Co-location Patterns Research Articles

Colocation Patterns of Foreign-Owned Firms in a Small Open Economy: Evidence from the Netherlands

This research addresses the colocation or agglomeration patterns of foreign-owned firms in the small open economy of the Netherlands. The empirical evidence shows that foreign-owned firms exhibit different regional colocation patterns than domestic firms for the following industries: mining, construction, transport and communications, services, and trade industry across the 12 Dutch provinces. In the agriculture industry, forestry and fishing industry, and the manufacturing industry the colocation patterns of the domestics and foreign-owned firms are similar. Empirical results also validate that firm size affects the agglomeration behaviour of foreign-owned firms; large foreign companies exhibit different collocation blueprints than smaller and, medium-sized enterprises. Related to industry, large foreign-owned firms target mainly the trade industry and the manufacturing industry. Results confirm that young established foreign-owned firms exhibit similar colocation patterns around older, more experienced foreign counterparts in the host economy. Furthermore, the colocation patterns of foreign-owned firms vary also according to different home countries. Firms coming from countries in proximity with the host economy reveal different colocation patterns than firms coming from more distanced countries. Our results strengthen the theoretical argumentation line that foreign-owned firms value location attributes differently depending on firm characteristics and they also exhibit a different location pattern than domestic counterparts.

Temporal pattern of expression and colocalization of microglia/macrophage phenotype markers following brain ischemic injury in mice

BackgroundEmerging evidence indicates that, similarly to what happens for peripheral macrophages, microglia can express different phenotypes depending on microenvironmental signals. In spite of the large literature on inflammation after ischemia, information on M/M phenotype marker expression, their colocalization and temporal evolution in the injured brain is lacking. The present study investigates the presence of microglia/macrophage phenotype markers, their temporal expression, whether they are concomitantly expressed by the same subpopulation, or they are expressed at distinct phases or locations in relation to the ischemic lesion.MethodsVolume of ischemic lesion, neuronal counts and TUNEL staining were assessed in C57Bl/6 mice at 6-12-24-48 h and 7d after permanent occlusion of the middle cerebral artery. At the same time points, the expression, distribution in the lesioned area, association with a definite morphology and coexpression of the microglia/macrophage markers CD11b, CD45, CD68, Ym1, CD206 were assessed by immunostaining and confocal microscopy.ResultsThe results show that: 1) the ischemic lesion induces the expression of selected microglia/macrophage markers that develop over time, each with a specific pattern; 2) each marker has a given localization in the lesioned area with no apparent changes during time, with the exception of CD68 that is confined in the border zone of the lesion at early times but it greatly increases and invades the ischemic core at 7d; 3) while CD68 is expressed in both ramified and globular CD11b cells, Ym1 and CD206 are exclusively expressed by globular CD11b cells.ConclusionsThese data show that the ischemic lesion is accompanied by activation of specific microglia/macrophage phenotype that presents distinctive spatial and temporal features. These different states of microglia/macrophages reflect the complexity of these cells and their ability to differentiate towards a multitude of phenotypes depending on the surrounding micro-environmental signals that can change over time. The data presented in this study provide a basis for understanding this complex response and for developing strategies resulting in promotion of a protective inflammatory phenotype.

Mining Spatial Co-Location Patterns for Fuzzy Objects

A spatial co-location pattern is a group of spatial objects whose instances are frequently located in the same region.The mining co-location pattern problem for certain and uncertain data had been investigated in the past,but not for fuzzy objects.Fuzzy objects could be applied to many areas such as biomedical image databases,GIS and more.This paper investigates the spatial co-location pattern mining problem for fuzzy objects.Firstly,it defines the related concepts of spatial co-location patterns mining on fuzzy objects,including fuzzy participation ratio,fuzzy participation index,etc.Secondly,this paper proposes an FB algorithm to mine co-location patterns from fuzzy objects.Then,three kinds of the improved algorithms,the pruning objects,reducing of the operation joining between spatial instances and optimizing the pruning steps,are put forward so as to improve the mining performance and accelerate the co-location rule generation.Finally,by extensive experiments,the efficiency and effectiveness of the algorithms are verified.

