Advancements and future directions in enzyme technology for biomass conversion

Enzymatic hydrolysis of pre-treated lignocellulosic biomass is an ideal alternative to acid hydrolysis for bio-ethanol production, limited primarily by pre-treatment requirements and economic considerations arising from enzyme production costs and specific activities. The quest for cheaper and better enzymes has prompted years of bio-prospecting, strain optimization through genetic engineering, enzyme characterization for simple and complex lignocellulosic feedstock, and the development of pre-treatment strategies to mitigate inhibitory effects. The recent shift to systematic characterizations of de novo mixtures of purified proteins is a promising indicator of maturation within this field of study, facilitating progression towards feedstock assay-based rapid enzyme mixture optimization. It is imperative that international standards be developed to enable meaningful comparisons between these studies and the construction of a database of enzymatic activities and kinetics, aspects of which are explored here-in. Complementary efforts to improve the economic viability of enzymatic hydrolysis through process integration and reactor design are also considered, where membrane-confinement shows significant promise despite the associated technological challenges. Significant advancements in enzyme technology towards the economic conversion of lignocellulosic biomass should be expected within the next few years as systematic research in enzyme activities conforms to that of traditional reaction engineering.     

Recent developments and future directions in computational genomics

Computational genomics is a subfield of computational biology that deals with the analysis of entire genome sequences. Transcending the boundaries of classical sequence analysis, computational genomics exploits the inherent properties of entire genomes by modelling them as systems. We review recent developments in the field, discuss in some detail a number of novel approaches that take into account the genomic context and argue that progress will be made by novel knowledge representation and simulation technologies.     

Paleobotany: Recent developments and future research directions

The current state of research in the field of paleobotany is reviewed, with emphasis on those areas that deal with more biological approaches to paleobotany. These would include such subjects as the reproductive biology of fossil plants, pollination biology in selected groups, paleobiochemistry, and information on the interaction of plants with other organisms (plant/animal interactions) and their environment (paleoecology). Also discussed are some of the more recent contributions to our understanding of Precambrian paleobiology and early angiosperm reproduction and evolution. Finally, we offer some speculation on the contributions that various areas of paleobotany may provide in the future.     

Understanding primate communities: Recent developments and future directions

In 1999, the edited volume Primate Communities presented several studies that examined broad‐scale patterns of primate diversity.¹ Similar studies were being conducted on nonprimate taxa; advances in data availability and statistical approaches were allowing scientists to investigate a variety of new questions and to reexamine classical questions in novel ways. While such studies on nonprimate taxa have continued at a steady pace, they have only crept forward for primate species (Fig. 1 ). In the intervening time, the field of macroecology (Box 1) rapidly developed and has resulted in several books 2 - 4 and the establishment of new research institutes. We suggest that examining primate communities, especially in a macroecological context, is an important line of research for our field to embrace and an area where biological anthropologists can provide major contributions. We review the current state of research, describe new datasets and research tools, and suggest future research directions.     

Catumaxomab: Clinical development and future directions

Catumaxomab, a monoclonal bispecific trifunctional antibody, was approved in the european Union in April 2009 for the intraperitoneal treatment of patients with malignant ascites. The marketing authorization holder Fresenius Biotech GmbH developed catumaxomab (Removab^®) together with its partner TRiOn Pharma GmbH, Germany. it is the first substance worldwide with a regulatory label for the treatment of malignant ascites due to epithelial carcinomas. Since the peritoneum is of mesothelial origin and therefore lacks epCAM expression, the intraperitoneal administration of catumaxomab is an attractive targeted immunotherapeutic approach. Catumaxomab is able to destroy epCAM positive tumor cells in the peritoneal cavity known as the main cause of malignant ascites. in addition, catumaxomab is a potential therapeutic option for several primary tumors since the epCAM molecule is expressed on the majority of epithelial carcinomas. This review focuses on the clinical development of catumaxomab and indicates future directions.Key words: catumaxomab, Removab^®, monoclonal antibody, trifunctional, EpCAM, malignant ascites, peritoneal carcinomatosis, immunotherapy     

我国土壤线虫生态学研究进展和展望

土壤线虫生态学主要探讨土壤线虫群落和其周围环境(包括生物和非生物)的相互关系, 包括不同生态系统中土壤线虫群落的分布和结构组成、线虫群落与土壤环境及其他土壤生物之间的相互作用等。本文回顾了我国研究者近年来在土壤线虫生态学研究领域的研究现状, 包括不同生态系统土壤线虫群落的分布、组成和多样性及其影响因素, 土壤线虫群落与全球气候环境变化的关系, 土壤线虫群落的生态功能以及土壤线虫群落生态学分析方法的发展及应用。重点评述近年来我国土壤线虫生态学的发展现状, 同时分析和比较了国内外土壤线虫生态学的发展态势, 提出建设全国范围的监测网络的重要性。未来我国土壤线虫生态学的发展方向应继续加强小尺度下土壤微食物网联通性和大尺度下全球气候变化对土壤线虫群落影响的研究以及加强相关新的研究技术方法的应用。     

