The effects of caffeine on the human Somatosensory evoked potential (SEP), visual evoked potential (VEP) and EEG

The effects of caffeine on central nervous system were investigated with SEP and VEP (EPs). The subjects were 25 healthy male volunteers aged 24-44 with a mean caffeine consumption of 251.4 mg/day, and were divided into the light and heavy consumer groups according to DSM-IV criteria for caffeine intoxication. They were given 3 mg/kg of body weight of caffeine or placebo in a double-blind cross-over design. EEGs containing SEPs evoked by electric stimuli to the right median nerve and VEPs by flash stimuli were recorded before, 30, 60, 90 minutes after dosing. The consecutive changes in EPs and EEG power% were studied and the following results were obtained. 1. Overall subjects had few components with significant changes in latencies and amplitudes of SEP and VEP after administration of caffeine. 2. EEGs recorded together with EPs showed a significant increase in α1 power% and a significant decrease in δ, θ and β２ power%. 3. There were also no significant differences in EPs measures and EEGs between the light and heavy consumer groups, except for EEG power% of VEP with the heavy costumer group showing an earlier appearance of changes. In conclusion, 3 mg/kg of body weight of caffeine administered in the present study did not effect on SEP and VEP as well as EEGs

Somatosensory Evoked Potential (SEP) in schizophrenics

The differences between schizophrenics and healthy subjects in Somatosensory Evoked Potential (SEP) were studied with 174 schizophrenics (98 male and 76 female) and 200 healthy subjects (100 male and 100 female). SEPs evoked by electric stimuli to the right median nerve were recorded through the two derivations (monopolar : C3’→A1+2; bipolar: C3’→Cz), averaging 100 responses, with 1024 msec of analysis time. Individual SEPs were subjected to the component analysis, and the following statistically significant results were obtained. 1. In male schizophrenics, the peak latencies of SEP components were significantly longer in short-latency component, P1 (bipolar), compared with healthy subjects, and shorter in middle-latency component, P2. In female schizophrenics, those were longer in middle-latency components, N2, P3, N3 (monopolar), and N1, P3, N3 (bipolar). 2. The inter-peak amplitudes in schizophrenics of both sexes were significantly larger in middle-latency components without any changes in short-latency components. 3. A few components with significant differences in latencies and inter-peak amplitudes between the subjects taking neuroleptics more than 600 mg, in chlorpromazine equivalent values, or not, as well as between medicated and unmedicated subjects, coincided with those also between the schizophrenics and healthy subjects. Theses differences in SEPs confirmed in the present study, regardless of schizophrenic subtypes, suggest the dysfunction in somatosensory information processing in schizophrenics, and SEP abnormalities may serve as possible elctrophysiological indices for cognitive dysfunction in schizophrenics

Visual Evoked Potential (VEP) in schizophrenics

The differences between schizophrenics and healthy subjects in Visual evoked potential (VEP) were studied with 174 schizophrenics (98 male and 76 female) and 200 healthy subjects (100 male and 100 female). VEPs evoked by flash stimuli were recorded through the two derivations (monopolar: O1→A1+2; bipolar: O1→Cz), averaging 100 responses, with 1024 msec of analysis time. Individual VEPs were subjected to the component analysis, and the following statistically significant results were obtained. 1. In schizophrenics, the latencies in short-latency components were significantly longer in P2 (male, monopolar), N2, P3, N3 (male, bipolar) and N3 (female, monopolar). Those in middle-latency components were significantly shorter in P4~N5 (male, monopolar) and P6 (female). 2. The inter-peak amplitudes in short-latency components were significantly smaller in P3-N3 (male, mopolar), and larger in P1-N1, N1-P2, P2-N2 (male, bipolar). Those in middle-latency components were significantly smaller in N3-P4 (male, monopolar), and larger in N4-P5 (female, bipolar). 3. A few components with significant differences in latencies and interpeak amplitudes between the subjects taking neuroleptics more than 600 mg, in chlorpromazine equivalent values, or not, as well as between medicated and unmedicated subjects, coincided with those also between the schizophrenics and healthy subjects. Theses differences in VEPs confirmed in the present study, regardless of schizophrenic subtypes, suggest the dysfunction in visual information processing in schizophrenics, and VEP abnormalities may serve as possible elctrophysiological indices for cognitive dysfunction in schizophrenics

Observation of biexcitonic emission at extremely low power density in tungsten disulfide atomic layers grown on hexagonal boron nitride

Monolayer transition metal dichalcogenides (TMDCs) including WS2, MoS2, WSe2 and WS2, are two-dimensional semiconductors with direct bandgap, providing an excellent field for exploration of many-body effects in 2-dimensions (2D) through optical measurements. To fully explore the physics of TMDCs, the prerequisite is preparation of high-quality samples to observe their intrinsic properties. For this purpose, we have focused on high-quality samples, WS2 grown by chemical vapor deposition method with hexagonal boron nitride as substrates. We observed sharp exciton emissions, whose linewidth is typically 22~23 meV, in photoluminescence spectra at room temperature, which result clearly demonstrates the high-quality of the current samples. We found that biexcitons formed with extremely low-excitation power (240 W/cm^2) at 80 K, and this should originate from the minimal amount of localization centers in the present high-quality samples. The results clearly demonstrate that the present samples can provide an excellent field, where one can observe various excitonic states, offering possibility of exploring optical physics in 2D and finding new condensates

