Implications of immune-mediated metastatic growth on metastatic dormancy,blow-up,early detection,and treatment

Metastatic seeding of distant organs can occur in the very early stages of primary tumor development. Once seeded, these micrometastases may enter a dormant phase that can last decades. Curiously, the surgical removal of the primary tumor can stimulate the accelerated growth of distant metastases, a phenomenon known as metastatic blow-up. Recent clinical evidence has shown that the immune response can have strong tumor promoting effects. In this work, we investigate if the pro-tumor effects of the immune response can have a significant contribution to metastatic dormancy and metastatic blow-up. We develop an ordinary differential equation model of the immune-mediated theory of metastasis. We include both anti- and pro-tumor immune effects, in addition to the experimentally observed phenomenon of tumor-induced immune cell phenotypic plasticity. Using geometric singular perturbation analysis, we derive a rather simple model that captures the main processes and, at the same time, can be fully analyzed. Literature-derived parameter estimates are obtained, and model robustness is demonstrated through a time dependent sensitivity analysis. We determine conditions under which the parameterized model can successfully explain both metastatic dormancy and blow-up. The results confirm the significant active role of the immune system in the metastatic process. Numerical simulations suggest a novel measure to predict the occurrence of future metastatic blow-up in addition to new potential avenues for treatment of clinically undetectable micrometastases.

     

The Genus Gluconobacter Oxydans: Comprehensive Overview of Biochemistry and Biotechnological Applications

ABSTRACT

The genus Gluconobacter comprises some of the most frequently used microorganisms when it comes to biotechnological applications. Not only has it been involved in “historical” production processes, such as vinegar production, but in the last decades many bioconversion routes for special and rare sugars involving Gluconobacter have been developed. Among the most recent are the biotransformations involved in the production of L-ribose and miglitol, both very promising pharmaceutical lead molecules. Most of these processes make use of Gluconobacter's membrane-bound polyol dehydrogenases. However, recently other enzymes have also caught the eye of industrial biotechnology. Among them are dextran dextrinase, capable of transglucosylating substrate molecules, and intracellular NAD-dependent polyol dehydrogenases, of interest for co-enzyme regeneration. As such, Gluconobacter is an important industrial microbial strain, but it also finds use in other fields of biotechnology, such as biosensor-technology. This review aims to give an overview of the myriad of applications for Gluconobacter, with a special focus on some recent developments.     

Exploring the role of circadian clock gene and association with cancer pathophysiology

ABSTRACT

Most of the processes that occur in the mind and body follow natural rhythms. Those with a cycle length of about one day are called circadian rhythms. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues.

The circadian system is responsible for regulating a variety of physiological and behavioral processes, including feeding behavior and energy metabolism. Studies revealed that the circadian clock system consists primarily of a set of clock genes. Several genes control the biological clock, including BMAL1, CLOCK (positive regulators), CRY1, CRY2, PER1, PER2, and PER3 (negative regulators) as indicators of the peripheral clock.

Circadian has increasingly become an important area of medical research, with hundreds of studies pointing to the body’s internal clocks as a factor in both health and disease. Thousands of biochemical processes from sleep and wakefulness to DNA repair are scheduled and dictated by these internal clocks. Cancer is an example of health problems where chronotherapy can be used to improve outcomes and deliver a higher quality of care to patients.

In this article, we will discuss knowledge about molecular mechanisms of the circadian clock and the role of clocks in physiology and pathophysiology of concerns.     

