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1.
Nature ; 601(7894): 595-599, 2022 01.
Article in English | MEDLINE | ID: mdl-34937941

ABSTRACT

Odours are a fundamental part of the sensory environment used by animals to guide behaviours such as foraging and navigation1,2. Primary olfactory (piriform) cortex is thought to be the main cortical region for encoding odour identity3-8. Here, using neural ensemble recordings in freely moving rats performing an odour-cued spatial choice task, we show that posterior piriform cortex neurons carry a robust spatial representation of the environment. Piriform spatial representations have features of a learned cognitive map, being most prominent near odour ports, stable across behavioural contexts and independent of olfactory drive or reward availability. The accuracy of spatial information carried by individual piriform neurons was predicted by the strength of their functional coupling to the hippocampal theta rhythm. Ensembles of piriform neurons concurrently represented odour identity as well as spatial locations of animals, forming an odour-place map. Our results reveal a function for piriform cortex in spatial cognition and suggest that it is well-suited to form odour-place associations and guide olfactory-cued spatial navigation.


Subject(s)
Olfactory Cortex , Piriform Cortex , Spatial Navigation , Animals , Odorants , Olfactory Bulb/physiology , Olfactory Cortex/physiology , Olfactory Pathways/physiology , Piriform Cortex/physiology , Rats , Smell/physiology
2.
Vascular ; 31(1): 178-181, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34854325

ABSTRACT

OBJECTIVES: This report aims to review the management and outcomes of Brucella-associated mycotic aortic aneurysms. METHODS: This is a retrospective chart review at a tertiary-level healthcare system. IRB approval was waived per policy. RESULTS: We describe a case of Brucella aortitis acquired from habitual contact with wild hogs. Clinical presentation included lower back pain and elevated white blood cell count. Diagnosis was confirmed with imaging showing an infrarenal abdominal aortic aneurysm and serology revealing elevated Brucella antibodies titers. The patient was initially managed with endovascular aortic repair and combined oral and intravenous antibiotics therapy. He then underwent explanation and extra-anatomical bypass due to symptomatic periaortic infection and interval development of type I endoleak. The patient was asymptomatic after his final operation at 24 months of follow-up and remained on suppressive oral antibiotic therapy. CONCLUSIONS: An aortic aneurysm secondary to Brucella is a rare entity. A detailed history of long-term exposure to animals may be a clue to obtain serologic testing. Operative debridement and re-establishing of reliable blood flow combined with long-term antibiotic suppression are the mainstay of treatment.


Subject(s)
Aneurysm, Infected , Aortic Aneurysm, Abdominal , Aortitis , Blood Vessel Prosthesis Implantation , Brucella , Male , Animals , Debridement , Aortitis/diagnostic imaging , Aortitis/drug therapy , Aortitis/surgery , Retrospective Studies , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Anti-Bacterial Agents/therapeutic use , Aneurysm, Infected/diagnostic imaging , Aneurysm, Infected/surgery , Treatment Outcome , Blood Vessel Prosthesis Implantation/adverse effects
3.
Clin Sci (Lond) ; 136(5): 309-321, 2022 03 18.
Article in English | MEDLINE | ID: mdl-35132998

ABSTRACT

Prostaglandin D2 (PGD2) released from immune cells or other cell types activates its receptors, D prostanoid receptor (DP)1 and 2 (DP1 and DP2), to promote inflammatory responses in allergic and lung diseases. Prostaglandin-mediated inflammation may also contribute to vascular diseases such as abdominal aortic aneurysm (AAA). However, the role of DP receptors in the pathogenesis of AAA has not been systematically investigated. In the present study, DP1-deficient mice and pharmacological inhibitors of either DP1 or DP2 were tested in two distinct mouse models of AAA formation: angiotensin II (AngII) infusion and calcium chloride (CaCl2) application. DP1-deficient mice [both heterozygous (DP1+/-) and homozygous (DP1-/-)] were protected against CaCl2-induced AAA formation, in conjunction with decreased matrix metallopeptidase (MMP) activity and adventitial inflammatory cell infiltration. In the AngII infusion model, DP1+/- mice, but not DP1-/- mice, exhibited reduced AAA formation. Interestingly, compensatory up-regulation of the DP2 receptor was detected in DP1-/- mice in response to AngII infusion, suggesting a potential role for DP2 receptors in AAA. Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA.


