The development of vaccines: how the past led to the future

The history of vaccine development has seen many accomplishments, but there are still many diseases that are difficult to target, and new technologies are being brought to bear on them. Past successes have been largely due to elicitation of protective antibodies based on predictions made from the study of animal models, natural infections and seroepidemiology. Those predictions have often been correct, as indicated by the decline of many infections for which vaccines have been made over the past 200 years.     

Eliminating the mystery from the concept of emergence

While some branches of complexity theory are advancing rapidly, the same cannot be said for our understanding of emergence. Despite a complete knowledge of the rules underlying the interactions between the parts of many systems, we are often baffled by their sudden transitions from simple to complex. Here I propose a solution to this conceptual problem. Given that emergence is often the result of many interactions occurring simultaneously in time and space, an ability to intuitively grasp it would require the ability to consciously think in parallel. A simple exercise is used to demonstrate that we do not possess this ability. Our surprise at the behaviour of cellular automata models, and the natural cases of pattern formation they mimic, is then explained from this perspective. This work suggests that the cognitive limitations of the mind can be as significant a barrier to scientific progress as the limitations of our senses.     

The plant Golgi apparatus--going with the flow

The plant Golgi apparatus is composed of many separate stacks of cisternae which are often associated with the endoplasmic reticulum and which in many cell types are motile. In this review, we discuss the latest data on the molecular regulation of Golgi function. The concept of the Golgi as a distinct organelle is challenged and the possibility of a continuum between the endoplasmic reticulum and Golgi is proposed.     

The plant Golgi apparatus--going with the flow

The plant Golgi apparatus is composed of many separate stacks of cisternae which are often associated with the endoplasmic reticulum and which in many cell types are motile. In this review, we discuss the latest data on the molecular regulation of Golgi function. The concept of the Golgi as a distinct organelle is challenged and the possibility of a continuum between the endoplasmic reticulum and Golgi is proposed.     

Strategies for the preparation of homogenous glycoproteins

The majority of human proteins are glycosylated, and many of them are known to be involved in important biological processes. This class of proteins is often expressed as a heterogeneous mixture of glycoforms, rendering the isolation of individual species for various studies a difficult task. Recent advances in the development of glycoprotein synthesis have provided promising strategies, which include enzymatic, chemical and in vivo suppressor tRNA methods to obtain homogenous products. Nevertheless, there are many remaining challenges to overcome in both the chemical and biochemical approaches to efficiently obtain homogenous glycoproteins for glycobiology research and for the production of pharmaceutical products.     

The role of primary cilia in the development and disease of the retina

The normal development and function of photoreceptors is essential for eye health and visual acuity in vertebrates. Mutations in genes encoding proteins involved in photoreceptor development and function are associated with a suite of inherited retinal dystrophies, often as part of complex multi-organ syndromic conditions. In this review, we focus on the role of the photoreceptor outer segment, a highly modified and specialized primary cilium, in retinal health and disease. We discuss the many defects in the structure and function of the photoreceptor primary cilium that can cause a class of inherited conditions known as ciliopathies, often characterized by retinal dystrophy and degeneration, and highlight the recent insights into disease mechanisms.     

The role of primary cilia in the development and disease of the retina

The normal development and function of photoreceptors is essential for eye health and visual acuity in vertebrates. Mutations in genes encoding proteins involved in photoreceptor development and function are associated with a suite of inherited retinal dystrophies, often as part of complex multi-organ syndromic conditions. In this review, we focus on the role of the photoreceptor outer segment, a highly modified and specialized primary cilium, in retinal health and disease. We discuss the many defects in the structure and function of the photoreceptor primary cilium that can cause a class of inherited conditions known as ciliopathies, often characterized by retinal dystrophy and degeneration, and highlight the recent insights into disease mechanisms.     

Expression and function of the insulin receptor substrate proteins in cancer

The Insulin Receptor Substrate (IRS) proteins are cytoplasmic adaptor proteins that function as essential signaling intermediates downstream of activated cell surface receptors, many of which have been implicated in cancer. The IRS proteins do not contain any intrinsic kinase activity, but rather serve as scaffolds to organize signaling complexes and initiate intracellular signaling pathways. As common intermediates of multiple receptors that can influence tumor progression, the IRS proteins are positioned to play a pivotal role in regulating the response of tumor cells to many different microenvironmental stimuli. Limited studies on IRS expression in human tumors and studies on IRS function in human tumor cell lines and in mouse models have provided clues to the potential function of these adaptor proteins in human cancer. A general theme arises from these studies; IRS-1 and IRS-4 are most often associated with tumor growth and proliferation and IRS-2 is most often associated with tumor motility and invasion. In this review, we discuss the mechanisms by which IRS expression and function are regulated and how the IRS proteins contribute to tumor initiation and progression.     