A Role for Rac3 GTPase in the Regulation of Autophagy

The process of autophagy is situated at the intersection of multiple cell signaling pathways, including cell metabolism, growth, and death, and hence is subject to multiple forms of regulation. We previously reported that inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final step in the post-translational prenylation of so-called CAAX proteins, results in the induction of autophagy which enhances cell death in some cancer cells. In this study, using siRNA-mediated knockdown of a group of small GTPases that are predicted Icmt substrates, we identify Rac3 GTPase as a negative regulator of the process of autophagy. Knockdown of Rac3, but not the closely related isoforms Rac1 and Rac2, results in induction of autophagy. Ectopic expression of Rac3, significantly rescues cells from autophagy and cell death induced by Icmt inhibition, strengthening the notion of an isoform-specific autophagy regulatory function of Rac3. This role of Rac3 was observed in multiple cell lines with varying Rac subtype expression profiles, suggesting its broad involvement in the process. The identification of this less-studied Rac member as a novel regulator provides new insight into autophagy and opens opportunities in identifying additional regulatory inputs of the process.

Event Centric Modeling Approach in Colocation Pattern Analysis From Spatial Data

Spatial co-location patterns are the subsets of Boolean spatial features whose instances are often located in close geographic proximity. Co-location rules can be identified by spatial statistics or data mining approaches. In data mining method, Association rule-based approaches can be used which are further divided into transaction-based approaches and distance-based approaches. Transaction-based approaches focus on defining transactions over space so that an Apriori algorithm can be used. The natural notion of transactions is absent in spatial data sets which are embedded in continuous geographic space. A new distance -based approach is developed to mine co-location patterns from spatial data by using the concept of proximity neighborhood. A new interest measure, a participation index, is used for spatial co-location patterns as it possesses an anti-monotone property. An algorithm to discover co-location patterns are designed which generates candidate locations and their table instances. Finally the co-location rules are generated to identify the patterns.

Coordinated increase in inhibitory and excitatory synapses onto retinal ganglion cells during development

BackgroundNeuronal output is shaped by a balance of excitation and inhibition. How this balance is attained in the central nervous system during development is not well understood, and is complicated by the fact that, in vivo, GABAergic and glycinergic synaptogenesis precedes that of glutamatergic synapses. Here, we determined the distributions of inhibitory postsynaptic sites on the dendritic arbors of individual neurons, and compared their developmental patterns with that of excitatory postsynaptic sites. We focused on retinal ganglion cells (RGCs), the output neurons of the retina, which receive excitatory input from bipolar cells and inhibitory input from amacrine cells. To visualize and map inhibitory postsynaptic sites, we generated transgenic mice in which RGCs express fluorescently tagged Neuroligin 2 (YFP-NL2) under the control of the Thy1 promoter. By labeling RGC dendrites biolistically in YFP-NL2-expressing retinas, we were able to map the spatial distribution and thus densities of inhibitory postsynaptic sites on the dendritic arbors of individual large-field RGCs across ages.ResultsWe demonstrate that YFP-NL2 is present at inhibitory synapses in the inner plexiform layer by its co-localization with gephyrin, the γ2 subunit of the GABAA receptor and glycine receptors. YFP-NL2 puncta were apposed to the vesicular inhibitory transmitter transporter VGAT but not to CtBP2, a marker of presynaptic ribbons found at bipolar cell terminals. Similar patterns of co-localization with synaptic markers were observed for endogenous NL2. We also verified that expression of YFP-NL2 in the transgenic line did not significantly alter spontaneous inhibitory synaptic transmission onto RGCs. Using these mice, we found that, on average, the density of inhibitory synapses on individual arbors increased gradually until eye opening (postnatal day 15). A small centro-peripheral gradient in density found in mature arbors was apparent at the earliest age we examined (postnatal day 8). Unexpectedly, the adult ratio of inhibitory/excitatory postsynaptic sites was rapidly attained, shortly after glutamatergic synaptogenesis commenced (postnatal day 7).ConclusionOur observations suggest that bipolar and amacrine cell synaptogenesis onto RGCs appear coordinated to rapidly attain a balanced ratio of excitatory and inhibitory synapse densities prior to the onset of visual experience.

