A mechanistic spatio-temporal modeling of COVID-19 data

Understanding the evolution of an epidemic is essential to implement timely and efficient preventive measures. The availability of epidemiological data at a fine spatio-temporal scale is both novel and highly useful in this regard. Indeed, having geocoded data at the case level opens the door to analyze the spread of the disease on an individual basis, allowing the detection of specific outbreaks or, in general, of some interactions between cases that are not observable if aggregated data are used. Point processes are the natural tool to perform such analyses. We analyze a spatio-temporal point pattern of Coronavirus disease 2019 (COVID-19) cases detected in Valencia (Spain) during the first 11 months (February 2020 to January 2021) of the pandemic. In particular, we propose a mechanistic spatio-temporal model for the first-order intensity function of the point process. This model includes separate estimates of the overall temporal and spatial intensities of the model and a spatio-temporal interaction term. For the latter, while similar studies have considered different forms of this term solely based on the physical distances between the events, we have also incorporated mobility data to better capture the characteristics of human populations. The results suggest that there has only been a mild level of spatio-temporal interaction between cases in the study area, which to a large extent corresponds to people living in the same residential location. Extending our proposed model to larger areas could help us gain knowledge on the propagation of COVID-19 across cities with high mobility levels.     

COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management

Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3–7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients.     

The comparative genomics of T-box genes.

T-box genes are defined by the presence of a conserved sequence, the so-called T-box; this codes for the T-domain, which is involved in DNA-binding and protein dimerisation. Members of this gene family have been found in all metazoans, from diploblasts to humans, and mutations in T-box gene family members in humans have been linked to several congenital disorders. Sequencing of the complete genomes of a range of invertebrate and vertebrate species has allowed the classification of individual T-box genes into five subfamilies: Brachyury, T-brain1, Tbx1, Tbx2 and Tbx6. This review will largely focus on T-box genes identified in organisms whose genomes have been fully sequenced, emphasising how comparative studies of the T-box gene family will help to reveal the roles of these genes during development and in the adult.     

Effect of antioxidants on the genetic stability of cryopreserved mint shoot tips by encapsulation–dehydration

The effect of antioxidants applied in one step of a cryopreservation protocol by encapsulation–dehydration on recovery and genetic stability of mint shoot tips has been studied. Glutathione (0.16 or 0.24 mM), ascorbic acid (0.28 or 0.43 mM) and α-tocopherol (vitamin E) were added to the preculture medium (0.3 M sucrose). DNA was extracted from three different types of samples: leaves from shoots, callus at the base of shoots and callus. RAPD and AFLP markers were used to assess the genetic stability. The use of antioxidants did not improve recovery after cryopreservation. One of the genotypes, ‘MEN 198’, showed higher percentage of stable samples than the other one, ‘MEN 186’ (56 vs. 37?%; considering all treatments and types of explant). The use of vitamin E improved the percentage of stable samples with respect to control treatment (no antioxidant) in ‘MEN 186’. No differences in the percentages of stable samples were observed among cryopreserved and non-cryopreserved (treated similarly without immersion in liquid nitrogen) plant material. Recovered shoots of both genotypes showed higher stability (76–80?% stable samples) than callus samples (14–22?%).     

Membrane-integration Characteristics of Two ABC Transporters, CFTR and P-glycoprotein

To what extent do corresponding transmembrane helices in related integral membrane proteins have different membrane-insertion characteristics? Here, we compare, side-by-side, the membrane insertion characteristics of the 12 transmembrane helices in the adenosine triphosphate-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and the cystic fibrosis transmembrane conductance regulator (CFTR). Our results show that 10 of the 12 CFTR transmembrane segments can insert independently into the ER membrane. In contrast, only three of the P-gp transmembrane segments are independently stable in the membrane, while the majority depend on the presence of neighboring loops and/or transmembrane segments for efficient insertion. Membrane-insertion characteristics can thus vary widely between related proteins.     

