X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor ?? 546 Conjugated

RRID:AB_142628

Antibody ID

AB_142628

Target Antigen

Goat IgG (H+L) goat

Proper Citation

(Molecular Probes Cat# A-11056, RRID:AB_142628)

Clonality

unknown

Comments

Discontinued; This product offered by Molecular Probes (Invitrogen), now part of Thermo Fisher:

Host Organism

donkey

Vendor

Molecular Probes

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease.

  • Sommer A
  • Cell Stem Cell
  • 2018 Jul 5

Literature context:


Abstract:

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD. Higher Th17 frequencies were found in the blood of PD patients and increased numbers of T lymphocytes were detected in postmortem PD brain tissues. We modeled this finding using autologous co-cultures of activated T lymphocytes and iPSC-derived MBNs of sporadic PD patients and controls. After co-culture with T lymphocytes or the addition of IL-17, PD iPSC-derived MBNs underwent increased neuronal death driven by upregulation of IL-17 receptor (IL-17R) and NFκB activation. Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death. Our findings indicate a critical role for IL-17-producing T lymphocytes in sporadic PD.

Funding information:
  • NIDCR NIH HHS - DE019075(United States)

Depression-resistant Phenotype in Mice Overexpressing Regulator of G Protein Signaling 8 (RGS8).

  • Kobayashi Y
  • Neuroscience
  • 2018 Jul 15

Literature context:


Abstract:

Regulator of G protein signaling (RGS) proteins are negative regulators of heterotrimeric G proteins that act by accelerating Gα-mediated GTPase activity to terminate G protein-coupled receptor-associated signaling. RGS8 is expressed in several brain regions involved with movement and mood. To investigate the role of RGS8 in vivo, we generated transgenic mice overexpressing brain RGS8 (RGS8tg). RGS8 gene and protein expressions were examined by real-time PCR and immunohistochemistry, respectively, and a significant increase in RGS8 protein was detected in the hippocampal CA1 region compared with wild-type mice (WT). We characterized the phenotypic traits, and found that RGS8tg showed decreased depressive-like behavior in the forced swimming test (FST). Previously, RGS8 was identified as a potent negative regulator of melanin-concentrating hormone receptor 1 (MCHR1), whose activation is mainly involved in energy homeostasis and emotional processing. Interestingly, acute oral administration of MCHR1 antagonist SNAP94847 did not have antidepressant-like effects on RGS8tg in the FST, but did show antidepressant effects on WT. In contrast, selective noradrenaline reuptake inhibitor desipramine had a significant effect on RGS8tg in the FST. MCHR1 is enriched in a subset of primary cilia, as sensory organelles that mediate extracellular signaling. Immunohistochemical analyses revealed significant elongation of MCHR1-positive cilia in the CA1 region of RGS8tg compared with WT. Taken together, these findings suggest that RGS8 participates in modulation of depression-like behavior through ciliary MCHR1 expressed in the CA1 region. The present study may support the possible modulation of RGS8 function in mood disorders.

Funding information:
  • NIAID NIH HHS - U19 AI046130(United States)

Hippo Signaling Plays an Essential Role in Cell State Transitions during Cardiac Fibroblast Development.

  • Xiao Y
  • Dev. Cell
  • 2018 Apr 23

Literature context:


Abstract:

During development, progenitors progress through transition states. The cardiac epicardium contains progenitors of essential non-cardiomyocytes. The Hippo pathway, a kinase cascade that inhibits the Yap transcriptional co-factor, controls organ size in developing hearts. Here, we investigated Hippo kinases Lats1 and Lats2 in epicardial diversification. Epicardial-specific deletion of Lats1/2 was embryonic lethal, and mutant embryos had defective coronary vasculature remodeling. Single-cell RNA sequencing revealed that Lats1/2 mutant cells failed to activate fibroblast differentiation but remained in an intermediate cell state with both epicardial and fibroblast characteristics. Lats1/2 mutant cells displayed an arrested developmental trajectory with persistence of epicardial markers and expanded expression of Yap targets Dhrs3, an inhibitor of retinoic acid synthesis, and Dpp4, a protease that modulates extracellular matrix (ECM) composition. Genetic and pharmacologic manipulation revealed that Yap inhibits fibroblast differentiation, prolonging a subepicardial-like cell state, and promotes expression of matricellular factors, such as Dpp4, that define ECM characteristics.

Funding information:
  • NIAAA NIH HHS - R01 AA020401(United States)

Generation of two induced pluripotent stem cell (iPSC) lines from p.F508del Cystic Fibrosis patients.

  • Fleischer A
  • Stem Cell Res
  • 2018 Mar 20

Literature context:


Abstract:

Cystic Fibrosis (CF) is a monogenic, lethal disease caused by mutations in the cystic fibrosis transmembrane conductance (CFTR) gene. Here we report the production of CF-iPS cell lines from two different p.F508del homozygous female patients (Table 1). Two different primary cell types, skin fibroblasts and keratinocytes, were transfected with retroviral cocktails containing four: c-MYC, KLF4, OCT4 and SOX2 (MKOS) or three: KLF4, OCT4 and SOX2 (KOS) reprogramming factors. Two fibroblast-derived MKOS lines are described in the main text. The lines carry the p.F508del mutation, have a normal karyotype, express pluripotency markers and are able to differentiate into the three germ layers.

