Liver mitochondrial membrane permeability modulation in insulin-resistant, uninephrectomised male rats by Clerodendrum volubile P. Beauv and Manihot esculenta Crantz

Background: Non-alcoholic fatty liver disease, which occurs in people who are not alcohol drinkers, describes some of the pathogenic conditions that may be in the least characterized by simple steatosis or can be as serious as non-alcoholic steatohepatitis and cirrhosis. Its mechanistic pathogenesis has been said to arise from insulin resistance and oxidative stress, which may be compounded by obesity. An experimental model showing, systemic insulin resistance, obesity and accumulated hepatic fatty acids was created in adult male rats using high-fat diet manipulation and surgical removal of the left kidney (uninephrectomy). This study sought to identify the impact of these multiple burdens on the liver mitochondrial membrane permeability transition pore opening, and the possible in vitro effects of the extracts of Clerodendrum volubile and Manihot esculenta leaves on the membrane permeabilization. Results: The results indicated that the methanolic extract of Clerodendrum volubile leaf inhibited mitochondrial membrane pore opening in the insulin resistance condition or when it is followed by uni-nephrectomy, while the ethanolic extract of Manihot esculenta leaf does the same in the insulin resistance condition both prior to and following uni-nephrectomy. Conclusion: Since the vegetable extracts were able to abrogate mitochondrial pore opening at low concentrations, the structural integrity of the mitochondria can possibly be restored over time if treated by the vegetable extracts. Research efforts should, therefore, be made to harness the drugability of the bioactives of these vegetables for use in the treatment of non-alcoholic fatty liver disease arising from insulin resistance and renal failure.Fil: Ajayi, Ebenezer Idowu O. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Osun State University; Nigeria. National Institute of Pharmaceutical Education and Research; IndiaFil: Molehin, Olorunfemi R.. Ekiti State University; NigeriaFil: Oloyede, Omotade I.. Ekiti State University; NigeriaFil: Kumar, Vinodu. National Institute of Pharmaceutical Education and Research; IndiaFil: Amara, Venkateswara R.. National Institute of Pharmaceutical Education and Research; IndiaFil: Kaur, Jasmine. National Institute of Pharmaceutical Education and Research; IndiaFil: Karpe, Pinakin. National Institute of Pharmaceutical Education and Research; IndiaFil: Tikoo, Kulbhushan B.. National Institute of Pharmaceutical Education and Research; Indi

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 >3 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 <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

The effects of 10 to >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

Uptake Rate of Cationic Mitochondrial Inhibitor MKT-077 Determines Cellular Oxygen Consumption Change in Carcinoma Cells

<div><h3>Objective</h3><p>Since tumor radiation response is oxygen-dependent, radiosensitivity can be enhanced by increasing tumor oxygenation. Theoretically, inhibiting cellular oxygen consumption is the most efficient way to increase oxygen levels. The cationic, rhodacyanine dye-analog MKT-077 inhibits mitochondrial respiration and could be an effective metabolic inhibitor. However, the relationship between cellular MKT-077 uptake and metabolic inhibition is unknown. We hypothesized that rat and human mammary carcinoma cells would take up MKT-077, causing a decrease in oxygen metabolism related to drug uptake.</p> <h3>Methods</h3><p>R3230Ac rat breast adenocarcinoma cells were exposed to MKT-077. Cellular MKT-077 concentration was quantified using spectroscopy, and oxygen consumption was measured using polarographic electrodes. MKT-077 uptake kinetics were modeled by accounting for uptake due to both the concentration and potential gradients across the plasma and mitochondrial membranes. These kinetic parameters were used to model the relationship between MKT-077 uptake and metabolic inhibition. MKT-077-induced changes in oxygen consumption were also characterized in MDA-MB231 human breast carcinoma cells.</p> <h3>Results</h3><p>Cells took up MKT-077 with a time constant of ∼1 hr, and modeling showed that over 90% of intracellular MKT-077 was bound or sequestered, likely by the mitochondria. The uptake resulted in a rapid decrease in oxygen consumption, with a time constant of ∼30 minutes. Surprisingly the change in oxygen consumption was proportional to uptake rate, not cellular concentration. MKT-077 proved a potent metabolic inhibitor, with dose-dependent decreases of 45–73% (p = 0.003).</p> <h3>Conclusions</h3><p>MKT-077 caused an uptake rate-dependent decrease in cellular metabolism, suggesting potential efficacy for increasing tumor oxygen levels and radiosensitivity <em>in vivo</em>.</p> </div

