Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population.

Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we here deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of the Spike gene in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets.

Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open.

Target 2035 is a global initiative that seeks to identify a pharmacological modulator of most human proteins by the year 2035. As part of an ongoing series of annual updates of this initiative, we summarise here the efforts of the EUbOPEN project whose objectives and results are making a strong contribution to the goals of Target 2035. EUbOPEN is a public-private partnership with four pillars of activity: (1) chemogenomic library collections, (2) chemical probe discovery and technology development for hit-to-lead chemistry, (3) profiling of bioactive compounds in patient-derived disease assays, and (4) collection, storage and dissemination of project-wide data and reagents.

Examining Protein Translocation by β-Barrel Membrane Proteins Using Reconstituted Proteoliposomes.

β-barrel membrane proteins populate the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts, playing significant roles in multiple key cellular pathways. Characterizing the functions of these membrane proteins in vivo is often challenging due to the complex protein network in the periplasm of Gram-negative bacteria (or intermembrane space in mitochondria and chloroplasts) and the presence of other outer membrane proteins. In vitro reconstitution into lipid-bilayer-like environments such as nanodiscs or proteoliposomes provides an excellent method for examining the specific function and mechanism of these membrane proteins in an isolated system.

Clonal reproduction of Moniliophthora roreri and the emergence of unique lineages with distinct genomes during range expansion.

The basidiomycete Moniliophthora roreri causes frosty pod rot of cacao (Theobroma cacao) in the western hemisphere. Moniliophthora roreri is considered asexual and haploid throughout its hemibiotrophic life cycle. To understand the processes driving genome modification, using long-read sequencing technology, we sequenced and assembled 5 high-quality M.

Single-base resolution methylomes of somatic embryogenesis in Theobroma cacao L. reveal epigenome modifications associated with somatic embryo abnormalities.

Propagation by somatic embryogenesis in Theobroma cacao has some issues to be solved, as many morphologically abnormal somatic embryos that do not germinate into plants are frequently observed, thus hampering plant production on a commercial scale. For the first time the methylome landscape of T. cacao somatic embryogenesis was examined, using whole-genome bisulfite sequencing technique, with the aim to understand the epigenetic basis of somatic embryo abnormalities.

Controlled release of low-molecular weight, polymer-free corticosteroid coatings suppresses fibrotic encapsulation of implanted medical devices.

Inflammation-driven foreign body reactions, and the frequently associated encapsulation by fibrogenic fibroblasts, reduce the functionality and longevity of implanted medical devices and materials. Anti-inflammatory drugs, such as dexamethasone, can suppress the foreign body reaction for a few days post-surgery, but lasting drug delivery strategies for long-term implanted materials remain an unmet need. We here establish a thin-coating strategy with novel low molecular weight corticosteroid dimers to suppress foreign body reactions and fibrotic encapsulation of subcutaneous silicone implants.

Subtractive manufacturing with swelling induced stochastic folding of sacrificial materials for fabricating complex perfusable tissues in multi-well plates.

Organ-on-a-chip systems that recapitulate tissue-level functions have been proposed to improve - correlation in drug development. Significant progress has been made to control the cellular microenvironment with mechanical stimulation and fluid flow. However, it has been challenging to introduce complex 3D tissue structures due to the physical constraints of microfluidic channels or membranes in organ-on-a-chip systems.

Physician- and Patient-reported Effectiveness Are Similar for Tofacitinib and TNFi in Rheumatoid Arthritis: Data From a Rheumatoid Arthritis Registry.

Objective: Tofacitinib (TOF) is an oral, small-molecule drug used for rheumatoid arthritis (RA) treatment and is one of several alternative treatments to tumor necrosis factor inhibitors (TNFi). We evaluated physician- and patient-reported effectiveness of TNFi compared to TOF, using real-world data from the Ontario Best Practices Research Initiative (OBRI).

Methods: Patients enrolled in the OBRI initiating TOF or TNFi between 2014 and 2019 were included.

Complete genome sequences of three newly discovered cacao mild mosaic virus isolates from Theobroma cacao L. in Brazil and Puerto Rico and evidence for recombination.

To analyze the DNA virome associated with cacao (Theobroma cacao L.) trees showing virus-like symptoms in Brazil (BR) and Puerto Rico (PR) during 2018-2019, total DNA was isolated from symptomatic leaves and subjected to high-throughput Illumina sequencing. The assembled complete badnaviral genome sequences were verified by PCR amplification, cloning, and DNA sequencing.

sp. nov.: A New Species Causing Black Pod Disease on Cacao in Brazil.

Black pod disease, caused by species, is among the main limiting factors of cacao ( L.) production. High incidence levels of black pod disease have been reported in Brazil, being induced by , , , and .

One-Step Formation of Protein-Based Tubular Structures for Functional Devices and Tissues.

Tubular biological structures consisting of extracellular matrix (ECM) proteins and cells are basic functional units of all organs in animals and humans. ECM protein solutions at low concentrations (5-10 milligrams per milliliter) are abundantly used in 3D cell culture. However, their poor "printability" and minute-long gelation time have made the direct extrusion of tubular structures in bioprinting applications challenging.