A continuum of myofibers in adult rabbit extraocular muscle: force, shortening velocity, and patterns of myosin heavy chain colocalization

Extraocular muscle (EOM) myofibers do not fit the traditional fiber typing classifications normally used in noncranial skeletal muscle, in part, due to the complexity of their individual myofibers. With single skinned myofibers isolated from rectus muscles of normal adult rabbits, force and shortening velocity were determined for 220 fibers. Each fiber was examined for myosin heavy chain (MyHC) isoform composition by densitometric analysis of electrophoresis gels. Rectus muscle serial sections were examined for coexpression of eight MyHC isoforms. A continuum was seen in single myofiber shortening velocities as well as force generation, both in absolute force (g) and specific tension (kN/m(2)). Shortening velocity correlated with MyHCIIB, IIA, and I content, the more abundant MyHC isoforms expressed within individual myofibers. Importantly, single fibers with similar or identical shortening velocities expressed significantly different ratios of MyHC isoforms. The vast majority of myofibers in both the orbital and global layers expressed more than one MyHC isoform, with up to six isoforms in single fiber segments. MyHC expression varied significantly and unpredictably along the length of single myofibers. Thus EOM myofibers represent a continuum in their histological and physiological characteristics. This continuum would facilitate fine motor control of eye position, speed, and direction of movement in all positions of gaze and with all types of eye movements-from slow vergence movements to fast saccades. To fully understand how the brain controls eye position and movements, it is critical that this significant EOM myofiber heterogeneity be integrated into hypotheses of oculomotor control.

TNF-α expression, not iNOS expression, is correlated with NF-κB activation in the spinal cord of rats following peripheral nerve injury

Previous studies have shown that pro-inflammatory cytokines were involved in the genesis and persistence of neuropathic pain. Nuclear factor kappa B (NF-κB) plays a crucial role in regulating proinflammatory cytokine gene expression. In this study, we examined the hypothesis that NF-κB would regulate the expression of spinal tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) following chronic constriction nerve injury (CCI) in rats. CCI induced a significant upregulation of NF-κB in the ipsilateral spinal cord on postoperative Day 7 as revealed by Western blot, immunohistochemistry and real time polymerase chain reaction (real time-PCR). Moreover, TNF-α mRNA expression was markedly upregulated by CCI, whereas only a low level of iNOS mRNA was detected in the ipsilateral spinal cord. The immunohistochemical data indicated a pattern of colocalization between NF-κB and TNF-α within spinal cord dorsal horn. These results show that NF-κB activation is correlated with TNF-α expression, but not iNOS expression, in the spinal cord after peripheral nerve injury. Key words: Neuropathic pain, chronic constriction nerve injury, NF-κB; TNF-α, iNOS.

Role of c-Cbl Carboxyl Terminus in Serotonin 5-HT2A Receptor Recycling and Resensitization

The 5-hydroxytryptamine 2A receptor (5-HT(2A)R) undergoes constitutive and agonist-dependent internalization. Despite many advances in our understanding of G protein-coupled receptor trafficking, the exact mechanism of endocytic sorting of G protein-coupled receptors remains obscure. Recently, we have reported a novel finding documenting a global role for the ubiquitin ligase c-Cbl in regulating vesicular sorting of epidermal growth factor receptor (Baldys, A., Göoz, M., Morinelli, T. A., Lee, M. H., Raymond, J. R., Jr., Luttrell, L. M., and Raymond, J. R., Sr. (2009) Biochemistry 48, 1462-1473). Thus, we tested the hypothesis that c-Cbl might play a role in 5-HT(2A)R recycling. In this study, we demonstrated an association of 5-HT(2A)R with c-Cbl. Furthermore, down-regulation of c-Cbl by RNA interference blocked efficient recycling of 5-HT(2A)R to the plasma membrane. Immunofluorescence microscopy revealed that 5-HT(2A) receptors were trapped in early endosome antigen 1- and Rab11-positive sorting endosomes in cells overexpressing c-Cbl mutants lacking carboxyl termini. This inhibitory effect was associated with a relative decrease in association of c-Cbl truncation proteins with the 5-HT(2A)R, compared with that observed for the full-length c-Cbl fusion protein. Consistent with the delayed recycling, 5-HT(2A)R resensitization was greatly attenuated in the presence of c-Cbl mutants lacking carboxyl termini, as detected by changes in the cytosolic calcium. Taken together, these studies have led to the discovery that the C-terminal region of c-Cbl plays a crucial role in the temporal and spatial control of 5-HT(2A)R recycling.

