ProtMiscuity: a database of promiscuous proteins.

Promiscuous behaviour in proteins and enzymes remains a challenging feature to understand the structure-function relationship. Here we present ProtMiscuity, a manually curated online database of proteins showing catalytic promiscuity. ProtMiscuity contains information about canonical and promiscuous activities comprising 88 different reactions in 57 proteins from 40 different organisms. It can be searched or browsed by protein names, organisms and descriptions of canonical and promiscuous reactions. Entries provide information on reaction substrates, products and kinetic parameters, mapping of active sites to sequence and structure and links to external resources with biological and functional annotations. ProtMiscuity could assist in studying the underlying mechanisms of promiscuous reactions by offering a unique and curated collection of experimentally derived data that is otherwise hard to find, retrieve and validate from literature.

Standard of care, institutional obligations, and distributive justice.

The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies - agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care.

Economical production of poly(ε-l-lysine) and poly(l-diaminopropionic acid) using cane molasses and hydrolysate of streptomyces cells by Streptomyces albulus PD-1.

Poly(ε-L-lysine) (ε-PL) and poly(L-diaminopropionic acid) (PDAP) co-production by Streptomyces albulus PD-1 from cane molasses and hydrolysate of strepyomyces cells (HSC) was investigated for the first time in this study. The optimal initial total sugar concentration of the cane molasses pretreated with sulfuric acid was determined to be 20 g L(-1), and HSC could substitute for yeast extract for ε-PL and PDAP co-production. When fed-batch fermentation was performed in 1t fermentor with pretreated cane molasses and HSC, 20.6 ± 0.5 g L(-1) of ε-PL and 5.2 ± 0.6 g L(-1) of PDAP were obtained. The amount of strepyomyces cells obtained in one fed-batch fermentation is sufficient to prepare the HSC to satisfy the demand of subsequent fermentations, thus the self-cycling of organic nitrogen source becomes available. These results suggest that the low-cost cane molasses and HSC can be used for the economical production of ε-PL and PDAP by S. albulus PD-1.

Promoting protein crystallization using a plate with simple geometry.

Increasing the probability of obtaining protein crystals in crystallization screening is always an important goal for protein crystallography. In this paper, a new method called the cross-diffusion microbatch (CDM) method is presented, which aims to efficiently promote protein crystallization and increase the chance of obtaining protein crystals. In this method, a very simple crystallization plate was designed in which all crystallization droplets are in one sealed space, so that a variety of volatile components from one droplet can diffuse into any other droplet via vapour diffusion. Crystallization screening and reproducibility tests indicate that this method could be a potentially powerful technique in practical protein crystallization screening. It can help to obtain crystals with higher probability and at a lower cost, while using a simple and easy procedure.

[Protein budget: cost estimating criteria for synthetic biology].

The aim of synthetic biology is to design artificial life systems. Such system is hoped to create a better production process with desired ability for bioproduction, biotransformation, adaption and environmental monitoring. However, to design a life system involves understanding the cellular regulation networks at multiple levels, in which the controls of protein level, subcelluar location, and activity are especially critical. Thus tuning protein expression has become essential tools in synthetic biology studies, such as part design, module assembly and compatibility optimization. Protein budget, just like budget for a factory, can be thought as the cost estimating criteria for an artificial cell factory. Protein budget control has provided a powerful optimization strategy for synthetic biology.

Modern-day challenges in therapeutic protein production.

The market for therapeutic proteins is on the rise, plagued by several challenges related to production amounts and costs. Solutions to these problems are widely thought to come from academia, governments and production companies. This conference aimed to bring experts in the industry together under one roof, in order to demystify several novel technologies in therapeutic protein development. Key topics included analytical tools for protein stability and ligand interactions, measurement of protein aggregates as small as 30 nm and reducing production costs, just to name a few. The need to eliminate protein aggregates early during bioprocessing was emphasized. Finally, several companies presented novel technologies related to therapeutic protein development.

Protein science research in China.

Proteins are major executors of life processes, carrying out essential and nonessential functions inside and outside of the cell, in species ranging from simple unicellular organisms to mammals. Thus, not surprisingly, studies of structure and function of proteins span the entire spectrum of molecular biology and modern biomedical sciences in general. Due to historical reasons, protein science research in China was isolated and limited in scope until late 1970s. In the last two decades, China has seen an outburst of research activities, government initiatives, and aggregation of human talents in protein science research. This article provides an overview of major initiatives in research funding, investment in infrastructures, and research forces for protein science research in China.

Economic issues with follow-on protein products.

The economic effects of the possible introduction of 'follow-on' protein products have been the subject of recent debate. Here, we aim to explore the economic issues surrounding this debate using three measures: total sales, product complexity and patent expiry. Our analysis shows that the sales of therapeutic protein products are concentrated in a relatively small number of branded products, which may be the most attractive targets for follow-on development. For the years 2013-2015, we estimate that products representing US$20 billion in annual sales--approximately half of all sales in 2006--can be expected to lose patent protection.

[A medical and economic study about use of hemostatic glues in cardiac surgery]. / Etude médicoéconomique en chirurgie cardiaque : application aux colles hémostatiques.

INTRODUCTION: The impact of the use of biological and synthetic glues in cardiac surgery was assessed by an economic and medical study. MATERIAL AND METHODS: The observational prospective study had duration of three months. All the patients undergoing cardiac surgery were included in the study. The end points were medical (blood transfusion) and economic (duration and cost of the stay in hospital). There were 2 groups: treated or not by glues. STATISTICAL ANALYSIS: T Student tests. RESULTS: Among 154 patients, the 2 principal indications were valvular replacement (48%) and coronary artery bypass grafting (37%). Fifty seven (37%) patients received a glue. The number of transfused globular units and the duration of the stay in the intensive care unit were significantly higher (p<0.05) by treated patients. CONCLUSION: Not only the use of glues did not decrease the post-operative bleedings but it increased also the cost of the stay in hospital. Guidelines were validated by the hospital Commission on drugs.