Subject(s)
Aortic Aneurysm, Abdominal/etiology , Receptors, Immunologic/physiology , Receptors, Prostaglandin/physiology , Angiotensin II/pharmacology , Animals , Aortic Aneurysm, Abdominal/prevention & control , Male , Mice , Receptors, Immunologic/antagonists & inhibitors , Receptors, Prostaglandin/antagonists & inhibitors
4.
Ann Vasc Surg ; 76: 599.e11-599.e14, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33508449

ABSTRACT

Coil migration into the colon is an extremely rare complication of aneurysm embolization and only three cases have been reported. Two of these cases were managed with resection of the involved colon and the remaining case was managed with serial imaging. We present a 70-year-old man who developed hematochezia 2 years after coil embolization of a ruptured left hypogastric artery aneurysm. The patient was successfully treated with diverting colostomy and endoscopic closure of the sigmoid colon defect. We present the only case report of the use of advanced endoscopy to treat endovascular coil migration.


Subject(s)
Aneurysm, Ruptured/therapy , Embolization, Therapeutic/adverse effects , Foreign-Body Migration/etiology , Iliac Aneurysm/therapy , Intestinal Fistula/etiology , Pelvis/blood supply , Sigmoid Diseases/etiology , Vascular Fistula/etiology , Aged , Aneurysm, Ruptured/diagnostic imaging , Colostomy , Embolization, Therapeutic/instrumentation , Endoscopy , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/surgery , Humans , Iliac Aneurysm/diagnostic imaging , Intestinal Fistula/diagnostic imaging , Intestinal Fistula/surgery , Male , Sigmoid Diseases/diagnostic imaging , Sigmoid Diseases/surgery , Treatment Outcome , Vascular Fistula/diagnostic imaging , Vascular Fistula/surgery
5.
Ann Vasc Surg ; 74: 522.e11-522.e14, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33831515

ABSTRACT

We report a case of mycotic thoracic aortic aneurysm managed by staged hybrid repair. A 30-year-old male patient with polysubstance abuse presented with chest pain and elevated white blood cell count. CTA performed showed a rapidly developing mycotic thoracic aortic pseudoaneurysm. He underwent emergent thoracic endovascular aortic repair followed 24 hours later by surgical debridement of the posterior mediastinum. Cultures grew Methicillin-resistant Staphylococcus aureus and patient was placed on long term antibiotics. The patient was asymptomatic on follow up one year after his final operation with complete exclusion of pseudoaneurysm with no endoleak.


Subject(s)
Aneurysm, Infected/surgery , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/surgery , Adult , Aneurysm, Infected/diagnostic imaging , Aneurysm, Infected/microbiology , Anti-Bacterial Agents/therapeutic use , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/microbiology , Debridement , Drug Users , Humans , Male , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Substance Abuse, Intravenous/complications , Treatment Outcome
6.
Proc Natl Acad Sci U S A ; 115(37): E8660-E8667, 2018 09 11.
Article in English | MEDLINE | ID: mdl-30139920

ABSTRACT

In response to vascular injury, vascular smooth muscle cells (VSMCs) may switch from a contractile to a proliferative phenotype thereby contributing to neointima formation. Previous studies showed that the long noncoding RNA (lncRNA) NEAT1 is critical for paraspeckle formation and tumorigenesis by promoting cell proliferation and migration. However, the role of NEAT1 in VSMC phenotypic modulation is unknown. Herein we showed that NEAT1 expression was induced in VSMCs during phenotypic switching in vivo and in vitro. Silencing NEAT1 in VSMCs resulted in enhanced expression of SM-specific genes while attenuating VSMC proliferation and migration. Conversely, overexpression of NEAT1 in VSMCs had opposite effects. These in vitro findings were further supported by in vivo studies in which NEAT1 knockout mice exhibited significantly decreased neointima formation following vascular injury, due to attenuated VSMC proliferation. Mechanistic studies demonstrated that NEAT1 sequesters the key chromatin modifier WDR5 (WD Repeat Domain 5) from SM-specific gene loci, thereby initiating an epigenetic "off" state, resulting in down-regulation of SM-specific gene expression. Taken together, we demonstrated an unexpected role of the lncRNA NEAT1 in regulating phenotypic switching by repressing SM-contractile gene expression through an epigenetic regulatory mechanism. Our data suggest that NEAT1 is a therapeutic target for treating occlusive vascular diseases.


