Function Of Different Regions Research Articles

A Novel Missense Mutation in the Second Extracellular Domain of GJB2, p.Ser183Phe, Causes a Syndrome of Focal Palmoplantar Keratoderma with Deafness

Gap junctions, which consist of connexins, are intercellular channels that mediate rapid intercellular communication. In the skin, connexins are involved in the regulation of epidermal growth and differentiation. GJB2 encodes connexin26, which is an important skin-expressed gap junction protein. Mutations in GJB2 cause a wide variety of unique disorders, but despite extensive research, their mechanisms of action are poorly understood. The identification of novel diseases caused by mutations in GJB2 may help to illuminate the genotype-phenotype correlation and elucidate the function of different regions of the protein. Here, we report the first account of a family with a GJB2 missense mutation in the second extracellular domain (p.Ser183Phe) that causes skin abnormalities in addition to sensorineural hearing loss. Using fluorescent connexin26-EGFP fusion proteins, we showed that the mutation induces a partial protein transport defect that cannot be rescued by wild-type protein. Dye-transfer experiments using a parachute assay revealed channel functionality. Although p.Ser183Phe affects the second extracellular domain, mutations in the first extracellular domain also lead to focal palmoplantar keratoderma and likewise perturb protein transport in a dominant-negative manner. Therefore, we hypothesize that focal palmoplantar keratoderma in gap junction skin disease may be specifically associated with connexin trafficking defects as well as with mutations affecting its extracellular domains, thus broadening the spectrum of GJB2-associated diseases.

Resonant transmission via magnetically bound states in periodic quantum structures

We study the magnetotransport properties of two typical periodic structures. It is found that the magnetic field has a dramatic impact on the resonant splittings via bound states in the structures. For an open periodic structure, the original $(n\ensuremath{-}2)$-fold resonant splitting rule at the beginning of the first conductance step is changed to $(n\ensuremath{-}1)$-fold splitting rule by magnetic modulation. The coupling effect of the edge states is very important to form the magnetically bound states corresponding to the $n\ensuremath{-}1$ resonant splitting peaks. For an electric superlattice consisting of $n$ barriers, the magnetic modulation turns the $n\ensuremath{-}1$ low quasibound states into true bound states; thus, the lower-energy resonant splitting in conductance disappears. Instead, $n\ensuremath{-}1$ resonant peaks via magnetically bound states appear at the beginning of the first conductance step. The high states are mainly confined in the potential barriers rather than in the wells, and their wave functions in different regions are coupled together by the edge states. One can find the ``fingerprint'' of the edge states from the probability densities of the high states.

The Discovery of Motor Cortex and its Background

In 1870 Gustav Fritsch and Edvard Hitzig showed that electrical stimulation of the cerebral cortex of a dog produced movements. This was a crucial event in the development of modern neuroscience because it was the first good experimental evidence for a) cerebral cortex involvement in motor function, b) the electrical excitability of the cortex, c) topographic representation in the brain, and d) localization of function in different regions of the cerebral cortex. This paper discusses their experiment and some developments in the previous two centuries that led to it including the ideas of Thomas Willis and Emanuel Swedenborg, the widespread interest in electricity and the localizations of function of Franz Joseph Gall, John Hughlings Jackson, and Paul Broca. We also consider the subsequent study of the motor cortex by David Ferrier and others.

Positronium formation as a three-body reaction. I. The second-order positron-electron interaction amplitude

We derive the exact analytic form for the second-order positron-electron interaction term in the Faddeev three-body approach which is applicable in the nonrelativistic high energy region. Although there is no nonintegrable singularity in the six-dimensional integral form of this amplitude, here the basic difficulty arises from the presence of complex nonintegral exponents in the components included in the integrand. Consequently, three brunch cuts must be handled simultaneously. However, by using an integral representation of the gamma function, these brunch cuts are removed from the integrand. Expanding the radial parts of the initial and final wave functions further reduces the second-order positron-electron interaction term to a one-variable integral in terms of Bessel functions of the third kind. The different final closed expressions are ultimately derived in terms of the generalized hypergeometric functions for different regions of the scattering angle.

The Variation in Secretory Function of Different Regions of the Human Colon

Introduction: The colonic epithelium has both secretory and absorptive functions and much work has been carried out on animals such as rat and guinea pig, or on colonic cell lines. Currently we are researching the secretory properties of human colonic epithelium, utilising intact fresh mucosal sheets in an Ussing chamber.