Developing cell-free biology for industrial applications.

Although cell-free protein synthesis has been practiced for decades as a research tool, only recently have advances suggested its feasibility for commercial protein production. This focused review, based on the 2005 Amgen Award lecture, summarizes the relevant progress from the Swartz laboratory. When our program began, projected costs were much too high, proteins with disulfide bonds could not be folded effectively, and no economical scale-up technologies were available. By focusing on basic biochemical reactions and by controlling cell-free metabolism, these limitations have been methodically addressed. Amino acid supply has been stabilized and central metabolism activated to dramatically reduce substrate costs. Control of the sulfhydral redox potential has been gained and a robust disulfide isomerase added to facilitate oxidative protein folding. Finally, simple scale-up technologies have been developed. These advances not only suggest production feasibility for pharmaceutical proteins, they also provide enabling technology for producing patient-specific vaccines, for evolving new enzymes to enable biological hydrogen production from sunlight, and for developing new and highly effective water filters. Although many challenges remain, this newly expanded ability to activate and control protein production holds much promise for both research and commercial applications.

Assessment of time and practice resources required to provide weekly or monthly erythropoiesis-stimulating protein therapy to chronic kidney disease patients in the physician office setting.

BACKGROUND: There is an epidemic of chronic kidney disease (CKD) and a high prevalence of anemia (47%) observed in CKD patients. Little is known about the cost in physician office resources of routine erythropoiesis-stimulating protein (ESP) administration to treat patients with nondialysis CKD. OBJECTIVES: The objectives of this research were (1) to explore the patterns of care in physician offices where nondialysis CKD patients receive routine ESP injections, (2) to examine differences in the monthly resources and related costs incurred by physician offices in treating patients receiving either weekly (QW) or monthly (QM) ESP regimens, and (3) to identify opportunities to minimize the burden of CKD treatment on physician offices. METHODS: An observational, cross-sectional time and motion assessment was performed in 10 community-based outpatient nephrology practices (5 QW and 5 QM practices); each practice had 40 patients on routine ESP therapy for nondialysis CKD. Three observers trained in health care research documented injection-related tasks and time associated with 91 ESP injection procedures (47 QW and 44 QM) from patients. arrival to and departure from the physician office, office personnel follow-up on billing and documentation, and injection-related staff time. Monthly injection times for QM were calculated by summing the time required to perform the tasks associated with administering a single injection of ESP to subjects, as documented by observers. Total monthly per-patient medical practice costs for providing QM ESP injections were calculated, including labor costs (calculated by applying average wage rates of practice staff to time observed for the specific activities performed) and supply costs (based on average list prices found in medical supply catalogs). Monthly injection times and costs for the QW regimen were calculated by summing the same list of activities as for the QM regimen and multiplying by 4.3 (4.3 weeks per month). Nephrology practice personnel completed a questionnaire summarizing practice characteristics and estimated the time required for some of the injection-related activities. The time and cost associated with each task were analyzed using descriptive and comparative statistics (i.e., Fisher.s exact test and t test). RESULTS: On average, patients spent 21 minutes in the clinic for a routine injection visit (QW: 17 minutes, QM: 25 minutes; P=0.053), during which 11 minutes (52%) were spent interacting with clinic staff (QW: 8.9 minutes, QM: 13.4 minutes; P=0.005). In the time spent interacting with staff, 3 minutes (QW: 2.9 minutes, QM: 3.6 minutes; P=0.065) were for dose administration and 8 minutes (QW: 5.3 minutes, QM: 9.8 minutes; P=0.011) were for staff providing various services to the patients, including registering patients on arrival, examining patients (vital signs, weight, blood work), consulting with patients, and scheduling patients. next visits. Each month, clinic staff spent a total visit average of 38 minutes providing anemia-related treatment for each QW injection patient, compared with 13 minutes for each QM injection patient (P <0.001). After patients. departure, clinic staff spent additional time (not quantified) on billing, filing claims, and other administrative responsibilities most of which could not be observed during our 1-day observation. The average total monthly practice cost of providing ESP therapy to a QW patient (17.00 dollars [95% confidence interval (CI), 13.00-27.13]) was more than double that for a QM patient (6.78 dollars [95% CI, 5.34-9.12]); (P=0.004). Differences in visit-related labor costs (QW: 8.34 dollars, QM: 3.43 dollars; P=0.108) and injection supply costs (QW: 4.39 dollars, QM: 1.67 dollars; P <0.001) accounted for the largest portions of the total monthly cost differential between the treatment regimens. QM dosing would require, on average, 83 hours less staff time and 2,044 dollars less estimated cost treating 200 patients per month compared with weekly administration per clinic. CONCLUSIONS: Administering routine ESP injections to nondialysis CKD patients for anemia using a QM regimen results in substantial time and cost savings compared with a QW therapy regimen. Managing patients on less frequent ESP dosing schedules may alleviate medical practice burden by reducing the staff time and supplies related to providing injections in the office.

Patent protection for protein structures and databases.

Patent protection is available for certain inventions in the field of structural genomics. A review of the patent application procedure is provided, and patentable aspects of protein structural information under US law are discussed. Strategic and international factors to consider when seeking patent protection for an invention also are presented.