Subject(s)
Gene Expression Regulation , Myocytes, Smooth Muscle/metabolism , RNA, Long Noncoding/genetics , Animals , Cell Movement/genetics , Cell Proliferation/genetics , Cells, Cultured , Humans , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/cytology , Neointima/genetics , Neointima/metabolism , Phenotype , RNA Interference , Rats , Vascular System Injuries/genetics , Vascular System Injuries/metabolism , Vascular System Injuries/pathology
9.
14.
bioRxiv ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39386694

ABSTRACT

Odors are a fundamental part of the sensory environment used by animals to inform behaviors such as foraging and navigation1,2. Primary olfactory (piriform) cortex is thought to be dedicated to encoding odor identity3-8. Here, using neural ensemble recordings in freely moving rats performing a novel odor-cued spatial choice task, we show that posterior piriform cortex neurons also carry a robust spatial map of the environment. Piriform spatial maps were stable across behavioral contexts independent of olfactory drive or reward availability, and the accuracy of spatial information carried by individual neurons depended on the strength of their functional coupling to the hippocampal theta rhythm. Ensembles of piriform neurons concurrently represented odor identity as well as spatial locations of animals, forming an "olfactory-place map". Our results reveal a previously unknown function for piriform cortex in spatial cognition and suggest that it is well-suited to form odor-place associations and guide olfactory cued spatial navigation.

15.
bioRxiv ; 2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38187593

ABSTRACT

Local field potentials (LFPs) reflect the collective dynamics of neural populations, yet their exact relationship to neural codes remains unknown1. One notable exception is the theta rhythm of the rodent hippocampus, which seems to provide a reference clock to decode the animal's position from spatiotemporal patterns of neuronal spiking2 or LFPs3. But when the animal stops, theta becomes irregular4, potentially indicating the breakdown of temporal coding by neural populations. Here we show that no such breakdown occurs, introducing an artificial neural network that can recover position-tuned rhythmic patterns (pThetas) without relying on the more prominent theta rhythm as a reference clock. pTheta and theta preferentially correlate with place cell and interneuron spiking, respectively. When rats forage in an open field, pTheta is jointly tuned to position and head orientation, a property not seen in individual place cells but expected to emerge from place cell sequences5. Our work demonstrates that weak and intermittent oscillations, as seen in many brain regions and species, can carry behavioral information commensurate with population spike codes.

16.
Ann Vasc Surg ; 26(2): 279.e13-6, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22304868

ABSTRACT

This report is the first to describe the clinical, radiographic, operative, and pathologic findings associated with large, bilateral dorsalis pedis artery true aneurysms in a single patient. A 61-year-old African American woman complained of difficulty in wearing shoes. She had a moderately firm, nontender, pulsatile mass on the dorsum of her right foot. Computed tomography and angiography confirmed dorsalis pedis artery aneurysm with sufficient collateralization. She underwent resection without reconstruction. Pathologic analysis revealed a true aneurysm (8 × 5.3 × 4.1 cm(3)) containing intralumenal thrombus. Treatment for small symptomatic and large dorsalis pedis artery aneurysms remains resection with or without reconstruction.


Subject(s)
Aneurysm/diagnosis , Foot/blood supply , Aneurysm/diagnostic imaging , Aneurysm/pathology , Aneurysm/surgery , Arteries/pathology , Female , Humans , Ligation , Middle Aged , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome , Vascular Surgical Procedures
17.
Vasc Endovascular Surg ; 56(8): 775-778, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35726740

ABSTRACT

Penetrating injuries of the neck involving major vessels are associated with high morbidity and mortality. A traumatic arteriovenous (AV) fistula can provide a protective effect by decompressing the injured arterial structure and prevent massive blood loss and airway compression. We present a novel description of CCA (common carotid artery) transection with associated protective AV fistula. Protective AV fistulae have been uncommonly described, and to our knowledge, this is the first case involving carotid transection with associated protective AV fistula ultimately allowing lifesaving operative repair.


