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1.
Angew Chem Int Ed Engl ; 62(3): e202215286, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36408901

RESUMEN

Among ferroelectric crystals based on small molecules, plastic/ferroelectric crystals are currently receiving particular attention because they can be used as bulk polycrystals. Herein, we show that an ionic molecular ferroelectric crystal, guanidinium tetrafluoroborate, exhibits significant malleability and multiaxial ferroelectricity despite the absence of a plastic crystal phase. Powder samples of this crystal can be processed into transparent bulk crystalline plates either by press-forming or by melt-growing. The plates show high ferroelectric performance and related properties, demonstrating the largest hitherto reported spontaneous polarization for bulk polycrystals of small-molecule-based ferroelectrics. Owing to the ready availability of large-scale materials and processability into various bulk crystalline forms, this ferroelectric crystal represents a highly promising functional material that will boost research on diverse applications as bulk crystals.

2.
Opt Express ; 29(22): 36353-36365, 2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34809047

RESUMEN

While ultrahigh-baud-rate optical signals are effective for extending the transmission distance of large capacity signals, they also reduce the number of wavelengths that can be arranged in a band because of their wider bandwidth. This reduces the flexibility of optical path configuration in reconfigurable optical add/drop multiplexing (ROADM) networks. Particularly in colorless, directionless and contentionless (CDC)-ROADM, the effect reduces the add/drop ratio at a node. Multiband ROADM systems are an effective countermeasure for overcoming this issue, but they make the node configuration more complicated and its operation more difficult. In this paper, we analyze the challenges of C + L band CDC-ROADM and show that optical switch devices that operate over multiple bands are effective in meeting them. For this purpose, we built a C + L band CDC-ROADM node based on C + L band wavelength-selective switches and multicast switches and confirmed its effectiveness experimentally. In particular, to simplify the node configuration, we propose a reduction in the number of optical amplifiers used for node loss compensation and experimentally verify its feasibility.

3.
Biotechnol Bioeng ; 118(9): 3569-3580, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34032276

RESUMEN

We evaluated filtration behavior and virus removal capability for a monoclonal antibodies (mAb) and plasma IgG under constant flow rate directly following flow-through column chromatography in an integrated process. mAb solution with quantified host cell protein (HCP) content processed in flow-through mode on in-series mixed-mode AEX and modified CEX columns connected to the Planova BioEX filter (pool-less) achieved HCP logarithmic reduction value (LRV) of 2.3 and 93.9% protein recovery, demonstrating comparable or higher HCP LRV with high protein recovery compared to previous reports. For 5-15 mg/ml plasma IgG run to 100 L/m2 , similar filtration behavior was achieved for flux of 10-100 LMH, and lower flux runs remained well below the maximum operating pressure, suggesting that higher throughput in continuous processing is achievable. Comparison of fit of plasma IgG and mAb filtration behavior to four blocking models showed little differences but slightly better fit to the cake filtration model. Viral clearance of the filtration step tested by in-line spiking X-MuLV or MVM into purified plasma IgG following the chromatography step showed robust removal at low flux. Integrating the Planova BioEX filter into continuous processes with column chromatography can achieve efficient downstream processing with reduced footprint and process time.


Asunto(s)
Anticuerpos Monoclonales/química , Inmunoglobulinas Intravenosas/química , Virus de la Leucemia Murina/química , Cromatografía , Filtración
4.
Gan To Kagaku Ryoho ; 47(13): 2355-2357, 2020 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-33468959

RESUMEN

Gastric adenocarcinoma with enteroblastic differentiation(GAED)is a rare disease that is classified as a special type in the 15th edition Japanese Classification of Gastric Carcinoma. GAED is considered to have a poor prognosis. We report about a 76-year-old man with GAED who presented with complaints of poor appetite and weight loss. He was suspected of having gastric cancer based on ultrasonography and computed tomography findings and was referred to our hospital by his home doctor. Upper gastrointestinal endoscopy revealed a gastric cancer in the lesser curvature of the gastric antrum. Distal gastrectomy was performed. Histopathology showed a moderately differentiated adenocarcinoma with a clear cytoplasm. Immunostaining was positive for Sal-like protein 4(SALL4)and negative for α-fetoprotein(AFP). The patient was diagnosed as having GAED. Vascular and lymphatic invasion were not observed. He was discharged on the 9th day after surgery. At 5 months postoperatively, he was treated with adjuvant chemotherapy, and no recurrence was noted. GAED is a rare disease with a poor prognosis. We report this case and discuss relevant literature.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Anciano , Diferenciación Celular , Gastrectomía , Humanos , Masculino , Recurrencia Local de Neoplasia , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía
5.
J Am Chem Soc ; 141(23): 9349-9357, 2019 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-31184147