Domains in proteins and proteoglycans of the extracellular matrix with functions in assembly and cellular activities

Most proteins of the extracellular matrix (ECM), such as the glycoproteins, collagens and proteoglycans, consist of many structurally autonomous domains that are often functionally distinct. Consequently these proteins are designated as mosaic proteins. Related domains are often found in several different ECM proteins. Domains which are of importance for assembly have been identified by fragmentation and other approaches. Triple-stranded coiled-coil domains in laminin and probably also in tenascin and thrombospondin are responsible for chain selection, a process which may be important for the formation of tissue specific isoforms. Globular domains at the C-terminus of collagenous domains are essential for the registration of the three chains and triple-helix formation. Fibrillar assemblies of these triple helices with constituent globular domains serve important assembly functions in many collagens including collagens IV and VI. Many other domains with more specialized functions in assembly have been identified in laminin, fibronectin and other ECM proteins. Cys-rich domains with either distant or close homology with epidermal growth factor are repeated manifold in rod-like regions of a number of ECM proteins including laminin, tenascin and thrombospondin. They may serve as spacer elements but as suggested for laminin some domains of this type may also function as signals for cellular growth and differentiation. Another important cellular function common to many ECM proteins is cell attachment. Several cell attachment sites have been localized in structurally unrelated domains of the same or of different ECM proteins.     

Common structural motifs in proteins of the extracellular matrix

Proteins of the extracellular matrix are composed of many structurally and often functionally different autonomous domains which frequently occur as modular units in several different extracellular matrix proteins, but also in proteins of different origin. Some domains serve related assembly functions in different proteins but for domains involved in cell attachment and other cellular activities only a few generalizations are possible.     

Kragge-woodlands in the Netherlands as a new community-type within the Alnion glutinosae

In the low-lying parts of The Netherlands peat-cutting in the past resulted in many large and small lakes. The larger ones were often reclaimed and turned into arable land. In smaller ones a process of secondary succession led to the establishment of reed and sedge fens. Due to changes in the management many of the still existing fens have been left over to natural developments over the last decades. Here succession rapidly led to woodland communities. These woodlands are initially often dominated by Salix species, soon followed by Alnus glutinosa and Betula pubescens. In species composition these young woodlands are closely related to the Carici elongatae-Alnetum glutinosae. There are, however, considerable differences in species composition. This woodland type as found in the western parts of The Netherlands was also recognized in relevés from Belgium, western Germany and Norfolk in the UK. As it also differs in ecological conditions from the brooks and rivulets accompanying forms of the Alnion glutinosae elsewhere in western Europe, it is here proposed to treat these communities as a separate community-type within the Alnion glutinosae.     

The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation

Ubiquitylation (also known as ubiquitination) regulates essentially all of the intracellular processes in eukaryotes through highly specific modification of numerous cellular proteins, which is often tightly regulated in a spatial and temporal manner. Although most often associated with proteasomal degradation, ubiquitylation frequently serves non-proteolytic functions. In light of its central roles in cellular regulation, it has not been surprising to find that many of the components of the ubiquitin system itself are regulated by ubiquitylation. This observation has broad implications for pathophysiology.     

The genetics of the protein 4.1 family: organizers of the membrane and cytoskeleton

Protein 4.1 (also called band 4.1 or simply 4.1) was originally identified as an abundant protein of the human erythrocyte, in which it stabilizes the spectrin/actin cytoskeleton. The protein and its relatives have since been found in many cell types of metazoan organisms and they are often concentrated in the nucleus, as well as in cell-cell junctions. They form multimolecular complexes with transmembrane and membrane-associated proteins, and these complexes may be important for both structural stability and signal transduction at sites of cell contact.     