Subject(s)
Arteriovenous Fistula , Vascular System Injuries , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/etiology , Arteriovenous Fistula/therapy , Carotid Artery, Common/diagnostic imaging , Carotid Artery, Common/surgery , Humans , Treatment Outcome , Vascular System Injuries/diagnostic imaging , Vascular System Injuries/etiology , Vascular System Injuries/surgery
18.
Neuron ; 56(1): 124-40, 2007 Oct 04.
Article in English | MEDLINE | ID: mdl-17920020

ABSTRACT

Membrane depolarization causes voltage-gated ion channels to transition from a resting/closed conformation to an activated/open conformation. We used voltage-clamp fluorometry to measure protein motion at specific regions of the Shaker Kv channel. This enabled us to construct new structural models of the resting/closed and activated/open states based on the Kv1.2 crystal structure using the Rosetta-Membrane method and molecular dynamics simulations. Our models account for the measured gating charge displacement and suggest a molecular mechanism of activation in which the primary voltage sensors, S4s, rotate by approximately 180 degrees as they move "outward" by 6-8 A. A subsequent tilting motion of the S4s and the pore domain helices, S5s, of all four subunits induces a concerted movement of the channel's S4-S5 linkers and S6 helices, allowing ion conduction. Our models are compatible with a wide body of data and resolve apparent contradictions that previously led to several distinct models of voltage sensing.


Subject(s)
Ion Channel Gating/physiology , Membrane Potentials/physiology , Shaker Superfamily of Potassium Channels/physiology , Animals , Dose-Response Relationship, Radiation , Electric Stimulation , Membrane Potentials/radiation effects , Models, Biological , Models, Molecular , Mutation/physiology , Oocytes , Patch-Clamp Techniques/methods , Protein Conformation , Protein Structure, Tertiary , Structure-Activity Relationship
19.
J Neurophysiol ; 105(4): 1711-21, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21289134

ABSTRACT

Insect pheromonal glomeruli are thought to track the fine spatiotemporal features of one or a few odorants to aid conspecific localization. However, it is not clear whether they function differently from generalist glomeruli, which respond to many odorants. In this study, we test how DA1, a model pheromonal glomerulus in the fruit fly, represents the spatial and temporal properties of its input, compared with other glomeruli. We combine calcium imaging and electrical stimulation in an isolated brain preparation for a simultaneous, unbiased comparison of the functional organization of many glomeruli. In contrast to what is found in other glomeruli, we find that ipsilateral and contralateral stimuli elicit distinct spatial patterns of activity within DA1. DA1's output shows a greater preference for ipsilateral stimuli in males than in females. DA1 experiences greater and more rapid inhibition than other glomeruli, allowing it to report slight interantennal delays in stimulus onset in a "winner-take-all" manner. DA1's ability to encode spatiotemporal input features distinguishes it from other glomeruli in the fruit fly antennal lobe but relates it to pheromonal glomeruli in other insect species. We propose that DA1 is specialized to help the fly localize and orient with respect to pheromone sources.


Subject(s)
Drosophila/physiology , Sex Attractants/physiology , Animals , Behavior, Animal/physiology , Calcium/metabolism , Electric Stimulation , Female , Male , Odorants , Olfactory Pathways/physiology
20.
Vasc Endovascular Surg ; 55(8): 864-868, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33906552

ABSTRACT

This is a report of an iatrogenic inferior vena cava (IVC) segmental resection and reconstruction utilizing bovine pericardium. A 48-year-old female patient presented for a planned right nephrectomy by the urology service secondary to xanthogranulomatous pyelonephritis. This was complicated by inadvertent resection of an 8 cm segment of the infrarenal IVC. Postoperatively, the patient did not tolerate IVC ligation due to severe lower extremity edema. She then underwent reconstruction with a bovine pericardium conduit as an interposition graft. The post-operative course was complicated by pulmonary embolism requiring percutaneous intervention. This report addresses the utility of bovine pericardium for IVC reconstruction in an infected field.


Subject(s)
Nephrectomy , Vena Cava, Inferior , Animals , Cattle , Female , Humans , Iatrogenic Disease , Middle Aged , Pericardium , Treatment Outcome , Vena Cava, Inferior/diagnostic imaging , Vena Cava, Inferior/surgery
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