工业微生物：创新与突破专刊序言(2021)

工业微生物及其产品广泛用于工业、农业、医药等诸多领域,相关产业在国民经济中具有举足轻重的地位。高效的菌株是提高生产效率的核心,而先进发酵技术和仪器平台对充分开发菌株代谢潜能也很重要。近年来,工业微生物领域的研究取得了快速进展,人工智能、高效基因组编辑技术和合成生物学技术逐渐广泛使用,相关产业应用也在不断扩展。为进一步促进工业微生物在生物制造等领域的应用,《生物工程学报》特组织出版专刊,从微生物菌株的多样性和生理代谢、菌株改造技术、发酵过程优化和放大,高通量微液滴培养装备开发以及工业微生物应用等方面,分别阐述目前的研究进展,并展望未来的发展趋势,为促进工业微生物及生物制造等产业的发展奠定基础。     

Treatment of breakthrough fungal infections: Is there one best drug strategy?

Widespread use of antifungal drugs in prophylactic and therapeutic settings is associated with breakthrough infections primarily due to Aspergillus and non-Aspergillus molds and non-albicans Candida. Reasons for breakthrough include worsening of initial infection, superinfection, and co-infection; subtherapeutic drug levels, emergence of antifungal resistance, and host factors may contribute to progression of the initial infection. Establishing an etiologic diagnosis is crucial because clinical and radiological features are nonspecific, and empirically chosen drug(s) may not provide appropriate antimicrobial coverage. Evidence-based data do not exist for the management of breakthrough infection. Current treatment strategies include switching therapy to a drug of another class, dose optimization, and combinations of drugs. Dosage adjustment of triazoles guided by serum concentrations may ensure optimal efficacy and avoidance of toxicity. A combination of an echinocandin plus a triazole or polyene appears to be synergistically effective against invasive aspergillosis. The treatment strategy needs to be individualized. For an optimal outcome, reversal of immunosuppression is essential.     

Modeling technology innovation: How science, engineering, and industry methods can combine to generate beneficial socioeconomic impacts

Background

The introduction of evidence-based programs and practices into healthcare settings has been the subject of an increasing amount of research in recent years. While a number of studies have examined initial implementation efforts, less research has been conducted to determine what happens beyond that point. There is increasing recognition that the extent to which new programs are sustained is influenced by many different factors and that more needs to be known about just what these factors are and how they interact. To understand the current state of the research literature on sustainability, our team took stock of what is currently known in this area and identified areas in which further research would be particularly helpful. This paper reviews the methods that have been used, the types of outcomes that have been measured and reported, findings from studies that reported long-term implementation outcomes, and factors that have been identified as potential influences on the sustained use of new practices, programs, or interventions. We conclude with recommendations and considerations for future research.

Methods

Two coders identified 125 studies on sustainability that met eligibility criteria. An initial coding scheme was developed based on constructs identified in previous literature on implementation. Additional codes were generated deductively. Related constructs among factors were identified by consensus and collapsed under the general categories. Studies that described the extent to which programs or innovations were sustained were also categorized and summarized.

Results

Although "sustainability" was the term most commonly used in the literature to refer to what happened after initial implementation, not all the studies that were reviewed actually presented working definitions of the term. Most study designs were retrospective and naturalistic. Approximately half of the studies relied on self-reports to assess sustainability or elements that influence sustainability. Approximately half employed quantitative methodologies, and the remainder employed qualitative or mixed methodologies. Few studies that investigated sustainability outcomes employed rigorous methods of evaluation (e.g., objective evaluation, judgement of implementation quality or fidelity). Among those that did, a small number reported full sustainment or high fidelity. Very little research has examined the extent, nature, or impact of adaptations to the interventions or programs once implemented. Influences on sustainability included organizational context, capacity, processes, and factors related to the new program or practice themselves.

Conclusions

Clearer definitions and research that is guided by the conceptual literature on sustainability are critical to the development of the research in the area. Further efforts to characterize the phenomenon and the factors that influence it will enhance the quality of future research. Careful consideration must also be given to interactions among influences at multiple levels, as well as issues such as fidelity, modification, and changes in implementation over time. While prospective and experimental designs are needed, there is also an important role for qualitative research in efforts to understand the phenomenon, refine hypotheses, and develop strategies to promote sustainment.     

