RNA-seq transcriptome analysis reveals long terminal repeat retrotransposon modulation in human peripheral blood mononuclear cells after in vivo lipopolysaccharide injection

Human endogenous retroviruses (HERVs) and mammalian apparent long terminal repeat (LTR) retrotransposons (MaLRs) are retroviral sequences that integrated into germ line cells millions of years ago. Transcripts of these LTR retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. Here, we focused on the HERV/MaLR expression and modulation in a scenario of immune system activation. We used a public data set of human peripheral blood mononuclear cells (PBMCs) RNA-Seq from 15 healthy participants to a clinical trial before and after exposure to lipopolysaccharide (LPS), for which we established an RNA-Seq workflow for the identification of expressed and modulated cellular genes and LTR retrotransposon elements. IMPORTANCE We described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4% of the LTR retrotransposon loci were expressed and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERV and MaLR loci that were modulated as a result of in vivo stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci as differentially expressed, checking their genomic context of insertion and observing a general colocalization with genes that are involved and modulated in the immune response, as a consequence of LPS stimulation. The analyses of HERV and MaLR expression and modulation show that these LTR retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR retrotransposons and the immune host response

Prostate-Specific Antigen testing in men between 40 and 70 years in Brazil: database from a check-up program

Objectives To evaluate the PSA in a large population of Brazilian men undergone to check up, and correlate the PSA cutoffs with prostate size and urinary symptoms. Materials and Methods This is a cross sectional study performed with men between 40 and 70 years undergone to check-up. All men were undergone to urological evaluation, digital rectal examination, prostate-specific antigen, and ultrasonography The exclusion criteria were men who used testosterone in the last six months, or who were using 5 alpha-reductase inhibitors. Results A total of 5015 men with an average age of 49.0 years completed the study. Most men were white and asymptomatic. The PSA in the three different aging groups were 0.9 ± 0.7ng/dL for men between 40 and 50; 1.2 ± 0.5ng/dL for men between 50 and 60; and 1.7 ± 1.5ng/dL for men greater than 60 years (p=0.001). A total of 192 men had PSA between 2.5 and 4ng/ml. From these men 130 were undergone to prostate biopsy. The predictive positive value of biopsy was 25% (32/130). In the same way, 100 patients had PSA >4ng/mL. From these men, 80 were undergone to prostate biopsy. In this group, the predictive positive value of biopsy was 40% (32/100). The Gleason score was 6 in 19 men (60%), 7 in 10 men (31%) and 8 in 3 men (9%). Conclusions The PSA level of Brazilian men undergone to check up was low. There was a positive correlation with aging, IPSS and prostate size.Universidade Federal de São Paulo (UNIFESP) Department of UrologyHospital Israelita Albert EinsteinWake Forest UniversityUNIFESP, Department of UrologySciEL

Complex organic molecules in low-mass protostars on Solar System scales -- II. Nitrogen-bearing species

The chemical inventory of planets is determined by the physical and chemical processes that govern the early phases of star formation. The aim is to investigate N-bearing complex organic molecules towards two Class 0 protostars (B1-c and S68N) at millimetre wavelengths with ALMA. Next, the results of the detected N-bearing species are compared with those of O-bearing species for the same and other sources. ALMA observations in Band 6 ($\sim$ 1 mm) and Band 5 ($\sim$ 2 mm) are studied at $\sim$ 0.5" resolution, complemented by Band 3 ($\sim$ 3 mm) data in a $\sim$ 2.5" beam. NH2CHO, C2H5CN, HNCO, HN13CO, DNCO, CH3CN, CH2DCN, and CHD2CN are identified towards the investigated sources. Their abundances relative to CH3OH and HNCO are similar for the two sources, with column densities that are typically an order of magnitude lower than those of O-bearing species. The largest variations, of an order of magnitude, are seen for NH2CHO abundance ratios with respect to HNCO and CH3OH and do not correlate with the protostellar luminosity. In addition, within uncertainties, the N-bearing species have similar excitation temperatures to those of O-bearing species ($\sim$ 100 $\sim$ 300 K). The similarity of most abundances with respect to HNCO, including those of CH2DCN and CHD2CN, hints at a shared chemical history, especially the high D/H ratio in cold regions prior to star formation. However, some of the variations in abundances may reflect the sensitivity of the chemistry to local conditions such as temperature (e.g. NH2CHO), while others may arise from differences in the emitting areas of the molecules linked to their different binding energies in the ice. The two sources discussed here add to the small number of sources with such a detailed chemical analysis on Solar System scales. Future JWST data will allow a direct comparison between the ice and gas abundances of N-bearing species.Comment: Accepted to A&A, 41 pages, 37 figure

Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis

Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection

Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism

KIT is a tyrosine kinase receptor expressed by several tumours, which has for specific ligand the stem cell factor (SCF). KIT is the main oncogene in gastrointestinal stromal tumours (GISTs), and gain-of-function KIT mutations are present in 70% of these tumours. The aim of the study was to measure and investigate the mechanisms of KIT activation in 80 KIT-positive GIST patients. KIT activation was quantified by detecting phosphotyrosine residues in Western blotting. SCF production was determined by reverse transcriptase–PCR, ELISA and/or immunohistochemistry. Primary cultures established from three GISTs were also analysed. The results show that KIT activation was detected in all cases, even in absence of KIT mutations. The fraction of activated KIT was not correlated with the mutational status of GISTs. Membrane and soluble isoforms of SCF mRNA were present in all GISTs analysed. Additionally, SCF was also detected in up to 93% of GISTs, and seen to be present within GIST cells. Likewise, the two SCF mRNA isoforms were found to be expressed in GIST-derived primary cultures. Thus, KIT activation in GISTs may in part result from the presence of SCF within the tumours

Water in the terrestrial planet-forming zone of the PDS 70 disk

Terrestrial and sub-Neptune planets are expected to form in the inner ($<10~$AU) regions of protoplanetary disks. Water plays a key role in their formation, although it is yet unclear whether water molecules are formed in-situ or transported from the outer disk. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks, similar to PDS 70, the first system with direct confirmation of protoplanet presence. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large ($\sim54~$AU) planet-carved gap separating an inner and outer disk. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H$_2$, and/or OH, and survival through water self-shielding. This is also supported by the presence of CO$_2$ emission, another molecule sensitive to UV photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.Comment: To appear in Nature on 24 July 2023. 21 pages, 10 figures; includes extended data. Part of the JWST MINDS Guaranteed Time Observations program's science enabling products. Spectra downloadable on Zenodo at https://zenodo.org/record/799102

Advances, Challenges and Opportunities in 3D CMOS Sequential Integration

3D sequential integration enables the full use of the third dimension thanks to its high alignment performance. In this paper, we address the major challenges of 3D sequential integration: in particular, the control of molecular bonding allows us to obtain pristine quality top active layer. With the help of Solid Phase Epitaxy, we can match the performance of top FET, processed at low temperature (600°C), with the bottom FET devices. Finally, the development of a stable salicide enables to retain bottom performance after top FET processing. Overcoming these major technological issues offers a wide range of applications

MINDS. Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI

MIRI/MRS on board the JWST allows us to probe the inner regions of protoplanetary disks. Here we examine the disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core. We focus on the H$_2$O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations. In order to model the molecular features in the spectrum, the continuum was subtracted and LTE slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H$_2$O lines of different excitation conditions, and the slab model fits were performed individually per region. We confidently detect CO, H$_2$O, OH, CO$_2$, and HCN in the emitting layers. The isotopologue H$^{18}_2$O is not detected. Additionally, no other organics, including C$_2$H$_2$, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H$_2$O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. The OH and CO$_2$ emission are relatively weak. It is likely that H$_2$O is not significantly photodissociated; either due to self-shielding against the stellar irradiation, or UV-shielding from small dust particles. The relative emitting strength of the different identified molecular features point towards UV-shielding of H$_2$O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.Comment: Submitted to A&A on May 25 2023. 18 pages, 11 figure