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1.
Nature ; 531(7594): 371-5, 2016 Mar 17.
Article in English | MEDLINE | ID: mdl-26958833

ABSTRACT

Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.


Subject(s)
Insulin-Like Growth Factor I/metabolism , Neural Inhibition , Neurons/metabolism , Vasoactive Intestinal Peptide/metabolism , Visual Cortex/cytology , Visual Cortex/physiology , Animals , Female , Male , Mice , Mice, Inbred C57BL , Neural Pathways , Neuronal Plasticity , Neurons/cytology , Pyramidal Cells/metabolism , Synapses/metabolism , Vision, Ocular/physiology
2.
J Vet Intern Med ; 23(3): 623-5, 2009.
Article in English | MEDLINE | ID: mdl-19645844

ABSTRACT

BACKGROUND: Equine sarcoidosis is a rare, multisystemic, noncaseating, granulomatous and lymphoplasmacytic disease of unknown etiology. A recent report described a horse with granulomatous skin disease displaying histologic, electron microscopic, and polymerase chain reaction (PCR) findings consistent with equine herpesvirus 2 (EHV-2). OBJECTIVE: To investigate the presence of EHV-2 and equine herpesvirus 1 (EHV-1) in 8 horses with sarcoidosis. ANIMALS: Eight horses with sarcoidosis, reported previously. METHODS: Retrospective study. PCR assays of the tissues were performed to detect DNA associated with EHV-1 and EHV-2. For both herpesviruses the target was their respective glycoprotein B gene. Positive controls consisted of DNA from viral cultures of culturettes from naturally occurring respiratory infections of EHV-1 and EHV-2. RESULTS: The PCR analyses for both equine herpesviruses' DNA were negative in all 8 horses. CONCLUSION: The failure to detect DNA from EHV-1 and EHV-2 in paraffin-embedded skin of these 8 horses does not discount EHV-1 or EHV-2 as causing some cases of ES, but lends support to the presumably multifactorial etiologic nature of the disease.


Subject(s)
Herpesvirus 1, Equid/isolation & purification , Horse Diseases/virology , Rhadinovirus/isolation & purification , Sarcoidosis/veterinary , Animals , Base Sequence , Horses , Paraffin Embedding , Polymerase Chain Reaction/veterinary , Sarcoidosis/virology , Specimen Handling/veterinary
3.
J Mol Biol ; 294(1): 121-37, 1999 Nov 19.
Article in English | MEDLINE | ID: mdl-10556033

ABSTRACT

The RFX protein family includes members from yeast to humans, which function in various biological systems, and share a DNA-binding domain and a conserved C-terminal region. In the human transcription regulator RFX1, the conserved C terminus is an independent functional domain, which mediates dimerization and transcriptional repression. This dimerization domain has a unique ability to mediate the formation of two alternative homodimeric DNA-protein complexes, the upper of which has been linked to repression. Here, we localize the complex formation capacity to several different RFX1 C-terminal subregions, each of which can function independently to generate the upper complex and repress transcription, thus correlating complex formation with repression. To gain an evolutionary perspective, we have examined whether the different properties of the RFX1 C terminus exist in the two yeast RFX proteins, which are involved in signaling pathways. Replacement of the RFX1 C terminus with those of Sak1 and Crt1, its orthologues from Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively, and analysis of fusions with the Gal4 DNA-binding domain, revealed that the ability to generate the two alternative complexes is conserved in the RFX family, from S. cerevisiae to man. While sharing this unique biochemical property, the three C termini differed from each other in their ability to mediate dimerization and transcriptional repression. In both functions, RFX1, Sak1, and Crt1 showed high capacity, moderate capacity, and no capacity, respectively. This comparative analysis of the RFX proteins, representing different evolutionary stages, suggests a gradual development of the conserved C terminus, from the appearance of the ancestral motif (Crt1), to the later acquisition of the dimerization/repression functions (Sak1), and finally to the enhancement of these functions to generate a domain mediating highly stable protein-protein interactions and potent transcriptional repression (RFX1).


Subject(s)
Cell Cycle Proteins , DNA-Binding Proteins/genetics , Repressor Proteins/genetics , Saccharomyces cerevisiae Proteins , Schizosaccharomyces pombe Proteins , Transcription Factors/genetics , Amino Acid Sequence , Conserved Sequence , DNA-Binding Proteins/metabolism , Dimerization , Evolution, Molecular , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation , Humans , Models, Genetic , Multigene Family , Protein Binding , Protein Structure, Tertiary , Recombinant Fusion Proteins/metabolism , Regulatory Factor X Transcription Factors , Regulatory Factor X1 , Repressor Proteins/metabolism , Saccharomyces cerevisiae/genetics , Schizosaccharomyces/genetics , Transcription Factors/metabolism , Transcription, Genetic
4.
J Vasc Res ; 34(4): 306-11, 1997.
Article in English | MEDLINE | ID: mdl-9256091

ABSTRACT

The treatment of patients with lymphedema is still controversial. Combined physical therapy with manual lymph drainage and compression therapy is most frequently used to reduce lymphatic leg swelling. However, objective evidence is rare that this empirical form of treatment has a scientific basis. In a prospective study fluorescence microlymphography and pressure measurements in cutaneous lymph capillaries were used to assess objectively the effect of combined decongestive physical therapy on abnormal microlymphatic dynamics in lymphedema. 12 patients with primary and secondary lymphedema were studied before treatment, after 2 weeks of intensive physical therapy and 3 months of continuing compression and ergotherapy. After 2 weeks of intensive manual lymph drainage and compression bandaging (phase 1) microlymphatic hypertension (12.8 +/- 5.7 mm Hg) was significantly (p = 0.01) reduced to a mean lymph capillary pressure of 5.9 +/- 4.5 mm Hg. More than 3 months later after continuing compression lymph capillary pressure (3.2 +/- 5.2 mm Hg) was still significantly (p = 0.03) reduced. Simultaneously the maximum spread of the fluorescent contrast medium in the superficial lymph capillary network decreased significantly (p = 0.01) from 21.3 +/- 14.3 to 11.3 +/- 4.8 mm. Accordingly the clinical condition improved, and the mean circumferences of the forefoot and ankle were significantly (p < 0.05) reduced. Combined decongestive physical therapy is an effective treatment for lymphedema which results in a normalization of microlymphatic hypertension and an improvement of the clinical appearance.


Subject(s)
Lymphedema/rehabilitation , Adult , Aged , Female , Humans , Hydrostatic Pressure , Leg , Lymphedema/physiopathology , Male , Middle Aged , Physical Therapy Modalities
5.
Bull Med Libr Assoc ; 61(2): 205-9, 1973 Apr.
Article in English | MEDLINE | ID: mdl-4739884

ABSTRACT

One hundred sixty-five search requests processed through the SUNY Biomedical Communication Network were analyzed to determine how many of the citations thus retrieved would have been retrievable by MEDLINE. The results showed that MEDLINE would have been capable of retrieving 78.7% of the SUNY citations. Almost half of the 21.3% of the citations not retrievable by MEDLINE were from foreign-language journals. A subject analysis of the data showed that in most subject areas MEDLINE was able to provide a relatively small percentage of the journal titles generated by SUNY. These few titles, however, contained a large percentage of the SUNY citations involved in the study.


Subject(s)
Information Systems , National Library of Medicine (U.S.) , Evaluation Studies as Topic , Information Services , New York , Periodicals as Topic , Time Factors , United States , Universities
6.
J Med Soc N J ; 69(1): 65-7, 1972 Jan.
Article in English | MEDLINE | ID: mdl-4500447
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