Production of the new cholera toxin by environmental isolates of Vibrio cholerae non-O1

One of five strains of Vibrio cholerae non-O1 isolated from environmental sources caused fluid accumulation in an initial rabbit ileal loop (RIL) test. The four strains that caused little or no accumulation of fluid gave a positive response after one-to-three consecutive passages through RILs. The amount of fluid produced increased after each passage. Filtrates of cultures of all five environmental isolates caused fluid accumulation similar to that produced by live cells. The enterotoxin showed a precipitin band with new cholera antitoxin and was neutralised completely by new cholera antitoxin diluted 1 in 32, indicating its close immunobiological relationship to the new cholera toxin. The present study indicates that V. cholerae non-O1 strains produce an enterotoxin that is similar to the new cholera toxin

Gigantism in unique biogenic magnetite at the Paleocene-Eocene Thermal Maximum

We report the discovery of exceptionally large biogenic magnetite crystals in clay-rich sediments spanning the Paleocene-Eocene Thermal Maximum (PETM) in a borehole at Ancora, New Jersey. Aside from previously-described abundant bacterial magnetofossils, electron microscopy reveals novel spearhead-like and spindle-like magnetite up to 4 μm long and hexaoctahedral prisms up to 1.4 μm long. Similar to magnetite produced by magnetotactic bacteria, these single-crystal particles exhibit chemical composition, lattice perfection, and oxygen isotopes consistent with an aquatic origin. Electron holography indicates single-domain magnetization despite their large crystal size. We suggest that the development of a thick suboxic zone with high iron bioavailability – a product of dramatic changes in weathering and sedimentation patterns driven by severe global warming – drove diversification of magnetite-forming organisms, likely including eukaryotes

Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats

<p>Abstract</p> <p>Background</p> <p>Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARγ agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats.</p> <p>Methods</p> <p>Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-γ expression were examined by western blotting.</p> <p>Results</p> <p>Our data shows involvement of TNF-α in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-γ in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-γ directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications.</p> <p>Conclusion</p> <p>To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer.</p

Cholera toxin, zonula occludens toxin and accessary cholera enterotoxin gene-negative Vibrio cholerae non-01 strains produce the new cholera toxin

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Studies on polyphenol oxidase in wheat grains

Polyphenol oxidase was partially purified from the bran fraction of mature grains of tall and dwarf varieties of wheat. The specific activity of the enzyme in dwarfs is distinctly higher than in tall varieties. Furthur, the enzyme in dwarfs is relatively more thermostable. Substrate specificity studies showed that diphenols are efficient substrates, whereas mono- and polyphenols are poor substrates. Fractionation of isoenzymes of polyphenol oxidase on acrylamide gel electrophoresis revealed three to five bands. Usually the isoenzymes of dwarf varieties are more stable on storage at 4° C. than their counterparts in the tall varieties

Reply to Comment on "Pervasive remagnetization of detrital zircon host rocks in the Jack Hills, Western Australia and implications for records of the early dynamo"

Determining the history of Earth's dynamo prior to the oldest known well-preserved rock record is one of the ultimate challenges in the field of paleomagnetism. Tarduno et al. (2015) argued that detrital zircons contain records of an active dynamo dating back to 4.2 billion years ago (Ga), 700 million years earlier than previously identified (Biggin et al., 2011 and Tarduno et al., 2010). However, this extraordinary claim requires evidence that the zircons have not been remagnetized during the intervening time since their formation. Weiss et al. (2015) argued that such evidence had yet to be provided, a conclusion that we find still firmly holds

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy &gt;3&nbsp;months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P &lt;0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes

T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon‐like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three‐dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities

The effects of 10 to &gt;160 GPa shock on the magnetic properties of basalt and diabase

© 2016. American Geophysical Union. All Rights Reserved.Hypervelocity impacts within the solar system affect both the magnetic remanence and bulk magnetic properties of planetary materials. Spherical shock experiments are a novel way to simulate shock events that enable materials to reach high shock pressures with a variable pressure profile across a single sample (ranging between ∼10 and >160 GPa). Here we present spherical shock experiments on basaltic lava flow and diabase dike samples from the Osler Volcanic Group whose ferromagnetic mineralogy is dominated by pseudo-single-domain (titano)magnetite. Our experiments reveal shock-induced changes in rock magnetic properties including a significant increase in remanent coercivity. Electron and magnetic force microscopy support the interpretation that this coercivity increase is the result of grain fracturing and associated domain wall pinning in multidomain grains. We introduce a method to discriminate between mechanical and thermal effects of shock on magnetic properties. Our approach involves conducting vacuum-heating experiments on untreated specimens and comparing the hysteresis properties of heated and shocked specimens. First-order reversal curve (FORC) experiments on untreated, heated, and shocked specimens demonstrate that shock and heating effects are fundamentally different for these samples: shock has a magnetic hardening effect that does not alter the intrinsic shape of FORC distributions, while heating alters the magnetic mineralogy as evident from significant changes in the shape of FORC contours. These experiments contextualize paleomagnetic and rock magnetic data of naturally shocked materials from terrestrial and extraterrestrial impact craters