Background and purpose
The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in ...cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized.
Methods
Forty‐five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited.
Results
Compared with NC, patients with PiB(−) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(−) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(−) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(−) SVaD. Compared with NC subjects, patients with PiB(−) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(−) SVaD exhibited additional deformities within the lateral head and inferior body.
Conclusions
Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.
Abstract
In cuprate superconductors, the doping of carriers into the parent Mott insulator induces superconductivity and various other phases whose characteristic temperatures are typically plotted ...versus the doping level
p
. In most materials,
p
cannot be determined from the chemical composition, but it is derived from the superconducting transition temperature,
T
c
, using the assumption that the
T
c
dependence on doping is universal. Here, we present angle-resolved photoemission studies of Bi
2
Sr
2
CaCu
2
O
8+
δ
, cleaved and annealed in vacuum or in ozone to reduce or increase the doping from the initial value corresponding to
T
c
= 91 K. We show that
p
can be determined from the underlying Fermi surfaces and that in-situ annealing allows mapping of a wide doping regime, covering the superconducting dome and the non-superconducting phase on the overdoped side. Our results show a surprisingly smooth dependence of the inferred Fermi surface with doping. In the highly overdoped regime, the superconducting gap approaches the value of 2Δ
0
= (4 ± 1)
k
B
T
c
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
Summary
Background The treatment of pemphigus is still challenging and some patients with pemphigus are unresponsive to conventional immunosuppressive treatments. Rituximab, a chimeric monoclonal ...anti‐CD20 antibody, binds to the CD20 antigen on the surface of B cells and has been reported to be effective for the treatment of recalcitrant pemphigus.
Objective To compare the efficacy of different doses of rituximab in patients with pemphigus who were unresponsive to conventional therapies.
Methods Twenty‐seven patients with pemphigus who received different doses of rituximab (375 mg m−2 per infusion weekly) were analysed retrospectively. We divided the patients into two groups: group 1 (n = 12) received two infusions of rituximab and group 2 (n = 15) received three or more infusions of rituximab at 1‐week intervals. The number of infusions was determined by the choice of each patient. The endpoints of the study were time to disease control, partial remission (PR) and complete remission (CR).
Results There was no significant difference in time to achieve PR between the two groups (147 vs. 135 days, P = 0·65). However, group 2 demonstrated better outcomes than group 1 in time to CR (443 vs. 149 days, P = 0·06) and relapse rate (0% vs. 67%, P < 0·01).
Conclusions We conclude that three or more infusions of rituximab are more effective than two infusions for the treatment of pemphigus.
Superhydrophobic and superoleophobic surfaces have so far been made by roughening a hydrophobic material. However, no surfaces were able to repel extremely-low-energy liquids such as fluorinated ...solvents, which completely wet even the most hydrophobic material. We show how roughness alone, if made of a specific doubly reentrant structure that enables very low liquid-solid contact fraction, can render the surface of any material superrepellent. Starting from a completely wettable material (silica), we micro- and nanostructure its surface to make it superomniphobic and bounce off all available liquids, including perfluorohexane. The same superomniphobicity is further confirmed with identical surfaces of a metal and a polymer. Free of any hydrophobic coating, the superomniphobic silica surface also withstands temperatures over 1000°C and resists biofouling.
The ability to manipulate droplets on a substrate using electric signals
-known as digital microfluidics-is used in optical
, biomedical
, thermal
and electronic
applications and has led to ...commercially available liquid lenses
and diagnostics kits
. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)
; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown
, electric charging
and biofouling
. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.
Objective
The purposes of this study were to isolate and characterize stem cells from inflamed pulp tissue of human functional deciduous teeth (iSHFD) and to evaluate the influence of fibroblastic ...growth factor‐2 (FGF‐2) on the regenerative potential.
Materials and methods
We successfully isolated mesenchymal stem cells (MSCs) from the inflamed dental pulp tissue of human deciduous teeth and demonstrated that their regenerative potential could be enhanced by the application of FGF‐2 (20 ng ml−1) during ex vivo expansion. Isolated stem cells expanded in FGF‐2 were characterized using a colony‐forming assay, proliferation, migration, in vitro differentiation, in vivo ectopic transplantation assay, and gene expression profiling.
Results
MSCs isolated from the inflamed pulp tissue of functional deciduous teeth potentially possess the qualities of those from human exfoliated deciduous teeth. FGF‐2 applied to iSHFD during expansion enhanced the colony‐forming efficiency of these cells, increased their proliferation and migration potential, and reduced their differentiation potential in vitro. However, the ectopic transplantation of iSHFD/FGF‐2 in vivo increased the formation of dentin‐like material.
Conclusion
FGF‐2 expansion of stem cells from inflamed pulp tissues of human deciduous teeth can be a good source of stem cells for future clinical applications and a novel way of using discarded inflamed tissues.
The mammalian target of rapamycin (mTOR) is a crucial signaling node that integrates environmental cues to regulate cell survival, proliferation and metabolism, and is often deregulated in human ...cancer. mTOR kinase acts in two functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), whose activities and substrate specificities are regulated by complex co-factors. Deregulation of this centralized signaling pathway has been associated with a variety of human diseases including diabetes, neurodegeneration and cancer. Although mTORC1 signaling has been extensively studied in cancer, recent discoveries indicate a subset of human cancers harboring amplifications in mTORC2-specific genes as the only actionable genomic alterations, suggesting a distinct role for mTORC2 in cancer as well. This review will summarize recent advances in dissecting the relative contributions of mTORC1 versus mTORC2 in cancer, their role in tumor-associated blood vessels and tumor immunity, and provide an update on mTOR inhibitors.
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.
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.
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