Large magnetoresistance and magnetocaloric effect above 70 K in Gd2Co2Al, Gd2Co2Ga and Gd7Rh3

The electrical resistivity, magnetization and heat-capacity behavior of the Gd-based compounds, Gd2Co2Al, Gd2Co2Ga and Gd7Rh3, ordering magnetically at TC= 78 K, TC= 76 K and TN= 140 K have been investigated as a function of temperature and magnetic field. All these compounds are found to show large magnetoresistance (with a negative sign) in the paramagnetic state at rather high temperatures with the magnitude peaking at respective magnetic ordering temperatures. There is a corresponding behavior in the magnetocaloric effect as inferred from the entropy derived from these data.Comment: Phys. Rev. 65 (2005) 49

Production of ent-kaurene from lignocellulosic hydrolysate in Rhodosporidium toruloides.

BACKGROUND:Rhodosporidium toruloides has emerged as a promising host for the production of bioproducts from lignocellulose, in part due to its ability to grow on lignocellulosic feedstocks, tolerate growth inhibitors, and co-utilize sugars and lignin-derived monomers. Ent-kaurene derivatives have a diverse range of potential applications from therapeutics to novel resin-based materials. RESULTS:The Design, Build, Test, and Learn (DBTL) approach was employed to engineer production of the non-native diterpene ent-kaurene in R. toruloides. Following expression of kaurene synthase (KS) in R. toruloides in the first DBTL cycle, a key limitation appeared to be the availability of the diterpene precursor, geranylgeranyl diphosphate (GGPP). Further DBTL cycles were carried out to select an optimal GGPP synthase and to balance its expression with KS, requiring two of the strongest promoters in R. toruloides, ANT (adenine nucleotide translocase) and TEF1 (translational elongation factor 1) to drive expression of the KS from Gibberella fujikuroi and a mutant version of an FPP synthase from Gallus gallus that produces GGPP. Scale-up of cultivation in a 2 L bioreactor using a corn stover hydrolysate resulted in an ent-kaurene titer of 1.4 g/L. CONCLUSION:This study builds upon previous work demonstrating the potential of R. toruloides as a robust and versatile host for the production of both mono- and sesquiterpenes, and is the first demonstration of the production of a non-native diterpene in this organism

Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials

\ua9 Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. OBJECTIVE: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics. METHODS: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists\u27 Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up. RESULTS: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use. CONCLUSION: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions

FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis

Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci) to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD

Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta

Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV

Aim: This thesis aims to provide a multidimensional assessment of infection risks and to evaluate strategies for HPV prevention including vaccination with quadrivalent HPVvaccines, dose-level vaccine effectiveness and condom use in high STI risk situations. Methods: Multiple population-based registers and questionnaire responses provided data for this thesis. Various multivariable and univariate regression models were fit. Findings: Overall, quadrivalent HPV-vaccination was highly effective against genital warts (GW) also referred to as condyloma, which is the first HPV disease endpoint possible to measure. However, effectiveness was contingent upon young age-at-first vaccination, with effectiveness declining steadily the older the age-at-first vaccination. Among women above 20 years of age there was low to immeasurable effectiveness and suggestive evidence vaccinations in this age group tended to reach women at high GW risk. There were marked socioeconomic disparities in the opportunistic (on-demand with co-pay) vaccination strategy evaluated, with women and girls who have parents with the highest education level compared to the lowest having a 15 times greater likelihood to be vaccinated (Study III). Once vaccination was initiated, however, high parental education level was unrelated to vaccination completion. Maximum protection against GW was found among girls vaccinated under the age of 17 who had received three doses of the vaccine. No differences in effectiveness were found for girls who received twodoses between ages 10-16 with that of those who received three-doses between ages 17- 19 (Study IV). GW affects more men than women in Sweden as of 2010 with 453 per 100 000 men and 365 per 100 000 women treated. A decline between 25-30% was seen between 2006 and 2010 among women in the age groups with the highest vaccination coverage. No decline was found amongst men and their GW incidence has steadily increased between 2006 and 2010 (Study II). Reported condom use in high risk situations was low among both men and women, with 41% of men and 34% of women reporting always/almost always condom use with temporary partners. STI risk perception was also low, with approximately 10% of sexually active respondents considering themselves at large risk of contracting an STI. There was no association between men’s condom use and their STI risk perception but there was an association for women (Study I). Conclusions: Results suggest that males bear a substantial burden of HPV-related condyloma where incidence has dropped among women. When planning HPVvaccination among females, efforts should target girls under age 14 for maximum effectiveness. Quadrivalent HPV-vaccination offers most protection against condyloma at three doses. Gross social inequity was found with opportunistic HPV-vaccination. There were large gender differences in factors associated with condom use in high risk situations and STI risk perceptions