Funding information:
  • NIDDK NIH HHS - R01-DK069983(United States)

DNER and NFIA are expressed by developing and mature AII amacrine cells in the mouse retina.

  • Keeley PW
  • J. Comp. Neurol.
  • 2018 Feb 15

Literature context:


Abstract:

The present study has taken advantage of publicly available cell type specific mRNA expression databases in order to identify potential genes participating in the development of retinal AII amacrine cells. We profile two such genes, Delta/Notch-like EGF repeat containing (Dner) and nuclear factor I/A (Nfia), that are each heavily expressed in AII amacrine cells in the mature mouse retina, and which conjointly identify this retinal cell population in its entirety when using antibodies to DNER and NFIA. DNER is present on the plasma membrane, while NFIA is confined to the nucleus, consistent with known functions of each of these two proteins. DNER also identifies some other subsets of retinal ganglion and amacrine cell types, along with horizontal cells, while NFIA identifies a subset of bipolar cells as well as Muller glia and astrocytes. During early postnatal development, NFIA labels astrocytes on the day of birth, AII amacrine cells at postnatal (P) day 5, and Muller glia by P10, when horizontal cells also transiently exhibit NFIA immunofluorescence. DNER, by contrast, is present in ganglion and amacrine cells on P1, also labeling the horizontal cells by P10. Developing AII amacrine cells exhibit accumulating DNER labeling at the dendritic stalk, labeling that becomes progressively conspicuous by P10, as it is in maturity. This developmental time course is consistent with a prospective role for each gene in the differentiation of AII amacrine cells.

Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit.

  • Arima Y
  • Elife
  • 2017 Aug 15

Literature context:


Abstract:

Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-of-hypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis.

Posterior parietal cortex of the rat: Architectural delineation and thalamic differentiation.

  • Olsen GM
  • J. Comp. Neurol.
  • 2016 Dec 15

Literature context:


Abstract:

This study refines the characterization of the rat parietal cortical domain in terms of cyto- and chemoarchitecture as well as thalamic connectivity. We recognize three subdivisions of the posterior parietal cortex (PPC), which are architectonically distinct from the neighboring somatosensory and visual cortices. Furthermore, we show that the different parietal areas are differently connected with thalamic nuclei. The medial portion of PPC (mPPC) is connected primarily with the medial portion of the lateral posterior nucleus (LP), whereas the lateral portion (lPPC) connects with the posterior complex (Po). The more caudolateral part of PPC (PtP) also projects to Po but can be distinguished from lPPC based on architectonic criteria. The primary somatic and visual cortices, neighboring PPC, are preferentially connected with the primary ventral posterior and dorsolateral geniculate nuclei, respectively, and less with the associational Po and LP. Particularly the border between the secondary visual cortex and the PPC has been a matter of controversy, but here we show that, although PPC subareas are connected with Po and medial LP, the medial and lateral secondary visual cortices are connected with lateral LP and a portion of medial LP different from that connected with PPC. The resulting delineations and specifications of connectivity with thalamic nuclei together with upcoming studies of cortical connectivity will facilitate detailed studies on the role of the subdivisions of PPC in the rat as diverse, higher order associative cortical areas, comparable to those described in the primate.for J. Comp. Neurol. 524:3774-3809, 2016. © 2016 Wiley Periodicals, Inc.

Funding information:
  • NHLBI NIH HHS - HL062571(United States)
  • NIMH NIH HHS - R01 MH084812(United States)

Insular projections to the parahippocampal region in the rat.

  • Mathiasen ML
  • J. Comp. Neurol.
  • 2015 Jun 15

Literature context:


Abstract:

The insular cortex is involved in the perception of interoceptive signals, coding of emotional and affective states, and processing information from gustatory, olfactory, auditory, somatosensory, and nociceptive modalities. This information represents an important component of episodic memory, mediated by the parahippocampal-hippocampal region. A comprehensive description of insular projections to the latter region is lacking. Previous studies reported that insular projections do not target any of the subdivisions in the hippocampal formation (the dentate gyus, the cornu ammonis [CA] fields 1, 2, and 3 and the subiculum), but, in contrast, target the parahippocampal region (perirhinal, postrhinal, lateral and medial entorhinal cortices, and pre- and parasubiculum). The present study examined the topographical and laminar organization of insular projections to the parahippocampal region in the rat with the use of anterograde tracing. Notably, our results corroborated the absence of hippocampal projections. We further showed that the perirhinal and the lateral entorhinal cortices received extensive projections from the insular cortex, primarily from its agranular areas. With the exception of a weak projection to the postrhinal cortex, projections to the remaining parahippocampal areas were either absent or very sparse. The projections to the lateral entorhinal cortex displayed a preference for the deep layers of its most lateral subdivisions, known also to receive hippocampal inputs. Projections to the perirhinal cortex primarily targeted the superficial layers with a preference for its ventral subdivision, referred to as area 35. Our findings indicate that only processed information, reflecting emotional and affective states, but not primary gustatory and viscerosensory information, has direct access to the parahippocampal-hippocampal system.

Bmp7 and Lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in medaka.

  • Ogino Y
  • Endocrinology
  • 2014 Feb 22

Literature context:


Abstract:

Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.

Funding information:
  • NICHD NIH HHS - HD007463(United States)
  • NIMH NIH HHS - 1R01 MH084803(United States)