10,524 research outputs found
La lamina di Demlfeld
No full textDescrizione multidisciplinare della lamina di bronzo iscritta da Demlfed, presso Anpass (A)
Both emerin and lamin C depend on lamin A for localization at the nuclear envelope
No full textPhysical interactions between lamins and emerin were
investigated by co-immunoprecipitation of in vitro
translated proteins. Emerin interacted with in vitro
translated lamins A, B1 and C in co-immunprecipitation
reactions. Competition reactions revealed a clear
preference for interactions between emerin and lamin C.
Structural associations between lamins and emerin were
investigated in four human cell lines displaying abnormal
expression and/or localisation of lamins A and C. In each
cell line absence of lamins A and C from the nuclear
envelope (NE) was correlated with mis-localisation of
endogenous and exogenous emerin to the ER. In two cell
lines that did not express lamin A but did express lamin C,
lamin C as well as emerin was mis-localised. When GFPlamin
A was expressed in SW13 cells (which normally
express only very low levels of endogenous lamin A and
mis-localise endogenous emerin and lamin C), all three
proteins became associated with the NE. When GFP-lamin
C was expressed in SW13 cells neither the endogenous nor
the exogenous lamin C was localised to the NE and emerin
remained in the ER. Finally, lamins A and C were
selectively eliminated from the NE of HeLa cells using a
dominant negative mutant of lamin B1. Elimination of these
lamins from the lamina led to the accumulation of emerin
as aggregates within the ER. Our data suggest that lamin
A is essential for anchorage of emerin to the inner nuclear
membrane and of lamin C to the lamina
nicholasjchua/megaphragma-lamina: resubmission_230708
No full textData and Jupyter notebooks for:
A complete reconstruction of the early visual system of an adult insect (2023)
Nicholas J. Chua, Anastasia A. Makarova, Pat Gunn, Sonia Villani, Ben Cohen, Myisha Thasin, Jingpeng Wu, Deena Shefter, Song Pang, C. Shan Xu, Harald Hess, Alexey A. Polilov, Dmitri B. Chklovskii
Electron microscopy data and lamina neuron reconstructions are available on https://waspem-lamina.flatironinstitute.or
Lamina-associated polypeptide 2 (LAP2) expression patterns in transformed and cancer cells
No full textThe Lamina-associated polypeptide two (LAP2) proteins comprising three human isoforms, LAP2 +- LAP2β and LAP2 have been shown to provide a structural framework in the nucleus and to facilitate nuclear assembly and disassembly during the cell cycle. Expression profiling studies, using microarrays, identified elevated levels of LAP2α in cervical cancer patient material compared to normal. Altered expression of LAP2 may thus have significance in the development of certain cancers. The aim of this project was thus to independently confirm the up-regulation of LAP2α in cancer material and to determine the effect of inhibiting its expression on the biology of cancer and transformed cells. LAP2α mRNA and protein expression was shown to be elevated in cervical cancer tissue compared to normal cervical tissue by Real-time RT-PCR and immunohistochemical analysis respectively. Interestingly, LAP2 (both the LAP2α and LAP2β isoforms) was shown to be overexpressed in cervical cancer cell lines compared to a normal primary cervical epithelial cell line. Higher LAP2 expression appears to associate with cellular transformation as increased expression was observed in transformed human fibroblast cells compared to normal fibroblasts. LAP2 expression was also elevated in oesophageal cancer cell lines compared to normal suggesting that the overexpression of LAP2 associates with multiple cancer types. In order to determine the role of LAP2 in cancer cell biology, its expression was inhibited using specific siRNA molecules. Inhibition of LAP2 did not have an effect on adherent cell proliferation; however under anchorage-independent growth conditions a significant decrease in cell proliferation and colony formation was observed in LAP2 knockdown cells. This was accompanied by a decrease in cyclin D1 levels and an increase in p16 levels in LAP2 siRNA transfected cells. Our results did not conclusively show xiii that this decrease in proliferation was as a result of an alteration in the cell cycle profile or due to an increase in apoptosis. In addition, inhibition of LAP2 expression resulted in a decrease in Rb protein expression. It is proposed that LAP2 plays a role in stabilizing the Rb protein, as inhibition of LAP2 expression did not affect Rb mRNA levels but substantially reduced the protein half-life. In summary, increased LAP2 expression associates with transformed and cancer cells and suggests potential for use as a cancer biomarker. Its potential as an anti-cancer therapeutic, however requires further investigation
The Cartridge: A Canonical Neural Circuit Abstraction of the Lamina Neuropil - Construction and Composition Rules
No full textThe Lamina is a neuropil that resides in the optic lobe of the early visual system of the fruit fly. Its neural circuit consists of some 700~800 cartridges. A cartridge is an atomic neural circuit abstraction whose I/O behavior can be studied in isolation. The anatomy of the neurons, neurotransmitter types and connectivity patterns of the neurons in the cartridge are briefly reviewed. A circuit-level model of a cartridge suitable for implementation on a GPU platform is presented in detail. Cartridge interconnects create neural circuits with different I/O characteristics. A number of cartridge composition rules for building neural circuits with different spatial I/O characteristics are discussed. We present a model neural circuit for initial functional evaluations and scaling of the Lamina and its interconnection with the Medulla. Implementation considerations of the Lamina neural circuit are discussed.Additional documentation about Neurokernel project are available at http://neurokernel.github.i
Agrin binds to the nerve-muscle basal lamina via laminin.