Electrothermal Atomic Absorption Spectrometry to Determine As,Cd, Cr,Cu, Hg,and Pb in Soils and Sediments: A Review and Perspectives

Environmental pollution from trace elements has been increasing in recent decades and has become an important concern for environmental agencies. The trace elements arsenic, cadmium, chromium, copper, mercury, and lead are among the elements that cause the greatest environmental impact and carry the highest risk to human health. Electrothermal atomic absorption spectrometry (ETAAS) has long been employed in trace element determination. In the last few years the main constraints of spectroscopy absorption methods have been overcome. These advances have increased the possibilities and the utility of ETAAS for trace element determination at μg L^?1 levels in difficult matrices such as soils and sediments, giving greater accuracy and precision, lower economic cost, and easier sample pretreatment than other methods. The main advances come from sample manipulation for matrix destruction and preconcentration, the use of new lab-on-valve FIA systems, the solid sampling, the use of new, more efficient modifiers and in situ trapping methods for analyte stabilization and pre-concentration, and the progress in the capacity to control the atomization temperature and to correct background spectral interferences. All of them have permitted an improvement in the sensitivity, decreasing the detection limits and manipulation process, and increasing the accuracy and precision of the analyses.

Moreover, the new technology in the optic and detector systems have given rise to high-resolution continuum source ETAAS (HR-CS ETAAS) spectrometers that solve most of the constraints presented by the more conventional line source ETAAS (LS ETAAS) spectrometers. HR-CS ETAAS enables a rapid detection of several elements at once, facilitates direct determination from solid sampling, and reduces the matrix interferences and background noise. Here we give an overview of the recent advances and the different possibilities of using ETAAS, drawing on studies from the last decade on methods to analyze As, Cd, Cu, Hg, and Pb in soils and sediments.     

手术医疗收费结构比例分析及对策探讨

目的 通过分析手术医疗收费结构比例,找出医疗收费结构中的缺陷。方法 对639例手术医疗收费情况进行数据处理,分析不同类别手术费用间价格的差异性。结果 在手术及麻醉医疗消费中,药品、耗材的费用在医疗消费中所占比例较大,医务人员的劳动价值在费用中未合理体现。结论 医疗费用的合理管控需要采取科学有效的措施作为保障,医务人员劳动价值需要公平合理的体现在医疗费用中。     

Chemical modification of proteases for wool cuticle scale removal

Over the last few decades several enzymatic processes to improve properties of wool fabrics like felting tendency, shrink resistance, dyeing ability and handling characteristics have been described. Previous investigations into the use of proteases to hydrolyse the cuticles at the surface of wool fibres, resulted in high strength and weight losses. Therefore restriction of the enzyme activity to the wool surface or control of enzyme diffusion to the cortex cells is required.

To change the diffusion behaviour of proteases in wool fibres, the soluble polymer PEG was covalently attached to a protease from Bacillus lentus. Modified enzymes with different molecular weights were compared. These modified enzymes retained up to 80% of their activity in the standard assay while hydrolysis of wool fibres was successfully restricted to cuticles, resulting in a 90% decrease in weight losses compared to non-modified enzymes.     

First global approach: morphological and biological variability in a genetically homogeneous population of the European pilchard, Sardina pilchardus (Walbaum, 1792) in the North Atlantic coast

The European pilchard Sardina pilchardus represents the most commercially relevant fisheries resource in many countries bordering north Atlantic coasts and the Mediterranean Sea, being especially significant along the coast of Morocco. The continuous exploitation of this pelagic species for several decades places Morocco as the leader in sardine production. However, the conditions of exploitation of this resource underwent a great change during the last recent years. In order to identify the populations of the European pilchard sardine (Sardina pilchardus, Walbaum, 1792) in the Atlantic coast of Morocco and Spain, we have combined the truss network data to conduct multivariate analysis with biologic parameters and genetic analysis based on Microsatellite and mitochondrial control region data. Sardine morphometrics data truss variables from 10 samples spanning the Atlantic coast of Morocco were analysed by multivariate analysis. Thirteen morphometric measurements and some biological parameters such as the sex and the age of fishes were made for each individual. Discriminant analysis on size-corrected truss variables and cluster analysis of mean fishes shape using landmark data indicate, that the shape of north Moroccan sardines is distinct from the shape of sardines from south Morocco. However the analysis of the mitochondrial region and four microsatellites loci (Sp2, Sp7, Sp8 and SpI5) demonstrated an homogeneity population in the Moroccan Atlantic coast, with a low but significant genetic differentiation, which followed an isolation-by-distance pattern according to Mantel test.     

