Canadian fruit and vegetable markets were significantly impacted by the spread of the novel coronavirus SARS‐CoV‐2 (and COVID‐19 disease), beginning in March 2020. Due to the closure of restaurants, ...bars, and schools, produce growers and distributors were forced to shift supplies almost entirely from the foodservice to the retail channel. Shippers reported labor and logistical constraints in making the change, but the fresh produce supply chain remained robust. In the long term, we expect lasting changes in consumers’ online food‐purchasing habits, heightened constraints on immigrant labor markets, and tighter concentration in fresh produce distribution and perhaps retailing.
Abstrait
Les marchés canadiens des fruits et légumes ont été considérablement touchés par la propagation du nouveau coronavirus SARS‐CoV‐2 (COVID‐19), à partir de mars 2020. En raison de la fermeture des restaurants, des bars et des écoles, les producteurs et distributeurs de fruits et légumes ont été forcés de déplacer les approvisionnements presque entièrement de la restauration au circuit de vente au détail. Les expéditeurs ont signalé des contraintes de main‐d'œuvre et de logistique pour effectuer le changement, mais la chaîne d'approvisionnement des produits frais est restée robuste. À long terme, nous nous attendons à ce que le changement dans les habitudes d'achat des aliments en ligne perdure, à des contraintes accrues sur l'accès au travail des immigrants et à une concentration plus forte dans la distribution de produits frais et peut‐être de la vente au détail.
Early vertebrate embryos must achieve totipotency and prepare for zygotic genome activation (ZGA). To understand this process, we determined the DNA methylation (DNAme) profiles of zebrafish gametes, ...embryos at different stages, and somatic muscle and compared them to gene activity and histone modifications. Sperm chromatin patterns are virtually identical to those at ZGA. Unexpectedly, the DNA of many oocyte genes important for germline functions (i.e., piwil1) or early development (i.e., hox genes) is methylated, but the loci are demethylated during zygotic cleavage stages to precisely the state observed in sperm, even in parthenogenetic embryos lacking a replicating paternal genome. Furthermore, this cohort constitutes the genes and loci that acquire DNAme during development (i.e., ZGA to muscle). Finally, DNA methyltransferase inhibition experiments suggest that DNAme silences particular gene and chromatin cohorts at ZGA, preventing their precocious expression. Thus, zebrafish achieve a totipotent chromatin state at ZGA through paternal genome competency and maternal genome DNAme reprogramming.
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•Sperm chromatin patterns mirror the blastomere at zygotic genome activation (ZGA)•Maternal chromatin patterns are reprogrammed to the paternal/sperm state by ZGA•Maternal reprogrammed/demethylated genes are all later methylated in development•Promoter DNA methylation prevents precocious expression of particular genes at ZGA
In the zebrafish zygote, the maternal genome undergoes considerable DNA methylation changes so that it conforms to the paternal pattern by the time zygotic genes are activated, a process that helps establish a totipotent zygotic genome.
Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes; however, the electrophysiological properties of hiPSC-derived cardiomyocytes have yet to be fully ...characterized. We performed detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating cardiomyocytes using a perforated patch method and had atrial-, nodal-, and ventricular-like properties. Ventricular-like APs were more common and had maximum diastolic potentials close to those of human cardiac myocytes, AP durations were within the range of the normal human electrocardiographic QT interval, and APs showed expected sensitivity to multiple drugs (tetrodotoxin, nifedipine, and E4031). Early afterdepolarizations (EADs) were induced with E4031 and were bradycardia dependent, and EAD peak voltage varied inversely with the EAD take-off potential. Gating properties of seven ionic currents were studied including sodium (I(Na)), L-type calcium (I(Ca)), hyperpolarization-activated pacemaker (I(f)), transient outward potassium (I(to)), inward rectifier potassium (I(K1)), and the rapidly and slowly activating components of delayed rectifier potassium (I(Kr) and I(Ks), respectively) current. The high purity and large cell numbers also enabled automated patch-clamp analysis. We conclude that these hiPSC-derived cardiomyocytes have ionic currents and channel gating properties underlying their APs and EADs that are quantitatively similar to those reported for human cardiac myocytes. These hiPSC-derived cardiomyocytes have the added advantage that they can be used in high-throughput assays, and they have the potential to impact multiple areas of cardiovascular research and therapeutic applications.
