Early Life Relict Feature in Peptide Mass Distribution

Molecular mass of a biomolecule is characterized in mass spectroscopy by the monoisitopic mass M~mono~ and the average isotopic mass M~av~. We found that peptide masses mapped on a plane made by two parameters derived from M~mono~ and M~av~ form a peculiar global feature in form of a band-gap 5-7 ppm wide stretching across the whole peptide galaxy, with a narrow (FWHM 0.2 ppm) line in the centre. The a priori probability of such a feature to emerge by chance is less than 1:100. Peptides contributing to the central line have elemental compositions following the rules S=0; Z = (2C - N - H)/2 =0, which nine out of 20 amino acid residues satisfy. The relative abundances of amino acids in the peptides contributing to the central line correlate with the consensus order of emergence of these amino acids, with ancient amino acids being overrepresented in on-line peptides. Thus the central line is a relic of ancient life, and likely a signature of its emergence in abiotic synthesis. The linear correlation between M~av~ and M~mono~ reduces the complexity of polypeptide molecules, which may have increased the rate of their abiotic production. This, in turn may have influenced the selection of these amino acid residues for terrestrial life. Assuming the line feature is not spurious, life has emerged from elements with isotopic abundances very close to terrestrial levels, which rules out most of the Galaxy

Wave packet evolution in non-Hermitian quantum systems

The quantum evolution of the Wigner function for Gaussian wave packets generated by a non-Hermitian Hamiltonian is investigated. In the semiclassical limit $\hbar\to 0$ this yields the non-Hermitian analog of the Ehrenfest theorem for the dynamics of observable expectation values. The lack of Hermiticity reveals the importance of the complex structure on the classical phase space: The resulting equations of motion are coupled to an equation of motion for the phase space metric---a phenomenon having no analog in Hermitian theories.Comment: Example added, references updated, 4 pages, 2 figure

Probiotics in digestive, emotional, and pain-related disorders

In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut

Application of deep learning-based image reconstruction in MR imaging of the shoulder joint to improve image quality and reduce scan time

OBJECTIVES To compare the image quality and diagnostic performance of conventional motion-corrected periodically rotated overlapping parallel line with enhanced reconstruction (PROPELLER) MRI sequences with post-processed PROPELLER MRI sequences using deep learning-based (DL) reconstructions. METHODS In this prospective study of 30 patients, conventional (19 min 18 s) and accelerated MRI sequences (7 min 16 s) using the PROPELLER technique were acquired. Accelerated sequences were post-processed using DL. The image quality and diagnostic confidence were qualitatively assessed by 2 readers using a 5-point Likert scale. Analysis of the pathological findings of cartilage, rotator cuff tendons and muscles, glenoid labrum and subacromial bursa was performed. Inter-reader agreement was calculated using Cohen's kappa statistic. Quantitative evaluation of image quality was measured using the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). RESULTS Mean image quality and diagnostic confidence in evaluation of all shoulder structures were higher in DL sequences (p value = 0.01). Inter-reader agreement ranged between kappa values of 0.155 (assessment of the bursa) and 0.947 (assessment of the rotator cuff muscles). In 17 cases, thickening of the subacromial bursa of more than 2 mm was only visible in DL sequences. The pathologies of the other structures could be properly evaluated by conventional and DL sequences. Mean SNR (p value = 0.01) and CNR (p value = 0.02) were significantly higher for DL sequences. CONCLUSIONS The accelerated PROPELLER sequences with DL post-processing showed superior image quality and higher diagnostic confidence compared to the conventional PROPELLER sequences. Subacromial bursa can be thoroughly assessed in DL sequences, while the other structures of the shoulder joint can be assessed in conventional and DL sequences with a good agreement between sequences. KEY POINTS • MRI of the shoulder requires long scan times and can be hampered by motion artifacts. • Deep learning-based convolutional neural networks are used to reduce image noise and scan time while maintaining optimal image quality. The radial k-space acquisition technique (PROPELLER) can reduce the scan time and has potential to reduce motion artifacts. • DL sequences show a higher diagnostic confidence than conventional sequences and therefore are preferred for assessment of the subacromial bursa, while conventional and DL sequences show comparable performance in the evaluation of the shoulder joint

