BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System

Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields

BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System

Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields

Real-Time Evaluation of the Effectiveness of Microwave Coagulation Therapy for Hepatocellular Carcinoma Using Color Doppler Imaging

Percutaneous microwave coagulation therapy (PMCT) is a new technique for the treatment of hepatocellular carcinoma (HCC). However, it is difficult to distinguish those lesions in which necrosis has been induced from the viable residual lesions during the procedure, because the margin of the tumor becomes unclear during PMCT. We determined the area of necrotic lesions during the procedure using color Doppler imaging. PMCT was performed on 10 patients (17 lesions) with recurrent HCC. The electrode of the microwave delivery system was moved around the tumor and the surrounding area until color mosaic images disappeared from the entire area of the tumor. The areas in which necrotic tissue was indicated by color Doppler imaging were later confirmed by other modalities such as angiography or contrast-enhanced computed tomography. This leads us to believe that real-time, effective evaluation of PMCT is possible with color Doppler imaging.</p

Dual-frequency injection-locked continuous-wave near-infrared laser

We report a dual-frequency injection-locked continuous-wave near-infrared laser. The entire system consists of a Ti:sapphire ring laser as a power oscillator, two independent diode-lasers employed as seed lasers, and a master cavity providing a frequency reference. Stable dual-frequency injection-locked oscillation is achieved with a maximum output power of 2.8 W. As fundamental performance features of this laser system, we show its single longitudinal/transverse mode characteristics and practical power stability. Furthermore, as advanced features, we demonstrate arbitrary selectivity of the two frequencies and flexible control of their relative powers by simply manipulating the seed lasers.Comment: 8 pages, 4 figure

Androgen receptor and 5α-reductase immunohistochemical profiles in extramammary Paget disease

Background Extramammary Paget disease is an uncommon skin tumour occurring mostly in the genitoperineal region. Previous reports have shown frequent expression of androgen receptor, suggesting a tumour-proliferative effect of androgens on Paget cells. Androgen-converting enzymes such as 5α-reductase, which locally produces a bioactive androgen, have recently gained attention in studies of the intratumoral actions of androgens. Objectives We investigated correlations between the androgenic microenvironment and invasiveness in extramammary Paget disease, particularly in terms of sex differences. Methods We examined 58 cases of extramammary Paget disease (32 men, 26 women; 42 noninvasive, 16 invasive) using immunohistochemistry for androgen receptor and 5α-reductase. Results In all 58 cases, expression rates were 57% for androgen receptor and 55% for 5α-reductase, with 38% double-positivity for androgen receptor and 5α-reductase. Only 5α-reductase expression rate was significantly higher in invasive cases (81%) than in noninvasive cases (45%; P = 0·042). For invasive cases, numbers of double-positive results for androgen receptor and 5α-reductase were significantly higher in men (70%) than in women (17%; P = 0·039). Conclusions Double positivity for androgen receptor and 5α-reductase in Paget cells suggests autocrine synthesis of androgens in extramammary Paget disease. The different hormonal microenvironments in male and female cases and intratumoral androgen levels affect the invasiveness of extramammary Paget disease. © 2010 British Association of Dermatologists

Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

The pathogenesis and therapeutics of depression are linked to the operation of the circadian system. Here, we studied the chronopharmacological action of a tricyclic antidepressant, imipramine. Male adult Wistar–Hannover rats were administered imipramine acutely or chronically in the morning or in the evening. The antidepressant action of imipramine was analyzed using the forced swim test (FST). A single dose of imipramine (30 mg/kg) in the morning, but not in the evening, reduced immobility and increased climbing in the FST. The plasma concentrations of imipramine and its metabolite, desipramine, were slightly higher in the morning than in the evening, which might explain the dosing time-dependent action of imipramine. Next, we analyzed the effect of chronic imipramine treatment. Rats received imipramine in the morning or in the evening for 2 weeks. The morning treatment resulted in larger effects in the FST than the evening treatment, and was effective at a dose that was ineffective when administered acutely. The levels of brain a-adrenergic receptors tended to decrease after chronic imipramine treatment. Imipramine might interact with noradrenergic neurons, and this interaction might chronically alter receptor expression. This alteration seemed greater in the morning than in the evening, which might explain the dosing time-dependent action of imipramine

Localized Brain Activation Related to the Strength of Auditory Learning in a Parrot

Parrots and songbirds learn their vocalizations from a conspecific tutor, much like human infants acquire spoken language. Parrots can learn human words and it has been suggested that they can use them to communicate with humans. The caudomedial pallium in the parrot brain is homologous with that of songbirds, and analogous to the human auditory association cortex, involved in speech processing. Here we investigated neuronal activation, measured as expression of the protein product of the immediate early gene ZENK, in relation to auditory learning in the budgerigar (Melopsittacus undulatus), a parrot. Budgerigar males successfully learned to discriminate two Japanese words spoken by another male conspecific. Re-exposure to the two discriminanda led to increased neuronal activation in the caudomedial pallium, but not in the hippocampus, compared to untrained birds that were exposed to the same words, or were not exposed to words. Neuronal activation in the caudomedial pallium of the experimental birds was correlated significantly and positively with the percentage of correct responses in the discrimination task. These results suggest that in a parrot, the caudomedial pallium is involved in auditory learning. Thus, in parrots, songbirds and humans, analogous brain regions may contain the neural substrate for auditory learning and memory

Hemosiderin Detection inside the Mammillary Bodies Using Quantitative Susceptibility Mapping on Patients with Wernicke-Korsakoff Syndrome

Hemorrhage inside the mammillary bodies (MMBs) is known to be one of the findings of Wernicke encephalopathy. Brain MRI of two patients with Wernicke-Korsakoff syndrome (WKS) demonstrated high susceptibility values representing hemosiderin deposition in MMBs by using quantitative susceptibility mapping (QSM). QSM provided additional information of susceptibility values to susceptibility-weighted imaging in diagnosis of WKS

Análisis de las comorbilidades en pacientes con colitis ulcerosa: una herramienta para prevenir las exacerbaciones en casos de colitis ulcerosa

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn’s disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient’s prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44–10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.Se trata de un análisis retrospectivo que estudia múltiples comorbilidades de índole inmunológico que se da en pacientes con colitis ulcerosa. Este estudio se llevó a cabo en el hospital universitario de la Universidad de Nagoya. Se recolectó datos de 105 pacientes con colitis ulcerosa, de los cuales 176 comorbilidades extraintestinales fueron analizadas. Se encontró que comorbilidades con manifestación activa de síntomas y con colitis ulcerosa en fase activa fueron significativamente correlacionadas en pacientes con comorbilidades inmunológicas, tales como artritis periféricas (r=O.97, P<O.OI ), artritis reumatoide (r=O.99, P<O.OI ), así como pacientes con colangitis esclerosa primaria (r=O.98, P<O.OI ). En conclusión, este análisis sugiere la importancia de tener plena comprensión de cómo las comorbilidades inmunológicas afectan el desarrollo natural de la colitis ulcerosa, lo cual es de vital importancia para prevenir mayores complicaciones de la colitis ulcerosa y ajustar adecuadamente el manejo de la enfermedad.Japón. Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología (Monbukagakusho)Artículo de investigació