RESUMEN

Molecular ferroelectric crystals have attracted growing interest as potential alternatives to conventional lead-based ceramic ferroelectrics. We have recently discovered that a class of compounds known as plastic crystals can show multiaxial ferroelectricity, which allows ferroelectric performance even in polycrystalline forms. Here, we report new plastic/ferroelectric ionic molecular crystals that exhibit remarkably small coercive electric fields at room temperature. The easily switchable ferroelectric polarization enables low-voltage switching operations and high-frequency performance. Such ferroelectric crystals can be readily processed into bulk polycrystalline forms with desired shapes that are characterized by unprecedentedly high pyroelectric figures of merit and large piezoelectricity. These multifunctional molecular crystals represent highly attractive prospects for device elements with a diverse range of applications, which will significantly boost the development of molecular ferroelectric crystals.

6.
Inorg Chem ; 58(22): 15410-15416, 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31692349

RESUMEN

Structural phase transitions of calcium strontium sulfoaluminate series, (Ca1-xSrx)8[AlO2]12(SO4)2 ((CS)AS-x) with x = 0.80-1.00, are systematically investigated by powder X-ray diffraction, dielectric measurements, and pyroelectric measurements, to clarify a phase diagram of (CS)AS-x (x = 0.80-1.00). A pure strontium sulfoaluminate, (CS)AS-1.00, is found to undergo three phase transitions, which take place successively on cooling from a prototypical cubic phase with the symmetry of Im3̅m. Though the room-temperature phase of (CS)AS-1.00 was previously reported to be of polar Pcc2, the pyroelectric measurements clarified a nonpolar character of the crystal symmetry. The dielectric measurements suggest a possibility of an antiferroelectric ground state of (CS)AS-x in the Sr-rich compositions. As x decreases, the ground state changes to a short-range-ordered state, implying a unique phase transition from the antiferroelectric state to the antiferroelectric-relaxor state. The present study provides an intriguing playground for designing new ferro/antiferroelectric materials.

7.
Hinyokika Kiyo ; 65(5): 151-155, 2019 May.
Artículo en Japonés | MEDLINE | ID: mdl-31247692

RESUMEN

A 69-year-old female was introduced to our department for a retroperitoneal mass, 25 mm in diameter, in the right perirenal space indicated by computed tomography (CT). On the basis of magnetic resonance imaging (MRI), retroperitoneal soft tissue sarcoma was suspected. Because she rejected surgical treatment, we continued imaging surveillance. Subsequently, the mass grew larger, but her intention did not change. At 21 months after initial consultation, CT revealed further increase of the above mass and a new lesion with calcification. Ultimately, she underwent mass resection with concomitant resection of the right kidney. Histological examination showed dedifferentiated liposarcoma with metaplastic bone formation and positive surgical margin, but she refused adjuvant chemotherapy. She has survived 7 months since the operation with no evidence of recurrence.


Asunto(s)
Liposarcoma , Neoplasias Retroperitoneales , Anciano , Femenino , Humanos , Liposarcoma/diagnóstico , Liposarcoma/cirugía , Recurrencia Local de Neoplasia , Osteogénesis , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/cirugía , Tomografía Computarizada por Rayos X
8.
J Neurosci ; 37(41): 9901-9916, 2017 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-28912162