Feasibility of time-lapse seismic methodology for monitoring the injection of small quantities of CO2 into a saline formation, CO2CRC Otway Project

A key objective of Stage 2 of the CO2CRC Otway Project is to explore the ability of geophysical methods to detect and monitor injection of greenhouse gas into a saline formation. For this purpose, injection of some 10,000 30,000 tonnes of CO2-rich mixture into the Paaratte formation, a saline aquifer located at a depth of about 1,400 m, is planned. Before such an injection experiment is undertaken, we assess the feasibility of geophysical monitoring using computer modelling. To examine the detectability of the plume we need to estimate the time-lapse signal and time- lapse noise. The time lapse signal is modelled using flow simulations, fluid substitution and seismic forward modelling. In order to assess the applicability of time-lapse seismic to monitor the injection, the predicted signal is compared to the time-lapse noise level from the recent 4D seismic survey acquired at the Otway site in 2009-2010. The methodology is applied to two alternative reservoir intervals located at a depth of 1392-1399 m and 1445-1465 m below the sea level, respectively. These intervals are considered to be the two possible options for the injection. The results show that injection into the lower interval will produce a plume of a larger thickness and smaller lateral extent, and a seismic response that is more likely to be detectable. The developed feasibility assessment workflow, and the results of its application to the Otway site, can be used to assess the ability of seismic methods to detect and monitor greenhouse gas leakage in other CCS projects

Wild chimpanzees are infected by Trypanosoma brucei

AbstractAlthough wild chimpanzees and other African great apes live in regions endemic for African sleeping sickness, very little is known about their trypanosome infections, mainly due to major difficulties in obtaining their blood samples. In present work, we established a diagnostic ITS1-based PCR assay that allows detection of the DNA of all four Trypanosoma brucei subspecies (Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma brucei evansi) in feces of experimentally infected mice. Next, using this assay we revealed the presence of trypanosomes in the fecal samples of wild chimpanzees and this finding was further supported by results obtained using a set of primate tissue samples. Phylogenetic analysis of the ITS1 region showed that the majority of obtained sequences fell into the robust T. brucei group, providing strong evidence that these infections were caused by T. b. rhodesiense and/or T. b. gambiense. The optimized technique of trypanosome detection in feces will improve our knowledge about the epidemiology of trypanosomes in primates and possibly also other endangered mammals, from which blood and tissue samples cannot be obtained.Finally, we demonstrated that the mandrill serum was able to efficiently lyse T. b. brucei and T. b. rhodesiense, and to some extent T. b. gambiense, while the chimpanzee serum failed to lyse any of these subspecies

Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort

[Background and Aims] Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. [Methods] A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. [Results] None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. [Conclusions] Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility.This study was supported, in part, by research grants from the Agencia Española del Medicamento and Fondo de Investigación Sanitaria (PS 09/01384). CIBERehd and Red Genómica del Cáncer are funded by Instituto de Salud Carlos III

EXPLORING THE IMPACT OF APOE POLYMORPHISM ON THE MOLECULAR, MORPHOLOGICAL AND FUNCTIONAL PROFILE OF iPSC-DERIVED ASTROCYTES FROM ALZHEIMER'S PATIENTS