From nutraceutical to clinical trial: frontiers in Ganoderma development

Ganoderma spp. are medical mushrooms with various pharmacological compounds which are regarded as a nutraceutical for improving health and treating diseases. This review summarizes current progress in the studies of Gamoderma ranging from bioactive metabolites, bioactivities, production techniques to clinical trials. Traditionally, polysaccharides and ganoderic acids have been reported as the major bioactive metabolites of Ganoderma possessing anti-tumor and immunomodulation functions. Moreover, recent studies indicate that Gandoerma also exerts other bioactivities such as skin lighting, gut microbiota regulation, and anti-virus effects. However, since these medical fungi are rare in natural environment, and that the cost of cultivation of fruiting bodies is high, industrial submerged fermentation of Ganoderma mycelia promotes the development of Ganoderma by dint of an increase of biomass and bioactive metabolites used for further application. In addition, various strategies for production of different metabolites are well developed, such as gene regulation, bi-stage pH, and oxygen control. To date, Ganoderma not only has become one of the most popular nutraceuticals worldwide but also has been applied to clinical trials for advanced diseases such as breast and non-small-cell lung cancer.

     

Aligning extracted LC-MS peak lists via density maximization

Rapid improvements in mass spectrometry sensitivity and mass accuracy combined with improved liquid chromatography separation technologies allow acquisition of high throughput metabolomics data, providing an excellent opportunity to understand biological processes. While spectral deconvolution software can identify discrete masses and their associated isotopes and adducts, the utility of metabolomic approaches for many statistical analyses such as identifying differentially abundant ions depends heavily on data quality and robustness, especially, the accuracy of aligning features across multiple biological replicates. We have developed a novel algorithm for feature alignment using density maximization. Instead of a greedy iterative, hence local, merging strategy, which has been widely used in the literature and in commercial applications, we apply a global merging strategy to improve alignment quality. Using both simulated and real data, we demonstrate that our new algorithm provides high map (e.g. chromatogram) coverage, which is critically important for non-targeted comparative metabolite profiling of highly replicated biological datasets.

     

Indexing winter gull numbers in Great Britain using data from the 1953 to 2004 Winter Gull Roost Surveys

Capsule Winter Gull Roost Survey data spanning 50 years were used to generate population indices.

Aims To evaluate how wintering numbers of five gull species have changed in Great Britain over the last five decades.

Methods Generalized linear models were used to relate gull numbers to habitat, site and year factors, and so derive species‐specific indices for nine regions of Great Britain. Regional models considered data from different timescales depending on coverage.

Results Patterns of change varied by species and region. All species showed increases in number over the period 1953 to 2004. In most regions, Black‐headed Gull Chroicocephalus ridibundus numbers have declined since peaks between 1973 and 1993; Common Gulls Larus canus have also declined recently in some regions. Lesser Black‐backed Gull L. fuscus numbers have increased dramatically since 1953, whereas numbers of Herring Gull L. argentatus showed large declines between 1963 and 1983. Great Black‐backed Gull L. marinus numbers have increased in the west and the Midlands, but recently declined in eastern regions.

Conclusions Numbers of wintering gulls in Great Britain have shown rapid changes over the last five decades, reflecting changes in the sizes of breeding populations. These changes are likely to be associated with changes in human activities and resource availability.     

The oldest monitoring site of the Alps revisited: accelerated increase in plant species richness on Piz Linard summit since 1835

Background: High-altitude ecosystems in the Alps have experienced severe environmental changes over the past decades, such as strong warming and increasing numbers of visitors and grazers. Few studies have followed the effects of such changes on the alpine flora over a period longer than a few decades. The summit of Piz Linard (3410 m, south-eastern Switzerland) is the oldest site in the Alps whose flora has been recorded, on average every 20 years since the Little Ice Age (1835).

Aims: We re-surveyed the summit flora of Piz Linard to trace its floristic changes and identify their patterns and possible drivers.