Essential Role of the \u3ci\u3eCrk\u3c/i\u3e Family-Dosage in DiGeorge-Like Anomaly and Metabolic Homeostasis

CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes CRKL and TBX1, Crk and Tbx1 also genetically interact, thus suggesting that pathways shared by the three genes participate in organogenesis affected in the syndrome. We also show that Crk and Crkl are required during mesoderm development, and Crk/Crkl deficiency results in small cell size and abnormal mesenchyme behavior in primary embryonic fibroblasts. Our systems-wide analyses reveal impaired glycolysis, associated with low Hif1a protein levels as well as reduced histone H3K27 acetylation in several key glycolysis genes. Furthermore, Crk/Crkl deficiency sensitizes MEFs to 2deoxy-D-glucose, a competitive inhibitor of glycolysis, to induce cell blebbing. Activated Rapgef1, a Crk/Crkl-downstream effector, rescues several aspects of the cell phenotype, including proliferation, cell size, focal adhesions, and phosphorylation of p70 S6k1 and ribosomal protein S6. Our investigations demonstrate that Crk/Crkl-shared pathways orchestrate metabolic homeostasis and cell behavior through widespread epigenetic controls

Changes in Plasma Metabolites Concentrations in Obese Dogs Supplemented With Anti-oxidant Compound

The aim of this study is to discuss the effect of anti-oxidant supplement (Rv-PEM01-99, Kibun Foods, Inc., Tokyo, Japan) on changes in energy metabolism in obese dogs. 200 mg/kg/day of Rv-PEM01-99 (equivalent to 5 mg kg/day of quercetin derivative) were applied for 6 weeks to the Beagle dogs fed high fat diet (HFD) or control diet (CD). In the present study, body weight (BW) decreasing effect of Rv-PEM 01-99 in obese dogs was not clear. However, plasma alkaline phosphatase (ALP) activities at the end of experiment were significantly decreased compared to those at the start of experiment in obese dogs supplemented with Rv-PEM 01-99 (paired-t test, p < 0.05). In control dogs supplemented with Rv-PEM 01-99, Plasma malondialdehyde (MDA), and triglycerides (TG) levels and lactate dehydrogenase (LDH) activities were significantly decreased compared to those at the start of experiment (paired-t test, p < 0.05). From these findings, Rv-PEM 01-99 seems to be not harmful for dogs. Anti-lipid peroxide effect and liver function improvement are expected in the dogs supplemented with Rv-PEM 01-99

Tamoxifen mechanically reprograms the tumor microenvironment via HIF‐1A and reduces cancer cell survival

The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen‐positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross‐linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein‐coupled estrogen receptor (GPER) and hypoxia‐inducible factor‐1 alpha (HIF‐1A). We show that tamoxifen reduces HIF‐1A levels by suppressing myosin‐dependent contractility and matrix stiffness mechanosensing. Tamoxifen also downregulates hypoxia‐regulated genes and increases vascularization in PDAC tissues. Our findings implicate the GPER/HIF‐1A axis as a master regulator of peri‐tumoral stromal remodeling and the fibrovascular tumor microenvironment and offer a paradigm shift for tamoxifen from a well‐established drug in breast cancer hormonal therapy to an alternative candidate for stromal targeting strategies in PDAC and possibly other cancers.See also: E Cortes et al (January 2019) andM Pein & T Oskarsson (January 2019)EMBO Reports (2019) 20: e46557Peer reviewe

Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae

ABSTRACT To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus, clarification of the mechanisms that underlie the regulation of ILC2 activation has received significant attention. Although ILCs are divided into three major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T (Treg) cells have not been well characterized. OBJECTIVE: We sought to determine the factors that induce regulatory ILCs (ILCregs). METHODS: IL-10+ ILCregs induced from ILC2s by retinoic acid (RA) were analyzed using RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissues from healthy individuals and patients with chronic rhinosinusitis with nasal polyp (CRSwNP), and in lung tissues from house dust mite (HDM)- or saline-treated mice. RESULTS: RA induced IL-10 secretion by human ILC2s, but not type-2 cytokines. IL-10+ ILCregs, converted from ILC2s by RA stimulation, expressed a Treg-like signature with the expression of IL-10, CTLA-4 and CD25, with down regulated effector type 2-related markers such as CRTH-2 and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy individuals or lung tissues from saline-treated mice, but were increased in nasal tissues from patients with CRSwNP and in lung tissues from HDM-treated mice. Enzymes for RA synthesis were up-regulated in airway epithelial cells during type-2 inflammation in vivo and by IL-13 in vitro. CONCLUSION: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs