Species concepts and speciation factors in cyanobacteria, with connection to the problems of diversity and classification

The cyanobacteria are the most important prokaryotic primary producers on Earth, inhabiting a great diversity of aquatic and terrestrial environments exposed to light. However, the evolutionary forces leading to their divergence and speciation remain largely enigmatic compared to macroorganisms due to their prokaryotic nature, including vast population sizes, and largely asexual reproduction. The advent of modern molecular techniques has facilitated an understanding of the important factors shaping cyanobacterial evolution, including horizontal gene transfer and homologous recombination. We review the forces shaping the evolution of cyanobacteria and discuss the role of cohesive forces on speciation. Further, while myriad species concepts and definitions are currently used, only a limited subset might be applied to cyanobacteria due to their asexual reproduction. Additionally, concepts based solely on phenotypes provide insufficient resolution. A monophyletic species concept which is universal may be ideal for cyanobacteria. Actual identification of the cyanobacteria is difficult due to cryptic diversity, lack of morphological variability, and frequent convergent evolutionary events. Thus, applied molecular techniques such as DNA barcoding will be useful for identifications of environmental samples. Lastly, we show that the real biodiversity of the cyanobacteria is widely underestimated, due in part to low sampling efforts, sensitivity to the molecular markers employed, and the species definitions employed by researchers. In conclusion, we anticipate a rapid increase in cyanobacterial taxa described and large revisions of the system in the future as scientists adopt a common approach to cyanobacterial systematics

Establishment of patient-derived tumor organoids to functionally inform treatment decisions in metastatic colorectal cancer

Colorectal cancer; Personalized medicine; ResistanceCáncer colorrectal; Medicina personalizada; ResistenciaCàncer colorectal; Medicina personalitzada; ResistènciaBackground Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model to elucidate tumor resistance to therapy, due to their high capacity to resemble tumor characteristics. Materials and methods We used viable tumor tissue from two cohorts of patients with mCRC, naïve or refractory to treatment, respectively, for generating PDTOs. The derived models were subjected to a 6-day drug screening assay (DSA) with a comprehensive pipeline of chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For the second cohort DSA data were matched with those from PDTO genotyping. Results A total of 40 PDTOs included in the two cohorts were derived from mCRC primary tumors or metastases. The first cohort included 31 PDTOs derived from patients treated in front line. For this cohort, DSA results were matched with patient responses. Moreover, RAS/BRAF mutational status was matched with DSA cetuximab response. Ten out of 12 (83.3%) RAS wild-type PDTOs responded to cetuximab, while all the mutant PDTOs, 8 out of 8 (100%), were resistant. For the second cohort (chemorefractory patients), we used part of tumor tissue for genotyping. Four out of nine DSA/genotyping data resulted applicable in the clinic. Two RAS-mutant mCRC patients have been treated with FOLFOX–bevacizumab and mitomycin–capecitabine in third line, respectively, based on DSA results, obtaining disease control. One patient was treated with nivolumab–second mitochondrial-derived activator of caspases mimetic (phase I trial) due to high tumor mutational burden at genotyping, experiencing stable disease. In one case, the presence of BRCA2 mutation correlated with DSA sensitivity to olaparib; however, the patient could not receive the therapy. Conclusions Using CRC as a model, we have designed and validated a clinically applicable methodology to potentially inform clinical decisions with functional data. Undoubtedly, further larger analyses are needed to improve methodology success rates and propose suitable treatment strategies for mCRC patients.This Translational Research Fellowship Project was supported by the ESMO with the aid of a grant from Amgen, by the Accelerator (ACRCelerator) [grant number A26825] and Ayuda a médicos jóvenes investigadores from Fundacion Científica—Asociacion Española Contra el Cancer (FC-AECC)/Associazione Italiana per la Ricerca sul Cancro (AIRC)/Cancer Research United Kingdom (CRUK) and by Familia Armangué. Any views, opinions, findings, conclusions or recommendations expressed in this material are those solely of the author(s) and do not necessarily reflect those of ESMO or Amgen. We thank Regione Campania (I-Cure Research Project) [grant number: Cup 21C17000030007], ESMO Translational Research Fellowship Program

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Prediction of amyloid aggregation in vivo

Alzheimer and prion diseases are among the conditions associated with the formation of amyloid fibrils. This review summarizes the available mathematical tools that rationalize the parameters of fibril formation and, for the first time, applies them to predict aggregation in vivo. The results correlate with experimental observations, demonstrating that the algorithms have direct utility in predicting aggregation in disease, industry and other contexts