu Fachuang , Timokhin Vitaliy I. , Fort Raymond C. , Ralph John , Hammel Kenneth E.
Published: September 2014

The white rot basidiomycete
Ceriporiopsis subvermispora
delignifies wood selectively and has potential biotechnological applications. Its ability to remove lignin before the substrate porosity has increased enough to admit enzymes suggests that small diffusible oxidants contribute to delignification. A key question is whether these unidentified oxidants attack lignin via single-electron transfer (SET), in which case they are expected to cleave its propyl side chains between C
α
and C
β
and to oxidize the
threo
-diastereomer of its predominating β-O-4-linked structures more extensively than the corresponding
erythro
-diastereomer. We used two-dimensional solution-state nuclear magnetic resonance (NMR) techniques to look for changes in partially biodegraded lignin extracted from spruce wood after white rot caused by
C. subvermispora
. The results showed that (i) benzoic acid residues indicative of C
α
—C
β
cleavage were the major identifiable truncated structures in lignin after decay and (ii) depletion of β-O-4-linked units was markedly diastereoselective with a
threo
preference. The less selective delignifier
Phanerochaete chrysosporium
also exhibited this diastereoselectivity on spruce, and a
P. chrysosporium
lignin peroxidase operating in conjunction with the
P. chrysosporium
metabolite veratryl alcohol did likewise when cleaving synthetic lignin
in vitro
. However,
C. subvermispora
was significantly more diastereoselective than
P. chrysosporium
or lignin peroxidase-veratryl alcohol. Our results show that the ligninolytic oxidants of
C. subvermispora
are collectively more diastereoselective than currently known fungal ligninolytic oxidants and suggest that SET oxidation is one of the chemical mechanisms involved.
Anaerobic Activation of
p
-Cymene in Denitrifying Betaproteobacteria: Methyl Group Hydroxylation versus Addition to Fumarate
Authors: Strijkstra Annemieke , Trautwein Kathleen , Jarling René , Wöhlbrand Lars , Dörries Marvin , Reinhardt Richard , Drozdowska Marta , Golding Bernard T. , Wilkes Heinz , Rabus Ralf
Published: September 2014

The betaproteobacteria “
Aromatoleum aromaticum
” pCyN1 and “
Thauera
” sp. strain pCyN2 anaerobically degrade the plant-derived aromatic hydrocarbon
p
-cymene (4-isopropyltoluene) under nitrate-reducing conditions. Metabolite analysis of
p
-cymene-adapted “
A. aromaticum
” pCyN1 cells demonstrated the specific formation of 4-isopropylbenzyl alcohol and 4-isopropylbenzaldehyde, whereas with “
Thauera
” sp. pCyN2, exclusively 4-isopropylbenzylsuccinate and tentatively identified (4-isopropylphenyl)itaconate were observed. 4-Isopropylbenzoate in contrast was detected with both strains. Proteogenomic investigation of
p
-cymene- versus succinate-adapted cells of the two strains revealed distinct protein profiles agreeing with the different metabolites formed from
p
-cymene. “
A. aromaticum
” pCyN1 specifically produced (i) a putative
p
-cymene dehydrogenase (CmdABC) expected to hydroxylate the benzylic methyl group of
p
-cymene, (ii) two dehydrogenases putatively oxidizing 4-isopropylbenzyl alcohol (Iod) and 4-isopropylbenzaldehyde (Iad), and (iii) the putative 4-isopropylbenzoate-coenzyme A (CoA) ligase (Ibl). The
p
-cymene-specific protein profile of “
Thauera
” sp. pCyN2, on the other hand, encompassed proteins homologous to subunits of toluene-activating benzylsuccinate synthase (termed [4-isopropylbenzyl]succinate synthase IbsABCDEF; identified subunits, IbsAE) and protein homologs of the benzylsuccinate β-oxidation (Bbs) pathway (termed BisABCDEFGH; all identified except for BisEF). This study reveals that two related denitrifying bacteria employ fundamentally different peripheral degradation routes for one and the same substrate,
p
-cymene, with the two pathways apparently converging at the level of 4-isopropylbenzoyl-CoA.
The Vanadium Iodoperoxidase from the Marine Flavobacteriaceae Species Zobellia galactanivorans Reveals Novel Molecular and Evolutionary Features of Halide Specificity in the Vanadium Haloperoxidase Enzyme Family
Authors: Fournier Jean-Baptiste , Rebuffet Etienne , Delage Ludovic , Grijol Romain , Meslet-Cladière Laurence , Rzonca Justyna , Potin Philippe , Michel Gurvan , Czjzek Mirjam , Leblanc Catherine
Published: September 2014

