Prolegomenon to a history of paleoanthropology: The study of human origins as a scientific enterprise. Part 2. Eighteenth to the twentieth century

Modern scientific theories of human origins can be traced directly back to the discoveries, arguments, and theories of the seventeenth century. But as we have seen in the first part of this paper, a great many critical steps had been taken, ideas proposed, and discoveries made long before this. The scientific advances of the sixteenth and seventeenth centuries owed much to ancient science, while still retaining many aspects of the medieval Christian world view. Yet both science and Christianity changed significantly as a result of the Renaissance, the Protestant Reformation, the Scientific Revolution, the voyages of exploration, and the changes wrought on European society as a result of industrialization. The question of human origins was directly affected by the archeological study of prehistoric ruins, new geological theories, the study of fossils, the discovery of “savage” peoples living in the New World, and the comparison of prehistoric stone implements from Europe with those collected in the New World. This proliferation of new discoveries, new theories, and the emergence of completely new scientific disciplines in the seventeenth century laid the foundation for the dramatic new discoveries and theories that came over the next three centuries.     

Unremitting progresses for phosphoprotein synthesis

Phosphorylation, one of the important protein post-translational modifications, is involved in many essential cellular processes. Site-specifical and homogeneous phosphoproteins can be used as probes for elucidating the protein phosphorylation network and as potential therapeutics for interfering their involved biological events. However, the generation of phosphoproteins has been challenging owing to the limitation of chemical synthesis and protein expression systems. Despite the pioneering discoveries in phosphoprotein synthesis, over the past decade, great progresses in this field have also been made to promote the biofunctional exploration of protein phosphorylation largely. Therefore, in this review, we mainly summarize recent advances in phosphoprotein synthesis, which includes five sections: 1) synthesis of the nonhydrolyzable phosphorylated amino acid mimetic building blocks, 2) chemical total and semisynthesis strategy, 3) in-cell and in vitro genetic code expansion strategy, 4) the late-stage modification strategy, 5) nonoxygen phosphoprotein synthesis.     

Important discoveries from analysing bacterial phenotypes

The ability to test hundreds to thousands of cellular phenotypes in a single experiment has opened up new avenues of investigation and exploration and led to important discoveries in very diverse applications of microbiological research and development. The information provided by global phenotyping is complementary to, and often more easily interpretable than information provided by global molecular analytical methods such as gene chips and proteomics. This report summarizes advances presented by scientists brought together to share their experiences and knowledge gained with high-throughput phenotyping.     

Medical perspectives of adults and embryonic stem cells

In the last 30 years, allogeneic bone marrow transplantation has become the treatment of choice for many hematologic malignancies or inherited disorders and a number of changes have been registered in terms of long-term survival rate of transplanted patients as well as of available sources of hematopoietic stem cell (HSC). In parallel to the publication of better results in HSC transplantation, several recent discoveries have opened a scientific and ethical debate on the therapeutical potential of stem cells isolated from adult or embryonic tissues. One of the major discoveries in this field is the capacity of bone marrow-derived stem cells to treat a genetic liver disease in a mouse model, thus justifying the concept of transdifferentiation of adult stem cell and raising hopes on its possible therapeutical applications. We have tried here to summarise the advances in this field and to discuss the limits of these biological data.     

Potential applications of DNA methylation testing technology in female tumors and screening methods

DNA methylation is a common epigenetic modification, and the current commonly used methods for DNA methylation detection include methylation-specific PCR, methylation-sensitive restriction endonuclease-PCR, and methylation-specific sequencing. DNA methylation plays an important role in genomic and epigenomic studies, and combining DNA methylation with other epigenetic modifications, such as histone modifications, may lead to better DNA methylation. DNA methylation also plays an important role in the development of disease, and analyzing changes in individual DNA methylation patterns can provide individualized diagnostic and therapeutic solutions. Liquid biopsy techniques are also increasingly well established in clinical practice and may provide new methods for early cancer screening. It is important to find new screening methods that are easy to perform, minimally invasive, patient-friendly, and affordable. DNA methylation mechanisms are thought to have an important role in cancer and have potential applications in the diagnosis and treatment of female tumors. This review discussed early detection targets and screening methods for common female tumors such as breast, ovarian, and cervical cancers and discussed advances in the study of DNA methylation in these tumors. Although existing screening, diagnostic, and treatment modalities exist, the high morbidity and mortality rates of these tumors remain challenging.     

