Половці: етнічна культура

У статті розглядаються структурні складові етнічної культури, формування якої відбувалося у процесі синтезу первинних і вторинних генеруючих чинників ретроспекції життєдіяльності номадів.В статье рассматриваются структурные составные этнической культуры, формирование которой осуществлялось в процессе синтеза первичных и вторичных генерирующих факторов ретроспекции жизнедеятельности номадов.Structural components of ethnic culture, formation of which was realized in the process of synthesis of primary and secondary generating factors of retrospection of nomads’ life activities are considered in the article

Molecular data show conserved DNA locations distinguishing lung cancer subtypes and regulation of immune genes

Introduction: Non-small-cell lung cancer exhibits a range of transcriptional and epigenetic patterns that not only define distinct phenotypes, but may also govern immune related genes, which have a major impact on survival. Methods: We used open-source RNA expression and DNA methylation data of the Cancer Genome Atlas with matched non-cancerous tissue to evaluate whether these pretreatment molecular patterns also influenced genes related to the immune system and overall survival. Results: The distinction between lung adenocarcinoma and squamous c

Sleep, vigilance, and thermosensitivity

The regulation of sleep and wakefulness is well modeled with two underlying processes: a circadian and a homeostatic one. So far, the parameters and mechanisms of additional sleep-permissive and wake-promoting conditions have been largely overlooked. The present overview focuses on one of these conditions: the effect of skin temperature on the onset and maintenance of sleep, and alertness. Skin temperature is quite well suited to provide the brain with information on sleep-permissive and wake-promoting conditions because it changes with most if not all of them. Skin temperature changes with environmental heat and cold, but also with posture, environmental light, danger, nutritional status, pain, and stress. Its effect on the brain may thus moderate the efficacy by which the clock and homeostat manage to initiate or maintain sleep or wakefulness. The review provides a brief overview of the neuroanatomical pathways and physiological mechanisms by which skin temperature can affect the regulation of sleep and vigilance. In addition, current pitfalls and possibilities of practical applications for sleep enhancement are discussed, including the recent finding of impaired thermal comfort perception in insomniacs

Timing of host feeding drives rhythms in parasite replication

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the hosts' peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the hosts' peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new arena for studying host-parasite-vector coevolution and has broad implications for applied bioscience

Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. METHODS: A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. RESULTS: ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≥ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. CONCLUSIONS: ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.The Belgian Foundation Against Cancer (grant number C/2014/227); Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (grant number 00000000116000000206); Royal College of Surgeons/Cancer Research UK (C19198/A1533); The Cancer Research Funds of Radiumhemmet, through the PCM program at KI (grant number 163012); The Erling-Persson family foundation (grant number 4-2689-2016); the Swedish Research Council (grant number K2010-70X-20430-04-3), and the Swedish Cancer Foundation (grant number 09-0677)

Synthesis of Furandicarboxylic Acid Esters From Nonfood Feedstocks Without Concomitant Levulinic Acid Formation

5-Hydroxymethylfurfural (HMF) is a versatile intermediate in biomass conversion pathways. However, the notoriously unstable nature of HMF imposes challenges to design selective routes to chemicals such as furan-2,5-dicarboxylic acid (FDCA). Here, a new strategy for obtaining furans is presented, bypassing the formation of the unstable HMF. Instead of starting with glucose/fructose and thus forming HMF as an intermediate, the new route starts from uronic acids, which are abundantly present in many agro residues such as sugar beet pulp, potato pulp, and citrus peels. Conversion of uronic acids, via ketoaldonic acids, to the intermediate formylfuroic acid (FFA) esters, and subsequently to FDCA esters, proceeds without formation of levulinic acid or insoluble humins. This new route provides an attractive strategy to valorize agricultural waste streams and a route to furanic building blocks without the co-production of levulinic acid or humins

Fermentation for the production of biobased chemicals in a circular economy : a perspective for the period 2022-2050

Chemicals and materials produced from non-renewable, petrochemical feedstocks contribute greatly to the quality of life we currently enjoy. To ensure that quality of life is maintained in the future, it is imperative that we move towards a circular economy, where care is taken to reuse or recycle materials at their end-of-life and new chemicals and materials are sourced from renewable carbon feedstocks such as biomass. To achieve this transition, efficient conversion methods by which biomass-derived feedstocks can be converted to chemicals are required. The high degree of functionalisation (i.e. high content of oxygen atoms) of biomass-derived feedstocks, makes their conversion by microbial fermentation an interesting option. This article provides an overview of currently available fermentation technologies that have the potential to play a role in the production of biobased bulk chemicals in a circular economy in the period up to 2050. Our focus is primarily on technologies that are sufficiently mature to have been implemented on (at least) industrial pilot scale. In addition to an overview of available technologies, we provide a critical assessment of their potential relevance for use in the production of bulk chemicals in a future circular economy. We conclude that seven fermentation processes for the production of (potential) bulk chemicals have already reached a stage of technological maturity where they are ready to be applied in a circular economy. A number of other processes may reach this stage of maturity in the coming years