Vanadium haloperoxidases (VHPO) are key enzymes that oxidize halides and are involved in the biosynthesis of organo-halogens. Until now, only chloroperoxidases (VCPO) and bromoperoxidases (VBPO) have been characterized structurally, mainly from eukaryotic species. Three putative VHPO genes were predicted in the genome of the flavobacterium
Zobellia galactanivorans
, a marine bacterium associated with macroalgae. In a phylogenetic analysis, these putative bacterial VHPO were closely related to other VHPO from diverse bacterial phyla but clustered independently from eukaryotic algal VBPO and fungal VCPO. Two of these bacterial VHPO, heterogeneously produced in
Escherichia coli
, were found to be strictly specific for iodide oxidation. The crystal structure of one of these vanadium-dependent iodoperoxidases, Zg-VIPO1, was solved by multiwavelength anomalous diffraction at 1.8 Å, revealing a monomeric structure mainly folded into α-helices. This three-dimensional structure is relatively similar to those of VCPO of the fungus
Curvularia inaequalis
and of
Streptomyces
sp. and is superimposable onto the dimeric structure of algal VBPO. Surprisingly, the vanadate binding site of Zg-VIPO1 is strictly conserved with the fungal VCPO active site. Using site-directed mutagenesis, we showed that specific amino acids and the associated hydrogen bonding network around the vanadate center are essential for the catalytic properties and also the iodide specificity of Zg-VIPO1. Altogether, phylogeny and structure-function data support the finding that iodoperoxidase activities evolved independently in bacterial and algal lineages, and this sheds light on the evolution of the VHPO enzyme family.
Dynamics of Gut Microbiota in Autoimmune Lupus
Authors: Zhang Husen , Liao Xiaofeng , Sparks Joshua B. , Luo Xin M.
Published: September 2014

Gut microbiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gut microbiota is often observed in the diseased state. However, little is known on the role of gut microbiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases inLachnospiraceaeand overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility- and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gut microbiota of lupus-prone mice were different between sexes, and an overrepresentation ofLachnospiraceaein females was associated with an earlier onset of and/or more severe lupus symptoms.ClostridiaceaeandLachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gut microbiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.
Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice
Authors: Huang Ying , Wang Jinfeng , Quan Guihua , Wang Xiaojun , Yang Longfei , Zhong Lili
Published: September 2014

The objective of this study was to investigate the effect of
Lactobacillus acidophilus
ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE
−/−
) mice. Eight-week-old ApoE
−/−
mice were fed a Western diet with or without
L. acidophilus
ATCC 4356 daily for 16 weeks.
L. acidophilus
ATCC 4356 protected ApoE
−/−
mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (
P
< 0.05) higher in the
L. acidophilus
ATCC 4356 treatment groups than in the control groups. Furthermore,
L. acidophilus
ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of
L. acidophilus
ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore,
L. acidophilus
ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis.
Incidence of short stature at 3 years of age in late preterm infants: a population-based study
Authors: Nagasaka Miwako , Morioka Ichiro , Yokota Tomoyuki , Fujita Kaori , Kurokawa Daisuke , Koda Tsubasa , Shibata Akio , Yamada Hideto , Ito Yoshiya , Uchino Eiko , Shirai Chika , Iijima Kazumoto
Published: September 2014

Objectives

This study aimed to investigate the incidence of short stature at 3 years of age in a Japanese cohort of late preterm infants who were born at 34–36 weeks’ gestational age (GA). We compared these late preterm infants with term infants (37–41 weeks’ GA), and evaluated the effect of birth weight on the incidence of short stature.

Methods

A longitudinal population-based study of 26 970 neonates who were born between 34 weeks’ and 41 weeks’ GA in 2006–2008 was conducted in Kobe, Japan. Of these neonates, 1414 were late preterm and 25 556 were term infants. The late preterm infants were then divided into three subgroups based on birth weight as determined by Japanese neonatal anthropometric charts for GA at birth: large-for-GA (n=140), appropriate-for-GA (AGA, n=1083), and small-for-GA (SGA, n=191). The incidence of short stature at 3 years of age was calculated in the late preterm group and compared with that in the term group, and between the AGA and SGA groups with late preterm birth.

Results

The incidence of short stature in the late preterm group was 2.9%, which was significantly higher than that in the term group (1.4%). Late preterm SGA infants developed short stature with a significantly higher (9.4%) incidence than that of late preterm AGA infants (2.1%).

Conclusions

The incidence of short stature in 3-year-old children who were late preterm infants has a 2-fold higher risk than that in term infants. The risk of developing short stature is increased 4.5-fold if they are SGA.
Exploring new avenues to assess the sharp end of patient safety: an analysis of nationally aggregated peer review data
Authors: Meeks Derek W , Meyer Ashley N D , Rose Barbara , Walker Yuri N , Singh Hardeep
Published: September 2014

Background

Many healthcare organisations (HCOs) use peer review to evaluate clinical performance, but it is unclear whether these data provide useful insights for assessing the sharp end of patient safety.

Objective

To describe outcomes of peer review within the Department of Veterans Affairs (VA) healthcare system and identify opportunities to leverage peer review data for measurement and improvement of safety.

