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61.
Immobilized small-molecule inhibitors are suited for enrichment of biomolecules by affinity chromatography, as it is shown for metalloproteinases and an immobilizable derivative of the hydroxamate-type inhibitor marimastat. A new asymmetric synthesis of marimastat is presented that allows for site-specific attachment to a solid surface, e.g., a chromatography matrix or a surface plasmon resonance sensor chip. The latter technique is shown to be a valuable tool for the optimization of binding and elution conditons of biomolecules in affinity chromatography.  相似文献   
62.
The Bioelectric Recognition Assay (BERA) is a whole-cell based biosensing system that detects the electric response of cultured cells, suspended in a gel matrix, to various ligands, which bind to the cell and/or affect its physiology. Previous studies have demonstrated the potential application of this method for rapid, inexpensive detection of viruses in a crude sample. However, the understanding, so far, of the fundamental processes that take place during cell-virus interactions within the probe has been rather limited. In the present study, we combined electrophysiological and fluorescence microscopical assays, so that we can prove that animal and plant cells immobilized in BERA sensors respond to different viruses primarily by changing their membrane potential. The response of immobilized cells against different viruses did not depend on the virus ability to penetrate the cell, but was modified after binding each virus to a virus-specific antibody or removal of its coat protein after treatment with a protease. Consequently, we were able to assay the presence of a virus in its complete form or fragments thereof. Combination of immunological recognition with the electrophysiological response of immobilized cells allows for a considerable increase of the specificity of the BERA biosensory assay. In addition, rather than simply detect the presence of a protein or genomic sequence, the method can help gain information on the bioactivity of a virus.  相似文献   
63.
Nature employs a set of 20 amino acids to produce a repertoire of protein structures endowed with sophisticated functions. Here, we combined design and selection to create an enzyme composed entirely from a set of only 9 amino acids that can rescue auxotrophic cells lacking chorismate mutase. The simplified protein captures key structural features of its natural counterpart but appears to be somewhat less stable and more flexible. The potential of a dramatically reduced amino acid alphabet to produce an active catalyst supports the notion that primordial enzymes may have possessed low amino acid diversity and suggests that combinatorial engineering strategies, such as the one used here, may be generally applied to create enzymes with novel structures and functions.  相似文献   
64.
Fras1 is a putative extracellular matrix protein that has been implicated in the structural adhesion of embryonic epidermis to dermis. Moreover, mutations in Fras1/FRAS1 have been associated with the mouse blebbed phenotype and the human rare genetic disorder Fraser syndrome, respectively. Here we report the mapping of Fras1 within the extracellular space and evaluate the effects of Fras1 deficiency on lung development in the mouse. Expression of Fras1 was detected in the mesothelial cells of the visceral pleura and in the conducting airway epithelia. Immunogold histochemistry identified Fras1 as a component of the extracellular matrix localized below the lamina densa of epithelial basement membranes in the embryonic lung. Embryos homozygous for a targeted mutation of Fras1 exhibited fused pulmonary lobes resulting from incomplete separation during development as well as a profound disarrangement of blood capillaries in the terminal air sacs. We demonstrate that loss of Fras1 causes alterations in the molecular composition of basement membranes, concomitant with local disruptions of epithelial-endothelial contacts and extravasation of erythrocytes into the embryonic respiratory lumen. Thus, our findings identify Fras1 as an important structural component of the sub-lamina densa of basement membranes required for lobar septation and the organization of blood capillaries in the peripheral lung.  相似文献   
65.
66.