Comunicación presentada a FENS Forum 2022Alzheimer¿s disease (AD) is pathologically characterised by the presence of amyloid-beta plaques, neurofibrillary tangles containing hyperphosphorylated Tau protein, neuroinflammation and neuronal death leading to progressive cognitive impairment. The ¿4 allele of the gene encoding apolipoprotein E (APOE), which is mainly expressed in glial cells, is the strongest genetic risk factor for sporadic AD. Increasing evidence has shown that APOE4 may disrupt normal astrocyte activity, potentially contributing to AD pathology, but the impact of different APOE alleles on astrocyte differentiation, maturation and function is not yet fully understood. To go in depth on these questions, we obtained induced pluripotent stem cells (iPSCs) from fibroblasts of AD patients carrying ¿3 and ¿4 alleles (in homozygosis) and from healthy patients. We also used gene-edited iPSC lines homozygous for the main APOE variants and an APOE knock-out line. iPSC-derived human astrocytes were generated by establishing a differentiation protocol through the consecutive addition of small molecules and growth factors, and the expression of typical markers (GFAP, GLT1, AQP4 and S100beta) and APOE was analysed. In addition, astrocytes exhibited functional features like glutamate uptake capacity and calcium waves production. They also responded to an inflammatory stimulus (IL-1beta and TNF-alpha) or to the presence of amyloid-beta 1-42 peptide by changing their morphology and increasing the expression levels of pro-inflammatory factors and cytokines. Our results shed light on the potential dual role of APOE polymorphism and the individual¿s genetic background in favouring or perhaps preventing AD pathology

ANALYSING THE MOLECULAR, MORPHOLOGICAL AND FUNCTIONAL PROFILE OF iPSC-DERIVED ASTROCYTES FROM ALZHEIMER'S DISEASE PATIENTS

Comunicación presentada en Global Summit on Neurodegenerative Diseases NEURO 2020/22The ε4 allele of the gene encoding apolipoprotein E (APOE), which is mainly expressed in glial cells, is the strongest genetic risk factor for sporadic AD. Increasing evidence has shown that APOE4 may disrupt normal astrocyte activity, potentially contributing to AD pathology, but the impact of different APOE alleles on astrocyte maturation and function as well as their inflammatory profile is not yet fully understood. To answer these questions, we obtained induced pluripotent stem cells (iPSCs) from fibroblasts of AD patients carrying ε3 and ε4 alleles (in homozygosis) and from healthy patients. We also used gene-edited iPSC lines homozygous for the main APOE variants and an APOE knock-out line. iPSC-derived human astrocytes were generated through the consecutive addition of small molecules and growth factors to the culture medium, and the expression of typical markers (GFAP, GLT1, AQP4 and S100beta) was analysed. In addition, astrocytes exhibited functional features like glutamate uptake capacity and calcium waves. They also responded to an inflammatory stimulus (IL-1beta and TNF-alpha) or to the presence of amyloid-beta 1-42 peptide by changing their morphology and increasing the expression levels of pro-inflammatory factors and cytokines. Our results shed light on the potential dual role of APOE polymorphism and the individual's genetic background in favouring or perhaps preventing AD pathology

Zwiespältige Bilanz für Afrika : die Milleniumsziele der UN haben keine Gleichberechtigung in der Entwicklungszusammenarbeit gebracht

An increasing number of pathologies have been linked to Toll-like receptor 4 (TLR4) activation and signaling, therefore new hit and lead compounds targeting this receptor activation process are urgently needed. We report on the synthesis and biological properties of glycolipids based on glucose and trehalose scaffolds which potently inhibit TLR4 activation and signaling in vitro and in vivo. Structure–activity relationship studies on these compounds indicate that the presence of fatty ester chains in the molecule is a primary prerequisite for biological activity and point to facial amphiphilicity as a preferred architecture for TLR4 antagonism. The cationic glycolipids here presented can be considered as new lead compounds for the development of drugs targeting TLR4 activation and signaling in infectious, inflammatory, and autoimmune diseases. Interestingly, the biological activity of the best drug candidate was retained after adsorption at the surface of colloidal gold nanoparticles, broadening the options for clinical development.Italian, Ministry of University and Research (MIUR), PRIN 2010 - 11Ministerio de Economía y Competitividad AF2013-44021- R, CTQ2010 - 15848Junta de Andalucía FQM 1467Slovenian Research Agency P4-176, J1 - 417