Design

We partnered with the VA's Risk Management Program Office to perform descriptive analyses of aggregated peer review data collected from 135 VA facilities between October 2011 and September 2012. We determined the frequency of screening factors used to initiate peer review and processes contributing to substandard care. We also evaluated peer review data for diagnosis-related performance concerns, an emerging area of interest in the patient safety field.

Results

During the study period, 23 287 cases were peer reviewed; 15 739 (68%) were sent to local peer review committees for final outcome determination after an initial review and 2320 cases were ultimately designated as substandard care (mean 17 cases/facility). In 20% of cases, the screening source was unspecified. The most common process contributing to substandard care was ‘timing and appropriateness of treatment’. Approximately 16% of committee reviewed cases had diagnosis-related performance concerns, which were estimated to occur in approximately 0.5% of total hospital admissions.

Conclusions

Peer review may be a useful tool for HCOs to assess their sharp end clinical performance, particularly safety events related to diagnostic and treatment errors. To address these emerging and largely preventable events, HCOs could consider revamping their existing peer review programmes to enable self-assessment, feedback and improvement.
Conscious sedation versus general anaesthesia during mechanical thrombectomy for stroke: a propensity score analysis
Authors: McDonald Jennifer S , Brinjikji Waleed , Rabinstein Alejandro A , Cloft Harry J , Lanzino Giuseppe , Kallmes David F
Published: September 2014

Background

Debate exists as to whether patients with acute ischemic stroke who are undergoing mechanical thrombectomy should receive general anaesthesia or conscious sedation during the procedure. Using a multihospital administrative database, we compared outcomes and complications of patients receiving mechanical thrombectomy, who were receiving general anaesthesia and conscious sedation, and studied trends in usage over time.

Materials and methods

Premier database patients who underwent mechanical thrombectomy from 2006 to 2013 for acute ischemic stroke were identified. Using propensity score analysis, recipients of general anaesthesia and conscious sedation underwent 1:1 matching. Outcomes including usage trends, discharge status, mortality, length of stay, haemorrhage and pneumonia were examined.

Results

A total of 2512 patients receiving mechanical thrombectomy were identified. 1999 (80%) received general anaesthesia and 513 (20%) received conscious sedation. Following 1:1 matching by the propensity score matching, 507 general anaesthesia and 507 conscious sedation patients were matched. Patients who received general anaesthesia during their procedure had significantly higher rates of in-hospital mortality (25% vs 12%, OR=2.37 95% CI 1.68 to 3.37, p<0.0001), and pneumonia (17.0% vs 9.3%, OR=2.0, 95% CI 1.35 to 2.96, p=0.0005) compared with patients of thrombectomy who received conscious sedation. ICH/SAH rates were similar between patients receiving general anaesthesia and patients receiving conscious sedation (11% vs 12%, p=0.62). Usage rate of general anaesthesia decreased from 83.8% in 2006 and 74.0% in 2013.

Conclusions

In our cohort, thrombectomy patients receiving conscious sedation have decreased in-hospital mortality, decreased rates of pneumonia, and lower hospital costs and lengths of stay when compared with patients who received general anaesthesia. However, most practitioners continue to use general anaesthesia in the setting of acute stroke interventions.
Comment on “Generation of a superposition of coherent states in a resonant cavity and its nonclassicality and decoherence”
Authors: Ren Gang
Published: September 2014

Arpita Ghosh and P.K. Das (Can. J. Phys. 86: 811 (2008) doi:10.1139/p08-013 ) derived an analytic expression for the Wigner function of a superposition of coherent state. We point out the incorrectness of this result.
British Pennsylvanian (Carboniferous) coal-bearing sequences: where is the time?
Authors: Scott Andrew C. , Stephens Rosemary S.
Published: September 2014

The Lower and Middle Coal Measures of Langsettian (Westphalian A) and Duckmantian (Westphalian B) age (together equals Bashkirian in part) in Britain comprise an alternation of clastic sediments and coal deposited on coastal and alluvial plains over a period of 2–3.5 million years, depending on which time scale is accepted. In both the Pennine and South Wales Basins there are no obvious unconformities. Many of the clastic sequences show evidence of rapid sedimentation (burial of trees, bivalve escape burrows) that may suggest that a significant amount of time is taken up during the peat-forming intervals. Thickness data from a range of boreholes that record continuous sections through this time period were collated. Coal and sediment thicknesses, as well as coal to sediment ratios, are compared both within and across the basins. Data on the coals has allowed consideration of the time taken to deposit the peats. This work considers the compaction of the peat to coal, as well as a range of peat accumulation rates. Assuming the largest de-compaction rates and slowest accumulation rates of the coal formation, less than 50% of the allocated time can be accounted for. In addition however, calculations suggest that peat formation accounts for less than 25% of the total time taken for sediment accumulation. It is suspected that there are major time gaps in the sequences, most probably occurring between seat-earths and coal and within the coals, and it is believed that this finding has significance for the debate over short-term climate changes in the Carboniferous and the causes of peat and sediment alternations.