Environmental Impacts of End-of-Life Options of Biobased and Fossil-Based Polyethylene Terephthalate and High-Density Polyethylene Packaging

Plastic waste production increasingly causes environmental pollution. However, end-of-life (EoL) research often lacks detail and timeliness and fails to integrate the end-of-life option into a product’s life cycle in a systemic perspective. This study addresses these knowledge gaps, by applying an improved anticipatory consequential life cycle assessment (LCA) approach. Reuse, mechanical and chemical recycling options were compared for (biobased and fossil-based) high-density polyethylene (HDPE) and polyethylene terephthalate (PET) plastic shampoo bottles in the European context using three types of impact categories: climate change, fossil resource scarcity and mineral resources scarcity. The completeness and detail of EoL were increased by modelling the polymer reprocessing within the collection system including all transport distances, while timeliness was improved by implementing the data applicable for the time of implementation of EoL options in the future. The results show that the reuse option has the largest benefits on climate change impact, and on fossil and mineral resource scarcity for both HDPE and PET, for both biobased and fossil plastics. Furthermore, all EoL options cause a net reduction in all climate change, fossil and mineral resource scarcity thanks to the avoided impact of virgin plastic. Finally, the improved LCA approach, utilized in this study, includes plastic production, use and EoL in one assessment, and thus can provide valuable information for adjusting policy and regulations for plastic manufacturers in their production of new virgin plastic polymer, as it requires alignment with its use and EoL options

New insights into the base catalyzed depolymerization of technical lignins: A systematic comparison

A first systematic approach on the base catalyzed depolymerization (BCD) of five technical lignins derived from various botanical origins (herbaceous, hardwood and softwood) and covering the main three industrial pulping methods (soda, kraft and organosolv) is reported. This study provides a first of its kind in-depth quantification and structural characterization of two main BCD fractions namely lignin oil and lignin residue, describing the influence of the BCD process conditions. Depolymerization is evaluated in terms of lignin conversion, lignin oil yield, phenolic monomer selectivity and the production of lignin residue and char. Lignin oils were extensively characterized by size exclusion chromatography (SEC), GC-MS, GC-FID, 13C-NMR, HSQC NMR and elemental analysis. GC × GC-FID was used to identify and quantify distinct groups of monomeric compounds (methoxy phenols, phenols, dihydroxy-benzenes) in the lignin oil. The lignin oil yields (w/w) ranged from 20-31% with total monomer contents ranging from 48 to 57% w/w. SEC analysis indicated the presence of dimers/oligomers in the lignin oil, which through HSQC NMR analysis were confirmed to contain new, non-native interunit linkages. 13C NMR analyses of the lignin oils suggest the presence of diaryl type linkages (i.e. aryl-aryl, aryl C-O) evidencing deconstruction and recombination of lignin fragments during BCD. Irrespective of the lignin source, a residue, often regarded as ‘unreacted’ residual lignin was the main product of BCD (43 to 70% w/w). Our study highlights that this residue has different structural properties and should not be considered as unreacted lignin, but rather as an alkali soluble condensed aromatic material. HSQC, DEPT-135, 13C, and 31P NMR and SEC analyses confirm that the BCD residues are indeed more condensed, with increased phenolic hydroxyl content and lower molecular weights compared to all feed lignins. Subsequent BCD of solid residual fractions produced only low oil yields (6-9% w/w) with lower phenolic monomer yields (4% w/w) compared to original lignin, confirming the significantly more recalcitrant structure. Our study improves the overall understanding of the BCD process, highlights important feedstock-dependent outcomes and ultimately contributes to the complete valorization of BCD-derived lignin streams

Endocrine activities of phthalate alternatives; Assessing the safety profile of furan dicarboxylic acid esters using a panel of human cell based reporter gene assays

FDCA esters are highly relevant biobased alternatives for currently used benzene dicarboxylic acid esters. Despite all the developments on 2,5-FDCA applications, to the best of our knowledge thus far no toxicological data were available for 2,5-FDCA esters. In the present study we aimed to fill this gap, by using an in vitro reporter gene assay approach to compare the activity profile of commonly used phthalates to that of their furan-based counterparts. The assay selection was aimed at the detection of endocrine activity, since several phthalates are heavily scrutinised for their endocrine disrupting properties. However, to avoid missing other relevant toxicological endpoints, several assays able to detect various forms of cellular stress were also included in the panel. The results showed that the (ortho)benzene dicarboxylic acid esters were predominantly active on several of the endocrine assays. In comparison, six of the seven furan dicarboxylic acid based diesters tested here showed no activity in any of the 13 assays used. Only the isobutyl derivative DIBF showed moderate estrogenic activity on one assay, compared to much more pronounced activities on four assays for the ortho-phthalate analogue. Overall, the results presented in this paper are a strong indication that 2,5-FDCA based diesters in general are not only technically viable alternatives to phthalates, but also offer significant toxicological benefits, which supports a non-regrettable substitution