Deconstructing membrane traffic

Intracellular movement of proteins and lipids between organelles is usually described in terms of cargo, carriers, traffic and docking, familiar terms that imply parallels to human activities. Over the past century, scientists have been criticized for constructing hypotheses that reflect too much of their current political and cultural values. In this article, concepts of membrane traffic are re-examined to see whether they reflect the cell’s view of the world or our own.     

Deconstructing membrane traffic

Intracellular movement of proteins and lipids between organelles is usually described in terms of cargo, carriers, traffic and docking, familiar terms that imply parallels to human activities. Over the past century, scientists have been criticized for constructing hypotheses that reflect too much of their current political and cultural values. In this article, concepts of membrane traffic are re-examined to see whether they reflect the cell’s view of the world or our own.     

Energetic adaptations: Metabolic control of endocytic membrane traffic

Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.     

The Golgi apparatus: defining the identity of Golgi membranes

The Golgi apparatus is a stack of compartments that serves as a central junction for membrane traffic, with carriers moving through the stack as well as arriving from, and departing toward, many other destinations in the cell. This requires that the different compartments in the Golgi recruit from the cytosol a distinct set of proteins to mediate accurate membrane traffic. This recruitment appears to reflect recognition of small GTPases of the Rab and Arf family, or of lipid species such as PtdIns(4)P and diacylglycerol, which provide a unique "identity" for each compartment. Recent work is starting to reveal the mechanisms by which these labile landmarks are generated in a spatially restricted manner on specific parts of the Golgi.     

Traffic Routes and Signals for the Tonoplast

Tonoplast, the membrane delimiting plant vacuoles, regulates ion, water and nutrient movement between the cytosol and the vacuolar lumen through the activity of its membrane proteins. Correct traffic of proteins from the endoplasmic reticulum (ER) to the tonoplast requires (i) approval by the ER quality control, (ii) motifs for exit from the ER and (iii) motifs that promote sorting to the tonoplast. Recent evidence suggests that this traffic follows different pathways that are protein‐specific and could also reflect vacuole specialization for lytic or storage function. The routes can be distinguished based on their sensitivity to drugs such as brefeldin A and C834 as well as using mutant plants that are defective in adaptor proteins of vesicle coats, or dominant‐negative mutants of Rab GTPases.     

Collective human mobility pattern from taxi trips in urban area

We analyze the passengers' traffic pattern for 1.58 million taxi trips of Shanghai, China. By employing the non-negative matrix factorization and optimization methods, we find that, people travel on workdays mainly for three purposes: commuting between home and workplace, traveling from workplace to workplace, and others such as leisure activities. Therefore, traffic flow in one area or between any pair of locations can be approximated by a linear combination of three basis flows, corresponding to the three purposes respectively. We name the coefficients in the linear combination as traffic powers, each of which indicates the strength of each basis flow. The traffic powers on different days are typically different even for the same location, due to the uncertainty of the human motion. Therefore, we provide a probability distribution function for the relative deviation of the traffic power. This distribution function is in terms of a series of functions for normalized binomial distributions. It can be well explained by statistical theories and is verified by empirical data. These findings are applicable in predicting the road traffic, tracing the traffic pattern and diagnosing the traffic related abnormal events. These results can also be used to infer land uses of urban area quite parsimoniously.     

A decentralized clustering scheme for transparent mode devices

Clustering multiple devices to form a single powerful device is a common method for improving performance. Most designs of the clustering schemes in the current literature are deploying a traffic splitter in front of devices in the cluster which acts as a centralized job dispatcher splitting workloads to backend devices. In this paper, we propose a decentralized clustering scheme, with no traffic splitter deployed, as an alternative solution on building a cluster system for those devices configured in transparent mode, such as bandwidth controllers, NIPSs, and traffic monitors. Devices in the cluster process the network traffic in parallel in a decentralized manner to scale the throughput. A device can also migrate its workload to others for the purpose of load balance or fault tolerance. Experiment results suggest that the proposed scheme can effectively improve performance of transparent mode devices in terms of throughput, load balance, and fault tolerance.     

Alterations in lymphocyte homing patterns within mice exposed to ultraviolet radiation

This report presents the results of an investigation designed to establish whether exposure of mice to ultraviolet radiation (UVR) is capable of influencing the factors that control the distribution of lymphoid cells in vivo. We found that such exposure resulted in a dramatic and long-lasting increase in the tropism of peripheral lymph nodes for circulating lymphoid cells. Termination of UVR exposure did not result in a reversal of this phenomenon. Since an increase in lymphocyte migration into the lymph nodes of UVR-exposed mice was apparent within 2 hr of infusion of the radiolabeled cells, we conclude that the homing assay data reflect a relatively increased binding of circulating lymphocytes to high endothelial venules (HEV) within the lymph nodes of irradiated animals. A histologic analysis of skin from UVR-exposed mice established that the dermal microvasculature had expanded in terms of size and number of vessels, a condition that also does not completely reverse after the termination of treatments. In spite of the increase in dermal microvasculature, very few inflammatory cells were detected in the irradiated skin site. These observations support our conclusion that the enhanced traffic of lymphocytes into peripheral lymph nodes of UVR-exposed mice occurs primarily via lymphocyte-HEV interactions rather than afferent drainage of the irradiated skin.     

Life cycle assessment of the construction of an unpaved road in an undisturbed tropical rainforest area in the vicinity of Manu National Park,Peru

Purpose

The main goal of this study is to provide a thorough environmental sustainability analysis of the construction, traffic, and maintenance of a 45.6-km section of the ‘Manu Road’, an unpaved tropical road that is currently being built in the vicinity of Manu National Park, in the region of Madre de Dios, Peru.

Methods

Life cycle assessment (LCA) using a set of 18 different impact categories was selected to conduct the environmental analysis. Modelling of machinery and vehicle emissions, as well as dust emissions, was performed to account for site-specific characteristics in terms of road construction and traffic. Similarly, direct land use changes were modelled with a particular emphasis on the decay of deforested biomass during construction. A set of different scenarios for the production system were considered to account for uncertainty regarding vehicle transit, amount of deforested biomass, and emission standards.

Results and discussion

Construction, maintenance, and traffic of the Manu Road varied considerably depending on methodological assumptions. Deforestation due to direct land use changes appears to be the main environmental hotspot in terms of climate change, whereas in the remaining impact categories, traffic was the main carrier of environmental burdens.

Conclusions

To the best of our knowledge, this study is the first LCA that focuses on the construction, maintenance, and traffic in a tropical rainforest environment. Despite the low requirements in terms of materials and technology to build this road, its derived environmental impacts are relevant in terms of climate change and particulate matter formation due to deforestation and dust emissions, respectively. Unpaved roads represent a relevant proportion of the entire road network worldwide, especially in developing tropical countries, playing a crucial role in the transportation of raw materials. Furthermore, road infrastructure is expected to expand explosively in the decades to come. Therefore, we suggest that LCA studies can and should improve the planning of road infrastructure in terms of life cycle inventories.

     

城市公园中慢行系统的选线与设计研究

城市公园作为城市中自然景观的重要组成部分，发挥着为人们提供散步漫游、休憩交往场所的重要作用，其内部慢行系统的研究对提升城市公园整体景观品质和游览体验有着重要的意义。以城市公园慢行系统为研究对象，通过实地调研和理论研究相结合的方法，从选线和设计两大方面探讨了城市公园慢行系统的构建。最后以黄山市滨江游园慢行系统为例，对其内部慢行系统的选线规划、景观规划和细节设计进行了具体的规划和设计，对理论研究结果进行验证和反馈，以期为同类型项目提供指导和借鉴。     

Toward the systems biology of vesicle transport

Systems biology aims to study complex biological processes, such as intracellular traffic, as a whole. Systematic genome-wide assays have the potential to identify the transport machinery, delineate pathways and uncover the molecular components of physiological processes that influence trafficking. A goal of this approach is to create predictive models of intracellular trafficking pathways that reflect these relationships. In this review, we highlight current genome-wide technologies of particular relevance to vesicle transport and describe recent applications of these technologies in the framework of systems biology. Systems approaches hold great promise for placing trafficking pathways in their cellular contexts.     