Supplementary material:

Borehole thickness data and references are available at
http://www.geolsoc.org.uk/SUP18788
XXIX. The Microscopical Examination of Rocks
Authors: Thompson George R.
Published: September 2014

I
n
the course of his remarks the writer pointed out the province of the microscope in the study of rocks, and that through its use a vast field, which was otherwise hid away from our unaided senses, was opened out for investigation. In many instances, of course, the component parts of rocks could be identified by the naked eye—granite, for example, and the coarser grits—but very little could be made of the finer igneous rocks, such as basalt, without the use of the lens. In the case of many of the fine Silurian greywackés, it was almost impossible to distinguish them from igneous rocks without microscopic aid, but when it was invoked the component particles were at once seen to be of a clastic nature.

The author then proceeded to examine the composition of the clastic and crystalline rocks, which were shown to have a definite structure or arrangement of their substances, as might be seen from the regular shape of the crystals where they have had free space to grow. The genesis of crystals as shown in glassy rocks was explained, as also the formation of crystallites, microliths, skeleton crystals, &c.

Mr. Thompson next pointed out how the different minerals could be recognised in microscopic sections by means of their physical and crystalline properties, such as shape, cleavage, colour, refracting index, and others. He ended his paper by giving a full and lucid description of the form of microscope best adapted for petrological work, with the production and use
IX.—
Fossil Soils of the Upper Old Red Sandstone of South Ayrshire
Authors: Burgess Iain C.
Published: September 2014

Cornstones, concretionary limestones in the Scottish Upper Old Red Sandstone, are the limestone horizons in fossil calcareous soils (pedocals). The soil profile comprises three horizons; the topmost of red-brown sand, the middle of black marl with small impure calcareous nodules, and the lowest of relatively pure limestone (the cornstone proper), often showing colour banding and oolitic structure. The cornstone may be up to 15 ft. thick, and was formed
in situ
by replacement of the detrital quartz and felspar grains of the parent sand by microcrystalline calcite. The Ayrshire cornstones seem to resemble closely the Pliocene caliche limestones of South-Central U.S.A..
XVI. On the Geology of Switzerland
Authors: Bell Dugald
Published: September 2014

I
n
these Notes on the Geology of Switzerland, the author embodied some observations made during a recent visit to that country. After remarking on the connection that exists between the scenery and the geology of a country, he alluded to the many eminent investigators who had illustrated the rock-formations of Switzerland—as Studer, Escher, E. de Beaumont, Favre, Desor, on the Continent, with Murchison, Lyell, Ramsay, and others of the English school. There also Charpentier, Rendu, Guyot, Agassiz, Forbes, and Tyndall had spent laborious but delightful days in studying the structure and action of glaciers. The “playground of Europe” had thus become classic ground to the geologist. He then gave an outline of the general structure of the country, in its three main divisions of the Jura mountains, the middle plain, and the Alpine districts, showing how the secondary rocks—oolitic and chalk—of the Jura are overlaid by tertiary strata (
Molasse
) in the middle plain, but reappear on the flanks of the Alps upheaved into lofty mountains, and are succeeded by mica-schist, gneiss, and granite, forming the central parts of the great Alpine chain and the back-bone of the European continent. The first point, accordingly, which struck one with regard to Swiss geology, was the comparatively recent age of these the loftiest mountains in Europe, composed as they are in great part of strata formed within the tertiary period. While our own higher mountains are made up of rocks belonging to an immense antiquity, the Alps, the Apennines, Pyrenees, Carpathians, in Europe,
XXIX. On Rocks and Minerals in Cornwall
Authors: White James
Published: September 2014

M
r
. W
hite
said that the strata in Cornwall are chiefly Devonian, but are much broken up and metamorphosed by the action of igneous rocks, traps, porphyries (locally known as “Elvans”), and granites. These latter are of many varieties of hardness and texture, and are used—the harder, for ornamental and heavy building purposes, like our own Aberdeen, Peterhead, and Mull granites; the softer and more earthy varieties, for the manufacture of china clay, of which about 80,000 tons are produced annually. London Bridge, and Waterloo Bridge, in London, and the docks at Chatham, are built of Cornish granite. The chief feature of the county, however, and that which has brought Cornwall its greatest riches, is the abundance of its metallic veins. The Cornish mines have been known and worked from time immemorial, in the ordinary, though not the geological, sense of that well-worn phrase; it is known that long before the Christian era Phœnician sailors visited the coast and other parts of the county for the purpose of trading in tin and various other metals. Tin occurs nowhere else in the British islands, and is here found in two forms—stream tin and vein tin. The former is found from the size of small grains to lumps of 10lbs. to 12lbs. weight, while occasionally large masses of rock occur richly impregnated with the mineral. These are found scattered over the surface of the hard rocks and overlaid by soft deposits, and are also got in gullies and water-courses. As stream tin is
XIII. Notes on the Discovery of a Fossil Scorpion (
Palæophonus Caledonicus
) in the Silurian Strata of Logan Water
Authors: Hunter John R. S.
Published: September 2014

I
n
two previous papers read to the Society

*

I referred to the results of former expeditions to the Logan Water district in the Lesmahagow hills, and I then described the geological features of this group of fossiliferous Silurian strata, known to all who are interested in Scottish palæontology.

