Bacterial nanocellulose (BNC), synthesized by the bacterium Gluconacetobacter xylinus, is composed of highly hydrated fibrils (99 % water) with high mechanical strength. These exceptional material ...properties make BNC a novel biomaterial for many potential medical and tissue engineering applications. Recently, BNC with cellulose content of 15 % has been proposed as an implant material for auricular cartilage replacement, since it matches the mechanical requirements of human auricular cartilage. This study investigates the biocompatibility of BNC with increased cellulose content (17 %) to evaluate its response in vitro and in vivo. Cylindrical BNC structures (Ø48 × 20 mm) were produced, purified in a built-in house perfusion system, and compressed to increase the cellulose content in BNC hydrogels. The reduction of endotoxicity of the material was quantified by bacterial endotoxin analysis throughout the purification process. Afterward, the biocompatibility of the purified BNC hydrogels with cellulose content of 17 % was assessed in vitro and in vivo, according to standards set forth in ISO 10993. The endotoxin content in non-purified BNC (2,390 endotoxin units (EU)/ml) was reduced to 0.10 EU/ml after the purification process, level well below the endotoxin threshold set for medical devices. Furthermore, the biocompatibility tests demonstrated that densified BNC hydrogels are non-cytotoxic and cause a minimal foreign body response. In support with our previous findings, this study concludes that BNC with increased cellulose content of 17 % is a promising non-resorbable biomaterial for auricular cartilage tissue engineering, due to its similarity with auricular cartilage in terms of mechanical strength and host tissue response.
Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of ...other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 × 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.
The strong coupling of quantum emitters to a cavity mode has been of paramount importance in the development of quantum optics. Recently, also the strong coupling to more than a single mode of an ...electromagnetic resonator has drawn considerable interest. We investigate how this multimode strong coupling regime can be harnessed to coherently control quantum systems. Specifically, we demonstrate that a Maxwell fish-eye lens can be used to implement a pulsed excitation exchange between two distant quantum emitters. This periodic exchange is mediated by single-photon pulses and can be extended to a photon-exchange between two atomic ensembles, for which the coupling strength is enhanced collectively.
Abstract Introduction Sleep timing regularity is an important component of overall sleep health. People with more irregular sleep-wake schedules may more rapidly incur marks of biological aging, such ...as altered DNA methylation (DNAm). Here, we test whether sleep regularity index (SRI), a metric of the consistency of sleep-wake epochs, is associated with accelerated epigenetic aging in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods SRI was calculated from scored sleep-wake epochs derived from actigraphy (wrist-worn ActiWatch Spectrum) collected over a week during the MESA Sleep Ancillary Study. Three epigenetic “clocks” representing markers of biological (Horvath DNAmAge 2018; developed by selecting DNAm sites associated with chronological age), phenotypic (Levine PhenoAge; developed by selecting DNAm sites associated with age-related biomarkers), and pace of aging (Belsky DunedinPACE; developed by selecting DNAm sites associated with individual trajectories of age-related biomarkers) were constructed from whole-blood DNAm data (EPIC Illumina Array) collected at MESA Exam 5, prior to actigraphy measurement. Associations between epigenetic age acceleration (outcome; the difference between chronological age and epigenetic age) and SRI (exposure, 10-unit increase) were evaluated with linear regression models adjusted for age, gender, study days between blood collection and actigraphy, self-reported race/ethnicity, study site, BMI, smoking status, depression score, and sleep duration. Results 431 MESA participants with valid actigraphy and DNAm data were included (mean chronological age=68 years, DNAm age=66 years, PhenoAge=56 years, pace of aging=1.01). Spearman correlations between chronological age and epigenetic aging measures were highest for biological aging (DNAmAge rho=0.89, PhenoAge rho=0.76, DunedinPACE rho=0.18). Results did not support an association between SRI and accelerated biological aging (DNAmAge; β=0.09, 95%CI:-0.23, 0.41) or phenotypic aging after additional adjustment for smoking (PhenoAge; β=-0.48, 95%CI:-1.0, 0.04). However, greater SRI was associated with slower pace of aging in fully adjusted models (10-unit SRI increase on DunedinPACE; β=-0.09, 95%CI:-0.02, -0.0004) and directionality was similar between PhenoAge and DunedinPACE. Conclusion Greater sleep regularity is associated with slower pace of aging in a cross-sectional analysis of older U.S. adults. Further work will assess epigenetic aging with other measures of sleep health. Support (if any) NIH-NHLBI K99HL166700, R35HL135818, R01HL098433, R01HL161012, Career Development Award from the Sleep Research Society Foundation.
The International Society of Nephrology has adopted a proactive approach to defining the current state of kidney care and unmet needs through a multifaceted Closing the Gaps initiative. As part of ...this initiative, the International Society of Nephrology convened a meeting of experts to develop an approach to tackle acute kidney injury and chronic kidney disease (CKD). This manuscript expands on the recently published International Society of Nephrology CKD Roadmap and reports on the discussions of the working group assigned to the task of reviewing the global impact of complication of CKD. The working group defined the following goals:
Goal 1: Optimize the management of anemia and endocrine and metabolic abnormalities associated with CKD. The impact of these conditions at a global level is not well understood, particularly in regions where renal replacement therapy is not readily available. Some treatment regimens may be affordable in low- and middle-income countries and if implemented, could have an impact on the burden of suffering associated with CKD.
