Edible unclonable functions Leem, Jung Woo; Kim, Min Seok; Choi, Seung Ho ...
Nature communications,
01/2020, Letnik:
11, Številka:
1
Journal Article
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Counterfeit medicines are a fundamental security problem. Counterfeiting medication poses a tremendous threat to patient safety, public health, and the economy in developed and less developed ...countries. Current solutions are often vulnerable due to the limited security levels. We propose that the highest protection against counterfeit medicines would be a combination of a physically unclonable function (PUF) with on-dose authentication. A PUF can provide a digital fingerprint with multiple pairs of input challenges and output responses. On-dose authentication can verify every individual pill without removing the identification tag. Here, we report on-dose PUFs that can be directly attached onto the surface of medicines, be swallowed, and digested. Fluorescent proteins and silk proteins serve as edible photonic biomaterials and the photoluminescent properties provide parametric support of challenge-response pairs. Such edible cryptographic primitives can play an important role in pharmaceutical anti-counterfeiting and other security applications requiring immediate destruction or vanishing features.
The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to ...many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.
Objective: To examine whether metacognitive psychological skills, acquired in mindfulness-based cognitive therapy (MBCT), are also present in patients receiving medication treatments for prevention ...of depressive relapse and whether these skills mediate MBCT's effectiveness. Method: This study, embedded within a randomized efficacy trial of MBCT, was the first to examine changes in mindfulness and decentering during 6-8 months of antidepressant treatment and then during an 18-month maintenance phase in which patients discontinued medication and received MBCT, continued on antidepressants, or were switched to a placebo. In total, 84 patients (mean age = 44 years, 58% female) were randomized to 1 of these 3 prevention conditions. In addition to symptom variables, changes in mindfulness, rumination, and decentering were assessed during the phases of the study. Results: Pharmacological treatment of acute depression was associated with reductions in scores for rumination and increased wider experiences. During the maintenance phase, only patients receiving MBCT showed significant increases in the ability to monitor and observe thoughts and feelings as measured by the Wider Experiences (p < .01) and Decentering (p < .01) subscales of the Experiences Questionnaire and by the Toronto Mindfulness Scale. In addition, changes in Wider Experiences (p < .05) and Curiosity (p < .01) predicted lower Hamilton Rating Scale for Depression scores at 6-month follow-up. Conclusions: An increased capacity for decentering and curiosity may be fostered during MBCT and may underlie its effectiveness. With practice, patients can learn to counter habitual avoidance tendencies and to regulate dysphoric affect in ways that support recovery.
Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation ...sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones->0.02 variant allele fraction (VAF)-due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0.0003 VAF. We apply these methods to study serially banked peripheral blood samples from healthy 50-60-year-old participants in the Nurses' Health Study. We observe clonal haematopoiesis, frequently harbouring mutations in DNMT3A and TET2, in 95% of individuals studied. These clonal mutations are often stable longitudinally and present in multiple haematopoietic compartments, suggesting a long-lived haematopoietic stem and progenitor cell of origin.
Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely ...unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection, not drift, is the major force shaping clonal hematopoiesis, provide bounds on the number of hematopoietic stem cells, and quantify the fitness advantages of key pathogenic variants, at single-nucleotide resolution, as well as the distribution of fitness effects (fitness landscape) within commonly mutated driver genes. These data are consistent with clonal hematopoiesis being driven by a continuing risk of mutations and clonal expansions that become increasingly detectable with age.
To characterize optic disc tilt and torsion in normal-tension glaucoma (NTG) patients with myopia and to evaluate the relationship between optic disc tilt and torsion with the location of visual ...field (VF) defect.
Retrospective, case-control design.
Two hundred twenty-five NTG patients.
Patients were divided into a myopic NTG group (spherical equivalent more than -2.00 diopters D or axial length more than 24.0 mm; n = 166) and nonmyopic NTG group (spherical equivalent less than -0.50 D or axial length less than 24.0 mm; n = 59). Disc tilt, which was identified by the tilt ratio, disc torsion, and area of peripapillary atrophy (PPA), was measured from disc photographs. Patients were divided further into superior and inferior defect groups according to the location of the VF defect in the pattern deviation map. Logistic regression analysis was used to determine the relationship between ocular factors, including tilt ratio, torsion degree, and the VF defect location.
Tilt ratio, torsion degree, PPA area, and location of VF defect.
Among 225 NTG eyes, 166 (73.8%) were myopic eyes. The myopic NTG group was significantly younger (42.85 years) than the nonmyopic NTG group (60.73 years). Disc tilt (45.8%) and torsion (75.9%) were significantly more prevalent in the myopic NTG group than in the nonmyopic NTG group. Although just short of statistical significance (P = 0.057), PPA area was larger in the myopic NTG group. The VF defect location was significantly different between the 2 groups, with superior defects more prevalent in the myopic NTG group (69.9%; P<0.001). Torsion degree was significantly different in the superior defect group (18.45°) compared with the inferior defect group (-3.81°; P = 0.001). Torsion degree was the only factor related to VF defect location in both univariate (P = 0.001) and multivariate (P = 0.014) logistic regression analyses.
Korean NTG patients had a high prevalence of myopia and young age. Optic disc tilt and torsion were highly prevalent in Korean NTG patients with myopia. The direction of the optic disc torsion may predict the location of damage.