The Light Chain 1 Subunit of the Microtubule-Associated Protein 1B (MAP1B) Is Responsible for Tiam1 Binding and Rac1 Activation in Neuronal Cells

Microtubule-associated protein 1B (MAP1B) is a neuronal protein involved in the stabilization of microtubules both in the axon and somatodendritic compartments. Acute, genetic inactivation of MAP1B leads to delayed axonal outgrowth, most likely due to changes in the post-translational modification of tubulin subunits, which enhances microtubule polymerization. Furthermore, MAP1B deficiency is accompanied by abnormal actin microfilament polymerization and dramatic changes in the activity of small GTPases controlling the actin cytoskeleton. In this work, we showed that MAP1B interacts with a guanine exchange factor, termed Tiam1, which specifically activates Rac1. These proteins co-segregated in neurons, and interact in both heterologous expression systems and primary neurons. We dissected the molecular domains involved in the MAP1B-Tiam1 interaction, and demonstrated that pleckstrin homology (PH) domains in Tiam1 are responsible for MAP1B binding. Interestingly, only the light chain 1 (LC1) of MAP1B was able to interact with Tiam1. Moreover, it was able to increase the activity of the small GTPase, Rac1. These results suggest that the interaction between Tiam1 and MAP1B, is produced by the binding of LC1 with PH domains in Tiam1. The formation of such a complex impacts on the activation levels of Rac1 confirming a novel function of MAP1B related with the control of small GTPases. These results also support the idea of cross-talk between cytoskeleton compartments inside neuronal cells.     

Visual Evoked Cortical Potential (VECP) Elicited by Sinusoidal Gratings Controlled by Pseudo-Random Stimulation

The contributions of contrast detection mechanisms to the visual cortical evoked potential (VECP) have been investigated studying the contrast-response and spatial frequency-response functions. Previously, the use of m-sequences for stimulus control has been almost restricted to multifocal electrophysiology stimulation and, in some aspects, it substantially differs from conventional VECPs. Single stimulation with spatial contrast temporally controlled by m-sequences has not been extensively tested or compared to multifocal techniques. Our purpose was to evaluate the influence of spatial frequency and contrast of sinusoidal gratings on the VECP elicited by pseudo-random stimulation. Nine normal subjects were stimulated by achromatic sinusoidal gratings driven by pseudo random binary m-sequence at seven spatial frequencies (0.4–10 cpd) and three stimulus sizes (4°, 8°, and 16° of visual angle). At 8° subtence, six contrast levels were used (3.12–99%). The first order kernel (K1) did not provide a consistent measurable signal across spatial frequencies and contrasts that were tested–signal was very small or absent–while the second order kernel first (K2.1) and second (K2.2) slices exhibited reliable responses for the stimulus range. The main differences between results obtained with the K2.1 and K2.2 were in the contrast gain as measured in the amplitude versus contrast and amplitude versus spatial frequency functions. The results indicated that K2.1 was dominated by M-pathway, but for some stimulus condition some P-pathway contribution could be found, while the second slice reflected the P-pathway contribution. The present work extended previous findings of the visual pathways contribution to VECP elicited by pseudorandom stimulation for a wider range of spatial frequencies.     

An extracellular vesicle epitope profile is associated with acute myocardial infarction

The current standard biomarker for myocardial infarction (MI) is high‐sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched‐controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface‐epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non‐inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.     

Phylogenomics of the hyperdiverse daisy tribes: Anthemideae,Astereae, Calenduleae,Gnaphalieae, and Senecioneae

Asteraceae account for 10% of all flowering plant species, and 35%–40% of these are in five closely related tribes that total over 10 000 species. These tribes include Anthemideae, Astereae, Calenduleae, Gnaphalieae, and Senecioneae, which form one of two enormous clades within Subfamily Asteroideae. We took a phylogenomics approach to resolve evolutionary relationships among these five tribes. We sampled the nuclear and plastid genomes via HybSeq target enrichment and genome skimming, and recovered 74 plastid genes and nearly 1000 nuclear loci, known as Conserved Orthologous Sequences. We tested for conflicting support in both data sets and used network analyses to assess patterns of reticulation to explain the early evolutionary history of this lineage, which has experienced whole‐genome duplications and rapid radiations. We found concordance and conflicting support in both data sets and documented four ancient hybridization events. Due to the timing of the early radiation of this five‐tribe lineage, shortly before the Eocene–Oligocene extinction event (34 MYA), early lineages were likely lost, obscuring some details of their early evolutionary history.