Goal 2: Improve the prevention and management of cardiovascular complications linked to CKD. Most research on cardiovascular complications of CKD has focused on atherosclerotic diseases (myocardial infarction, ischemic stroke, and peripheral gangrene). There has been growing recognition that other forms of cardiovascular diseases, such as heart failure, valvular disease and arrhythmias, have a major impact on patient outcomes. Much less is known about the mechanisms and treatment of these non-atherosclerotic complications.
Goal 3: Improve the diagnosis and management of symptoms associated with CKD. Symptom management is one of the greatest challenges in the management of CKD, with limited knowledge about the mechanisms associated with the development of these common problems and how best to characterize them into usable clinical phenotypes.
Improved understanding of the complications of CKD may alleviate suffering and prolong life among millions of people worldwide both in developed countries and in regions where renal replacement therapy is not widely available.
It is well accepted that expression of mutant p53 involves the gain of oncogenic-specific activities accentuating the malignant phenotype. Depending on the specific cancer type, mutant p53 can ...contribute to either the early or the late events of the multiphase process underlying the transformation of a normal cell into a cancerous one. This multifactorial system is evident in ~50% of human cancers. Mutant p53 was shown to interfere with a variety of cellular functions that lead to augmented cell survival, cellular plasticity, aberration of DNA repair machinery and other effects. All these effects culminate in the acquisition of drug resistance often seen in cancer cells. Interestingly, drug resistance has also been suggested to be associated with cancer stem cells (CSCs), which reside within growing tumors. The notion that p53 plays a regulatory role in the life of stem cells, coupled with the observations that p53 mutations may contribute to the evolvement of CSCs makes it challenging to speculate that drug resistance and cancer recurrence are mediated by CSCs expressing mutant p53.
Almost three decades ago Alec Jeffreys published his seminal Nature papers on the use of minisatellite probes for DNA fingerprinting of humans (Jeffreys and colleagues Nature 1985, 314:67-73 and ...Nature 1985, 316:76-79). The new technology was soon adopted for many other organisms including plants, and when Hilde Nybom, Kurt Weising and Alec Jeffreys first met at the very First International Conference on DNA Fingerprinting in Berne, Switzerland, in 1990, everybody was enthusiastic about the novel method that allowed us for the first time to discriminate between humans, animals, plants and fungi on the individual level using DNA markers. A newsletter coined "Fingerprint News" was launched, T-shirts were sold, and the proceedings of the Berne conference filled a first book on "DNA fingerprinting: approaches and applications". Four more conferences were about to follow, one on each continent, and Alec Jeffreys of course was invited to all of them. Since these early days, methodologies have undergone a rapid evolution and diversification. A multitude of techniques have been developed, optimized, and eventually abandoned when novel and more efficient and/or more reliable methods appeared. Despite some overlap between the lifetimes of the different technologies, three phases can be defined that coincide with major technological advances. Whereas the first phase of DNA fingerprinting ("the past") was dominated by restriction fragment analysis in conjunction with Southern blot hybridization, the advent of the PCR in the late 1980s gave way to the development of PCR-based single- or multi-locus profiling techniques in the second phase. Given that many routine applications of plant DNA fingerprinting still rely on PCR-based markers, we here refer to these methods as "DNA fingerprinting in the present", and include numerous examples in the present review. The beginning of the third phase actually dates back to 2005, when several novel, highly parallel DNA sequencing strategies were developed that increased the throughput over current Sanger sequencing technology 1000-fold and more. High-speed DNA sequencing was soon also exploited for DNA fingerprinting in plants, either in terms of facilitated marker development, or directly in the sense of "genotyping-by-sequencing". Whereas these novel approaches are applied at an ever increasing rate also in non-model species, they are still far from routine, and we therefore treat them here as "DNA fingerprinting in the future".
•Pressure distributions in rectangular steel silos are predicted.•The importance of relative stiffness of solid and wall is explored.•A validated finite element model with nonlinear solid is used.•A ...predictive model is presented.•The predictions can produce more efficient silos designs.
The pressures exerted on the walls of rectangular planform steel flexible-walled silos by several different stored granular bulk solids are investigated using a validated finite element model that has been used in several previous studies. These pressures and the state of stress in the bulk solid are explored for a range of silo geometries and stored bulk solids. The results show that the horizontal pressure distribution across a silo wall is generally not uniform. This demonstrates that widely used theories may be adequate for stiff concrete silos, are far from suited to flexible-walled steel silos, and the differences can be used to produce much lighter structures. These findings match previously published experimental and analytical results for square planform silos where much larger pressures develop in the corners. The present analyses show that rectangular silos differ from those of square section, in that the mean pressure and degree of pressure variation is different on the two walls. The mechanisms causing these changes are investigated. The results further demonstrate that relatively small changes in the properties of a stored solid can produce significant changes in the pressure magnitudes and patterns, and hence greatly influence the silo structural design. The paper concludes that existing design guidance is seriously deficient and leads to metal silos that are considerably more expensive than is necessary.
Different 25-hydroxyvitamin D 25(OH)D thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other ...characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown.
The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation.
A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D 1,25(OH)2D concentrations from baseline to 16 wk.
Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was −3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: –5; 95% CI: –8, –2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D 25(OH)D was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (–10; 95% CI: –15, –6 pg/mL), whereas 25(OH)D of 20–30 ng/mL was not (–2; 95% CI: –6, 1 pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI, and eGFR did not modify vitamin D treatment response. There was no significant change in 1,25(OH)2D in either treatment group.
Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency. This trial was registered at clinicaltrials.gov as NCT02925195.
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