Mining spatial colocation patterns: a different framework

Recently, there has been considerable interest in mining spatial colocation patterns from large spatial datasets. Spatial colocation patterns represent the subsets of spatial events whose instances are often located in close geographic proximity. Most studies of spatial colocation mining require the specification of two parameter constraints to find interesting colocation patterns. One is a minimum prevalent threshold of colocations, and the other is a distance threshold to define spatial neighborhood. However, it is difficult for users to decide appropriate threshold values without prior knowledge of their task-specific spatial data. In this paper, we propose a different framework for spatial colocation pattern mining. To remove the first constraint, we propose the problem of finding N-most prevalent colocated event sets, where N is the desired number of colocated event sets with the highest interest measure values per each pattern size. We developed two alternative algorithms for mining the N-most patterns. They reduce candidate events effectively and use a filter-and-refine strategy for efficiently finding colocation instances from a spatial dataset. We prove the algorithms are correct and complete in finding the N-most prevalent colocation patterns. For the second constraint, a distance threshold for spatial neighborhood determination, we present various methods to estimate appropriate distance bounds from user input data. The result can help an user to set a distance for a conceptualization of spatial neighborhood. Our experimental results with real and synthetic datasets show that our algorithmic design is computationally effective in finding the N-most prevalent colocation patterns. The discovered patterns were different depending on the distance threshold, which shows that it is important to select appropriate neighbor distances.

Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4

BackgroundThe cellular response of malignant tumors to hypoxia is diverse. Several important endogenous metabolic markers are upregulated under hypoxic conditions. We examined the staining patterns and co-expression of HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4 with the exogenous hypoxic cell marker pimonidazole and the association of marker expression with clinicopathological characteristics.Methods20 biopsies of advanced head and neck carcinomas were immunohistochemically stained and analyzed. All patients were given the hypoxia marker pimonidazole intravenously 2 h prior to biopsy taking. The tumor area positive for each marker, the colocalization of the different markers and the distribution of the markers in relation to the blood vessels were assessed by semiautomatic quantitative analysis.ResultsMCT1 staining was present in hypoxic (pimonidazole stained) as well as non-hypoxic areas in almost equal amounts. MCT1 expression showed a significant overall correlation (r = 0.75, p < 0.001) and strong spatial relationship with CAIX. LDH-5 showed the strongest correlation with pimonidazole (r = 0.66, p = 0.002). MCT4 and GLUT-1 demonstrated a typical diffusion-limited hypoxic pattern and showed a high degree of colocalization. Both MCT4 and CAIX showed a higher expression in the primary tumor in node positive patients (p = 0.09 both).ConclusionsColocalization and staining patterns of metabolic and hypoxia-related proteins provides valuable additional information over single protein analyses and can improve the understanding of their functions and environmental influences.

Identification of Novel Ryanodine Receptor 1 (RyR1) Protein Interaction with Calcium Homeostasis Endoplasmic Reticulum Protein (CHERP)

The ryanodine receptor type 1 (RyR1) is a homotetrameric Ca(2+) release channel located in the sarcoplasmic reticulum of skeletal muscle where it plays a role in the initiation of skeletal muscle contraction. A soluble, 6×-histidine affinity-tagged cytosolic fragment of RyR1 (amino acids 1-4243) was expressed in HEK-293 cells, and metal affinity chromatography under native conditions was used to purify the peptide together with interacting proteins. When analyzed by gel-free liquid chromatography mass spectrometry (LC-MS), 703 proteins were identified under all conditions. This group of proteins was filtered to identify putative RyR interacting proteins by removing those proteins found in only 1 RyR purification and proteins for which average spectral counts were enriched by less than 4-fold over control values. This resulted in 49 potential RyR1 interacting proteins, and 4 were selected for additional interaction studies: calcium homeostasis endoplasmic reticulum protein (CHERP), endoplasmic reticulum-Golgi intermediate compartment 53-kDa protein (LMAN1), T-complex protein, and phosphorylase kinase. Western blotting showed that only CHERP co-purified with affinity-tagged RyR1 and was eluted with imidazole. Immunofluorescence showed that endogenous CHERP co-localizes with endogenous RyR1 in the sarcoplasmic reticulum of rat soleus muscle. A combination of overexpression of RyR1 in HEK-293 cells with siRNA-mediated suppression of CHERP showed that CHERP affects Ca(2+) release from the ER via RyR1. Thus, we propose that CHERP is an RyR1 interacting protein that may be involved in the regulation of excitation-contraction coupling.

The double immunostaining of CD133 and Ki-67 favours a significant co-localization pattern in fibroblastic subtype of meningiomas

Background and purposeA unique molecular and/or cellular marker for meningiomas, the most common intracranial tumours, has not been identified yet. Material and methodsWe investigated the co-localization fraction of CD133/Ki-67 in meningioma tissue array slide composed of 80 meningioma tissue samples of various histological variants. CD133 – a cell membrane stem cell marker – was previously proved to be associated with the initiation and progression of intracerebral gliomas and medulloblastomas. ResultsImmunohistochemical co-localization of CD133/Ki-67 was significantly higher in fibroblastic variant than in meningothelial and transitional subtypes. However, since there were only 3 atypical and 1 malignant meningioma spots in the tumour tissue array slide, it is difficult to draw a firm conclusion regarding the actual co-localization percentage and persistence of CD133/Ki-67 in atypical and malignant meningiomas. ConclusionsFar higher co-staining percentage of CD133/Ki-67 in fibroblastic meningioma samples compared to meningothelial subtype, a histological meningioma variant, architectonically resembling the non-neoplastic meningeal cells, gave us the impression that CD133 may play a role in the formation and progression of fibroblastic meningioma variants. The persistency and the validity of this finding need to be verified by further histopathological and molecular research in order to clarify the possible role of CD133 in meningiogenesis.

Ultrastructural Characterization of Olfactory Sensilla and Immunolocalization of Odorant Binding and Chemosensory Proteins from an Ectoparasitoid Scleroderma Guani (Hymenoptera: Bethylidae)

The three-dimensional structures of two odorant binding proteins (OBPs) and one chemosensory protein (CSP) from a polyphagous ectoparasitoid Scleroderma guani (Hymenoptera: Bethylidae) were resolved bioinformatically. The results show that both SguaOBP1 and OBP2 are classic OBPs, whereas SguaCSP1 belongs to non-classic CSPs which are considered as the "Plus-C" CSP in this report. The structural differences between the two OBPs and between OBP and CSP are thoroughly described, and the structural and functional significance of the divergent C-terminal regions (e.g., the prolonged C-terminal region in SguaOBP2 and the additional pair of cysteines in SguaCSP1) are discussed. The immunoblot analyses with antisera raised against recombinant SguaOBP1, OBP2, and CSP1, respectively, indicate that two SguaOBPs are specific to antennae, whereas SguaCSP1, which are more abundant than OBPs and detected in both male and female wasps, expresses ubiquitously across different tissues.We also describe the ultrastructure of the antennal sensilla types in S. guani and compare them to 19 species of parasitic Hymenoptera. There are 11 types of sensilla in the flagellum and pedicel segments of antennae in both male and female wasps. Seven of them, including sensilla placodea (SP), long sensilla basiconica (LSB), sensilla coeloconica (SC), two types of double-walled wall pore sensilla (DWPS-I and DWPS-II), and two types of sensilla trichodea (ST-I and ST-II), are multiporous chemosensilla. The ultralsturctures of these sensilla are morphologically characterized. In comparison to monophagous specialists, the highly polyphagous generalist ectoparasitoids such as S. guani possess more diverse sensilla types which are likely related to their broad host ranges and complex life styles. Our immunocytochemistry study demonstrated that each of the seven sensilla immunoreacts with at least one antiserum against SguaOBP1, OBP2, and CSP1, respectively. Anti-OBP2 is specifically labeled in DWPS-II, whereas the anti-OBP1 shows a broad spectrum of immunoactivity toward four different sensilla (LSB, SP, ST-I and ST-II). On the other hand, anti-CSP1 is immunoactive toward SP, DWPS-I and SC. Interestingly, a cross co-localization pattern between SguaOBP1 and CSP1 is documented for the first time. Given that the numbers of OBPs and CSPs in many insect species greatly outnumber their antennal sensilla types, it is germane to suggest such phenomenon could be the rule rather than the exception.