Emerging features of mRNA decay in bacteria

The problem of mRNA decay in E. coli has recently seen exciting progress, with the discoveries that key degradation enzymes are associated together in a high molecular weight degradosome and that polyadenylation promotes decay. Recent advances make it clear that mRNA decay in bacteria is far more interesting enzymatically than might have been predicted. In-depth study of specific mRNAs has revealed multiple pathways for degradation. Which pathway a given mRNA follows appears to depend in large part on the location of the initiating endonucleolytic cleavage within the mRNA. During the steps of mRNA decay, stable RNA structures pose formidable barriers to the 3' --> 5' exonucleases. However, polyadenylation is now emerging as a process that plays an important role in maintaining the momentum of exonucleolytic degradation by adding single-stranded extensions to the 3' ends of mRNAs and their decay intermediates, thereby facilitating further exonuclease digestion.     

The impact of Arabidopsis on human health: diversifying our portfolio

Studies of the model plant Arabidopsis thaliana may seem to have little impact on advances in medical research, yet a survey of the scientific literature shows that this is a misconception. Many discoveries with direct relevance to human health and disease have been elaborated using Arabidopsis, and several processes important to human biology are more easily studied in this versatile model plant.     

The emergence of regulated histone proteolysis

Proliferating cells need to synthesize large amounts of histones to rapidly package nascent DNA into nucleosomes. This is a challenging task for cells because changes in rates of DNA synthesis lead to an accumulation of excess histones, which interfere with many aspects of DNA metabolism. In addition, cells need to ensure that histone variants are incorporated at the correct chromosomal location. Recent discoveries have highlighted the importance of regulated histone proteolysis in preventing both the accumulation of excess histones and the mis-incorporation of histone variants at inappropriate loci.     

Mechanisms of fidelity in pre-mRNA splicing

The pre-mRNA splicing machinery consists of five small nuclear RNAs (U1, U2, U4, U5 and U6) and more than fifty proteins. Over the past year, important advances have been made in understanding how these factors function to achieve fidelity in splicing. Of particular note were the discoveries that the splicing factor U2AF(35) recognizes the AG dinucleotide at the 3' splice site early in spliceosome assembly, that a DEAD-box ATPase, Prp28, triggers specific rearrangements of the spliceosome, and that the splicing factor hSlu7 functions in the fidelity of AG choice during catalytic step II of splicing.     

Nucleosome structural studies

Chromatin plays a fundamental role in eukaryotic genomic regulation, and the increasing awareness of the importance of epigenetic processes in human health and disease emphasizes the need for understanding the structure and function of the nucleosome. Recent advances in chromatin structural studies, including the first structures of nucleosomes containing the Widom 601 sequence and the structure of a chromatin protein-nucleosome assembly, have provided new insight into stretching of nucleosomal DNA, nucleosome positioning, binding of metal ions, drugs and therapeutic candidates to nucleosomes, and nucleosome recognition by nuclear proteins. These discoveries ensure promising future prospects for unravelling structural attributes of chromatin.     

Structure and design of broadly-neutralizing antibodies against HIV

Since the discovery more than 30 years ago of human immunodeficiency virus (HIV) as the causative agent of the deadly disease, acquired immune deficiency disease (AIDS), there have been no efficient vaccines against the virus. For the infection of the virus, the HIV surface glycoprotein gp120 first recognizes the CD4 receptor on the target helper T-cell, which initiates HIV fusion with the target cell and, if unchecked, leads to destruction of the patient's immune system. Despite the difficulty of developing appropriate immune responses in HIV-infected individuals, patient sera often contain antibodies that have broad neutralization activity, indicating the possibility of immunological treatment and prevention. Recently, through extensive structural studies of neutralizing antibodies of HIV in complex with gp120, the critical mechanisms of broad neutralization against HIV have been elucidated. Based on these discoveries, the structure-aided designs of antibodies and novel scaffolds were performed to create extremely potent neutralizing antibodies against HIV. These new discoveries and advances shed light on the road to development of efficient immunological therapies against AIDS.     

Collections‐based science in the 21st Century

Discoveries from collections‐based science change the way we perceive ourselves, our environment, and our place in the universe. The 18^th Century saw the beginning of formal classification with Linnaeus proposing a system to classify all of life. The 19^th Century ushered in the age of exploration as naturalists undertook large‐scale collecting expeditions leading to major scientific advances (the founding of Physical Geography, Meteorology, Ecology, Biogeography, and Evolution) and challenging long held beliefs about nature. In the 20^th Century collections were central to paradigm shifts, including theories of Continental Drift and Phylogenetic Systematics; Molecular Phylogenetics added testable hypotheses, and computerized specimen records gave rise to the field of Biodiversity. In the first 15 years of the 21^st Century we have seen tree‐thinking pervade the life sciences, leading to the emergence of Evolutionary Medicine, Evolutionary Ecology, and new Food Safety methods. More advances are on the way: (i) Open access to large amounts of specimen data & images, (ii) Linking of collections and climate data to phylogenies on a global scale, and (iii) Production of vast quantities of genomic data allowing us to address big evolutionary questions. As a result of collections‐based science people see themselves not as the center of all things but rather as part of a complex universe. It is essential that we integrate new discoveries with knowledge from the past (e.g., collections) in order to understand this planet we all inhabit. To ensure the health of collections‐based science we must come together and plan for the future.     