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

The location of regions that regulate transcription of the murine Emilin1 gene was investigated in a DNA fragment of 16.8 kb, including the entire gene and about 8.7 and 0.6 kb of 5'- and 3'-flanking sequences, respectively. The 8.7-kb segment contains the 5'-end of the putative 2310015E02Rik gene and the sequence that separates it from Emilin1, whereas the 0.6-kb fragment covers the region between Emilin1 and Ketohexokinase genes. Sequence comparison between species identified several conserved regions in the 5'-flanking sequence. Most of them contained chromatin DNase I-hypersensitive sites, which were located at about -950 (HS1), -3100 (HS2), -4750 (HS3), and -5150 (HS4) in cells expressing Emilin1 mRNA. Emilin1 transcription initiates at multiple sites, the major of which correspond to two Initiator sequences. Promoter assays suggest that core promoter activity was mainly dependent on Initiator1 and on Sp1-binding sites close to the Initiators. Moreover, one important regulatory region was contained between -1 and -169 bp and a second one between -630 bp and -1.1 kb. The latter harbors a putative binding site for transcription factor AP1 matching the location of HS1. The function of different regions was studied by expressing lacZ constructs in transgenic mice. The results show that the 16.8-kb segment contains regulatory sequences driving high level transcription in all the tissues where Emilin1 is expressed. Moreover, the data suggest that transcription in different tissues is achieved through combinatorial cooperation between various regions, rather than being dependent on a single cis-activating region specific for each tissue.

Association of segmentation of the epididymal interstitium with segmented tubule function in rats and mice.

The epithelium of the epididymal tubule has different biological functions in different regions of the tubule. Each region is further organized into lobules or intra-regional segments surrounded by connective tissue septa (CTS). Epididymal segmentation has received little direct attention, yet there is considerable evidence that expression of mRNA and protein often begins or ends precisely at the CTS border of a segment. How such 'on-off' regulation occurs coincident with the passing of the tubule from one segment to the next is unknown. This study examined the segmentation of epididymides in rats and mice. The average adult Sprague-Dawley rat and C57BL/6 mouse caput, corpus and cauda epididymides has seven, two and four, and three, one and two segments, respectively. The apoptosis response of the caput epididymal epithelium to deprivation of lumicrine factors 24 h after efferent duct ligation in rats and the epididymal expression of a marker protein, beta-galactosidase, in mice were segmented precisely. This validated both at a general response and at a specific protein level that many epididymal functions are regulated within segments. Blue dextran (molecular weight 20000) and erythrocine red (molecular weight 880) dyes infused into the interstitial space of specific segments by micropuncture were retained by the CTS of the segments. In similar micropuncture experiments, [(3)H]H(2)O (molecular weight 18) was able to diffuse into an adjacent segment relatively freely whereas [(14)C]polyethylene glycol (molecular weight 4000) could not. These studies indicate that the interstitium of intra-regional segments is organized into different physiological compartments and that these compartments play a role in regulating the epididymal epithelium.

Association of segmentation of the epididymal interstitium with segmented tubule function in rats and mice

The epithelium of the epididymal tubule has different biological functions in different regions of the tubule. Each region is further organized into lobules or intra-regional segments surrounded by connective tissue septa (CTS). Epididymal segmentation has received little direct attention, yet there is considerable evidence that expression of mRNA and protein often begins or ends precisely at the CTS border of a segment. How such 'on-off' regulation occurs coincident with the passing of the tubule from one segment to the next is unknown. This study examined the segmentation of epididymides in rats and mice. The average adult Sprague-Dawley rat and C57BL/6 mouse caput, corpus and cauda epididymides has seven, two and four, and three, one and two segments, respectively. The apoptosis response of the caput epididymal epithelium to deprivation of lumicrine factors 24 h after efferent duct ligation in rats and the epididymal expression of a marker protein, beta-galactosidase, in mice were segmented precisely. This validated both at a general response and at a specific protein level that many epididymal functions are regulated within segments. Blue dextran (molecular weight 20000) and erythrocine red (molecular weight 880) dyes infused into the interstitial space of specific segments by micropuncture were retained by the CTS of the segments. In similar micropuncture experiments, [(3)H]H(2)O (molecular weight 18) was able to diffuse into an adjacent segment relatively freely whereas [(14)C]polyethylene glycol (molecular weight 4000) could not. These studies indicate that the interstitium of intra-regional segments is organized into different physiological compartments and that these compartments play a role in regulating the epididymal epithelium.