Methods: We mapped each species' highest location, distribution and abundance in the uppermost 30 m of the Piz Linard summit in 2011, and compared species composition and species’ altitudinal distribution over time.

Results: Species richness increased at an accelerated rate since 1992 and rose from 12 to 16 species since the previous record in 2003. Most already present species increased in abundance and colonised new areas of the summit, while new arrivals mainly established at sites with already high species richness. Species appeared after 1992 differed from species already present previously by having had lower maximum altitudes elsewhere in south-eastern Switzerland.

Conclusions: Temporal and spatial patterns of colonisations and former altitudinal ranges of species all point to climate warming as the principal driver of floristic change on Piz Linard.     

Different paths in social life cycle impact assessment (S-LCIA)—a classification of type II impact pathway approaches

Purpose

In social life cycle assessment (S-LCA), we can distinguish two main types of impact assessment (LCIA): type I can be seen as a reporting approach with the use of performance reference points and type II aims at including cause-effect chains or impact pathways in the analysis. Given the heterogeneity of those type II approaches, this review provides a classification of existing type II approaches.

Methods

We reviewed a total of 28 articles against the background of their main purpose, the method used, the issues covered and the origin of data (observation/characterization/ measurement). We checked the articles against (i) the reflection of an impact pathway, (ii) the availability of so-called inventory and impact indicators, and (iii) the presence of characterization models or factors translating correlations or causality.

Results and discussion

The analysis reveals three main paths to include impact pathways in S-LCA, which differ in authors’ intentions: (1) some studies identify and propose variables composing impact pathways, or frameworks gathering several pathways; (2) other studies investigate or test known pathways empirically, and until now seek mainly to link income data with health impacts at a macro scale, and (3) a last batch applies known and already quantified characterization models or factors from other research works in case studies. Until now, these case studies focus mainly on income-related social effects or on health impacts. Further, each path is further characterized and classified under nine approaches. Our findings highlight not only the heterogeneous nature of approaches, but also their common denominator which is to not consider phenomena or impacts in isolation but to consider them in relation to their sources or further impacts. It should be noted that type II studies are not only limited to quantitative approaches and variables, but can also use more qualitative variables and methods.

Conclusions

The presented classification may be used as a guidance tool for authors to make their methodological choices. Also, our findings indicate the opportunity of extending future type II S-LCA research to variables tackled in type I studies (e.g., safe and fair employment and working conditions), beyond pathways including incomes and health impacts. This can be done by using theories from social sciences for the identification of impact pathways. Those could then further be investigated through statistical approaches or in the framework of S-LCA case studies, with specific data and potentially more qualitative methods to analyze causality or social mechanisms.

     

滨海湿地生态系统微生物驱动的氮循环研究进展

滨海湿地生态系统介于陆地生态系统和海洋生态系统之间,其类型多种多样,环境差异极大,微生物种类丰富。近年来,随着人为氮源的大量输入,造成滨海湿地生态系统富营养化污染问题日趋严重。本文主要总结了滨海湿地生态系统微生物驱动的固氮、硝化、反硝化、厌氧氨氧化、NO_3~-还原成铵等主要氮循环过程,并综述了通过功能基因(如nifH、amoA、hzo、nirS、nirK、nrfA)检测微生物群落多样性及其环境影响因素的相关研究,旨在更好理解微生物驱动氮循环过程以去除氮,以期为减轻富营养化和危害性藻类爆发提供科学依据。     

Production of entomopathogenic nematodes in submerged monoxenic culture: A review

Monoxenic liquid culture is the most suitable technology for scaling up to industrial production of entomopathogenic nematodes (EPNs); however, the variability of the yield production remains a current problem in the process. The aim of this study was to analyze the parameters and criteria for EPN production in liquid culture based on scientific and technological knowledge from the last two decades. While experimental research has permitted the yield production of Heterorhabditis bacteriophora (362 × 10³ infective juveniles [IJs]/ml) and Steinernema carpocapsae (252 × 10³ IJs/ml), simultaneously, theoretical approaches have contributed to the understanding of the culture process, based on biological parameters of the bacterium–nematode complex and hydrodynamic and rheological parameters of the complex gas–liquid–solid system. Under this interdisciplinary research approach, bioprocess and biosystem engineering can contribute to design the various control strategies of the process variables, increase the productivity, and reduce the variability that until now distinguishes the in vitro production of EPNs by the liquid culture.     