Podocytes require the engagement of cell surface heparan sulfate proteoglycans for adhesion to extracellular matrices

Podocytes adhere to the glomerular basement membrane by cell surface receptors. Since in other cells these adhesions are enhanced by cell surface proteoglycans, we examined the contribution of these molecules and their glycosaminoglycan side chains to podocyte adhesion by developing immortalized podocyte cell lines with (control) or without (mutant) heparan sulfate glycosaminoglycan chains. In adhesion assays control podocytes attached, spread, and migrated more efficiently compared with mutants, indicating a requirement for heparan sulfate chains in these processes. The proteoglycan syndecan-4 is known to have direct effects on cell attachment, spreading, and cytoskeletal organization. We found it localized to focal adhesions in control podocytes coincident with stress fiber formation. In mutant cells, syndecan-4 was associated with smaller focal contacts and cortical actin organization. Analysis by flow cytometry showed that mutant cells had twice the amount of surface syndecan-4 of control cells. Protein kinase Cα, a signaling molecule bound to and activated by syndecan-4, showed a fourfold increase in membrane localization-activation than that seen in control cells. In vivo, the loss of heparan sulfate glycosaminoglycans in PEXTKO mice led to a loss of glomerular syndecan-4. Overall, our study provides further evidence for a dynamic role of cell surface heparan sulfate glycosaminoglycans in podocyte activity.

Distribution and chemical coding of sympathetic neurons in the caudal mesenteric ganglion projecting to the ovary in sexually mature gilts

The distribution and co-localisation patterns of dopamine-beta-hydroxylase (DβH), neuropeptide Y (NPY), somatostatin (SOM) and galanin (GAL) were investigated by use of retrograde neuronal tracing and double-labelling immunofluorescence techniques in the caudal mesenteric ganglion (CaMG) neurons supplying the ovary of adult pigs. The existence and density of nerve fibres that are immunoreactive (IR) for the above-mentioned neuroactive substances were also evaluated. Injections of a fluorescent tracer (Fast Blue; FB) into the ovaries revealed the presence of small- (76.38%) and large-sized (23.62%) FB-positive postganglionic neurons in the CaMG. Noradrenergic FB-positive cells were simultaneously NPY- (43.38%), SOM- (18.77%) and GAL- (18.31%) IR. Of the examined FB-positive neurons, 53.49% were DβH-IR but NPY-immunonegative (IN), 79.06% were DβH-IR but SOM-IN, and 77.16% were DβH-IR but GAL-IN. Small- or large-sized subsets of traced neurons were supplied by only one or a few nerve fibres, exhibiting DβH-, NPY-, SOM- and/or GAL-IR. Our data show the specific morphological as well as immunochemical structural organisation of the sympathetic neurons in the CaMG in adult gilts. The occurrence of an abundant population of noradrenergic perikarya in the CaMG may suggest their important physiological role in the regulation of gonadal function(s) in these animals.

Postendocytic Sorting of Constitutively Internalized Dopamine Transporter in Cell Lines and Dopaminergic Neurons

The dopamine transporter (DAT) mediates reuptake of released dopamine and is the target for psychostimulants, such as cocaine and amphetamine. DAT undergoes marked constitutive endocytosis, but little is known about the fate and sorting of the endocytosed transporter. To study DAT sorting in cells lines, we fused the one-transmembrane segment protein Tac to DAT, thereby generating a transporter (TacDAT) with an extracellular antibody epitope suited for trafficking studies. TacDAT was functional and endocytosed constitutively in HEK293 cells. According to an ELISA-based assay, TacDAT intracellular accumulation was increased by the lysosomal protease inhibitor leupeptin and by monensin, an inhibitor of lysosomal degradation and recycling. Monensin also reduced TacDAT surface expression consistent with partial recycling. In both HEK293 cells and in the dopaminergic cell line 1Rb3An27, constitutively internalized TacDAT displayed primary co-localization with the late endosomal marker Rab7, less co-localization with the "short loop" recycling marker Rab4, and little co-localization with the marker of "long loop" recycling endosomes, Rab11. Removal by mutation of N-terminal ubiquitination sites did not affect this sorting pattern. The sorting pattern was distinct from a bona fide recycling membrane protein, the beta(2)-adrenergic receptor, that co-localized primarily with Rab11 and Rab4. Constitutively internalized wild type DAT probed with the fluorescently tagged cocaine analogue JHC 1-64, exhibited the same co-localization pattern as TacDAT in 1Rb3An27 cells and in cultured midbrain dopaminergic neurons. We conclude that DAT is constitutively internalized and sorted in a ubiquitination-independent manner to late endosomes/lysosomes and in part to a Rab4 positive short loop recycling pathway.