Current Risk Assessment Approaches to Address Petroleum Hydrocarbon Mixtures in Soils

Products that exist as complex chemical mixtures, such as petroleum products, are used widely in commerce, and accidental releases of these products into the environment have led to thousands of contaminated sites nationwide. Developing sound estimates of potential health risks posed by these sites is challenging because of the composition of these products, their behavior in the environment, and the paucity of toxicological information available for many of the component compounds. In developing risk based cleanup goals for petroleum products and other complex commercial mixtures, the simplest approach is to assume that the entire mixture is comprised of the most toxic constituent, particularly when standards are unavailable for each of the components of the mixture. This approach often results in excessively conservative regulatory goals; thus, methods are needed which more accurately reflect the actual composition and aggregate toxicity of the mixture. Three approaches for the development of risk based soil cleanup goals for petroleum hydrocarbon mixtures are identified and illustrated using mineral spirits as an example. For the examples presented, estimates of the proportions of components in mineral spirits were based on virgin, unused product; however, detailed component analysis of weathered samples may permit the calculation of more precise, site specific cleanup goals.     

Th17 cells in immunity to Candida albicans

Our understanding of immunity to fungal pathogens has advanced considerably in recent years. Particularly significant have been the parallel discoveries in the C-type lectin receptor family and the Th effector arms of immunity, especially Th17 cells and their signature cytokine, IL-17. Many of these studies have focused on the most common human fungal pathogen, Candida albicans, which is typically a commensal microbe in healthy individuals but causes various disease manifestations in immunocompromised hosts, ranging from mild mucosal infections to lethal disseminated disease. Here, we discuss emerging fundamental discoveries with C.?albicans that have informed our overall molecular understanding of fungal immunity. In particular, we focus on the importance of pattern recognition receptor-mediated fungal recognition and subsequent IL-17 responses in host defense against mucosal candidiasis. In light of these recent advances, we also discuss the implications for anticytokine biologic therapy and vaccine development.     

Hypertension in Pregnancy: The Use of Ultrasound

Great advances in ultrasound instrumentation have enabled the physician to delineate subtle intrauterine changes. Not only can specific measurements of the fetal body be obtained but tissue textures within fetal organs can be appreciated. The perinatologist is constantly searching for ways to learn more about the fetus, and ultrasound has clearly become a major implement in this search. The following discussion will focus on information made available by ultrasound for aid in the modern management of hypertension, one of the most challenging conditions complicating pregnancy.     

土壤与水体有机污染的生物修复及其应用研究进展

系统论述了土壤、水有机污染物的主要来源、特点、有机污染生物修复的概念、应用范围、成功实例与研究进展等,特别是对于泄漏石油污染的生物成功降解方法、效果,土壤中易爆炸物如ＴＮＴ、废水中有机污染的有效降解等,评价了生物修复所具有突出优势,对有机、无机污染物降解过程中植物、微生物筛选、基因修饰、分子克隆与转基因植物方面近年来所取得的惊人成果与突破性进展,无疑正激励着人们开拓更大的应用范围。预计不久的将来,更多具有环境净化与生物修复功能的商业性综合技术与高效性工程生物将投入应用。     

Leech locomotion: swimming, crawling, and decisions

Research on the neuronal control of locomotion in leeches spans almost four decades. Recent advances reviewed here include discoveries that: (1) interactions between multiple hormones modulate initiation of swimming; (2) stretch receptors associated with longitudinal muscles interact with the central oscillator circuit via electrical junctions; (3) intersegmental interactions, according to theoretical analyses, must be relatively weak compared to oscillator interactions within ganglia; and (4) multiple interacting neurons control the expression of alternative modes of locomotion. The innovative techniques that facilitated these advances include optical recording of membrane potential changes, simultaneous intracellular injection of high and low molecular weight fluorescent dyes, and detailed modeling via an input-output systems engineering approach.     

Some health aspects of high-energy society.

The intensive use of inanimate energy in industrialized or high-energy society has subsidized research, development, and higher education and has brought about changes in nutrition and life-style that have led to great advances in public health and medicine. The emergence of high-energy society, however, has brought with it a new set of health problems, within which the direct effects of measurable pollution may turn out to be more easily dealt with than some of the indirect and hard-to-calculate consequences of high energy use. High-energy society is critically dependent on energy-intensive transport systems, and these systems in turn are dependent upon a continual supply of petroleum products. In the short-term, the aorta of any industrialized nation is its petroleum-supply network. In the longer run, high-energy society faces the depletion and exhaustion of all the nonrenewable resources on which it has fed. Even if technology provides adequate substitute energy systems, high-energy society may deteriorate socially from inability to cope with affluence.