BNNT- Mediated Irreversible Electroporation: It\u27s Potential on Cancer Cells

Irreversible lethal electroporation (IRE) is a new non-thermal ablation modality that uses short pulses of high amplitude static electric fields (up 1000V/cm) to create irreversible pores in the cell membrane, thus, causing cell death. Recently, IRE has emerged as a promising clinical modality for cancer disease treatment. Here, we investigated the responses of tumour human He La cells when subjected to IRE in the presence of BNNTs. These consist of tiny tubes of B and N atoms (arranged in hexagons) with diameters ranging from a 1 to 3 nanometres and lengths \u3c2 μm. BNNTs have attracted wide attention because of their unique electrical properties. We speculate that BNNTs, when interacting with cells exposed to static electrical fields, amplify locally the electric field, leading to cell death. In this work, electroporation assays were performed with a commercial electroporator using the cell-specific protocol suggested by the supplier (exponential decay wave, time constant 20ms) with the specific aim to compare IRE in absence and in presence of BNNTs. We observed that BNNTs have the capacity to decrease substantially the voltage required for IRE. When cells were pulsed at 800V/cm, we observed a 2,2-fold reduction in cell survival in the presence of BNNTs compared to controls. We conclude that the death of the tumour cells exposed to IRE is strongly enhanced in the presence of BNNTs, indicating their potential therapeutic application

Comparison of Performance and Economics of a Long-yearling and Calf-fed System

Performance and economics of calf feeding and feeding long-yearlings was compared from University of Nebraska research conducted from 1996 to 2004. All calves in these studies were spring born and purchased the subsequent fall. The heaviest calves (292 ± 5 kg) were placed into the feedlot and fed an average of 168 d (calf-feds), whereas the lighter calves (239 ± 5 kg) were placed into a long-yearling system consisting of corn residue grazing followed by summer grazing before entering the feedlot for finishing. Long-yearlings were fed in the feedlot for an average of 90 d. At the beginning of the finishing period, long-yearlings were 143 kg heavier than calf-feds (P \u3c 0.01). Although daily DMI was greater for long-yearlings (P \u3c 0.01), calf-feds consumed more total DM during finishing (P \u3c 0.01). Long-yearlings had greater ADG compared with calf-feds during finishing (P \u3c 0.01); however, calf-feds were 18.7% more efficient (P \u3c 0.01). Long-yearlings were 38 kg heavier (P \u3c 0.01) than calf-feds and had 24 kg heavier hot carcass weight (P \u3c 0.01). Quality grade was not affected by production system (P \u3e 0.10); however, calf-feds had 0.15 cm greater fat thickness (P \u3c 0.01). Long-yearlings were more profitable than calf-feds (P \u3c 0.01) due to lower feed cost (P \u3c 0.01), yardage (P \u3c 0.01), and initial animal cost (P \u3c 0.01). However, long-yearlings had higher interest cost (P \u3c 0.01) and total cost (P = 0.02). Long-yearlings produced greater final BW leading to an improvement in profitability compared with calf-feds

Voluntary Exercise Reduces Alzheimer’s-like Pathology After Inflammation in Mice

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has previously shown that 7 consecutive peripheral injections of a bacterial mimetic led to systemic inflammation, increased levels of Ab in the brain, and cognitive dysfunction (Kahn et al., 2012; Weintraub et al., 2013). Currently there are very few effective treatments that diminish AD symptomology. One documented way to decrease inflammation without the use of pharmaceuticals is through regular physical exercise (Cho et al., 2003; Cotman & Berchtold, 2002; Cotman et al., 2007). The present study tested the hypothesis that voluntary exercise would decrease the level of brain Ab following inflammation. Interestingly, we found that two weeks of voluntary wheel running after inflammation led to a reduction of Ab when compared to sedentary recovery. These results indicate that exercise may be an effective modality to reduce AD-like pathology, and that these effects appear to be facilitated by higher versus lower levels of exercise, as measured by total distance run

A restatement of the natural science evidence base concerning grassland management, grazing livestock and soil carbon storage

Approximately a third of all annual greenhouse gas emissions globally are directly or indirectly associated with the food system, and over a half of these are linked to livestock production. In temperate oceanic regions, such as the UK, most meat and dairy is produced in extensive systems based on pasture. There is much interest in the extent to which such grassland may be able to sequester and store more carbon to partially or completely mitigate other greenhouse gas emissions in the system. However, answering this question is difficult due to context-specificity and a complex and sometimes inconsistent evidence base. This paper describes a project that set out to summarize the natural science evidence base relevant to grassland management, grazing livestock and soil carbon storage potential in as policy-neutral terms as possible. It is based on expert appraisal of a systematically assembled evidence base, followed by a wide stakeholders engagement. A series of evidence statements (in the appendix of this paper) are listed and categorized according to the nature of the underlying information, and an annotated bibliography is provided in the electronic supplementary material

The pulse of the Amazon: fluxes of dissolved organic carbon, nutrients, and ions from the world's largest river