UNC-5 Function Requires Phosphorylation of Cytoplasmic Tyrosine 482, but Its UNC-40-Independent Functions also Require a Region between the ZU-5 and Death Domains

Members of the UNC-5 protein family are transmembrane receptors for UNC-6/netrin guidance cues. To analyze the functional roles of different UNC-5 domains, we sequenced mutations in seven severe and three weak alleles of unc-5 in Caenorhabditis elegans . Four severe alleles contain nonsense mutations. Two weak alleles are truncations of the cytodomain, but one is a missense mutation in an extracellular immunoglobulin domain. To survey the function of different regions of UNC-5, wild-type and mutant unc-5::HA transgenes were tested for their ability to rescue the unc-5(e53) null mutant. Our data reveal partial functional requirements for the extracellular domains and identify a portion of the cytoplasmic juxtamembrane (JM) region as essential for rescue of migrations. When nine cytodomain tyrosines, including seven in the JM region, are mutated to phenylalanine, UNC-5 function and tyrosine phosphorylation are largely compromised. When F482 in the JM region of the mutant protein is reverted to tyrosine, UNC-5 tyrosine phosphorylation and in vivo function are largely recovered, suggesting that Y482 phosphorylation is critical to UNC-5 function in vivo . Our data also show that part of the ZU-5 motif is required for UNC-40-independent signaling of UNC-5.

UNC-5 Function Requires Phosphorylation of Cytoplasmic Tyrosine 482, but Its UNC-40-Independent Functions also Require a Region between the ZU-5 and Death Domains

Members of the UNC-5 protein family are transmembrane receptors for UNC-6/netrin guidance cues. To analyze the functional roles of different UNC-5 domains, we sequenced mutations in seven severe and three weak alleles of unc-5 in Caenorhabditis elegans. Four severe alleles contain nonsense mutations. Two weak alleles are truncations of the cytodomain, but one is a missense mutation in an extracellular immunoglobulin domain. To survey the function of different regions of UNC-5, wild-type and mutant unc-5::HA transgenes were tested for their ability to rescue the unc-5(e53) null mutant. Our data reveal partial functional requirements for the extracellular domains and identify a portion of the cytoplasmic juxtamembrane (JM) region as essential for rescue of migrations. When nine cytodomain tyrosines, including seven in the JM region, are mutated to phenylalanine, UNC-5 function and tyrosine phosphorylation are largely compromised. When F482 in the JM region of the mutant protein is reverted to tyrosine, UNC-5 tyrosine phosphorylation and in vivo function are largely recovered, suggesting that Y482 phosphorylation is critical to UNC-5 function in vivo. Our data also show that part of the ZU-5 motif is required for UNC-40-independent signaling of UNC-5.

The difference of economic function and the trends of industrial development in central cities along the Xijiang River

The Xijiang River is an important link between Guangdong Province and the Guangxi Zhuang Autonomous Region, and a tie between its basin and the world. The zone which consists of 12 cities backing onto the main channel, including Guangzhou, Shenzhen, Nanning and Bose, etc., is an economic growing point and industry spreading origin of all the river basin. According to the nonagricultural population scale, these cities are divided into four grades. By analyzing seven indexes (GDP, nonagricultural population, gross values of industrial output, postal and telecommunication service scales, social commodity total volume of retail sales, resident saving balance, student sum in college), these cities are divided into four kinds of growing points, which show the different radiating function in different regions. The 12 cities, which have differed obviously in industry structure and the scale of the secondary & tertiary industry, are divided into three industry steps. By studying the difference of urban industrial function specialization in the 12 cities, the problems have been revealed in the urban industry structure developing. They are about the lower levels of the three industries, the lack of coordination with city status in the development of specialized departments, the similarity of the industry structure and the specialized departments, and so on. Based on the pattern of urban industry structure developing and the theory of regional economic step transferring, some suggestions have been discussed. They include the trends of cities’ industry developing, the change and improvement of the percentage of the three industries, the adjustment and amendment of the region and industry structure, and the labor division and location of cities manufacture.

Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF(1))-like immunoreactivity in the mouse brain: light microscopy analysis using an antibody directed against the C-terminus.