In June, 1883, I started on another expedition to Logan Water, under canvas, and for the first few days experienced weather wet and stormy enough to try the patience of the oldest campaigner. Nor were the rocks more favourable to us than the elements, and our earliest explorations were absolutely barren of results. But patience and perseverance conquer many difficulties, so after a visit home to procure dry clothing, we set to work with renewed vigour to open up a new horizon. Here a splendid specimen of an organism which appeared to be entirely new to me was turned out. Its curious comb-like structure suggested strongly to my mind the fact that it bore a great and general resemblance to a recent Scorpion. Soon after plant remains were discovered on the same horizon, and the probability became all the stronger that here we had disentombed a land-inhabiting and air-breathing animal from a lower position in the earth’s crust than any previously known to us. If this supposition proved correct, here was a find surpassing any of my former discoveries in the Logan Water Silurians, and rendering the hardships we had undergone as nothing in comparison.

Later in the year, when I had
XVII. Notes on some of the Principal Geological Papers read at the British Association Meeting, Aberdeen, 1885
Authors: Murdoch James B.
Published: September 2014

A
fter
giving a short account of the more important papers submitted to Section C. (Geology), Mr. Murdoch referred to those bearing on two subjects which were of more than usual interest, viz., the age of the Elgin Sandstones and the succession of the North-West Highland Rocks.

The papers which introduced the former subject were—“The Elgin Sandstones,” by Mr. J. G. Phillips, keeper of the Elgin Museum; and “On a new Reptile from New Spynie,” by Dr. R. H. Traquair, F.R.S.E., Museum of Science and Art, Edinburgh.

Curiously enough, these Yellow Elgin Sandstones had been a subject of great contention at the previous meeting in Aberdeen—that of 1859—and now their age, which had been thought to be then finally settled, again came up for discussion at the meeting of 1885.

Up till 1852 there had been no question that these rocks were of undoubted Old Red Sandstone age, but in that year Mr. Patrick Duff of Elgin discovered in them the remains of a lizard (
Telerpeton
), while in 1859 Prof. Huxley found in the collection of the Rev. Dr. Gordon of Birnie, from the same strata, crocodilian remains (
Stagonolepis
) and those of another lizard (
Hyperodapedon
); and at the recent meeting Dr. Traquair reported the discovery of another form of lizard (which he named provisionally
Dicynodon
). The discovery of these reptilians, all of Triassic age, was supposed to finally settle the question, and the Elgin sandstones were therefore classed as belonging to the New Red formation, when lately in the same horizon,
Actin dynamics is rapidly regulated by the PTEN and PIP2 signaling pathways leading to myocyte hypertrophy
Authors: Li Jieli , Tanhehco Elaine J. , Russell Brenda
Published: September 2014

Mature cardiac myocytes are terminally differentiated, and the heart has limited capacity to replace lost myocytes. Thus adaptation of myocyte size plays an important role in the determination of cardiac function. The hypothesis tested is that regulation of the dynamic exchange of actin leads to cardiac hypertrophy. ANG II was used as a hypertrophic stimulant in mouse heart and neonatal rat ventricular myocytes (NRVMs) in culture for assessment of a mechanism for regulation of actin dynamics by phosphatidylinositol 4,5-bisphosphate (PIP2). Actin dynamics in NRVMs rapidly increased in a PIP2-dependent manner, measured by imaging and fluorescence recovery after photobleaching (FRAP). A significant increase in PIP2 levels was found by immunoblotting in both adult mouse heart tissue and cultured NRVMs. Inhibition of phosphatase and tensin homolog (PTEN) in NRVMs markedly blunted ANG II-induced increases in actin dynamics, the PIP2 level, and cell size. Furthermore, PTEN activity was dramatically upregulated in ANG II-treated NRVMs but downregulated when PTEN inhibitors were used. The time course of the rise in the PIP2 level was inversely related to the fall in the PIP3 level, which was significant by 30 min in ANG II-treated NRVMs. However, significant translocation of PTEN to the plasma membrane occurred by 10 min, suggesting a crucial initial step for PTEN for the cellular responses to ANG II. In conclusion, PTEN and PIP2 signaling may play an important role in myocyte hypertrophy by the regulation of actin filament dynamics, which is induced by ANG II stimulation.
Effects of Differing Dosages of Pomegranate Juice Supplementation after Eccentric Exercise
Authors: Machin Daniel R. , Christmas Kevin M. , Chou Ting-Heng , Hill Sarah C. , Van Pelt Douglas W. , Trombold Justin R. , Coyle Edward F.
Published: September 2014

Dietary supplementation with pomegranate juice improves isometric strength recovery after unaccustomed eccentric exercise. The purpose of this study was to determine if there is a dose response effect of pomegranate juice supplementation after eccentric exercise isometric strength recovery. Forty-five nonresistance trained, recreationally active men were assigned once-daily pomegranate juice, twice-daily pomegranate juice, or placebo supplementation. On day four of supplementation, 20 min of downhill running and 40 maximal eccentric elbow flexion repetitions were performed. Isometric knee extensor and elbow flexor strength, muscular soreness, and serum myoglobin concentrations were measured prior to exercise and 2, 24, 48, 72, and 96 h after exercise. Throughout the postexercise time period, while isometric knee extensor and elbow flexor strength were similar between once-daily and twice-daily pomegranate juice supplementation groups, isometric strength was significantly higher in pomegranate juice groups than placebo. Knee extensor soreness, elbow flexor soreness, and myoglobin increased in response to exercise but were similar between groups. It is apparent that pomegranate juice supplementation improves strength recovery in leg and arm muscles following eccentric exercise; however, no dose response effect was present. We conclude that once-daily pomegranate juice supplementation is not different from twice-daily supplementation in regards to strength recovery after eccentric exercise.
Targeting Cancer Stem–like Cells as an Approach to Defeating Cellular Heterogeneity in Ewing Sarcoma
Authors: Cornaz-Buros Sandrine , Riggi Nicolo , DeVito Claudio , Sarre Alexandre , Letovanec Igor , Provero Paolo , Stamenkovic Ivan
Published: September 2014

Plasticity in cancer stem–like cells (CSC) may provide a key basis for cancer heterogeneity and therapeutic response. In this study, we assessed the effect of combining a drug that abrogates CSC properties with standard-of-care therapy in a Ewing sarcoma family tumor (ESFT). Emergence of CSC in this setting has been shown to arise from a defect in TARBP2-dependent microRNA maturation, which can be corrected by exposure to the fluoroquinolone enoxacin. In the present work, primary ESFT from four patients containing CD133+ CSC subpopulations ranging from 3% to 17% of total tumor cells were subjected to treatment with enoxacin, doxorubicin, or both drugs. Primary ESFT CSC and bulk tumor cells displayed divergent responses to standard-of-care chemotherapy and enoxacin. Doxorubicin, which targets the tumor bulk, displayed toxicity toward primary adherent ESFT cells in culture but not to CSC-enriched ESFT spheres. Conversely, enoxacin, which enhances miRNA maturation by stimulating TARBP2 function, induced apoptosis but only in ESFT spheres. In combination, the two drugs markedly depleted CSCs and strongly reduced primary ESFTs in xenograft assays. Our results identify a potentially attractive therapeutic strategy for ESFT that combines mechanism-based targeting of CSC using a low-toxicity antibiotic with a standard-of-care cytotoxic drug, offering immediate applications for clinical evaluation. Cancer Res; 74(22); 6610–22. ©2014 AACR.
DEAR1, a Novel Tumor Suppressor That Regulates Cell Polarity and Epithelial Plasticity
Authors: Chen Nanyue , Balasenthil Seetharaman , Reuther Jacquelyn , Killary Ann McNeill
Published: September 2014

Elucidation of the regulatory controls on epithelial plasticity is pivotal not only to better understand the nature of metastasis but also for the design of targeted therapies to prevent the earliest steps in migration and invasion from the primary tumor. This review will highlight the role of the novel TRIM protein DEAR1 (annotated as TRIM62) in the regulation of apical–basal polarity and acinar morphogenesis as well as its function as a chromosome 1p35 tumor suppressor and negative regulator of TGFβ-driven epithelial–mesenchymal transition (EMT). DEAR1 binds to and promotes the ubiquitination of SMAD3, the major effector of TGFβ-mediated EMT, as well as downregulates SMAD3 targets SNAIL1/2, master transcriptional regulators of EMT. Cumulative results suggest a novel paradigm for DEAR1 in the regulation of the breast tumor microenvironment, polarity, and EMT. Because DEAR1 undergoes loss-of-function mutations, homozygous deletion, as well as copy-number losses in multiple epithelial cancers, including breast cancer, DEAR1 has clinical use as a predictive and prognostic biomarker as well as for stratifying breast cancers and potentially other epithelial tumor types for targeted therapies aimed at the pathways regulated by DEAR1. Cancer Res; 74(20); 5683–9. ©2014 AACR.
GPx2 Suppression of H2O2 Stress Links the Formation of Differentiated Tumor Mass to Metastatic Capacity in Colorectal Cancer
Authors: Emmink Benjamin L. , Laoukili Jamila , Kipp Anna P. , Koster Jan , Govaert Klaas M. , Fatrai Szabolcs , Verheem Andre , Steller Ernst J.A. , Brigelius-Flohé Regina , Jimenez Connie R. , Borel Rinkes Inne H.M. , Kranenburg Onno
Published: September 2014