Current trends and future directions in flower development research

Flowers, the reproductive structures of the approximately 400 000 extant species of flowering plants, exist in a tremendous range of forms and sizes, mainly due to developmental differences involving the number, arrangement, size and form of the floral organs of which they consist. However, this tremendous diversity is underpinned by a surprisingly robust basic floral structure in which a central group of carpels forms on an axis of determinate growth, almost invariably surrounded by two successive zones containing stamens and perianth organs, respectively. Over the last 25 years, remarkable progress has been achieved in describing the molecular mechanisms that control almost all aspects of flower development, from the phase change that initiates flowering to the final production of fruits and seeds. However, this work has been performed almost exclusively in a small number of eudicot model species, chief among which is Arabidopsis thaliana. Studies of flower development must now be extended to a much wider phylogenetic range of flowering plants and, indeed, to their closest living relatives, the gymnosperms. Studies of further, more wide-ranging models should provide insights that, for various reasons, cannot be obtained by studying the major existing models alone. The use of further models should also help to explain how the first flowering plants evolved from an unknown, although presumably gymnosperm-like ancestor, and rapidly diversified to become the largest major plant group and to dominate the terrestrial flora. The benefits for society of a thorough understanding of flower development are self-evident, as human life depends to a large extent on flowering plants and on the fruits and seeds they produce. In this preface to the Special Issue, we introduce eleven articles on flower development, representing work in both established and further models, including gymnosperms. We also present some of our own views on current trends and future directions of the flower development field.     

The orienting response, and future directions of its development

The orienting response (OR) is a specific behavioral act directed towards extraction of information from the environment. Head and eye movements represent only the tip of the iceberg of internal responses, which includes vascular modifications, EEG changes, and event-related potentials. Two mechanisms of the OR have to be differentiated: voluntary and involuntary. In the event-related potential, such a differentiation is expressed in mismatch negativity (involuntary effect) and processing negativity (voluntary effect). Single unit studies have shown that hippocampal neurones are simulating specific features of the OR as a response to novelty. Repeated presentation of stimuli results in a selective habituation of novelty detectors in hippocampus and of the OR. The trace of a standard stimulus formed at the level of hippocampal neurones matches the features of the standard stimulus and can be called a "neuronal model of the stimulus." The OR is triggered by mismatch between the test stimulus and the elaborated neuronal model, and is activated by verbal instruction, by reinforcement during the initial stage of conditioned reflex elaboration, and by differentiation of signal and non-signal stimuli. A promising new area of practical application of the OR lies in the evaluation of a corridor of optimal functional state for efficient computer-based learning. Registration of the OR and defensive responses can be used for an objective evaluation of the functional state of the student, or, in a wider sense, of the industrial operator. New avenues of OR research are opened by recent techniques that isolate single-trial event related potentials, and their correlation with autonomic and behavioral manifestations of the OR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Optimization protocols and improved strategies of cross-linked enzyme aggregates technology: current development and future challenges

Cross-linked enzyme aggregate (CLEA) technology has been regarded as an effective carrier-free immobilization method. This method is very attractive due to its simplicity and robustness, as well as for the possibility of using the crude enzyme extract and the opportunity to co-immobilize multiple different enzymes. The resulting CLEAs generally exhibit high catalyst productivities, improved storage and operational stability and are easy to recycle. Nowadays, although the technology has been applied to various enzymes, some undesirable properties have limited its further application. To overcome these limitations, novel strategies have been developing in recent years. This mini-review focuses on process optimization, new improved strategies and the latest advances on CLEAs technology.     

Angiotensin‐converting enzyme 2 in the brain: properties and future directions

Angiotensin (Ang)‐converting enzyme (ACE) 2 cleaves Ang‐II into the vasodilator peptide Ang‐(1–7), thus acting as a pivotal element in balancing the local effects of these peptides. ACE2 has been identified in various tissues and is supposed to be a modulator of cardiovascular function. Decreases in ACE2 expression and activity have been reported in models of hypertension, heart failure, atherosclerosis, diabetic nephropathy and others. In addition, the expression level and/or activity are affected by other renin–angiotensin system components (e.g., ACE and AT1 receptors). Local inhibition or global deletion of brain ACE2 induces a reduction in baroreflex sensitivity. Moreover, ACE2‐null mice have been shown to exhibit either blood pressure or cardiac dysfunction phenotypes. On the other hand, over‐expression of ACE2 exerts protective effects in local tissues, including the brain. In this review, we will first summarize the major findings linking ACE2 to cardiovascular function in the periphery then focus on recent discoveries related to ACE2 in the CNS. Finally, we will unveil new tools designed to address the importance of central ACE2 in various diseases, and discuss the potential for this carboxypeptidase as a new target in the treatment of hypertension and other cardiovascular diseases.     