Corticotropin-releasing hormone (CRH) receptor type 1 (CRF(1)) is a member of the receptor family mediating the effects of CRH, a critical neuromediator of stress-related endocrine, autonomic, and behavioral responses. The detailed organization and fine localization of CRF(1)-like immunoreactivity (CRF(1)-LI) containing neurons in the rodent have not been described, and is important to better define the functions of this receptor. Here we characterize in detail the neuroanatomical distribution of CRF(1)-immunoreactive (CRF(1)-ir) neurons in the mouse brain, using an antiserum directed against the C-terminus of the receptor. We show that CRF(1)-LI is abundantly yet selectively expressed, and its localization generally overlaps the target regions of CRH-expressing projections and the established distribution of CRF(1) mRNA, with several intriguing exceptions. The most intensely CRF(1)-LI-labeled neurons are found in discrete neuronal systems, i.e., hypothalamic nuclei (paraventricular, supraoptic, and arcuate), major cholinergic and monoaminergic cell groups, and specific sensory relay and association thalamic nuclei. Pyramidal neurons in neocortex and magnocellular cells in basal amygdaloid nucleus are also intensely CRF(1)-ir. Finally, intense CRF(1)-LI is evident in brainstem auditory associated nuclei and several cranial nerves nuclei, as well as in cerebellar Purkinje cells. In addition to their regional specificity, CRF(1)-LI-labeled neurons are characterized by discrete patterns of the intracellular distribution of the immunoreaction product. While generally membrane associated, CRF(1)-LI may be classified as granular, punctate, or homogenous deposits, consistent with differential membrane localization. The selective distribution and morphological diversity of CRF(1)-ir neurons suggest that CRF(1) may mediate distinct functions in different regions of the mouse brain.

Neuropsychiatric aspects of frontotemporal dementias.

Frontotemporal dementia (FTD) is a clinically distinct disorder that is under-recognized. A primary focus of recent research has been to delineate neuropsychiatric features that best discriminate FTD from other dementias, and to identify test instruments that elicit differentiating characteristics most effectively. Additional studies have taken advantage of the clinical and anatomic selectivity that is the hallmark of FTD to explore the functions of different regions of the frontal and temporal lobes. Symptomatic treatments for FTD have shown some promise, raising the potential for improved management in the future.

Mapping Subdomains in the C-terminal Region of Troponin I Involved in Its Binding to Troponin C and to Thin Filament

Troponin I (TnI) is the inhibitory component of troponin, the ternary complex that regulates skeletal and cardiac muscle contraction. Previous work showed that the C-terminal region of TnI, when linked to the "inhibitory region" (residues 98-116), possesses the major regulatory functions of the molecule (Farah, C. S., Miyamoto, C. A., Ramos, C. H. I., Silva, A. C. R., Quaggio, R. B., Fujimori, K., Smillie, L. B., and Reinach, F. C. (1994) J. Biol. Chem. 269, 5230-5240). To investigate these functions in more detail, serial deletion mutants of the C-terminal region of TnI were constructed. These experiments showed that longer C-terminal deletions result in lower inhibition of the actomyosin ATPase activity and weaken the interaction with the N-terminal domain of troponin C (TnC), consistent with the antiparallel model for the interaction between these two proteins. The conclusion is that the whole C-terminal region of TnI is necessary for its full regulatory activity. The region between residues 137 and 144, which was shown to have homology with residues 108-115 in the inhibitory region (Farah, C. S., and Reinach, F. C. (1995) FASEB J. 9, 755-767), is involved in the binding to TnC. The region between residues 98 and 129 is involved in modulating the affinity of TnC for calcium. The C-terminal residues 166-182 are involved in the binding of TnI to thin filament. A model for the function of TnI is discussed.

Curvature of Swimming Fish Midlines as an Index of Muscle Strain Suggests Swimming Muscle Produces Net Positive Work

The axial muscle used in steady swimming by fish is geometrically complex and this has required the study ofin vivomuscle swimming mechanics to be done with largely inferential techniques. Currently there is some debate concerning the variation in muscle function in different regions of the body, and the importance of negative work production by muscles in posterior locations. We have used video taped kinematics of steady swimming in mackerel and then analysed the lateral flexion of the body that is thought to reflect the cycle of length change in the axial muscles. A comparison of several of the techniques used in the past to estimate muscle length changes are shown not to be equivalent. Specifically, we find that peak values of lateral deflection of the body are not correlated in time or axial position with peaks in curvature of the body midline. This is important because the timing of the muscle strain cycle is often inferred from such information. Having documented this observation in a swimming mackerel, we use analytical geometry to show that this result is a consequence of the curves that describe swimming fish midlines. Since this observation is shown to be the geometric consequence of an amplitude envelope that is not constant, it should therefore apply to other animals that propel themselves with axial undulations of increasing amplitude. Our minor result is that care must be taken when estimating the phase of swimming muscle strain from kinematics. Our major results is that appreciation of the geometric character of the kinematics these fish adopt may resolve much of the current debate concerning the mechanical performance of swimming muscle in fish. Specifically, using our estimate of the phase of muscle shortening and data on EMG timing in the mackerel we conclude that all axial muscles are activated before peak length and in a manner that should produce net positive work within each shortening cycle.