Identification of functionally distinct regions that mediate biological activity of the protein kinase a homolog Tpk2

Kinases regulate key signaling processes that are increasingly implicated in development and disease. Kinase modulators have become important therapeutic tools and often target catalytic domains that are among the most structurally and functionally conserved regions of these enzymes. Such therapies lose efficacy as mutations conferring resistance arise. Because interactions between distinct and often distant regions of kinases can be critical, we took an unbiased genetic approach to identify sites within the protein kinase A homolog Tpk2 that contribute to its biological activity. Because many of these map outside the conserved core, this approach should be broadly useful in identifying new, more kinase-specific therapeutic targets.     

Vegetation complexity and the dynamics of modelled grazing systems

Summary The dynamics of a one-herbivore-many-plants system can often be summarised by a one-herbivore-one-plant model. The many plants are modelled as if they were a single plant species whose intrinsic rate of increase equals the harmonic mean of the specific intrinsic rates. The relationship between the parameters of the simple and complex system is given, and exceptions, nuances and stability properties are explored.     

侵染细胞质膜附近小泡的来源及其作用

箭舌豌豆根瘤幼龄侵染细胞的壁和质膜比较光滑,成熟侵染细胞与此不同,不仅细胞壁厚薄均,有较多的胞间连丝,而且质膜常常内陷形成各种突起,然后离质膜形成小泡。这些位于质膜附近的小泡体积较小,多呈圆形,既可单独存在,也可多个聚在一起。在向细胞中央移动中,有的小泡靠近细胞质膜,甚至与细菌周期融合,有的小泡不民附近的小液泡融合变为较大液泡,并常用降解程度不同的细菌位于其中,在衰老侵染细胞中,细胞壁附近有小泡,     

Insects as a piece of the puzzle to mitigate global problems: an opportunity for ecologists

Although scientists have studied and touted the importance of insects to many ecosystem services for decades, insects and insect science are often poorly perceived by the public and by policy makers. Because insects do have important influences on many ecosystem services, they have even greater potential to be used to solve some anthropogenically-caused current global problems. We give several examples where insects are currently being used, or are being considered for future use, as a part of the solution to a global problem, including their potential roles as a part of the solution to sustainable fuel and food systems, deforestation and other environmental degradation, and global inequities. Ecologists have an important role to play in assessing how many of the proposed uses of insects will alter ecological processes and ecosystem services, or how their use may be effectively implemented.     

Carl Friedrich Naumann and the introduction of enantio terminology: a review and analysis on the 150th anniversary

Enantiomorphism and enantiomorphous were the first enantio-based terms, introduced 150 years ago, by Carl Friedrich Naumann, a German crystallographer, to refer to non-superposable mirror-image crystals. The terminology was not adopted by Pasteur, the discoverer of molecular chirality, and was not embraced at first in the stereochemical context, until it was accepted in 1877 by Van't Hoff in the German edition of his proposal for the tetrahedral asymmetric carbon atom. In the 1890s the use of enantio terms began to spread in the research literature, and many new derivatives of Naumann's original two terms were subsequently introduced. Problems in the usage of some of the terms are often found in the literature, e.g., enantiomorphism is sometimes confused with chirality; enantiomeric is often misused; the meaning of some of the many derived terms, e.g., enantiosymmetric, enantioposition, etc., is unclear. All in all, Naumann should be remembered as the creator of essential terminology in the realm of chirality.     

On the ultrastructure of resting cambium of Fagus sylvatica L.

Summary Cells of the resting cambium contain strands of smooth endoplasmic reticulum which is often arranged as a series of parallel membranes. Single membrane bound bodies of different types including lipid droplets, protein bodies, many different intermediate forms, and structures that are empty and vacuolelike are present. The possibility that vacuoles are formed by the progressive dissolution of stored lipids and protein, during the onset of cambial activity, is suggested.     

The complexity in regulating the expression of tenascins

The tenascins are a growing family of extracellular matrix proteins of typical multidomain structure. The prototype to be discovered was tenascin-C. It shows a highly regulated expression pattern during embryonic development and is often transiently associated with morphogenetic tissue interactions during organogenesis. In the adult organism reexpression of tenascin-C occurs in tumors and many other pathological conditions. Tenascin-C expression can be regulated by many different growth factors and hormones. Furthermore, mechanical strain exerted by fibroblasts seems to induce the expression of tenascin-C. This could represent a mechanism of translating mechanical forces into protein patterns, a step of potential relevance in the organization of embryogenesis. Tenascin-C as well as tenascin-R are believed to counteract the cell adhesion and spreading activity of fibronectin, thereby facilitating cell movement.