Reductions in cardiac sarcoplasmic reticulum calcium-ATPase (Serca2a) levels are thought to underlie the prolonged calcium (Ca(2+)) transients and consequent reduced contractile performance seen in human cardiac hypertrophy and heart failure. In freshly isolated cardiac myocytes from rats with monocrotaline-induced right ventricular hypertrophy we found reduced sarcoplasmic reticulum Serca2a expression and prolonged Ca(2+)transients, characteristic of hypertrophic cardiac disease.Modulation of intracellular Ca(2+)levels, Ca(2+) kinetics or Ca(2+)sensitivity is the focus of many current therapeutic approaches to improve contractile performance in the hypertrophic or failing heart. However, the functional effects of increasing Serca2a expression on Ca(2+) handling properties in myocytes from an animal model of cardiac hypertrophy are largely unknown. Here, we describe enhancement of the deficient Ca(2+) handling properties evident in myocytes from hypertrophied hearts following adenoviral-mediated transfer of the human Serca2a gene to these myocytes.These results highlight the importance of Serca2a deficiencies in the hypertrophic phenotype of cardiac muscle and suggest a simple, effective approach for manipulation of normal cardiac function.  相似文献   
67.
Moose (Alces alces) have experienced considerable declines along the periphery of their range in the northeastern United States. In Vermont, the population declined 45% from 2010 to 2017 despite minimal hunter harvest and adequate habitat. Similarly, nearby populations recently experienced epizootics characterized by >50% mortality. Declines have largely been associated with the effects of winter ticks (Dermacentor albipictus), but uncertainty exists about the effects of environmental and other parasite-related conditions on moose survival. We examined patterns of moose survival among a radio-collared population (n = 127) in Vermont from 2017 to 2019. Our objectives were to estimate causes of mortality and model survival probability as a function of individual and landscape variables for calves (<1 yr) and adults (≥1 yr). Observed adult survival was 90% in 2017, 84% in 2018, and 86% in 2019, and winter calf survival was 60% in 2017, 50% in 2018, and 37% in 2019. Winter tick infestation was the primary cause of mortality (91% of calves, 25% of adults), and 32% of all mortalities had evidence of meningeal worm (Parelaphostrongylus tenuis). Other sources of mortality such as vehicles, harvest, predation, deep snow, and other parasitic infections were negligible. The best supported calf model included sex differences and negative effects of tick engorgement (%/week) and parasite level (roundworm and lungworm). The best supported adult model included the effect of cumulative tick engorgement (cumulative %/week), which negatively affected survival. Our results indicate that winter tick engorgement strongly affects survival, and is probably compounded by the presence of meningeal worm and other parasites. Reduced tick effects may be achieved by decreasing moose density through harvest and managing late winter habitat to minimize tick density. Management of white-tailed deer (Odocoileus virginianus) density may also affect the transmission of meningeal worm. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society.  相似文献   
68.
Hydrobiologia - Temperature plays a fundamental role in determining phytoplankton community structure, distribution, and abundance. With climate models predicting increases in ocean surface...  相似文献   
69.
In order to analyse the structure and regeneration patterns of the Juniperus excelsa Bieb. stands on the slopes of the Nestos valley, 40 sample plots were established and more than 120 J. excelsa trees and seedlings were cut and collected. The main results of this research indicate that stand structure, species mixture, age structure and stand development patterns were strongly determined by the interaction of anthropogenic disturbances such as grazing and illegal cuttings, and the facilitation of adult J. excelsa trees in the establishment of the J. excelsa seedlings. Their effect was influenced by site quality and J. excelsa together with other species ecology. Under present conditions, almost all J. excelsa seedlings, except for a small number of plants, are found under the facilitation of nurse plants that belong to the same species. It seems that the layer of litter underneath the nurse plants combined with the protection of seedlings against grazing play an important role in the establishment and growth of J. excelsa seedlings.  相似文献   
70.
The last years, there is a steadily growing demand for methods and materials appropriate to create patterns of biomolecules for bioanalytical applications. Here, a photolithographic method for patterning biomolecules onto a silicon surface coated with a polymeric layer of high protein binding capacity is presented. The patterning process does not affect the polymeric film and the activity of the immobilized onto the surface biomolecules. Therefore, it permits sequential immobilization of different biomolecules on spatially distinct areas on the same solid support. The polymeric layer is based on a commercially available photoresist (AZ5214) that is cured at high temperature in order to provide a stable substrate for creation of protein microarrays by the developed photolithographic process. The photolithographic material consists of a (meth)acrylate copolymer and a sulfonium salt as a photoacid generator, and it is lithographically processed by thermal treatment at temperatures 相似文献   
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