The eed mutation disrupts anterior mesoderm production in mice

Mouse embryos homozygous for the mutation embryonic ectoderm development (eed) exhibit a growth defect and fail to gastrulate normally. While extraembryonic mesoderm is produced extensively, very little embryonic mesoderm is detected in eed mutant embryos, and there is no subsequent organization of mesoderm into node, notochord, or somites. The phenotype is consistent with a defect in the distal primitive streak. Here we report additional phenotypic analyses that include mRNA in situ hybridization of genes whose expression reflects the function of different regions of the primitive streak and their derivatives. These studies have confirmed that mesoderm derived from the proximal primitive streak is specified appropriately. Despite the absence of a morphologically distinct node, sparse axial mesoderm cells in eed mutant embryos are specified, as reflected by expression of Brachyury (T), Sonic hedgehog, and Tcf3b/HNF-3 beta, and definitive endoderm is produced. Specification of these cell types is also independent of correct expression of nodal, Fgf4, and gsc. Finally, T and Evx1 display ectopic expression in cells not normally fated to ingress through the primitive streak. The data presented are discussed in terms of mechanisms for establishment of the eed phenotype, and are consistent with the eed gene product playing an early role in primitive streak formation and/or organization.

Bound state variational principle employing a discontinuous trial function

A new variational principle for the bound state energy eigenvalues of a quantum system is presented. In it, not only ∇ψ(r) but also ψ(r) itself can be discontinuous across a surface. That is, the trial ψ(r) can have both a kink and a jump across a surface. This allows the use of different basis functions in different regions of space without having to impose any matching conditions across the surface. All parameters appearing in the principle can be variational parameters; none are needed to help invoke any continuity conditions on the trial function. Although the principle is not a definite (minimum) one, good results are obtained in several examples.

Mathieu functions and their applications to scattering by a coated strip

The elliptic-cylinder harmonics, known as Mathieu (1868) functions, are reviewed. These functions are then used to describe EM scattering by confocal elliptic cylinders where each cylinder's dielectric constant is different. A peculiarity of this problem is that the Mathieu functions in different regions are not orthogonal at regional boundaries. Hence, each boundary couples all harmonics from both sides together, and infinite sets of coefficients must be simultaneously evaluated. Numerical results are given for the special case where the innermost region is a perfect conductor. The authors consider both TE and TM illumination. Only normal incidence is actually treated, although oblique generalization is conceptually easy.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

On the use of different basis functions for different regions of space

A new approach to the use of different basis functions for different regions of space in quantum-chemical calculations is presented and illustrated with a simple example.

Actomyosin Organization in Mitotic Dictyostelium Amoebaea

Immunofluorescence localization of actin and myosin during mitosis indicates the significant roles of these cytoskeletons for cytokinesis. High frequency mitosis was induced by synchronous culture using temperature shift (T. Kitanishi-Yumura and Y. Fukui, 1987), and high resolution fluorescence microscopy was performed by the agar-overlay method (S. Yumura and Y. Fukui, 1984). It was shown that actin and myosin are dissociated from the cortex in prophase and reassembled in anaphase to form unique cortical structures: the contractile ring and/or polar lamellipodial network. Conventional myosin (myosin-II) is only localized in the contractile ring, whereas a low-molecular weight isozyme (myosin-I) is localized in the polar leading edge (Y. Fukui, T. Lynch, H. Brzeska, and E. Korn, 1989). Actin is localized in both structures and also forms a unique array in the furrow oriented perpendicular to the plane of constriction (Y. Fukui and S. Inoué, manuscript in preparation). The study suggests that conventional myosin provides the major force of constriction, whereas myosin-I participates in projecting lamellipodia, and actin is involved in several different functions in different regions of the cytoplasm.