Fungicide resistance in cucurbit downy mildew – methodological, biological and population aspects

Cucurbit downy mildew, caused by Pseudoperonospora cubensis, is among the most devastating diseases of cucurbitaceous plants. In spite of improved cultural practices and breeding for resistant cultivars, chemical control is still a very important tool to manage the disease. During the last several decades, many fungicides from various chemical classes have been developed. The occurrence of strains of P. cubensis resistant/tolerant to some fungicides encouraged research of this phenomenon. The first part of this article summarises the many different methodological approaches such as field trials, in vitro testing on active plant tissues or molecular diagnoses developed for the detection of resistant/tolerant strains of P. cubensis, as well as methods to collect and maintain pathogen isolates. The second part outlines the commonly used fungicides to control P. cubensis and their features like systemicity, biological and biochemical mode of action and translocation behaviour within plants. The last part deals with geographical aspects such as first appearance of resistance problems, distribution of resistance, temporal development of resistance under selection pressure by a fungicide, fitness of resistant subpopulations in competition with sensitive ones in the absence of a fungicide, as well as genetic and molecular sources of resistance.     

Sampling bias in the determination of first and last occurrences

Background: Past studies of first and last occurrence dates of phenological events have revealed close associations with climatic parameters. Consequently, it is widely acknowledged that recent shifts in the beginning, duration or ending of such events are a response to present climate change. In addition, in recent times, there have tended to be many more observers than in earlier times, especially in urban areas. Furthermore, the number of individuals (plants or animals) observed has often changed markedly. In many situations it is not possible to obtain the average first or last occurrence date of a group of individuals, and only the most extreme occurrence is recorded. This common observational difficulty leads to sampling bias that needs to be taken into account.

Aim: Our aim is to use statistical models to quantify the sampling bias and its dependence on sample size and the variability and correlation amongst the individuals under consideration.

Methods: n-dimensional multivariate normal distribution and two-way fixed-effects analysis of variance models were developed to examine the dependence of the sampling bias on the above factors. Our results are compared with real data.

Results: For first and last occurrence observations, which are the most common index in many phenological studies, we found that changes in observational practice and sample size can, in certain circumstances, easily produce changes in bias that can swamp (or indeed reverse) any climatic change effects.

Conclusions: Our new, realistic statistical models allow the sampling bias to be quantified and calculated in terms of the number of individuals under observation, their variability and the degree of correlation between individuals.     

Biodiversity restoration of formerly extracted raised bogs: vegetation succession and recovery of other trophic groups

Central European raised bogs are unique and fragile ecosystems inhabited by specialists of higher plants, fungi, and insects. Many of these ecosystems have suffered and are still suffering due to peat harvesting and drainage. The respective specialists, so-called tyrphobionts, and their abundance can serve as good indicators of restoration processes after the disturbance. Various taxonomic groups may differ in the response to the processes. This study shows successional trends in two disturbed raised bogs compared to adjoining undisturbed reference raised bogs. During the growing season of 2019 we compared species richness of successional stages with reference sites for the following five groups of organisms: vascular plants, mosses, fungi, butterflies, and moths. After three decades of spontaneous succession, the species composition did not reach the reference site for any taxonomic group. Instead an alternative, near-natural woodland developed. The different groups of organisms exhibited very similar trends in species richness and participation of tyrphobionts. About half of these specialists occurring at the reference sites were able to colonise the disturbed sites, but mostly in low quantity. Water table and pH appeared significant environmental variables. It seems that habitat limitations play a more important role than dispersal limitations in this restoration process. More successful restoration might be possible by substantially increasing the water table in the disturbed raised bogs.