Colorectal tumorigenesis is accompanied by the generation of oxidative stress, but how this controls tumor development is poorly understood. Here, we studied how the H2O2-reducing enzyme glutathione peroxidase 2 (GPx2) regulates H2O2 stress and differentiation in patient-derived “colonosphere” cultures. GPx2 silencing caused accumulation of radical oxygen species, sensitization to H2O2-induced apoptosis, and strongly reduced clone- and metastasis-forming capacity. Neutralization of radical oxygen species restored clonogenic capacity. Surprisingly, GPx2-suppressed cells also lacked differentiation potential and formed slow-growing undifferentiated tumors. GPx2 overexpression stimulated multilineage differentiation, proliferation, and tumor growth without reducing the tumor-initiating capacity. Finally, GPx2 expression was inversely correlated with H2O2-stress signatures in human colon tumor cohorts, but positively correlated with differentiation and proliferation. Moreover, high GPx2 expression was associated with early tumor recurrence, particularly in the recently identified aggressive subtype of human colon cancer. We conclude that H2O2 neutralization by GPx2 is essential for maintaining clonogenic and metastatic capacity, but also for the generation of differentiated proliferating tumor mass. The results reveal an unexpected redox-controlled link between tumor mass formation and metastatic capacity. Cancer Res; 74(22); 6717–30. ©2014 AACR.
An Open-Label Phase Ib Dose-Escalation Study of TRC105 (Anti-Endoglin Antibody) with Bevacizumab in Patients with Advanced Cancer
Authors: Gordon Michael S. , Robert Francisco , Matei Daniela , Mendelson David S. , Goldman Jonathan W. , Chiorean E. Gabriela , Strother Robert M. , Seon Ben K. , Figg William D. , Peer Cody J. , Alvarez Delia , Adams Bonne J. , Theuer Charles P. , Rosen Lee S.
Published: September 2014

Purpose: Endoglin, an endothelial cell membrane receptor expressed on angiogenic tumor vessels, is essential for angiogenesis and upregulated in the setting of VEGF inhibition. TRC105 is an anti-endoglin IgG1 monoclonal antibody that potentiates VEGF inhibitors in preclinical models. This study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in combination with bevacizumab.

Experimental Design: Patients (n = 38) with advanced solid tumors, Eastern Cooperative Group performance status 0–1, and normal organ function were treated with escalating doses of TRC105 plus bevacizumab until disease progression or unacceptable toxicity using a standard 3 + 3 phase I design.

Results: TRC105 and bevacizumab were well tolerated at their recommended single-agent doses (10 mg/kg) when the initial dose of TRC105 was delayed by one week and divided over 2 days to limit the frequency of headache. The concurrent administration of bevacizumab and TRC105 did not otherwise potentiate known toxicities of TRC105 or bevacizumab. Hypertension and proteinuria were observed, though not at rates expected for single-agent bevacizumab. Several patients who had previously progressed on bevacizumab or VEGF receptor tyrosine kinase inhibitor (VEGFR TKI) treatment experienced reductions in tumor volume, including two partial responses by RECIST, and 6 remained without progression for longer periods than during their prior VEGF inhibitor therapy.

Conclusions: TRC105 was well tolerated with bevacizumab and clinical activity was observed in a VEGF inhibitor–refractory population. Ongoing clinical trials are testing TRC105 in combination with bevacizumab in glioblastoma and with VEGFR TKIs in renal cell carcinoma, hepatocellular carcinoma, and soft tissue sarcoma. Clin Cancer Res; 20(23); 5918–26. ©2014 AACR.
Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin
Authors: Schindler Mandana , Drozdenko Gennadiy , Kühl Anja Andrea , Worm Margitta
Published: September 2014

Background: Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE. Methods: Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically. Results: Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production. Conclusions: Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies.
Clinical Preventability of 30‐Day Readmission After Percutaneous Coronary Intervention
Authors: Wasfy Jason H. , Strom Jordan B. , Waldo Stephen W. , O'Brien Cashel , Wimmer Neil J. , Zai Adrian H. , Luttrell Jennifer , Spertus John A. , Kennedy Kevin F. , Normand Sharon‐Lise T. , Mauri Laura , Yeh Robert W.
Published: September 2014

Background

Early readmission after
PCI
is an important contributor to healthcare expenditures and a target for performance measurement. The extent to which 30‐day readmissions after
PCI
are preventable is unknown yet essential to minimizing their occurrence.