The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin‐releasing hormone and neurokinin B neurons

Kisspeptin signaling via the kisspeptin receptor G-protein-coupled receptor-54 plays a fundamental role in the onset of puberty and the regulation of mammalian reproduction. In this immunocytochemical study we addressed the (i) topography, (ii) sexual dimorphism, (iii) relationship to gonadotropin-releasing hormone (GnRH) neurons and (iv) neurokinin B content of kisspeptin-immunoreactive hypothalamic neurons in human autopsy samples. In females, kisspeptin-immunoreactive axons formed a dense periventricular plexus and profusely innervated capillary vessels in the infundibular stalk. Most immunolabeled somata occurred in the infundibular nucleus. Many cells were also embedded in the periventricular fiber plexus. Rostrally, they formed a prominent periventricular cell mass (magnocellular paraventricular nucleus). Robust sex differences were noticed in that fibers and somata were significantly less numerous in male individuals. In dual-immunolabeled specimens, fine kisspeptin-immunoreactive axon varicosities formed axo-somatic, axo-dendritic and axo-axonal contacts with GnRH neurons. Dual-immunofluorescent studies established that 77% of kisspeptin-immunoreactive cells in the infundibular nucleus synthesize the tachykinin peptide neurokinin B, which is known to play crucial role in human fertility; 56 and 17% of kisspeptin fibers in the infundibular and periventricular nuclei, respectively, contained neurokinin B immunoreactivity. Site-specific co-localization patterns implied that kisspeptin neurons in the infundibular nucleus and elsewhere contributed differentially to these plexuses. This study describes the distribution and robust sexual dimorphism of kisspeptin-immunoreactive elements in human hypothalami, reveals neuronal contacts between kisspeptin-immunoreactive fibers and GnRH cells, and demonstrates co-synthesis of kisspeptins and neurokinin B in the infundibular nucleus. The neuroanatomical information will contribute to our understanding of central mechanisms whereby kisspeptins regulate human fertility.

Two Cities, Five Industries: Similarities and Differences within and between Cultural Industries in New York and Los Angeles

Recent work has pointed towards the possibility that industries are not tied to their specific urban location as much as to their linkages with particular types of infrastructure and to their social and economic networks. Industries have similar clustering patterns even in very different cities. Using Bureau of Labor Statistics data, we conducted geographic information systems (GIS) analysis to compare cultural industries in Los Angeles and New York City, two cities with very different types of geography and urban environments. Two distinct findings emerged: (1) when cultural industries are disaggregated into distinct industrial subsectors (art, fashion, music, design), important differences among them emerge; and (2) cultural industries “behave” similarly in each city because their subsectors tend to colocate (e.g., art with design; music with film) in similar ways, and this colocation pattern remains consistent in both locations. Such notable clustering tendencies of cultural industries help inform future research and further enlighten our understanding of their location patterns.

A Soluble Form of the Pilus Protein FimA Targets the VDAC-Hexokinase Complex at Mitochondria to Suppress Host Cell Apoptosis

Inhibition of apoptotic response of host cells during an early phase of infection is a strategy used by many enteroinvasive bacterial pathogens to enhance their survival. Here, we report the identification of a soluble form of the pilus protein FimA from the culture supernatants of E. coli K1, Salmonella, and Shigella that can potently inhibit Bax-mediated release of cytochrome c from isolated mitochondria. Similar to the infected cells, HCT116 cells stably expressing FimA display a delay in the integration of Bax into outer mitochondrial membrane induced by apoptotic stimuli. FimA targets to mitochondria through binding to VDAC1, which is a prerequisite step for E. coli K1 to render the short-term blockade of apoptotic death in the host cells. Interestingly, FimA strengthens the VDAC1-hexokinase interaction and prevents dissociation of hexokinase from VDAC1 triggered by apoptotic stimuli. Together, these data thus reveal a paradigm of antiapoptosis mechanism undertaken by the enteroinvasive bacteria.