Amphibian road mortality in Europe: a meta-analysis with new data from Poland

While the increasing vehicular traffic is widely suspected to play a role in the worldwide amphibian population decline, the research of amphibian road mortality is scarce, fragmented, fraught with methodological problems, and largely inconclusive. As the first attempt at a synthesis, we analyzed all available data on amphibian mortality in Europe and combined them with four previously unpublished surveys conducted by us. Based on our recalculation of road-kill counts in terms of species-specific road-kill recordability, we conclude that, in lowland Central Europe, the common toads, Bufo bufo, are the most common victims of vehicular traffic in suburban landscapes, while the common frogs, Rana temporaria and Triturus newts, prevail in rural landscapes. The green frogs also tend to be more frequent in rural areas. Common tree frogs, Hyla arborea, are unexpectedly rare in the road-kill record despite their terrestrial and migratory habits. In consideration of problems with obtaining accurate amphibian population estimates, we further propose the road kills-to-spawners ratio (R/S) as a working measure of the impact of road mortality on a local population. While the R/S ratio may not reflect the losses to an entire local amphibian population, it is free of the errors of whole-population estimates, which are notoriously difficult for amphibians. When corrected for species-specific road-kill recordability, most results suggest that the impact of roads on newts may have been underestimated and that the impact on common frog populations may be higher than on those of common toads. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Communicated by H. Kierdorf     

The worldwide airline network and the dispersal of exotic species: 2007–2010

International air travel has played a significant role in driving recent increases in the rates of biological invasion and spread of infectious diseases. By providing high speed, busy transport links between spatially distant, but climatically similar regions of the world, the worldwide airline network (WAN) increases the risks of deliberate or accidental movements and establishment of climatically sensitive exotic organisms. With traffic levels continuing to rise and climates changing regionally, these risks will vary, both seasonally and year-by-year. Here, detailed estimates of air traffic trends and climate changes for the period 2007-2010 are used to examine the likely directions and magnitudes of changes in climatically sensitive organism invasion risk across the WAN. Analysis of over 144 million flights from 2007-2010 shows that by 2010, the WAN is likely to change little overall in terms of connecting regions with similar climates, but anticipated increases in traffic and local variations in climatic changes should increase the risks of exotic species movement on the WAN and establishment in new areas. These overall shifts mask spatially and temporally heterogenous changes across the WAN, where, for example, traffic increases and climatic convergence by July 2010 between parts of China and northern Europe and North America raise the likelihood of exotic species invasions, whereas anticipated climatic shifts may actually reduce invasion risks into much of eastern Europe.     

Cdc42 controls secretory and endocytic transport to the basolateral plasma membrane of MDCK cells

Cdc42 is a Rho-family GTPase that in yeast is important in establishing polarized bud growth. Here we show that Cdc42 is also essential in establishing and maintaining polarity in epithelial cells. Functional deletion of Cdc42 in Madin-Darby canine kidney (MDCK) cells results in the selective depolarization of basolateral membrane proteins; the polarity of apical proteins remains unaffected. This phenotype does not reflect major alterations in the actin cytoskeleton, but rather results from the selective inhibition of membrane traffic to the basolateral plasma membrane in both the endocytic and the secretory pathways. Thus, Cdc42 plays a critical part in epithelial-cell polarity, by, unexpectedly, regulating the fidelity of membrane transport.     

Actin Dependence of Polarized Receptor Recycling in Madin-Darby Canine Kidney Cell Endosomes

Mammalian epithelial cell plasma membrane domains are separated by junctional complexes supported by actin. The extent to which actin acts elsewhere to maintain cell polarity remains poorly understood. Using latrunculin B (Lat B) to depolymerize actin filaments, several basolateral plasma membrane proteins were found to lose their polarized distribution. This loss of polarity did not reflect lateral diffusion through junctional complexes because a low-density lipoprotein receptor mutant lacking a functional endocytosis signal remained basolateral after Lat B treatment. Furthermore, Lat B treatment did not facilitate membrane diffusion across the tight junction as observed with ethylenediaminetetraacetic acid or dimethyl sulfoxide treatment. Detailed analysis of transferrin recycling confirmed Lat B depolarized recycling of transferrin from endosomes to the basolateral surface. Kinetic analysis suggested sorting was compromised at both basolateral early endosomes and perinuclear recycling endosomes. Despite loss of function, these two endosome populations remained distinct from each other and from early endosomes labeled by apically internalized ligand. Furthermore, apical and basolateral early endosomes were functionally distinct populations that directed traffic to a single common recycling endosomal compartment even after Lat B treatment. Thus, filamentous actin may help to guide receptor traffic from endosomes to the basolateral plasma membrane.     