SMAC is expressed de novo in a subset of cervical cancer tumors

BACKGROUND: Smac/Diablo is a recently identified protein that is released from mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation and cell death. In view of its activity it might participate in carcinogenesis. In the present study, we analyzed Smac expression in a panel of cervical cancer patients. METHODS: We performed semi quantitative RT-PCR on 41 cervical tumor and 6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17 stage III; and a control group of 6 samples of normal cervical squamous epithelial tissue. RESULTS: Smac mRNA expression was below the detection limit in the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical cancer biopsies showed detectable levels of this transcript. The samples expressing Smac were distributed equally among the stages (5 in stage I, 4 in stage II and 4 in stage III) with similar expression levels. We found no correlation between the presence of Smac mRNA and histology, menopause, WHO stage or disease status. CONCLUSIONS: Smac is expressed de novo in a subset of cervical cancer patients, reflecting a possible heterogeneity in the pathways leading to cervical cancer. There was no correlation with any clinical variable

Expedition 391 Preliminary Report : Walvis Ridge Hotspot: drilling Walvis Ridge, Southeast Atlantic Ocean, to test models of ridge hotspot interaction, isotopic zonation, and the hotspot reference frame

Hotspot tracks (quasilinear chains of seamounts, ridges, and other volcanic structures) provide important records of plate motions, as well as mantle geodynamics, magma flux, and mantle source compositions. The Tristan-Gough-Walvis Ridge (TGW) hotspot track, extending from the active volcanic islands of Tristan da Cunha and Gough through a province of guyots and then along Walvis Ridge to the Etendeka flood basalt province, forms one of the most prominent and complex global hotspot tracks. The TGW hotspot track displays a tight linear age progression in which ages increase from the islands to the flood basalts (covering ~135 My). Unlike Pacific tracks, which are simple chains of seamounts that are often compared to chains of pearls, the TGW track is alternately a steep-sided narrow ridge, an oceanic plateau, subparallel linear ridges and chains of seamounts, and areas of what appear to be randomly dispersed seamounts. The track displays isotopic zonation over the last ~70 My. The zonation appears near the middle of the track just before it splits into two to three chains of ridge- and guyot-type seamounts. The older ridge is also overprinted with age-progressive late-stage volcanism, which was emplaced ~30–40 My after the initial eruptions and has a distinct isotopic composition. The plan for Expedition 391 was to drill at six sites, three along Walvis Ridge and three in the seamount (guyot) province, to gather igneous rocks to better understand the formation of track edifices, the temporal and geochemical evolution of the hotspot, and the variation in paleolatitudes at which the volcanic edifices formed. After a delay of 18 days to address a shipboard outbreak of the coronavirus disease 2019 (COVID-19) virus, Expedition 391 proceeded to drill at four of the proposed sites: three sites on the eastern Walvis Ridge around Valdivia Bank, an ocean plateau within the ridge, and one site on the lower flank of a guyot in the Center track, a ridge located between the Tristan subtrack (which extends from the end of Walvis Ridge to the island of Tristan da Cunha) and the Gough subtrack (which extends from Walvis Ridge to the island of Gough). One hole was drilled at Site U1575, located on a low portion of the northeastern Walvis Ridge north of Valdivia Bank. At this location, 209.9 m of sediments and 122.4 m of igneous basement were cored. The latter comprised 10 submarine lava units consisting of pillow, lobate, sheet, and massive lava flows, the thickest of which was ~21 m. Most lavas are tholeiitic, but some alkalic basalts were recovered. A portion of the igneous succession consists of low-Ti basalts, which are unusual because they appear in the Etendeka flood basalts but have not been previously found on Walvis Ridge. Two holes were drilled at Site U1576 on the west flank of Valdivia Bank. The