Modeling technology innovation: How science, engineering, and industry methods can combine to generate beneficial socioeconomic impacts

ABSTRACT: BACKGROUND: Government-sponsored science, technology, and innovation (STI) programs support the socioeconomic aspects of public policies, in addition to expanding the knowledge base. For example, beneficial healthcare services and devices are expected to result from investments in research and development (R&D) programs, which assume a causal link to commercial innovation. Such programs are increasingly held accountable for evidence of impact--that is, innovative goods and services resulting from R&D activity. However, the absence of comprehensive models and metrics skews evidence gathering toward bibliometrics about research outputs (published discoveries), with less focus on transfer metrics about development outputs (patented prototypes) and almost none on econometrics related to production outputs (commercial innovations). This disparity is particularly problematic for the expressed intent of such programs, as most measurable socioeconomic benefits result from the last category of outputs. METHODS: This paper proposes a conceptual framework integrating all three knowledge-generating methods into a logic model, useful for planning, obtaining, and measuring the intended beneficial impacts through the implementation of knowledge in practice. Additionally, the integration of the Context-Input-Process-Product (CIPP) model of evaluation proactively builds relevance into STI policies and programs while sustaining rigor. RESULTS: The resulting logic model framework explicitly traces the progress of knowledge from inputs, following it through the three knowledge-generating processes and their respective knowledge outputs (discovery, invention, innovation), as it generates the intended sociobeneficial impacts. It is a hybrid model for generating technology-based innovations, where best practices in new product development merge with a widely accepted knowledgetranslation approach. Given the emphasis on evidence-based practice in the medical and health fields and "bench to bedside" expectations for knowledge transfer, sponsors and grantees alike should find the model useful for planning, implementing, and evaluating innovation processes. CONCLUSIONS: High-cost/high-risk industries like healthcare require the market deployment of technologybased innovations to improve domestic society in a global economy. An appropriate balance of relevance and rigor in research, development, and production is crucial to optimize the return on public investment in such programs. The technology-innovation process needs a comprehensive operational model to effectively allocate public funds and thereby deliberately and systematically accomplish socioeconomic benefits.     

The demonstrationin vivo of more than one form ofP fr

Summary Phototransformation studies of pumpkin phytochromein vivo indicate two populations, a slow and a fast one. The ratio between the two populations can be altered by different light-dark-pretreatments. The destruction kinetics ofP _fr also show a deviation from a first order curve which indicates the existence of two populations ofP _fr with respect to decay. No significantP _fr P _r dark reversion could be detected. Two models are discussed, which could explain the shape of the destruction kinetics observed and the different ratios of the two populations obtained from phototransformation measurements.     

Like one of the family: race,ethnicity, and the paradox of US national identity

The tensions between individual rights promised to US citizens and group discrimination targeted against African Americans and similar racial/ethnic groups constitute one enduring paradox of US society. This essay examines this paradox by exploring how a gendered family rhetoric contributes to understandings of race and US national identity. Using African American women's experiences as a touchstone for analysis, the article suggests that African American women's treatment as second-class citizens reflects a belief that they are 'like one of the family', that is, legally part of the US nation-state, but simultaneously subordinated within it. To investigate these relationships, the article examines 1) how intersecting social hierarchies of race and ethnicity foster racialized understandings of US national identity; 2) how the gendered rhetoric of the American family ideal naturalizes and normalizes social hierarchies; and 3) how gendered family rhetoric fosters racialized constructions of US national identity as a large national family.     

The secotioid form of Lentinus tigrinus: genetics and development of a fungal morphological innovation

Secotioid fungi resemble gasteromycetes, but are presumably closely related to agaricoid fungi. Lentinus tigrinus is a wood-decaying mushroom that has both a secotioid and an agaricoid form. We examined ontogeny and heritability of the secotioid phenotype in L. tigrinus with a combination of formal genetic crosses, scanning electron microscopy, and macroscopic observation of cultured sporocarps. For F1 analysis, we crossed single-spore isolates (SSIs) representing four mating types derived from a secotioid dikaryon and four mating types from an agaricoid dikaryon. All F1 sporocarps had typical agaricoid morphology. For F2 analysis, 200 SSIs from one F1 sporocarp and 100 SSIs from another F1 sporocarp were backcrossed to tester SSIs from sporocarps produced by the parental secotioid dikaryon. Ratios of secotioid to agaricoid dikaryons thus produced were 47:49 and 84:109, which confirms previous reports that the secotioid phenotype is conferred by a recessive allele at a single locus (χ² = 0.0417, P > 0.05, χ² = 3.2383, P > 0.05, respectively). Early ontogeny of the secotioid form is indistinguishable from that of the agaricoid form. Later, the hymenophore is obscured by a weft of hyphae that proliferates from the margins of the developing lamellae. Longevity of the sporocarps and rate and duration of sporocarp growth are approximately equal in the secotioid and agaricoid forms. Developmental evolution of the secotioid form is interpreted as an example of von Baerian differentiation, rather than paedomorphosis, which has been implicated in evolution of other secotioid taxa.     

Imprinting: focusing on the center

Recent studies have focused on the identification of imprinting centers and on the elucidation of the mechanisms by which they control imprinting. These studies begin to shed light on the means by which imprinting marks are established in the gametes and on the various molecular strategies utilized to execute differential expression of the two parental alleles.     