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 35(4), (2021): e2020GB006895, https://doi.org/10.1029/2020GB006895.The Amazon River drains a diverse tropical landscape greater than 6 million km2, culminating in the world's largest export of freshwater and dissolved constituents to the ocean. Here, we present dissolved organic carbon (DOC), organic and inorganic nitrogen (DON, DIN), orthophosphate (PO43−), and major and trace ion concentrations and fluxes from the Amazon River using 26 samples collected over three annual hydrographs. Concentrations and fluxes were predominantly controlled by the annual wet season flood pulse. Average DOC, DON, DIN, and PO43− fluxes (±1 s.d.) were 25.5 (±1.0), 1.14 (±0.05), 0.82 (±0.03), and 0.063 (±0.003) Tg yr−1, respectively. Chromophoric dissolved organic matter absorption (at 350 nm) was strongly correlated with DOC concentrations, resulting in a flux of 74.8 × 106 m−2 yr−1. DOC and DON concentrations positively correlated with discharge while nitrate + nitrite concentrations negatively correlated, suggesting mobilization and dilution responses, respectively. Ammonium, PO43−, and silica concentrations displayed chemostatic responses to discharge. Major and trace ion concentrations displayed clockwise hysteresis (except for chloride, sodium, and rubidium) and exhibited either dilution or chemostatic responses. The sources of weathered cations also displayed seasonality, with the highest proportion of carbonate- and silicate-derived cations occurring during peak and baseflow, respectively. Finally, our seasonally resolved weathering model resulted in an average CO2 consumption yield of (3.55 ± 0.11) × 105 mol CO2 km−2 yr−1. These results represent an updated and temporally refined quantification of dissolved fluxes that highlight the strong seasonality of export from the world's largest river and set a robust baseline against which to gauge future change.This work was supported by a grant from the Harbourton Foundation to R. G. M. Spencer and R. M. Holmes. T. W. Drake was supported by ETH Zurich core funding to J. Six. R. G. M. Spencer was additionally supported by NSF OCE-1333157.2021-09-1

Electron-ion recombination of Mg6 + forming Mg5 + and of Mg7 + forming Mg6 + : laboratory measurements and theoretical calculations

We have measured electron–ion recombination for C-like Mg6+ forming Mg5+, and for B-like Mg7+ forming Mg6+. These studies were performed using a merged electron–ion beam arrangement at the TSR heavy ion storage ring located in Heidelberg, Germany. Both primary ions have metastable levels with significant lifetimes. Using a simple cascade model we estimate the population fractions in these metastable levels. For the Mg6+ results, we find that the majority of the stored ions are in a metastable level, while for Mg7+ the metastable fraction is insignificant. We present the Mg6+ merged beams recombination rate coefficient for DR via N = 2 → N = 2 core electron excitations (ΔN = 0 DR) and for Mg7+ via 2 → 2 and 2 → 3 core excitations. Taking the estimated metastable populations into account, we compare our results to state-of-the-art multiconfiguration Breit–Pauli theoretical calculations. Significant differences are found at low energies where theory is known to be unreliable. Moreover, for both ions we observe a discrepancy between experiment and theory for ΔN = 0 DR involving capture into high-n Rydberg levels and where the stabilization is primarily due to a radiative transition of the excited core electron. This is consistent with previous DR experiments on M-shell iron ions which were performed at TSR. The large metastable content of the Mg6+ ion beam precludes generating a plasma recombination rate coefficient (PRRC). However, this is not an issue for Mg7+ and we present an experimentally derived Mg7+ PRRC for plasma temperatures from 400 K to 107 K with an estimated uncertainty of less than 27% at a 90% confidence level. We also provide a fit to our experimentally derived PRRC for use in plasma modeling codes

Autoimmune and infectious skin diseases that target desmogleins

Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects

Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland

Bovine tuberculosis (bTB) is a costly, epidemiologically complex, multi-host, endemic disease. Lack of understanding of transmission dynamics may undermine eradication efforts. Pathogen whole-genome sequencing improves epidemiological inferences, providing a means to determine the relative importance of inter- and intra-species host transmission for disease persistence. We sequenced an exceptional data set of 619 Mycobacterium bovis isolates from badgers and cattle in a 100 km2 bTB 'hotspot' in Northern Ireland. Historical molecular subtyping data permitted the targeting of an endemic pathogen lineage, whose long-term persistence provided a unique opportunity to study disease transmission dynamics in unparalleled detail. Additionally, to assess whether badger population genetic structure was associated with the spatial distribution of pathogen genetic diversity, we microsatellite genotyped hair samples from 769 badgers trapped in this area. Birth death models and TransPhylo analyses indicated that cattle were likely driving the local epidemic, with transmission from cattle to badgers being more common than badger to cattle. Furthermore, the presence of significant badger population genetic structure in the landscape was not associated with the spatial distribution of M. bovis genetic diversity, suggesting that badger-to-badger transmission is not playing a major role in transmission dynamics. Our data were consistent with badgers playing a smaller role in transmission of M. bovis infection in this study site, compared to cattle. We hypothesize, however, that this minor role may still be important for persistence. Comparison to other areas suggests that M. bovis transmission dynamics are likely to be context dependent, with the role of wildlife being difficult to generalize.ISSN:2057-585

Chiang Kai-shek’s “secret deal” at Xian and the start of the Sino-Japanese War

Using newly available archives, particularly the diary and the presidential papers of Chiang Kai-shek, this article challenges the conventional interpretations of the Xian Incident (1936), in particular the widely held belief that the kidnapping of China’s leader Chiang by two rebellious generals forced him to form a united front with the Communist Party to confront Japanese aggression, and of the outbreak of the Sino-Japanese War 7 months later. It puts forth the interpretation that full-scale war between China and Japan was started not by Japan but by Chiang after a Japanese provocation, and the united front was only formed after Chiang ordered his best army units to attack Japanese forces in Shanghai in August 1937 turning it into the largest land battle after the First World War. It must be noted, however, that Japan acted provocatively and aggressively in a local incident outside Beijing a month earlier. Chiang decided on war not because he reached an agreement with the Chinese Communists to form a united front whilst a captive in Xian but because in Xian he received a signal from Josef Stalin that the Soviet Union would support him in a war with Japan. Chiang read Stalin right and the Soviet Union became the largest supplier of weapons to China in the first 4 years of China’s 8-year war with Japan. The hitherto unknown or “secret deal” Chiang made in Xian was an implicit one with Stalin, not with the Chinese Communist Party or its man on the spot Zhou Enlai