first hole was terminated because a bit jammed shortly after penetrating igneous basement. Hole U1576A recovered a remarkable ~380 m thick sedimentary section consisting mostly of chalk covering a nearly complete sequence from Paleocene to Late Cretaceous (Campanian). These sediments display short and long cyclic color changes that imply astronomically forced and longer term paleoenvironmental changes. The igneous basement yielded 11 submarine lava units ranging from pillows to massive flows, which have compositions varying from tholeiitic basalt to basaltic andesite, the first occurrence of this composition recovered from the TGW track. These units are separated by seven sedimentary chalk units that range in thickness from 0.1 to 11.6 m, implying a long-term interplay of sedimentation and lava eruptions. Coring at Site U1577, on the extreme eastern flank of Valdivia Bank, penetrated a 154 m thick sedimentary section, the bottom ~108 m of which is Maastrichtian–Campanian (possibly Santonian) chalk with vitric tephra layers. Igneous basement coring progressed only 39.1 m below the sediment-basalt contact, recovering three massive submarine tholeiite basalt lava flows that are 4.1, 15.5, and >19.1 m thick, respectively. Paleomagnetic data from Sites U1577 and U1576 indicate that their volcanic basements formed just before the end of the Cretaceous Normal Superchron and during Chron 33r, shortly afterward, respectively. Biostratigraphic and paleomagnetic data suggest an east–west age progression across Valdivia Bank, becoming younger westward. Site U1578, located on a Center track guyot, provided a long and varied igneous section. After coring through 184.3 m of pelagic carbonate sediments mainly consisting of Eocene and Paleocene chalk, Hole U1578A cored 302.1 m of igneous basement. Basement lavas are largely pillows but are interspersed with sheet and massive flows. Lava compositions are mostly alkalic basalts with some hawaiite. Several intervals contain abundant olivine, and some of the pillow stacks consist of basalt with remarkably high Ti content. The igneous sequence is interrupted by 10 sedimentary interbeds consisting of chalk and volcaniclastics and ranging in thickness from 0.46 to 10.19 m. Paleomagnetic data display a change in basement magnetic polarity ~100 m above the base of the hole. Combining magnetic stratigraphy with biostratigraphic data, the igneous section is inferred to span >1 My. Abundant glass from pillow lava margins was recovered at Sites U1575, U1576, and U1578. Although the igneous penetration was only two-thirds of the planned amount, drilling during Expedition 391 obtained samples that clearly will lead to a deeper understanding of the evolution of the Tristan-Gough hotspot and its track. Relatively fresh basalts with good recovery will provide ample samples for geochemical, geochronologic, and paleomagnetic studies. Good recovery of Late Cretaceous and early Cenozoic chalk successions provides samples for paleoenvironmental study

The construction of ethnic identity: insights from identity process theory

Ethnicity has received much empirical and theoretical attention in the social sciences. Yet, it has scarcely been explored in terms of its relationship with the motivational principles of identity. Here it is argued that there is much heuristic and predictive value in applying identity process theory (IPT), a socio-psychological model of identity threat, to the substantive literature on ethnicity. The paper explores the potential psychological benefits of ethnic identification. Key theoretical strands from anthropology and sociology, such as the ‘relational self’ in ethnic identification, are discussed in relation to IPT. The intergroup dimension of ethnic identification is explored through the discussion of ethnic 'boundaries'. Finally, the paper discusses the construct of 'hybridization' in relation to social psychology. This paper attempts to reconcile psychological and sociological perspectives on ethnic identification, advocating a multi-methodological approach. Key theoretical points are outlined in the form of testable hypotheses which are open to empirical exploration

A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model

Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5