Seed dormancy and ABA signaling: The breakthrough goes on

The seed is an important organ in higher plants, it is an important organ for plant survival and species dispersion. The transition between seed dormancy and germination represents a critical stage in the plant life cycle and it is an important ecological and commercial trait. A dynamic balance of synthesis and catabolism of two antagonistic hormones, abscisic acid (ABA) and giberellins (GAs), controls the equilibrium between seed dormancy and germination. Embryonic ABA plays a central role in induction and maintenance of seed dormancy and also inhibits the transition from embryonic to germination growth. Therefore, the ABA metabolism must be highly regulated at both temporal and spatial levels during phase of dessication tolerance. On the other hand, the ABA levels do not depend exclusively on the seeds because sometimes it becomes a strong sink and imports it from the roots and rhizosphere through the xylem and/or phloem. These events are discussed in depth here. Likewise, the role of some recently characterized genes belonging to seeds of woody species and related to ABA signaling are also included. Finally, although four possible ABA receptors have been reported, not much is known about how they mediate ABA signaling transduction. However, new publications seem to show that almost all these receptors lack several properties to consider them as such.Key words: ABA/GA balance, ABA in woody plants, ABA-receptors, biosynthetic ABA mutants, rhizosphere ABA, seed dormancy     

e-Health in cardiology: How to cure the infarcted innovation implementation

Netherlands Heart Journal -     

The antibody paradox: Trying on a pair of genes

Rodney Porter's separation of antibody molecules into Fab and Fc fragments engendered the notion that a single antibody polypeptide chain might be coded by two or more genes. This concept profoundly influenced the development of molecular immunology over the past 25 years. Our current knowledge of antibody gene organization has enabled investigators to recombine antibody genes to create 'chimeric' antibodies with a number of potentially useful applications.     

The Levinthal paradox of the interactome

The central biological question of the 21st century is: how does a viable cell emerge from the bewildering combinatorial complexity of its molecular components? Here, we estimate the combinatorics of self-assembling the protein constituents of a yeast cell, a number so vast that the functional interactome could only have emerged by iterative hierarchic assembly of its component sub-assemblies. A protein can undergo both reversible denaturation and hierarchic self-assembly spontaneously, but a functioning interactome must expend energy to achieve viability. Consequently, it is implausible that a completely “denatured” cell could be reversibly renatured spontaneously, like a protein. Instead, new cells are generated by the division of pre-existing cells, an unbroken chain of renewal tracking back through contingent conditions and evolving responses to the origin of life on the prebiotic earth. We surmise that this non-deterministic temporal continuum could not be reconstructed de novo under present conditions.     

Implementing the Habitats Directive: How science can support decision making

The overall goal of the Habitats Directive is to maintain or restore natural habitats and species in a favourable conservation status. An important role in the implementation process is assigned to science. For three core elements, defining the favourable conservation status, development of best practice measures, and monitoring of the conservation status, we outline how science can support decision making. To do so, we use experiences from the ongoing process in Flanders (northern Belgium). First, when determining the favourable conservation status, information on reference values are embedded in a specifically developed calibration model where thresholds on range, area, and quality are set for habitats. Subsequently, socio-economical requirements are taken into consideration, without compromising the favourable conservation status. When it comes to conducting measures, science adds to the knowledge on developing and optimizing cost-effective conservation and restoration management measures. Finally, monitoring of the conservation status will be based on the principle of statistically sound methodologies, enabling the identification of reliability in the assessments made. For habitats, information on area will be gathered through a surface-covering mapping, while quality will be assessed via a sample-oriented monitoring scheme. For species, maximal collaboration with non-governmental organisations will be undertaken, with scientific support on data recording and processing. Overall, the obtained insights will help policy makers to define the framework and set priorities, take the appropriate measures, and keep a finger on the pulse through monitoring data.     

The paradox of the parasites: implications for biological invasion

The enemy-release hypothesis for biological invasions supposes that invasive species may be more successful in their introduced ranges than in their native ranges owing to the absence of coevolved natural enemies. Recent studies supporting this hypothesis have found that introduced plants and animals are less parasitized in their introduced ranges than in their native ranges. Expanding on this theory, I hypothesize that the role of enemy release may differ among the introduction, establishment and spread phases of an invasion. I present a simple model indicating that parasite release is unlikely to greatly affect the chance of establishment in populations with and without an immune subpopulation. The specific numerical relationship between the number of individuals introduced and the chance of establishment depends on a relationship between virulence, here conceptualized as the chance for the extinction of a lineage, and the fraction of the population infected at introduction. These results support the idea of a 'filter effect' in which different biological processes regulate the different phases of an invasion.