Plant virology in the 21st century in China: Recent advances and future directions

Plant viruses are a group of intracellular pathogens that persistently threaten global food security. Significant advances in plant virology have been achieved by Chinese scientists over the last 20 years, including basic research and technologies for preventing and controlling plant viral diseases. Here, we review these milestones and advances, including the identification of new crop-infecting viruses, dissection of pathogenic mechanisms of multiple viruses, examination of multilayered interac...     

Antiviral peptide engineering for targeting membrane-enveloped viruses: Recent progress and future directions

Membrane-enveloped viruses are a major cause of global health challenges, including recent epidemics and pandemics. This mini-review covers the latest efforts to develop membrane-targeting antiviral peptides that inhibit enveloped viruses by 1) preventing virus-cell fusion or 2) disrupting the viral membrane envelope. The corresponding mechanisms of antiviral activity are discussed along with peptide engineering strategies to modulate membrane-peptide interactions in terms of potency and selectivity. Application examples are presented demonstrating how membrane-targeting antiviral peptides are useful therapeutics and prophylactics in animal models, while a stronger emphasis on biophysical concepts is proposed to refine mechanistic understanding and support potential clinical translation.     

Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions

By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization.     

Recent progress and advanced technology in carbohydrate-based drug development

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Therapeutics for advanced hepatocellular carcinoma: Recent advances,current dilemma,and future directions

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth. In recent years, molecular targeted therapy and immunotherapy have also made great progress, bringing new hope to patients with advanced HCC. In this study, therapeutic advances, current dilemma, and future directions of advanced HCC are reviewed, which might serve as a summary for clinicians and may stimulate future research.     

Therapeutic peptides: Historical perspectives,current development trends,and future directions

Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts. We maintain a comprehensive dataset on peptides that have entered human clinical studies that includes over 150 peptides in active development today. Here we provide an overview of the peptide therapeutic landscape, including historical perspectives, molecular characteristics, regulatory benchmarks, and a therapeutic area breakdown.     

Residual DNA analysis in biologics development: review of measurement and quantitation technologies and future directions

Residual DNA (rDNA) is comprised of deoxyribonucleic acid (DNA) fragments and longer length molecules originating from the host organism that may be present in samples from recombinant biological processes. Although similar in basic structural base pair units, rDNA may exist in different sizes and physical forms. Interest in measuring rDNA in recombinant products is based primarily on demonstration of effective purification during manufacturing, but also on some hypothetical concerns that, in rare cases, depending on the host expression system, some DNA sequences may be potentially infectious or oncogenic (e.g., HIV virus and the Ras oncogene, respectively). Recent studies suggest that a sequence known as long interspersed nucleotide element-1 (LINE-1), widely distributed in the mammalian genome, is active as a retrotransposon that can be transcribed to RNA, reverse-transcribed into DNA and inserts into a new site in genome. This integration process could potentially disrupt critical gene functions or induce tumorigenesis in mammals. Genomic DNA from microbial sources, on the other hand, could add to risk of immunogenicity to the target recombinant protein being expressed, due to the high CpG content and unmethylated DNA sequence. For these and other reasons, it is necessary for manufacturers to show clearance of DNA throughout production processes and to confirm low levels in the final drug substance using an appropriately specific and quantitative analytical method. The heterogeneity of potential rDNA sequences that might be makes the testing of all potential analytes challenging. The most common methodology for rDNA quantitation used currently is real-time polymerase chain reaction (RT-PCR), a robust and proven technology. Like most rDNA quantitation methods, the specificity of RT-PCR is limited by the sequences to which the primers are directed. To address this, primase-based whole genome amplification is introduced herein. This paper will review the recent advancement in rDNA quantitation and recent findings regarding potential risks of immunogenicity, infectivity, and oncogenicity of rDNA.     

Deep learning for reconstructing protein structures from cryo-EM density maps: Recent advances and future directions

Cryo-Electron Microscopy (cryo-EM) has emerged as a key technology to determine the structure of proteins, particularly large protein complexes and assemblies in recent years. A key challenge in cryo-EM data analysis is to automatically reconstruct accurate protein structures from cryo-EM density maps. In this review, we briefly overview various deep learning methods for building protein structures from cryo-EM density maps, analyze their impact, and discuss the challenges of preparing high-quality data sets for training deep learning models. Looking into the future, more advanced deep learning models of effectively integrating cryo-EM data with other sources of complementary data such as protein sequences and AlphaFold-predicted structures need to be developed to further advance the field.     

New advances and future directions in plant polyspermy

Plants have evolved a battery of mechanisms that potentially act as polyspermy barriers. Supernumerary sperm fusion to one egg cell has consequently long remained a hypothetical concept. The recent discovery that polyspermy in flowering plants is not lethal but generates viable triploid plants is a game changer affecting the field of developmental biology, evolution, and plant breeding. The establishment of protocols to artificially induce polyspermy together with the development of a high‐throughput assay to identify and trace polyspermic events in planta now provide powerful tools to unravel mechanisms of polyspermy regulation. These achievements are likely to open new avenues for animal polyspermy research as well, where forward genetic approaches are hampered by the fatal outcome of supernumerary sperm fusion.