Methods and Results

PCI
patients readmitted to hospital at which
PCI
was performed within 30 days of discharge at the Massachusetts General Hospital and Brigham and Women's Hospital were identified, and their medical records were independently reviewed by 2 physicians. Each reviewer used an ordinal scale (0, not; 1, possibly; 2, probably; and 3, definitely preventable) to rate clinical preventability, and a total sum score ≥2 was considered preventable. Characteristics of preventable and unpreventable readmissions were compared, and predictors of clinical preventability were assessed by using multivariate logistic regression. Of 9288
PCI
s performed, 9081 (97.8%) patients survived to initial hospital discharge and 1007 (11.1%) were readmitted to the index hospital within 30 days. After excluding repeat readmissions, 893 readmissions were reviewed. Fair agreement between physician reviewers was observed (weighted κ statistic 0.44 [95%
CI
0.39 to 0.49]). After aggregation of scores, 380 (42.6%) readmissions were deemed preventable and 513 (57.4%) were deemed not preventable. Common causes of preventable readmissions included staged
PCI
without new symptoms (14.7%), vascular/bleeding complications of
PCI
(10.0%), and congestive heart failure (9.7%).

Conclusions

Nearly half of 30‐day readmissions after
PCI
may have been prevented by changes in clinical decision‐making. Focusing on these readmissions may reduce readmission rates.
Josephus on the Servile Origins of the Jews
Authors: Friedman David A.
Published: September 2014

The story of the Israelites’ slavery in Egypt and subsequent redemption is the central narrative element of the Pentateuch. Josephus’ claim that he was providing an accurate account of the Jews’ ancient history in Jewish Antiquities thus meant that he had to address the Jews’ servile origins; however, first-century Roman attitudes toward slaves and freedmen would have made this problematic for ideological and political reasons. Although Josephus added references to Jews’ slavery to the account of Jewish history in Jewish Antiquities, he appears deliberately to downplay the Jews’ servile origins at key parts of the narrative, including God’s promise to Abraham in Gen 15 and the account of the Jews’ enslavement in Exod 1. Josephus also demonstrates a concern with the servile status of Jacob’s secondary wives Zilpah and Bilhah. The account of Joseph’s life in Jewish Antiquities emphasizes his non-servile qualities and his chance enslavement. Roman hostility to slaves and freedmen, Josephus’ own personal experience of captivity, and the likely presence in Rome of Jewish freedmen might explain Josephus’ sensitivity to the Jews’ servile origins.
Samaritan Self-Consciousness in the First Half of the Second Century b.c.e. in Light of the Inscriptions from Mount Gerizim and Delos
Authors: Kartveit Magnar
Published: September 2014

Yitzhak Magen and his team have secured 395 inscriptions and fragments of inscriptions in Hebrew and Aramaic on the summit of Mount Gerizim. The number of inscriptions in one place is noteworthy, and calls for attention. Another find was made on the island of Delos in the Aegean Sea. Two inscriptions which praise benefactors for their support for the “Israelites who send their temple tax to Argarizein” were uncovered. The author suggests a new understanding of these inscriptions, and by reading them together it is possible to have a unique glimpse of how early Samaritan self-consciousness took shape by distancing itself from the Jewish position. Many of the phrases in the Gerizim corpus find parallels in comparable material from Egypt, the Sinai peninsula, Mesopotamia and Turkey. The phrase “in this place,” however, has no parallels in other inscriptions, and together with the references to the home village of the dedicators this gives an impression of a community dedicated to their own place of worship, Mount Gerizim, and living in its vicinity. The community behind the Delos inscriptions term themselves “Israelites,” and directs their religious focus towards Mount Gerizim. This is the earliest attestation of this name for the Samaritans.
Measures of the Principle of Good Faith in European Consumer Protection and Islamic Law, a Comparative Analysis
Authors: Fayyad Mahmoud
Published: September 2014

Evaluation of the success of consumer protection regulations in many Islamic states reflects defeated outcomes with regard to the application of many declared rights and objectives; it requires the fair implementation of the principle of good faith where clear and specific measures are required. It would be better for Muslim lawmakers to benefit from the European practice and Islamic guidelines; those criteria and measures are provided in the European Proposal of Consumer Rights (the Proposal). The Proposal provides that “A term is off in conjunction with this principle since it creates a significant imbalance of rights and obligations between the contracting parties”. Clear common used terms are provided in the lists of the Proposal. This voice is also well known in Islamic law; contracts of honesty (amāna) and rules of disproportion between the contradictable interests indicate this implementation.
‘Corporate Business Diplomacy’: Reflections on the Interdisciplinary Nature of the Field
Authors: Søndergaard Mikael
Published: September 2014

This article illustrates the interdisciplinary nature of the field of corporate business diplomacy using examples from academic disciplines, such as economics and political science, which can contribute to the understanding of corporate business diplomacy. Examples also show that corporate business diplomacy can complement business theories such as stakeholder theory and agency theory. Examples from practice show that in a broad sense, corporate business diplomacy is concerned with managing external stakeholders, while in a narrow sense, it is concerned with managing internal stakeholders. The usefulness of an analytical research triangulation is illustrated.