No full textAgrin is a heparan sulfate proteoglycan that is required for the formation and maintenance of neuromuscular junctions. During development, agrin is secreted from motor neurons to trigger the local aggregation of acetylcholine receptors (AChRs) and other proteins in the muscle fiber, which together compose the postsynaptic apparatus. After release from the motor neuron, agrin binds to the developing muscle basal lamina and remains associated with the synaptic portion throughout adulthood. We have recently shown that full-length chick agrin binds to a basement membrane-like preparation called Matrigel. The first 130 amino acids from the NH2 terminus are necessary for the binding, and they are the reason why, on cultured chick myotubes, AChR clusters induced by full-length agrin are small. In the current report we show that an NH2-terminal fragment of agrin containing these 130 amino acids is sufficient to bind to Matrigel and that the binding to this preparation is mediated by laminin-1. The fragment also binds to laminin-2 and -4, the predominant laminin isoforms of the muscle fiber basal lamina. On cultured myotubes, it colocalizes with laminin and is enriched in AChR aggregates. In addition, we show that the effect of full-length agrin on the size of AChR clusters is reversed in the presence of the NH2-terminal agrin fragment. These data strongly suggest that binding of agrin to laminin provides the basis of its localization to synaptic basal lamina and other basement membranes
Involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization
No full textThe nuclear lamina is a meshwork of intermediate-type filament proteins (lamins) that lines the inner nuclear membrane. The lamina is proposed to be an important determinant of nuclear structure, but there has been little direct testing of this idea. To investigate lamina functions, we have characterized a novel lamin B1 mutant lacking the middle approximately 4/5 of its alpha-helical rod domain. Though retaining only 10 heptads of the rod, this mutant assembles into intermediate filament-like structures in vitro. When expressed in cultured cells, it concentrates in patches at the nuclear envelope. Concurrently, endogenous lamins shift from a uniform to a patchy distribution and lose their complete colocalization, and nuclei become highly lobulated. In vitro binding studies suggest that the internal rod region is important for heterotypic associations of lamin B1, which in turn are required for proper organization of the lamina. Accompanying the changes in lamina structure induced by expression of the mutant, nuclear pore complexes and integral membrane proteins of the inner membrane cluster, principally at the patches of endogenous lamins. Considered together, these data indicate that lamins play a major role in organizing other proteins in the nuclear envelope and in determining nuclear shape
Projection neurons in lamina III of the rat spinal cord are selectively innervated by local dynorphin-containing excitatory neurons
No full textLarge projection neurons in lamina III of the rat spinal cord that express the neurokinin 1 receptor are densely innervated by peptidergic primary afferent nociceptors and more sparsely by low-threshold myelinated afferents. However, we know little about their input from other glutamatergic neurons. Here we show that these cells receive numerous contacts from nonprimary boutons that express the vesicular glutamate transporter 2 (VGLUT2), and form asymmetrical synapses on their dendrites and cell bodies. These synapses are significantly smaller than those formed by peptidergic afferents, but provide a substantial proportion of the glutamatergic synapses that the cells receive (over a third of those in laminae I–II and half of those in deeper laminae). Surprisingly, although the dynorphin precursor preprodynorphin (PPD) was only present in 4–7% of VGLUT2 boutons in laminae I–IV, it was found in 58% of the VGLUT2 boutons that contacted these cells. This indicates a highly selective targeting of the lamina III projection cells by glutamatergic neurons that express PPD, and these are likely to correspond to local neurons (interneurons and possibly projection cells). Since many PPD-expressing dorsal horn neurons respond to noxious stimulation, this suggests that the lamina III projection cells receive powerful monosynaptic and polysynaptic nociceptive input. Excitatory interneurons in the dorsal horn have been shown to possess IA currents, which limit their excitability and can underlie a form of activity-dependent intrinsic plasticity. It is therefore likely that polysynaptic inputs to the lamina III projection neurons are recruited during the development of chronic pain states
Internal iamin structures within G1 nuclei of human dermal fibroblasts
No full textThe nuclear lamina is a mesh-like network of fibres subjacent
to the inner nuclear membrane that is believed
to be involved in the specific spatial reorganisation of
chromatin after mitosis. To determine how the lamina
might be involved in chromatin reorganisation, we have
performed indirect immunofluorescence studies on quiescent
and proliferating human dermal fibroblasts
(HDF). Two monoclonal antibodies recognising human
lamins A and C and three different fixation methods
were employed. In indirect immunofluorescence studies,
cultures of quiescent cells displayed a uniform perinuclear
distribution of the antibodies. In proliferating cultures
two distinct populations of cells were observed:
one population displayed a typical perinuclear antibody
distribution, while the second population displayed an
unusual pattern consisting of a series of spots and fibres
within the nucleus. By inducing cell-cycle synchrony in
cultures we were able to determine that the unusual
internal distribution of the lamin antibodies was
restricted to cells in G1. Optical sectioning and 3-D
reconstruction of the lamina structures in G1 nuclei was
performed with a confocal laser scanning microscope
(CLSM). This revealed that the internal lamin structures
consisted of small foci and fibres proliferating
throughout the nucleus. These structures were shown to
be closely associated with areas of condensed chromatin
but not nuclear membrane. As cells progress towards S
phase the internal lamin foci disappear
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