The RSC chromatin remodeler slides and ejects nucleosomes, utilizing a catalytic subunit (Sth1) with DNA translocation activity, which can pump DNA around the nucleosome. A central question is ...whether and how DNA translocation is regulated to achieve sliding versus ejection. Here, we report the regulation of DNA translocation efficiency by two domains residing on Sth1 (Post-HSA and Protrusion 1) and by actin-related proteins (ARPs) that bind Sth1. ARPs facilitated sliding and ejection by improving “coupling”—the amount of DNA translocation by Sth1 relative to ATP hydrolysis. We also identified and characterized Protrusion 1 mutations that promote “coupling,” and Post-HSA mutations that improve ATP hydrolysis; notably, the strongest mutations conferred efficient nucleosome ejection without ARPs. Taken together, sliding-to-ejection involves a continuum of DNA translocation efficiency, consistent with higher magnitudes of ATPase and coupling activities (involving ARPs and Sth1 domains), enabling the simultaneous rupture of multiple histone-DNA contacts facilitating ejection.
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•Actin-related proteins and the P1 domain regulate Sth1 DNA translocation efficiency•The Post-HSA domain regulates Sth1 ATPase activity and DNA translocation speed•A blend of moderate-to-high ATPase activity and efficiency enable nucleosome ejection•Strong upregulation of DNA translocation confers chromatin changes and cell lethality
Clapier et al. establish that the chromatin remodeling complex RSC conducts regulated ATP-dependent DNA translocation. Distinct domains and actin-related proteins separately regulate ATPase activity and DNA translocation efficiency. These parameters combine to tune nucleosome sliding, and at higher levels, to cause the simultaneous rupture of multiple histone-DNA contacts, enabling ejection.
Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. ...We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies.
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•Technology for high-throughput single-cell RNA sequencing and genotyping•Variable cell-type composition of AML correlates to genetics and outcome•Primitive AML cells aberrantly co-express stemness and myeloid priming genes•Differentiated AML cells express immunomodulatory factors and suppress T cells
A combination of transcriptomics and mutational analyses in single cells from acute myeloid leukemia patients reveals the existence of distinct functional subsets and their associated drivers.
To develop a mathematical model to estimate the relative differences in postoperative stromal tensile strength following photorefractive keratectomy (PRK), LASIK, and small incision lenticule ...extraction (SMILE).
Using previously published data where in vitro corneal stromal tensile strength was determined as a function of depth, a mathematical model was built to calculate the relative remaining tensile strength by fitting the data with a fourth order polynomial function yielding a high correlation coefficient (R(2) = 0.930). Calculating the area under this function provided a measure of total stromal tensile strength (TTS), based only on the residual stromal layer for PRK or LASIK and the residual stromal layers above and below the lenticule interface for SMILE.
Postoperative TTS was greatest after SMILE, followed by PRK, then LASIK; for example, in a 550-μm cornea after 100-μm tissue removal, postoperative TTS was 75% for SMILE (130-μm cap), 68% for PRK, and 54% for LASIK (110-μm flap). The postoperative TTS decreased for thinner corneal pachymetry for all treatment types. In LASIK, the postoperative TTS decreased with increasing flap thickness by 0.22%/μm, but increased by 0.08%/μm for greater cap thickness in SMILE. The model predicted that SMILE lenticule thickness could be approximately 100 μm greater than the LASIK ablation depth and still have equivalent corneal strength (equivalent to approximately 7.75 diopters).
This mathematical model predicts that the postoperative TTS is considerably higher after SMILE than both PRK and LASIK, as expected given that the strongest anterior lamellae remain intact. Consequently, SMILE should be able to correct higher levels of myopia.
Water is fundamental to life and to the maintenance of an appropriate environment for physiological functions at the molecular, cellular, and organismal level. Water balance is also the principal ...mechanism of volume regulation in animals. The physical properties of water have profound effects on all biological structures and their function. Animal Osmoregulation has three main themes. The first deals with the physical properties of water, and its interactions with proteins, lipids, and biological membranes. Solutes affect the activity of water and thus the magnitude of the gradients driving water movement through osmosis. The distribution and transport of water in biological systems depends therefore on the properties of solutes, their distribution, and their transport. The second theme involves a detailed physical description of osmosis. This is followed by an explanation of the significance of osmotic regulation in animals inhabiting a wide variety of environments. Examples are explored for marine, freshwater, and terrestrial animals. A broad phylogenetic array of animals is discussed. Thirdly, the book deals with membranes as compartmental barriers. By definition, osmosis occurs through semi-permeable membranes. Membranes also, however, play a fundamental role in energy storage, energy transduction, solute transport, and sensory physiology. This volume approaches animal osmoregulation from the perspective of the physical laws that influence the structure of biological systems. It extends these concepts to explore the diversity of adaptations in the animal kingdom that deal with osmotic challenges in a variety of environments.
The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely ...heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device - the nanoclip - for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.
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