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1.
The therapeutic potential of interfering with dysregulated proteins by inducing its selective degradation has been pursued using different mechanisms. In the present article, we review representative examples of monovalent protein-degraders that, contrary to the proteolysis targeting chimeras, achieve target degradation without displaying recognition motifs for the recruitment of E3 ubiquitin ligases. We also highlight new technologies and assays that may brought to bear on the discovery of common elements that could predict and enable the selective degradation of pathogenic targets by monovalent protein-degraders. The successful application of these methods would pave the way to the advancement of new drugs with unique efficacy and tolerability properties.  相似文献   

2.
In this review we summarize factors determining the plant availability of soil potassium (K), the role of K in crop yield formation and product quality, and the dependence of crop stress resistance on K nutrition. Average soil reserves of K are generally large, but most of it is not plant-available. Therefore, crops need to be supplied with soluble K fertilizers, the demand of which is expected to increase significantly, particularly in developing regions of the world. Recent investigations have shown that organic exudates of some bacteria and plant roots play a key role in releasing otherwise unavailable K from K-bearing minerals. Thus, breeding for genotypes that have improved mechanisms to gain access to this fixed K will contribute toward more sustainable agriculture, particularly in cropping systems that do not have access to fertilizer K. In K-deficient crops, the supply of sink organs with photosynthates is impaired, and sugars accumulate in source leaves. This not only affects yield formation, but also quality parameters, for example in wheat, potato and grape. As K has beneficial effects on human health, its concentration in the harvest product is a quality parameter in itself. Owing to its fundamental roles in turgor generation, primary metabolism, and long-distance transport, K plays a prominent role in crop resistance to drought, salinity, high light, or cold as well as resistance to pests and pathogens. Despite the abundance of vital roles of K in crop production, an improvement of K uptake and use efficiency has not been a major focus of conventional or transgenic breeding in the past. In addition, current soil analysis methods for K are insufficient for some common soils, posing the risk of imbalanced fertilization. A stronger prioritization of these areas of research is needed to counter declines in soil fertility and to improve food security.  相似文献   

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Last summer we officially launched the Journal of Ethnobiology and Ethnomedicine, published by BioMedCentral, with the aim of establishing a serious, peer-reviewed, open-access online journal that focuses on the multidisciplinary, interdisciplinary, and transdisciplinary fields of ethnobiology and ethnomedicine, drawing on approaches and methods from both the social and biological sciences. The strong start vindicates the widely held belief that the journal responds to a real need within the research community. The success of the journal has been most gratifying. The steady influx of submissions of high scientific standards illustrates the strong demand for a dynamic, proactive, and open-minded scientific journal in these research areas. Our aim has been to dedicate JEE to the "scientific communities" worldwide, particularly those in the developing countries.  相似文献   

4.
As part of an ongoing research program aiming at monitoring molecular changes in the tissues and metabolite trafficking in the hydrosphere of algae subjected to chemical stresses, we are discussing the various analytical techniques that have been employed to characterize, and sometimes to quantity these metabolites. High-field multinuclear and solid-state nuclear magnetic resonance (NMR) spectroscopies are powerful tools for metabolite characterization from extracts and in vivo, but quantification and kinetic aspects show some limitations. Modern MS (mass spectrometry) is extremely useful for fingerprinting samples against databases and when dealing with very low concentrations of metabolites, the limitations being set by the type of chromatographic separation and mode of detection coupled with the mass spectrometer. Regarding chemical communication, optimization in terms of resolution and efficiency of hydrosphere chemical analysis can theoretically be achieved in a system which integrates (i) a multiparametric incubation chamber, (ii) a gasphase or a liquid-phase separation system and (iii) mass spectrometer(s) equipped with one or two detectors responding to the analytical and quantitative needs. This text reviews some of the techniques that have been employed in various types of plant metabolic studies, which may serve as a basis towards an integrative analytical strategy directly applicable to the metabolomics of selected marine macrophytes.  相似文献   

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Over the past few decades, a considerable attention has been focused on the microbial polyhydroxyalkanoates (PHAs) owing to its multifaceted properties, i.e. biodegradability, biocompatibility, non-toxicity and thermo-plasticity. This article presents a critical review of the foregoing research, current trends and future perspectives on the value added applications of PHAs in the biomedical, environmental and industrial domains of life.  相似文献   

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The article deals with the historical development of material use in the Bohemia and Moravia-Silesia/Czechoslovakia in 1855–2007. We calculate domestic material consumption (DMC), an indicator based on the concept of socio-economic metabolism and economy-wide material flow analysis, and relate it to various socio-economic factors such as changes in political regimes, industrialization and consequent growth in GDP and population. DMC is good at reflecting the gradual industrialization which took place up to the First World War, then the strong focus on the development of heavy industry under communist rule, and finally the swing to a more consumer industry and service-oriented economy after the fall of the communist regime and the subsequent transition from a centrally planned to a market economy. The comparable DMC figures per capita for Czechoslovakia and the United Kingdom prove that we arrived at feasible values of material consumption.  相似文献   

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Ca2+ release-activated Ca2+ (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca2+ entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders.  相似文献   

12.
Franz Bairlein 《Bird Study》2013,60(3):243-253
Capsule Routes and destinations have been unveiled but modern techniques offer the chance to explore much more.