Climatic similarity and biological exchange in the worldwide airline transportation network

Recent increases in the rates of biological invasion and spread of infectious diseases have been linked to the continued expansion of the worldwide airline transportation network (WAN). Here, the global structure of the WAN is analysed in terms of climatic similarity to illuminate the risk of deliberate or accidental movements of climatically sensitive organisms around the world. From over 44,000 flight routes, we show, for each month of an average year, (i) those scheduled routes that link the most spatially distant but climatically similar airports, (ii) the climatically best-connected airports, and (iii) clusters of airports with similar climatic features. The way in which traffic volumes alter these findings is also examined. Climatic similarity across the WAN is skewed (most geographically close airports are climatically similar) but heavy-tailed (there are considerable numbers of geographically distant but climatically similar airports), with climate similarity highest in the June-August period, matching the annual peak in air traffic. Climatically matched, geographically distant airports form subnetworks within the WAN that change throughout the year. Further, the incorporation of passenger and freight traffic data highlight at greater risk of invasion those airports that are climatically well connected by numerous high capacity routes.     

QoS Support by the HiperLAN/2 MAC Protocol: A Performance Evaluation

HiperLAN/2 (HIgh PErformance Radio Local Area Network) is a new standard from ETSI (European Telecommunications Standards Institute) for high-speed wireless LANs, interconnecting portable devices to each other and to broadband core networks, based on different networking technologies such as IP, ATM, IEEE 1394, and others. This paper introduces the basic features of the HiperLAN/2 MAC protocol. It presents performance evaluation results, specifically related to the mechanisms provided by HiperLAN/2 to manage bandwidth resource requests and granting. These results are assessed in terms of their flexibility and efficiency in supporting delay sensitive traffic, such as voice and Web data traffic, which are expected to be transported by broadband wireless LANs.     

Sar1 promotes vesicle budding from the endoplasmic reticulum but not Golgi compartments

Two new members (Sar1a and Sar1b) of the SAR1 gene family have been identified in mammalian cells. Using immunoelectron microscopy, Sar1 was found to be restricted to the transitional region where the protein was enriched 20-40-fold in vesicular carriers mediating ER to Golgi traffic. Biochemical analysis revealed that Sar1 was essential for an early step in vesicle budding. A Sar1-specific antibody potently inhibited export of vesicular stomatitis virus glycoprotein (VSV-G) from the ER in vitro. Consistent with the role of guanine nucleotide exchange in Sar1 function, a trans-dominant mutant (Sar1a[T39N]) with a preferential affinity for GDP also strongly inhibited vesicle budding from the ER. In contrast, Sar1 was not found to be required for the transport of VSV-G between sequential Golgi compartments, suggesting that components active in formation of vesicular carriers mediating ER to Golgi traffic may differ, at least in part, from those involved in intra-Golgi transport. The requirement for novel components at different stages of the secretory pathway may reflect the recently recognized differences in protein transport between the Golgi stacks as opposed to the selective sorting and concentration of protein during export from the ER.     

Wer denkt,der Mensch oder sein Gehirn?

Who decides – humans or their brains? Philosophers' justify their criticism of how brain researchers interpret their results primarily on the basis of the classical philosophical approach of the definition of terms. For instance, they argue that it is nonsensical to assert that the brain is capable of thought, since only a human being possesses this faculty. Brain research has shown, however, that the processes taking place within the brain are necessary and sufficient in order to explain how we think. The author contends that the definition of terms does not advance our knowledge of brain function, the reason being that during a language's development those terms reflect the world‐view current at the time. If terms coined earlier are still used today, they may be outdated and hence, when defined, misleading.