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•Cr(VI) is a major public health concern for neurotoxicity.•Cr(VI) literature suggests it does not contribute to brain cancers.•Cr(VI)( may contribute to etiology of autism spectrum ...disorder.•The highest Cr levels observed in human brain were in the pituitary and temporal lobe.•Animal studies show Cr(VI) induced widespread neurodegeneration and oxidative damage.
Hexavalent chromium Cr(VI) is a global environmental pollutant that increases risk for several types of cancers and is increasingly being recognized as a neurotoxicant. Traditionally, the brain has been viewed as a largely post-mitotic organ due to its specialized composition of neurons, and consequently, clastogenic effects were not considered in neurotoxicology. Today, we understand the brain is composed of at least eight distinct cell types – most of which continue mitotic activity throughout lifespan. We have learned these dividing cells play essential roles in brain and body health. This review focuses on Cr(VI), a potent clastogen and known human carcinogen, as a potentially neurotoxic agent targeting mitotic cells of the brain. Despite its well-established role as a human carcinogen, Cr(VI) neurotoxicity studies have failed to find a significant link to brain cancers. In the few studies that did find a link, Cr(VI) was identified as a risk for gliomas. Instead, in the human brain, Cr(VI) appears to have more subtle deleterious effects that can impair childhood learning and attention development, olfactory function, social memory, and may contribute to motor neuron diseases. Studies of Cr(VI) neurotoxicity with animal and cell culture models have demonstrated elevated markers of oxidative damage and redox stress, with widespread neurodegeneration. One study showed mice exposed to Cr(VI)-laden tannery effluent exhibited longer periods of aggressive behavior toward an “intruder” mouse and took longer to recognize mice previously encountered, recapitulating the social memory deficits observed in humans. Here we conducted a critical review of the available literature on Cr(VI) neurotoxicity and synthesize the collective observations to thoroughly evaluate Cr(VI) neurotoxicity – much remains to be understood and recognized.
Assembly factors (AFs) prevent premature translation initiation on small (40S) ribosomal subunit assembly intermediates by blocking ligand binding. However, it is unclear how AFs are displaced from ...maturing 40S ribosomes, if or how maturing subunits are assessed for fidelity, and what prevents premature translation initiation once AFs dissociate. Here we show that maturation involves a translation-like cycle whereby the translation factor eIF5B, a GTPase, promotes joining of large (60S) subunits with pre-40S subunits to give 80S-like complexes, which are subsequently disassembled by the termination factor Rli1, an ATPase. The AFs Tsr1 and Rio2 block the mRNA channel and initiator tRNA binding site, and therefore 80S-like ribosomes lack mRNA or initiator tRNA. After Tsr1 and Rio2 dissociate from 80S-like complexes Rli1-directed displacement of 60S subunits allows for translation initiation. This cycle thus provides a functional test of 60S subunit binding and the GTPase site before ribosomes enter the translating pool.
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► 60S ribosomes join maturing pre-40S subunits in a translation-like cycle ► This cycle is conserved, eIF5B-dependent, and provides a fidelity checkpoint ► The resulting 80S-like ribosomes are not translation initiation intermediates ► Rli1•Dom34 disassemble 80S-like ribosomes for translation initiation
Discovery of a translation-like cycle that involves the assembly and disassembly of inactive 80S-like ribosomes lacking mRNA and tRNA identifies a quality control step where cells test the functionality of immature 40S subunits before the final stages of ribosome maturation are allowed to proceed.
Highlights • Vasopressin 1a receptor binding is diffuse and widespread in the titi monkey brain. • Oxytocin receptor binding is much more limited, with the densest binding in the hippocampus. • There ...is considerable interspecies variation in neuropeptide receptor expression in primates. • ALS-II-69 is a selective antagonist for the titi monkey oxytocin receptor. • SR49059 is a selective antagonist for the titi monkey vasopressin 1a receptor.
Abstract Despite its debilitating symptoms, the pathophysiology of bipolar disorder (BD) remains unclear. One consistently compelling finding, however, has been the presence of oxidative stress. In ...the present investigation, we conducted a meta-analysis of studies that measured oxidative stress markers in BD patients compared to healthy controls. Search terms and selection criteria were determined a priori to identify and include all studies that measured a marker of oxidative stress in BD compared to healthy controls. Eight markers were included: superoxide dismutase, catalase, protein carbonyl, glutathione peroxidase, 3-nitrotyrosine, lipid peroxidation, nitric oxide, and DNA/RNA damage. A meta-analysis of standardized means was conducted using a random-effects model with generic inverse weighting. Between-study heterogeneity, publication bias, and sensitivity analyses were also examined for each marker. Twenty-seven papers were included in the meta-analysis, which comprised a total of 971 unique patients with BD and 886 healthy controls. Lipid peroxidation, DNA/RNA damage, and nitric oxide were significantly increased in BD patients compared to healthy controls. Additionally, the effect size for lipid peroxidation was very high. Publication bias was not detected for any of the markers. The main limitations in this meta-analysis are the high degree of heterogeneity between studies and the small number of studies used in the analysis of some markers. Additionally, the sensitivity analysis indicated that some results are not very robust. The results from this meta-analysis support the role of oxidative stress in bipolar disorder, especially to DNA, RNA, and lipids.
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