The complex interplay of spin, charge, orbital and lattice degrees of freedom provides a plethora of exotic phases and physical phenomena. In recent years, complex spin topologies have emerged as a ...consequence of the electronic band structure and the interplay between spin and spin-orbit coupling in materials. Here we produce complex topologies of electrical polarization--namely, nanometre-scale vortex-antivortex (that is, clockwise-anticlockwise) arrays that are reminiscent of rotational spin topologies--by making use of the competition between charge, orbital and lattice degrees of freedom in superlattices of alternating lead titanate and strontium titanate layers. Atomic-scale mapping of the polar atomic displacements by scanning transmission electron microscopy reveals the presence of long-range ordered vortex-antivortex arrays that exhibit nearly continuous polarization rotation. Phase-field modelling confirms that the vortex array is the low-energy state for a range of superlattice periods. Within this range, the large gradient energy from the vortex structure is counterbalanced by the corresponding large reduction in overall electrostatic energy (which would otherwise arise from polar discontinuities at the lead titanate/strontium titanate interfaces) and the elastic energy associated with epitaxial constraints and domain formation. These observations have implications for the creation of new states of matter (such as dipolar skyrmions, hedgehog states) and associated phenomena in ferroic materials, such as electrically controllable chirality.
Aspergillus comprises a diverse group of species based on morphological, physiological and phylogenetic characters, which significantly impact biotechnology, food production, indoor environments and ...human health. Aspergillus was traditionally associated with nine teleomorph genera, but phylogenetic data suggest that together with genera such as Polypaecilum, Phialosimplex, Dichotomomyces and Cristaspora, Aspergillus forms a monophyletic clade closely related to Penicillium. Changes in the International Code of Nomenclature for algae, fungi and plants resulted in the move to one name per species, meaning that a decision had to be made whether to keep Aspergillus as one big genus or to split it into several smaller genera. The International Commission of Penicillium and Aspergillus decided to keep Aspergillus instead of using smaller genera. In this paper, we present the arguments for this decision. We introduce new combinations for accepted species presently lacking an Aspergillus name and provide an updated accepted species list for the genus, now containing 339 species. To add to the scientific value of the list, we include information about living ex-type culture collection numbers and GenBank accession numbers for available representative ITS, calmodulin, β-tubulin and RPB2 sequences. In addition, we recommend a standard working technique for Aspergillus and propose calmodulin as a secondary identification marker.
Identification of the specific cell types expressing CFTR (cystic fibrosis CF transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full ...characterization of CFTR expression in normal human airway epithelia is missing.
To identify the cell types that contribute to
expression and function within the proximal-distal axis of the normal human lung.
Single-cell RNA (scRNA) sequencing (scRNA-seq) was performed on freshly isolated human large and small airway epithelial cells. scRNA
hybridization (ISH) and single-cell qRT-PCR were performed for validation.
culture systems correlated CFTR function with cell types. Lentiviruses were used for cell type-specific transduction of wild-type CFTR in CF cells.
scRNA-seq identified secretory cells as dominating
expression in normal human large and, particularly, small airway superficial epithelia, followed by basal cells. Ionocytes expressed the highest
levels but were rare, whereas the expression in ciliated cells was infrequent and low. scRNA ISH and single-cell qRT-PCR confirmed the scRNA-seq findings. CF lungs exhibited distributions of
and ionocytes similar to those of normal control subjects. CFTR mediated Cl
secretion in cultures tracked secretory cell, but not ionocyte, densities. Furthermore, the nucleotide-purinergic regulatory system that controls CFTR-mediated hydration was associated with secretory cells and not with ionocytes. Lentiviral transduction of wild-type CFTR produced CFTR-mediated Cl
secretion in CF airway secretory cells but not in ciliated cells.
Secretory cells dominate CFTR expression and function in human airway superficial epithelia. CFTR therapies may need to restore CFTR function to multiple cell types, with a focus on secretory cells.
The introduction of a trifluoromethyl (CF
) group can dramatically improve a compound's biological properties. Despite the well-established importance of trifluoromethylated compounds, general ...methods for the trifluoromethylation of alkyl C-H bonds remain elusive. Here we report the development of a dual-catalytic C(sp
)-H trifluoromethylation through the merger of light-driven, decatungstate-catalysed hydrogen atom transfer and copper catalysis. This metallaphotoredox methodology enables the direct conversion of both strong aliphatic and benzylic C-H bonds into the corresponding C(sp
)-CF
products in a single step using a bench-stable, commercially available trifluoromethylation reagent. The reaction requires only a single equivalent of substrate and proceeds with excellent selectivity for positions distal to unprotected amines. To demonstrate the utility of this new methodology for late-stage functionalization, we have directly derivatized a broad range of approved drugs and natural products to generate valuable trifluoromethylated analogues. Preliminary mechanistic experiments reveal that a 'Cu-CF
' species is formed during this process and the critical C(sp
)-CF
bond-forming step involves the copper catalyst.
MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. However, bacterial RNAs comparable in size to eukaryotic miRNAs (18–22 nucleotides) have received little ...attention. Recently, a novel class of small RNAs similar in size to miRNAs (miRNA-size, small RNAs or msRNAs) have also been found in several bacteria. Like miRNAs, msRNAs are approximately 15 to 25 nucleotides in length, and their precursors are predicted to form a hairpin loop secondary structure. Here, we identified msRNAs in the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola. We examined these msRNAs using a deep sequencing method and characterized dozens of msRNAs through bioinformatic analysis. Highly expressed msRNAs were selected for further validation. The findings suggest that this class of small RNAs is well conserved across the domains of life. Indeed, msRNAs secreted via bacterial outer membrane vesicles (OMVs) were detected. The ability of bacterial OMVs to deliver RNAs into eukaryotic cells was also observed. These msRNAs in OMVs allowed us to identify their potential human immune-related target genes. Furthermore, we found that exogenous msRNAs could suppress expression of certain cytokines in Jurkat T cells. We propose msRNAs may function as novel bacterial signaling molecules that mediate bacteria-to-human interactions. Furthermore, this study may provide fresh insight into bacterial pathogenic mechanisms of periodontal diseases.
OBJECTIVE:--Type 2 diabetes is the leading cause of end-stage renal disease worldwide. Aside from hyperglycemia and hypertension, other metabolic factors may determine renal outcome. We examined risk ...associations of metabolic syndrome with new onset of chronic kidney disease (CKD) in 5,829 Chinese patients with type 2 diabetes enrolled between 1995 and 2005. RESEARCH DESIGN AND METHODS--Metabolic syndrome was defined by National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of obesity. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula modified for the Chinese population. New onset of CKD was defined as eGFR <60 ml/min per 1.73 m² at the time of censor. Subjects with CKD at baseline were excluded from the analysis. RESULTS:--After a median follow-up duration of 4.6 years (interquartile range: 1.9-7.3 years), 741 patients developed CKD. The multivariable-adjusted hazard ratio (HR) of CKD was 1.31 (95% CI 1.12-1.54, P = 0.001) for subjects with metabolic syndrome compared with those without metabolic syndrome. Relative to subjects with no other components of metabolic syndrome except for diabetes, those with two, three, four, and five metabolic syndrome components had HRs of an increased risk of CKD of 1.15 (0.83-1.60, P = 0.407) 1.32 (0.94-1.86, P = 0.112), 1.64 (1.17-2.32, P = 0.004), and 2.34 (1.54-3.54, P < 0.001), respectively. The metabolic syndrome traits of central obesity, hypertriglyceridemia, hypertension, and low BMI were independent predictors for CKD. CONCLUSIONS:--The presence of metabolic syndrome independently predicts the development of CKD in subjects with type 2 diabetes.
The Askaryan Radio Array (ARA) is an ultrahigh energy (UHE, > 1017 eV) neutrino detector designed to observe neutrinos by searching for the radio waves emitted by the relativistic products of ...neutrino-nucleon interactions in Antarctic ice. In this paper, we present constraints on the diffuse flux of ultrahigh energy neutrinos between 1016 and 1021 eV resulting from a search for neutrinos in two complementary analyses, both analyzing four years of data (2013–2016) from the two deep stations (A2, A3) operating at that time. We place a 90% CL upper limit on the diffuse all flavor neutrino flux at 1018 eV of EF(E) = 5.6 × 10−16 cm−2 s−1 sr−1. This analysis includes four times the exposure of the previous ARA result and represents approximately 1 / 5 th the exposure expected from operating ARA until the end of 2022.
Summary
Background
Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 and TSC2, leading to mammalian target of rapamycin hyperactivation. Patients with TSC develop hamartomas in brain, ...lungs, liver and skin. Two epidemiological studies, performed in Minnesota, U.S.A., have estimated the incidence of TSC to be 0·28–0·56 per 100 000 person‐years (PY), based on < 12 patients. Furthermore, whether common comorbidities are associated with this rare disease is not known.
Objectives
To estimate the incidence of TSC and investigate the associations of TSC with other comorbidities, including diabetes, peptic ulcers, stroke and myocardial infarction.
Methods
We estimated the incidence and prevalence of TSC and its comorbidities from 1997 to 2010, based on the Catastrophic Illness Certificate disease database and a beneficiary cohort of 1 million people.
Results
The incidence of TSC in Taiwan is 0·153 per 100 000 PY. The number of patients identified with TSC in Taiwan doubled from 206 in 2006 to 471 in 2010. In 2010, the prevalence of TSC in Taiwan was estimated to be 1·58 in 100 000. We confirmed that female patients with TSC are more likely to develop renal tumours than male patients. Surprisingly, patients with TSC have a significantly decreased risk of developing peptic ulcers compared with controls.
Conclusions
This is the first large‐scale and longitudinal incidence study of TSC. This study provides compelling evidence that TSC mutations in humans are associated with a decreased risk of peptic ulcers.
What's already known about this topic?
Patients with tuberous sclerosis complex (TSC) develop systemic hamartomas with significant psychosocial burdens.
Two small epidemiological studies have estimated the incidence of TSC to be 0·28–0·56 per 100 000 person‐years (PY) in the U.S.A.
What does this study add?
This 14‐year‐long longitudinal study estimated the incidence of TSC in Taiwan to be 0·153 per 100 000 PY.
The prevalence of TSC in 2010 in Taiwan was 1·58 in 100 000.
A significantly lower risk of peptic ulcer is found in patients with TSC compared with healthy controls.
Linked Comment: Morrison and Donnelly. Br J Dermatol 2016; 174: 1184–1185.
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