Ringing of birds unveiled many mysteries of avian migrations, notably routes and destinations. However, there is still much to be explored by the use of ringing and other marks. Satellite tracking, geolocation and global positioning systems, and even electronic tags may enable much more detailed insights into the migration patterns of individual birds and populations. But also a more elaborated colour-marking approach is recommended. Moreover, particular chemical and molecular markers appear to be very useful in the study of bird migration by delineating the origin of birds and connectivity between breeding and non-breeding grounds. Co-ordinated, collaborative, standardized and large-scale migration networks provide another elaborate tool to study differential migration and patterns of migratory timing and fuelling. Although our understanding of bird migration has gained much from captive studies about the internal mechanisms in the control of bird migration, we still lack knowledge about external factors, such as food availability, weather, competitors, parasites or diseases. Such data are also required to refine theoretical models of migration strategies. Future migration research must aim at much more comparative research and a more integrative approach at various spatial and temporal scales, and link various subdisciplines. It must also consider that migration is only one part of the life of a migrating species. Thus, linking migration and breeding is another future challenge, both for basic science and for effective protection of migratory birds.  相似文献   

13.
Type material of two poorly known species of Macromitrium, described from East Africa and Madagascar, was examined and both were found to belong to the genus Macrocoma. Macromitrium megalosporum Thér. & Naveau was found to be morphologically very close to Macrocoma abyssinica (Müll.Hal.) Vitt., with the only significant difference between these taxa being the large multicellular spores of M. megalosporum, which is also the first report of multicellular spores for the genus Macrocoma. This name is here transferred to Macrocoma as Macrocoma abyssinica var. megalospora (Thér. & Naveau) Wilbraham comb. nov. Macrocoma abyssinica var. megalospora is reported new for the Comoros, which is the first record for the species in the East African Islands. Macromitrium adelphinum Cardot in Grandidier was found to be conspecific with Macrocoma tenuis (Hook. & Grev.) Vitt. subsp. tenuis and an appropriate synonymy is proposed. Macrocoma tenuis. subsp. tenuis is also reported here new to the Comoros.  相似文献   

14.
One hundred and thirty-nine taxa of mosses are reported from the montane forest zone of southwest Ethiopia. Of these, 53 taxa are new country records and Meteoriopsis reclinata (Müll.Hal.) M.Fleisch. ex Broth. is, in addition, new to Africa. Most of the new records are of species also found in Uganda, Kenya or Tanzania, but there are some surprises, such as Fabronia perciliata Müll.Hal. with the closest location in South Africa and Namibia, Entodontella cameruniae Broth. previously known only from West Africa and Bryomaltaea obtusifolia (Hook.) Goffinet, otherwise reported only from the Democratic Republic of the Congo. We list all taxa and give a short account of their frequency and in which habitat and on which substrate they grow. That such a large proportion of the species are new to the country suggests that Ethiopia is bryologically very under-explored, and that further exploration will reveal many additional species. In particular, the remnant forests of southwest Ethiopia are likely to be of great importance as bryophyte hotspots.  相似文献   

15.
《Palaeoworld》2016,25(2):138-148
Molecular paleobiology is a subfield of paleontology that uses molecular biological methods on extant organisms to address geoscientifically relevant questions. Progress in the field was last reviewed in 2007, and here we highlight some of the more recent developments, with a focus on ancient animal evolution, in areas such as the application of molecular clocks to estimate clade ages, the evolution of biomineralization, and the evolution of key traits. We argue that molecular paleobiology has much to offer and will be central to paleontological research and evolutionary biology in general, but we also discuss some remaining challenges and future directions of the discipline.  相似文献   

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In this review we discuss features of mRNA synthesis and modifications used to minimize immune response and prolong efficiency of the translation process in vivo. Considerable attention is given to the use of liposomes and nanoparticles containing lipids and polymers for the mRNA delivery. Finally we briefly discuss mRNAs which are currently in the clinical trials for cancer immunotherapy, vaccination against infectious diseases, and replacement therapy.  相似文献   

18.
Extensive research in the past two decades has led to the realization of Immunoglobulin-M (IgM) as a potential therapeutic and diagnostic agent. In order to fully exploit the potential of IgM, large quantities, in a highly pure and active form, must be available at low cost for performing clinical trials, characterization studies and quantitative-structure activity analyses. The complex physico–chemical properties, in particular its large size and labile nature renders downstream purification of IgM difficult. This review discusses the limitations and challenges associated with the current IgM purification strategies and proposes future directions for research. The uniqueness of affinity chromatography, specifically biomimetic affinity chromatography for protein purification is highlighted and its potential for IgM purification is discussed.  相似文献   

19.
Cancer represents a heterogeneous disease with multiple levels of regulation and a dynamic environment that sustains the evolution of the malignant mass. This dynamic is in part sustained by a class of extracellular vesicles termed exosomes that are able to imprint the pathological state by incorporating differential cargos in order to facilitate cell-to-cell communication. Exosomes are stable within the extracellular medium and function as shuttles secreted by healthy or pathological cells, being further taken by the accepting cell with direct effects on its phenotype. The exosomal trafficking is deeply involved in multiple levels of cancer development with roles in all cancer hallmarks. Nowadays, studies are constantly exploring the ability of exosomes to sustain the malignant progression in order to attack this pathological trafficking and impair the ability of the tumor mass to expand within the organisms. As important, the circulatory characteristics of exosomes represent a steady advantage regarding the possibility of using them as minimally invasive diagnosis tools, where cancer patients’ present modified exosomal profiles compared to the healthy ones. This last characteristic, as novel diagnosis tools, has the advantage of a possible rapid transition within the clinic, compared to the studies that evaluate the therapeutic meaning.  相似文献   

20.
In 1994, Chang and Moore reported on the latest of the gammaherpesviruses to infect humans, human herpesvirus 8 (HHV-8) [1]. This novel herpesvirus has and continues to present challenges to define its scope of involvement in human disease. In this review, aspects of HHV-8 infection are discussed, such as, the human immune response, viral pathogenesis and transmission, viral disease entities, and the virus's epidemiology with an emphasis on HHV-8 diagnostics.  相似文献   

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