Ancestral roles of atypical cadherins in planar cell polarity.

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in , a member of phylum Cnidaria a sister group of bilaterian.

QTL mapping and identification of SNP-haplotypes affecting yield components of L.

Cacao is a crop of global relevance that faces constant demands for improved bean yield. However, little is known about the genomic regions controlling the crop yield and genes involved in cacao bean filling. Hence, to identify the quantitative trait loci (QTL) associated with cacao yield and bean filling, we performed a QTL mapping in a segregating mapping population comprising 459 trees of a cross between 'TSH 1188' and 'CCN 51'.

Identification of Climate and Genetic Factors That Control Fat Content and Fatty Acid Composition of L. Beans.

The main ingredients of chocolate are usually cocoa powder, cocoa butter, and sugar. Both the powder and the butter are extracted from the beans of the cacao tree ( L.).

SMuRF: a novel tool to identify regulatory elements enriched for somatic point mutations.

Background: Single Nucleotide Variants (SNVs), including somatic point mutations and Single Nucleotide Polymorphisms (SNPs), in noncoding cis-regulatory elements (CREs) can affect gene regulation and lead to disease development. Several approaches have been developed to identify highly mutated regions, but these do not take into account the specific genomic context, and thus likelihood of mutation, of CREs.

Results: Here, we present SMuRF (Significantly Mutated Region Finder), a user-friendly command-line tool to identify these significantly mutated regions from user-defined genomic intervals and SNVs.

Climate change could threaten cocoa production: Effects of 2015-16 El Niño-related drought on cocoa agroforests in Bahia, Brazil.

Climate models predict a possible increase in the frequency of strong climate events such as El Niño-Southern Oscillation (ENSO), which in parts of the tropics are the cause of exceptional droughts, these threaten global food production. Agroforestry systems are often suggested as promising diversification options to increase farmers' resilience to extreme climatic events. In the Northeastern state of Bahia, where most Brazilian cocoa is grown in wildlife-friendly agroforests, ENSOs cause severe droughts which negatively affect forest and agriculture.

Transcription Factors: Their Role in the Regulation of Somatic Embryogenesis in Theobroma cacao L. and Other Species.

Transcription factors are proteins that help with the control and regulation in the transcription of the DNA to mRNA by binding to special DNA sequences. With the aim to understand more about gene transcription regulation in Theobroma cacao L., this review outlines the principal transcription factors that were reported in other plants especially Arabidopsis thaliana and attempts at looking for the homologies with transcription factors in T.

Somatic Embryogenesis in Theobroma cacao L.

Theobroma cacao L. is a tropical tree originating in the Amazon, where it grows naturally in the shade of tropical rainforests. Cacao sub-products, such as butter and powder, are produced as principal components of chocolate and contain important nutritional compounds such as polyphenols and flavonoids.

Mapping of a Major QTL for Wilt Disease in an F1 Population of .

Cacao is an important crop, its beans are key raw materials for the chocolate and cosmetic industries. wilt of cacao (CWC) caused by is a lethal disease for the crop. Therefore, the selection of resistant cacao varieties is one of the viable ways to minimize losses in cacao production.

Genetic Parameters and the Impact of Off-Types for L. in a Breeding Program in Brazil.

Breeding programs of cacao ( L.) trees share the many challenges of breeding long-living perennial crops, and genetic progress is further constrained by both the limited understanding of the inheritance of complex traits and the prevalence of technical issues, such as mislabeled individuals (off-types). To better understand the genetic architecture of cacao, in this study, 13 years of phenotypic data collected from four progeny trials in Bahia, Brazil were analyzed jointly in a multisite analysis.

Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma: A Report From the Transatlantic RPS Working Group.

Objective: To investigate the safety of radical resection for retroperitoneal sarcoma (RPS).

Background: The surgical management of RPS frequently involves complex multivisceral resection. Improved oncologic outcomes have been demonstrated with this approach compared to marginal excision, but the safety of radical resection has not been shown in a large study population.

Comparative evaluation of total RNA extraction methods in Theobroma cacao using shoot apical meristems.

Theobroma cacao is a species of great economic importance with its beans used for chocolate production. The tree has been a target of various molecular studies. It contains many polyphenols, which complicate the extraction of nucleic acids with the extraction protocols requiring a large amount of plant material.

Identification of candidate genes involved in Witches' broom disease resistance in a segregating mapping population of Theobroma cacao L. in Brazil.

Background: Witches' broom disease (WBD) caused by the fungus Moniliophthora perniciosa is responsible for considerable economic losses for cacao producers. One of the ways to combat WBD is to plant resistant cultivars. Resistance may be governed by a few genetic factors, mainly found in wild germplasm.

Correction: Gravely, S., et al. Awareness, Trial, and Current Use of Electronic Cigarettes in 10 Countries: Findings from the ITC Project. Int. J. Environ. Res. Public Health 2014, 11, 11691-11704.

The authors wish to make the following amendments to their paper published in International Journal of Environmental Research and Public Health.