RESUMEN

Different cortical regions processing distinct information, such as the hippocampus and the neocortex, share common cellular components and circuit motifs but form unique networks by modifying these cardinal units. Cortical circuits include diverse types of GABAergic interneurons (INs) that shape activity of excitatory principal neurons (PNs). Canonical IN types conserved across distinct cortical regions have been defined by their morphological, electrophysiological, and neurochemical properties. However, it remains largely unknown whether canonical IN types undergo specific modifications in distinct cortical regions and display "regional variants." It is also poorly understood whether such phenotypic variations are shaped by early specification or regional cellular environment. The chandelier cell (ChC) is a highly stereotyped IN type that innervates axon initial segments of PNs and thus serves as a good model with which to address this issue. Here, we show that Cadherin-6 (Cdh6), a homophilic cell adhesion molecule, is a reliable marker of ChCs and Cdh6-CreER mice (both sexes) provide genetic access to hippocampal ChCs (h-ChCs). We demonstrate that, compared with neocortical ChCs (nc-ChCs), h-ChCs cover twice as much area and innervate twice as many PNs. Interestingly, a subclass of h-ChCs exhibits calretinin (CR) expression, which is not found in nc-ChCs. Furthermore, we find that h-ChCs appear to be born earlier than nc-ChCs. Surprisingly, despite the difference in temporal origins, ChCs display host-region-dependent axonal/synaptic organization and CR expression when transplanted heterotopically. These results suggest that local cellular environment plays a critical role in shaping terminal phenotypes of regional IN variants in the hippocampus and the neocortex.SIGNIFICANCE STATEMENT Canonical interneuron (IN) types conserved across distinct cortical regions such as the hippocampus and the neocortex are defined by morphology, physiology, and gene expression. However, it remains unknown whether they display phenotypic variations in different cortical regions. In addition, it is unclear whether terminal phenotypes of regional IN variants belonging to a canonical IN type are determined intrinsically or extrinsically. Our results provide evidence of striking differences in axonal/synaptic organization and calretinin expression between hippocampal chandelier cells (ChCs) and neocortical ChCs. They also reveal that local cellular environment in distinct cortical regions regulates these terminal phenotypes. Therefore, our study suggests that local cortical environment shapes the phenotypes of regional IN variants, which may be required for unique circuit operations in distinct cortical regions.


Asunto(s)
Forma de la Célula/fisiología , Hipocampo/citología , Hipocampo/fisiología , Interneuronas/fisiología , Neocórtex/citología , Neocórtex/fisiología , Animales , Axones/fisiología , Cadherinas/genética , Cadherinas/fisiología , Calbindina 2/biosíntesis , Calbindina 2/genética , Microambiente Celular , Femenino , Técnicas de Sustitución del Gen , Interneuronas/trasplante , Interneuronas/ultraestructura , Masculino , Ratones , Sinapsis/fisiología
9.
Nature ; 490(7419): 226-31, 2012 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-23060193

RESUMEN

The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the cell's response to a stimulus in the centre of its receptive field, a phenomenon called surround suppression. Whether cortical circuits contribute to surround suppression or whether the phenomenon is entirely relayed from earlier stages of visual processing is debated. Here we show that, in contrast to pyramidal cells, the response of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround. This difference results from the preferential excitation of SOMs by horizontal cortical axons. By perturbing the activity of SOMs, we show that these neurons contribute to pyramidal cells' surround suppression. These results establish a cortical circuit for surround suppression and attribute a particular function to a genetically defined type of inhibitory neuron.


Asunto(s)
Sumación de Potenciales Postsinápticos/fisiología , Corteza Visual/fisiología , Animales , Axones/metabolismo , Ratones , Células Piramidales/metabolismo , Neuronas Retinianas/citología , Neuronas Retinianas/fisiología
10.
Nature ; 488(7411): 379-83, 2012 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-22878719

RESUMEN

Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.


