The recovery and analysis of ancient DNA and protein from archaeological bone is time-consuming and expensive to carry out, while it involves the partial or complete destruction of valuable or rare ...specimens. The fields of palaeogenetic and palaeoproteomic research would benefit greatly from techniques that can assess the molecular quality prior to sampling. To be relevant, such screening methods should be effective, minimally-destructive, and rapid. This study reports results based on spectroscopic (Fourier-transform infrared spectroscopy in attenuated total reflectance FTIR-ATR; n = 266), palaeoproteomic (collagen content; n = 226), and palaeogenetic (endogenous DNA content; n = 88) techniques. We establish thresholds for three different FTIR indices, a) the infrared splitting factor IRSF that assesses relative changes in bioapatite crystals' size and homogeneity; b) the carbonate-to-phosphate C/P ratio as a relative measure of carbonate content in bioapatite crystals; and c) the amide-to-phosphate ratio Am/P for assessing the relative organic content preserved in bone. These thresholds are both extremely reliable and easy to apply for the successful and rapid distinction between well- and poorly-preserved specimens. This is a milestone for choosing appropriate samples prior to genomic and collagen analyses, with important implications for biomolecular archaeology and palaeontology.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 ...increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The challenge of understanding the widespread biological roles of animal microRNAs (miRNAs) has prompted the development of genetic and functional genomics technologies for miRNA loss-of-function ...studies. However, tools for exploring the functions of entire miRNA families are still limited. We developed a method that enables antagonism of miRNA function using seed-targeting 8-mer locked nucleic acid (LNA) oligonucleotides, termed tiny LNAs. Transfection of tiny LNAs into cells resulted in simultaneous inhibition of miRNAs within families sharing the same seed with concomitant upregulation of direct targets. In addition, systemically delivered, unconjugated tiny LNAs showed uptake in many normal tissues and in breast tumors in mice, coinciding with long-term miRNA silencing. Transcriptional and proteomic profiling suggested that tiny LNAs have negligible off-target effects, not significantly altering the output from mRNAs with perfect tiny LNA complementary sites. Considered together, these data support the utility of tiny LNAs in elucidating the functions of miRNA families in vivo.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We suggest a convenient version of the omnibus test for normality, using skewness and kurtosis based on Shenton and Bowman Journal of the American Statistical Association (1977) Vol. 72, pp. 206–211, ...which controls well for size, for samples as low as 10 observations. A multivariate version is introduced. Size and power are investigated in comparison with four other tests for multivariate normality. The first power experiments consider the whole skewness–kurtosis plane; the second use a bivariate distribution which has normal marginals. It is concluded that the proposed test has the best size and power properties of the tests considered.
•Electrocoagulation (EC) of wastewater from a petroleum refinery is a promising tool for removing selenium.•Selenium is removed by adsorption and/or co-precipitation with iron hydroxides.•Current ...density has crucial importance for the removal efficiency.
In the present work, an electrocoagulation technique was tested as a possible technological alternative for the treatment of selenium in wastewater from a petroleum refinery. For this purpose, a batch airlift reactor with air stirring was used. The sacrificial electrodes were made of iron to generate the necessary ferrous ions for the process. The results indicated a selenium removal of 90% from the wastewater after 6 h of treatment, achieving a decrease in concentration from 0.30 mg L−1 to 0.03 mg L−1. The current density was found to be an important variable for the process. In conclusion, the electrocoagulation process seems to be a feasible selenium removal technique applied to petroleum refinery wastewater.
Objective
To examine the possible influence of cognitive ability and education at age 50 or 60 on number of teeth at age 70.
Setting
Community‐dwelling population in Copenhagen, Denmark.
Participants
...Men and women born in 1914 (N = 302).
Measurements
Cognitive ability was assessed using the Wechsler Adult Intelligence Scale at age 50 or 60. A global cognitive ability measure was used as a continuous measure and according to tertile. Information on education was gathered using a questionnaire at age 50 or 60. A clinical oral examination took place at age 70, and oral health was measured according to number of teeth (<6 vs ≥6). Baseline covariates were smoking, alcohol, sex, and income.
Results
Logistic regression analyses revealed that greater cognitive ability and educational attainment had a protective effect against risk of tooth loss. The associations were significant and persisted after adjusting for confounders and a two‐way interaction between cognitive ability and education.
Conclusion
Higher education level and cognitive ability measured at age 50 or 60 were associated with having more teeth at age 70. Whether these findings are due to the interaction of these factors with oral health, related socioeconomic factors, or other factors remains to be studied.
BackgroundThe COVID-19 pandemic was of major concern in Greenland. There was a high possibility of rapid transmission in settlements, and an increased risk of morbidity and mortality because of ...comorbidities in the population and limited access to specialised healthcare in remote areas.AimTo describe the epidemiology of the COVID-19 pandemic in Greenland and evaluate the effects of a strict COVID-19 strategy until risk groups were immunised.MethodsWe studied the epidemiology during March 2020 to June 2022. We describe the non-pharmaceutical interventions (NPIs), PCR-confirmed COVID-19 cases and vaccination coverage with data from the registries of the Greenlandic health authority.ResultsWe found 21,419 confirmed cases per 100,000 inhabitants (54% female, 46% male), 342 per 100,000 were hospitalised and 16 per 100,000 were admitted to the intensive care unit. The COVID-19 mortality rate was 39 per 100,000, all those affected were aged above 65 years. No excess overall mortality was observed. The vaccination coverage by June 2022 was 71.67 and 41% for one, two and three doses, respectively.ConclusionSARS-CoV-2 circulation in Greenland was low, given strict restrictions until all eligible inhabitants had been offered immunisation. The main impact of the pandemic was from May 2021 onwards with increasing numbers of confirmed cases. This occurred after introduction of the vaccine programme, which may have had an influence on the severity of the associated morbidity and mortality experienced. Halting community transmission of SARS-CoV-2 with NPIs until the majority of the population had been immunised was a successful strategy in Greenland.
•5 out of 13 mine tailings can possess chemical contribution as SCM.•3 out of 13 mine tailings can possess physical contribution as SCM.•Mine tailings possess significantly different characteristics ...than CFA and cement.•Chemical and physical pretreatment can potentially optimize mine tailings usage.
In order to reduce emissions of CO2 from cement production and avoid severe environmental pollution from the deposition of mine waste, this study investigated the possibility of utilizing mine tailings as supplementary cementitious materials (SCM) for partially replacement of cement in concrete. This study provides a characterization study of mine tailings to evaluate their potential for contributing chemically or physically as SCM. 13 mine tailing samples were characterized in regards to chemical composition (XRF, Loss on Ignition, CaCO3 and pH), mineralogical content (XRD) and physical characteristics (Grain size distribution, Specific Surface Area, SEM-analysis). The characterization study showed five mine tailings to possess potential chemical contribution as SCM based on their chemical composition (SiO2, Al2O3, Fe2O3 and CaO) and amorphous content. Three mine tailings showed potential physical contribution as SCM based on grain size and grain morphology. The remainder mine tailing characteristics suggest that their potential as SCM may be improved by pretreatment such as milling and/or thermal treatment.
Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, ...obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09-145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.
Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and ...characterize a novel diet-induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model.
Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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