Asunto(s)
Interneuronas/fisiología , Corteza Visual/citología , Corteza Visual/fisiología , Percepción Visual/fisiología , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/deficiencia , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Channelrhodopsins , Aprendizaje Discriminativo , Ratones , Modelos Neurológicos , Inhibición Neural/fisiología , Parvalbúminas/metabolismo , Rodopsinas Microbianas/metabolismo , Vigilia/fisiología , Ácido gamma-Aminobutírico/metabolismo
11.
Gan To Kagaku Ryoho ; 45(3): 536-538, 2018 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-29650930

RESUMEN

A 74-year-old man was referred to our hospital for further investigation of a cystic lesion in the pancreatic body, which had been detected by ultrasonography at a local hospital. He was diagnosed as intraductal papillary mucinous neoplasm(IPMN) and further preoperative examinations were conducted. Upper gastrointestinal endoscopy demonstrated a type 0-II c tumor of the greater curvature in the upper third of the stomach. Endoscopic ultrasonography showed no sign of submucosal invasion. Endoscopic submucosal dissection(ESD)was carried out and pathological examination of a specimen revealed well differentiated adenocarcinoma with submucosal invasion, which fulfilled the indication for additional gastrectomy with lymph node dissection. Laparoscopy-assisted proxymal gastrectomy with D1 plus lymph node dissection and distal pancreatectomy with splenectomy was performed. Pathological examination demonstrated intraductal papillary mucious adenoma(IPMA)in the pancreatic body and no residual gastric cancer in a specimen, however 7lymph node metastases from gastric cancer was confirmed(pN3a), including 3 metastatic lymph nodes incidentally-detected adjacent to the pancreatic parenchyma. We report a rare case of early gastric cancer with N3 lymph node metastases, with a brief literature review.


Asunto(s)
Neoplasias Gástricas/cirugía , Anciano , Resección Endoscópica de la Mucosa , Humanos , Metástasis Linfática , Masculino , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Tomografía Computarizada por Rayos X
12.
Gan To Kagaku Ryoho ; 45(3): 477-479, 2018 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-29650910

RESUMEN

With the aging of the population of Japan and Westernization of the dietary life, the number of cases in which cardiovascular diseases are merged in non-cardiac surgery is increasing year by year.Many of the abdominal aortic aneurysms are asymptomatic and it is not uncommon to be discovered accidentally in preoperative examination of non-cardiac surgery.When gastrointestinal surgery involves malignant diseases of the gastrointestinal tract and abdominal aortic aneurysm, the two life prognosis-related diseases are merged, depending on the severity and urgency of the disease for each case, its treatment to determine the priority order.Abdominal aortic aneurysm occurred at the time of malignant disease surgery in 14 cases of gastrointestinal cancer patients who underwent surgery at the department during the 5 years from 2012 to 2016.T he actual condition of treatment for these cases was investigated.


Asunto(s)
Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/cirugía , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/cirugía , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Digestivo , Humanos , Masculino , Complicaciones Posoperatorias , Stents
13.
Gan To Kagaku Ryoho ; 45(3): 468-470, 2018 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-29650907

RESUMEN

The clinical condition of oncologic emergency associated with colorectal cancer includes hemorrhage, perforation and obstruction. Obstructive colorectal cancer is an oncologic emergency commonly observed in our daily clinical practice. Colonic stent placement for obstructive colorectal cancer is relatively easy and safe and may be considered as an effective treatment method that enables favorable intestinal decompression preoperatively and one-stage resection. Colonic stent use can be a bridge to surgery, enabling shorter duration of hospitalization, and reduced postoperative complications, and colostomy rates, as compared to emergency surgery. From January 2009 to December 2016, this study was designed to evaluate the clinical outcomes of 68 patients who underwent surgery for obstructive colorectal cancer. The patients were divided into 2 groups: 32 cases receiving colonic stent placement(the S group), 36 cases receiving ileus tube and emergency surgery(the NS group). There was no significant difference in terms of morbidity or survival rate between the 2 groups. For the S group, 31 out of 32 could one-stage resection(94%). The colostomy rate in the S group was significantly lower than that in the NS group(3% vs 33%). In the S group, number of dissected lymph nodes was significantly larger and the duration of postoperative stay was shorter than that in the NS Group.


Asunto(s)
Neoplasias Colorrectales/cirugía , Obstrucción Intestinal/cirugía , Stents , Adulto , Anciano , Anciano de 80 o más Años , Colectomía , Neoplasias Colorrectales/complicaciones , Servicios Médicos de Urgencia , Femenino , Humanos , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad
14.
J Neurosci ; 36(14): 4000-9, 2016 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-27053207

RESUMEN

Cortical inhibition is mediated by diverse inhibitory neuron types that can each play distinct roles in information processing by virtue of differences in their input sources, intrinsic properties, and innervation targets. Previous studies in brain slices have demonstrated considerable cell-type specificity in laminar sources of local inputs. In contrast, little is known about possible differences in distant inputs to different cortical interneuron types. We used the monosynaptic rabies virus system, in conjunction with mice expressing Cre recombinase in either parvalbumin-positive, somatostatin-positive (SST+), or vasoactive intestinal peptide-positive (VIP+) neurons, to map the brain-wide input to the three major nonoverlapping classes of interneurons in mouse somatosensory cortex. We discovered that all three classes of interneurons received considerable input from known cortical and thalamic input sources, as well as from probable cholinergic cells in the basal nucleus of Meynert. Despite their common input sources, these classes differed in the proportion of long-distance cortical inputs originating from deep versus superficial layers. Similar to their laminar differences in local input, VIP+ neurons received inputs predominantly from deep layers while SST+ neurons received mostly superficial inputs. These classes also differed in the amount of input they received. Cortical and thalamic inputs were greatest onto VIP+ interneurons and smallest onto SST+ neurons. SIGNIFICANCE STATEMENT: These results indicate that all three major interneuron classes in the barrel cortex integrate both feedforward and feedback information from throughout the brain to modulate the activity of the local cortical circuit. However, differences in laminar sources and magnitude of distant cortical input suggest differential contributions from cortical areas. More input to vasoactive intestinal peptide-positive (VIP+) neurons than to somatostatin-positive (SST+) neurons suggests that disinhibition of the cortex via VIP+ cells, which inhibit SST+ cells, might be a general feature of long-distance corticocortical and thalamocortical circuits.


Asunto(s)
Mapeo Encefálico , Corteza Cerebral/fisiología , Interneuronas/fisiología , Sinapsis/fisiología , Animales , Núcleo Basal de Meynert/citología , Núcleo Basal de Meynert/fisiología , Corteza Cerebral/citología , Femenino , Procesamiento de Imagen Asistido por Computador , Masculino , Ratones , Sistema Nervioso Parasimpático/citología , Sistema Nervioso Parasimpático/fisiología , Virus de la Rabia/genética , Corteza Somatosensorial/anatomía & histología , Corteza Somatosensorial/fisiología , Somatostatina/metabolismo , Tálamo/citología , Tálamo/fisiología , Péptido Intestinal Vasoactivo/metabolismo
15.
Gastric Cancer ; 20(1): 126-135, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26874951

RESUMEN

BACKGROUND: We previously demonstrated the potential of circulating tumor DNA (ctDNA) for the amplification of detecting HER2 in patients with gastric cancer (GC). In the present study, we focused on the clinical courses of patients who developed recurrence with GC, and investigated the potential clinical utility of the ddPCR-based HER2 copy number (CN) as a marker for the temporal and/or spatial heterogeneities of GC during treatment progress. METHOD: We enrolled 30 healthy volunteers and 60 patients with GC who underwent surgery, including 17 patients who developed recurrence. Using ribonuclease P RNA component H1 (RPPH1) as a reference gene, plasma HER2 to RPPH1 ratios (the HER2 ratio) were determined using ddPCR. RESULTS: The preoperative plasma HER2 ratio correlated with the tumor HER2 status (p < 0.001), and sensitivity and specificity were 0.733 and 0.933, respectively. Analyses of plasma samples during the postoperative follow-up periods revealed that high plasma HER2 ratios were detected at the time of recurrence in 7 of 13 cases, which were diagnosed as being HER2 negative at the time of surgery. These results were supported by continuously increasing HER2 ratios thereafter with the progression of recurrent cancer. CONCLUSION: The plasma HER2 ratio determined by ddPCR is a repeatable and noninvasive approach for real-time evaluations of the HER2 status to monitor the effects of treatments for patients with HER2-positive GC and enable treatment options for patients with HER2-negative GC but positive conversion of the HER2 status after recurrence.


Asunto(s)
Biomarcadores de Tumor/genética , Variaciones en el Número de Copia de ADN/genética , ADN de Neoplasias/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Adenocarcinoma/sangre , Adenocarcinoma/genética , Adenocarcinoma/secundario , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , ADN de Neoplasias/sangre , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Peritoneales/sangre , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/secundario , Pronóstico , Receptor ErbB-2/sangre , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología
16.
Nature ; 472(7342): 191-6, 2011 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-21179085

RESUMEN

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.


Asunto(s)
Técnicas de Trazados de Vías Neuroanatómicas , Vías Olfatorias/citología , Vías Olfatorias/fisiología , Percepción Olfatoria/fisiología , Sinapsis/metabolismo , Amígdala del Cerebelo/anatomía & histología , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Animales , Axones/fisiología , Sesgo , Mapeo Encefálico , Células HEK293 , Humanos , Ratones , Ratones Transgénicos , Odorantes/análisis , Bulbo Olfatorio/anatomía & histología , Bulbo Olfatorio/citología , Bulbo Olfatorio/fisiología , Vías Olfatorias/anatomía & histología , Percepción Olfatoria/genética , Neuronas Receptoras Olfatorias/citología , Neuronas Receptoras Olfatorias/fisiología , Virus de la Rabia/fisiología , Sinapsis/genética
17.
J Stroke Cerebrovasc Dis ; 26(5): 1013-1019, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28108097

RESUMEN

BACKGROUND: Percutaneous endoscopic gastrostomy may be performed in dysphagic stroke patients. However, some patients regain complete oral intake without gastrostomy. This study aimed to investigate the predictive factors of intake, thereby determining gastrostomy indications. METHOD: Stroke survivors admitted to our convalescent rehabilitation ward who underwent gastrostomy or nasogastric tube placement from 2009 to 2015 were divided into 2 groups based on intake status at discharge. Demographic data and Functional Independence Measure (FIM), Dysphagia Severity Scale (DSS), National Institutes of Health Stroke Scale, and Glasgow Coma Scale (GCS) scores on admission were compared between groups. We evaluated the factors predicting intake using a stepwise logistic regression analysis. RESULTS: Thirty-four patients recovered intake, whereas 38 achieved incomplete intake. Mean age was lower, mean body mass index (BMI) was higher, and mean time from stroke onset to admission was shorter in the complete intake group. The complete intake group had less impairment in terms of GCS, FIM, and DSS scores. In the stepwise logistic regression analysis, BMI, FIM-cognitive score, and DSS score were significant independent factors predicting intake. The formula of BMI × .26 + FIM cognitive score × .19 + DSS score × 1.60 predicted recovery of complete intake with a sensitivity of 88.2% and a specificity of 84.2%. CONCLUSIONS: Stroke survivors with dysphagia with a high BMI and FIM-cognitive and DSS scores tended to recover oral intake.


Asunto(s)
Trastornos de Deglución/rehabilitación , Deglución , Ingestión de Alimentos , Esófago/fisiopatología , Gastrostomía , Intubación Gastrointestinal , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/terapia , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Cognición , Técnicas de Apoyo para la Decisión , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/psicología , Evaluación de la Discapacidad , Femenino , Escala de Coma de Glasgow , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/psicología , Factores de Tiempo , Resultado del Tratamiento
18.
J Neurosci ; 35(37): 12869-89, 2015 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-26377473

RESUMEN

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT: Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons.


Asunto(s)
Corteza Cerebral/citología , Neuronas GABAérgicas/citología , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/fisiología , Interneuronas/citología , Proteínas del Tejido Nervioso/fisiología , Neurogénesis/fisiología , Proteínas Supresoras de Tumor/fisiología , Animales , Biomarcadores , Calbindina 2/análisis , Moléculas de Adhesión Celular Neuronal/análisis , Linaje de la Célula , Movimiento Celular , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/patología , Proteínas de la Matriz Extracelular/análisis , Neuronas GABAérgicas/metabolismo , Perfilación de la Expresión Génica , Interneuronas/clasificación , Interneuronas/metabolismo , Ratones , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Proteína Reelina , Serina Endopeptidasas/análisis , Proteínas Supresoras de Tumor/deficiencia , Péptido Intestinal Vasoactivo/análisis
19.
Br J Cancer ; 113(10): 1467-76, 2015 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-26505678

RESUMEN

BACKGROUND: This study aims to explore novel microRNAs in plasma for screening cancer and predicting clinical outcomes in pancreatic cancer (PCa) patients using a microRNA array-based approach. METHODS: We used the Toray 3D-Gene microRNA array-based approach to compare plasma levels between PCa patients and healthy volunteers. RESULTS: (1) Six oncogenic microRNAs (miR-615-5p, -744, -575, -557, -675, and -550a) with high expression in plasma were selected. (2) By quantitative RT-PCR using plasma samples from 94 PCa patients and 68 healthy volunteers, a significantly higher level of plasma miR-744 in PCa patients than in healthy volunteers was validated in small-scale analysis (P=0.0038), two independent cohort analyses, and large-scale analysis (P<0.0001, AUC 0.8307). (3) miR-744 expression was significantly higher in PCa tissues (P=0.0069) and PCa cell lines (P=0.0074) than in normal tissues and fibroblasts, respectively. Preoperative plasma level of miR-744 was significantly reduced in postoperative samples (P=0.0063). (4) A high level of plasma miR-744, which was correlated with lymph node metastasis (P=0.0407) and recurrences (P=0.0376), was an independent poor prognostic factor of PCa patients after pancreatectomy (P=0.0007, HR 21.2 (3.17-436)). Furthermore, a high level of plasma miR-744 contributed to poorer progression-free survival of non-operable PCa patients who underwent gemcitabine-based chemotherapy (P=0.0533). Overexpression of miR-744 in PCa cells induced significant chemoresistance to gemcitabine in vitro. CONCLUSIONS: Plasma miR-744 might be useful biomarker for screening PCa, monitoring, and predicting poor prognosis and chemoresistance in PCa patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , MicroARNs/sangre , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Anciano , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Resistencia a Antineoplásicos , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Pronóstico , Análisis de Secuencia de ARN , Regulación hacia Arriba , Gemcitabina
20.
J Neurosci ; 33(27): 11145-54, 2013 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-23825418

RESUMEN

A characteristic feature in the primary visual cortex is that visual responses are suppressed as a stimulus extends beyond the classical receptive field. Here, we examined the role of inhibitory neurons expressing somatostatin (SOM⁺) or parvalbumin (PV⁺) on surround suppression and preferred receptive field size. We recorded multichannel extracellular activity in V1 of transgenic mice expressing channelrhodopsin in SOM⁺ neurons or PV⁺ neurons. Preferred size and surround suppression were measured using drifting square-wave gratings of varying radii and at two contrasts. Consistent with findings in primates, we found that the preferred size was larger for lower contrasts across all cortical depths, whereas the suppression index (SI) showed a trend to decrease with contrast. We then examined the effect of these metrics on units that were suppressed by photoactivation of either SOM⁺ or PV⁺ neurons. When activating SOM⁺ neurons, we found a significant increase in SI at cortical depths >400 µm, whereas activating PV⁺ neurons caused a trend toward lower SIs regardless of cortical depth. Conversely, activating PV⁺ neurons significantly increased preferred size across all cortical depths, similar to lowering contrast, whereas activating SOM⁺ neurons had no systematic effect on preferred size across all depths. These data suggest that SOM⁺ and PV⁺ neurons contribute differently to spatial integration. Our findings are compatible with the notion that SOM⁺ neurons mediate surround suppression, particularly in deeper cortex, whereas PV⁺ activation decreases the drive of the input to cortex and therefore resembles the effects on spatial integration of lowering contrast.


Asunto(s)
Sensibilidad de Contraste/fisiología , Neuronas/metabolismo , Parvalbúminas/biosíntesis , Somatostatina/biosíntesis , Corteza Visual/metabolismo , Animales , Femenino , Masculino , Ratones , Ratones Transgénicos , Estimulación Luminosa/métodos , Percepción Espacial/fisiología
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