Role Of Beta Research Articles

Role of beta-(1→3)(1→6)-D-glucan derived from yeast on natural killer (NK) cells and breast cancer cell lines in 2D and 3D cultures

BackgroundBeta-(1,3)(1,6)-D-glucan is a complex polysaccharide, which is found in the cell wall of various fungi, yeasts, bacteria, algae, barley, and oats and has immunomodulatory, anticancer and antiviral effects. In the present study, we investigated the effect of beta-(1,3)(1,6)-D-glucan derived from yeast on the proliferation of primary NK cells and breast cancer cell lines in 2D and 3D models, and on the cytotoxicity of primary NK cells against breast cancer cell lines in 2D and 3D models.MethodsIn this study, we investigated the effects of different concentrations of yeast-derived beta-(1→3)(1→6)-D-glucan on the proliferation and cytotoxicity of human NK cells and breast cancer cell lines in 2D and 3D models using the XTT cell proliferation assay and the CellTiter-Glo® 2.0 assay to determine the cytotoxicity of human NK cells on breast cancer cell lines in 2D and 3D models.ResultsWe found that the co-incubation of NK cells with beta-glucan in the absence of IL2 at 48 h significantly increased the proliferation of NK cells, whereas the co-incubation of NK cells with beta-glucan in the presence of IL2 (70 U/ml) increased the proliferation of NK cells but not significantly. Moreover, beta-glucan significantly inhibited the proliferation of breast cancer cell lines in 2D model and induced a weak, non-significant growth inhibitory effect on breast cancer multicellular tumor spheroids (3D). In addition, the cytotoxicity of NK cells against breast cancer cell lines was examined in 2D and 3D models, and beta-glucan significantly increased the cytotoxicity of NK cells against MCF-7 (in 2D).ConclusionsYeast derived beta-(1,3)(1,6)-D-glucan could contribute to the treatment of cancer by enhancing NK cell immune response as well as contributing to inhibition of breast cancer cell growth.

Role of beta 2 microglobulin in chronic kidney disease

The aim: to study the relationship of beta-2-microglobulin (beta-2 MG) with clinical and laboratory manifestations of chronic kidney disease (CKD).Patients and Methods. The results of a comprehensive examination of 284 people (118 males and 166 females) aged 18 to 86 years with various types of socially significant diseases were studied. All patients underwent thorough collection of clinical and anamnestic data, laboratory monitoring with the determination of the level of systolic and diastolic blood pressure (BP), body mass index, red blood, beta-2-microglobulin (B2M), lipid profile and proteinuria. Kidney function was assessed according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula using serum creatinine. The main group included 113 patients (55 men and 58 women, mean age 50.9±15.8 years), diagnosed with chronic kidney disease (CKD). The control group consisted of 171 people (63 men and 108 women) with various forms of socially significant diseases, but without signs of CKD. Statistical analysis was carried out using the programs Statistica 10.0 (StatSoft Inc., USA) and Microsoft Office Excel 2010 (Microsoft Corp., USA).Results. In the subgroup of patients with CKD, signs of renal failure were observed in 46 people in 40.7 % of cases. As CKD progressed, the signs of impaired metabolism of B2M were more severe: its serum level was 8.646 (7.892; 12.231) mg/l at C4 and 18.444 (11.225; 23.717) mg/l at C5 stages of CKD, and urinary excretion was 2.502 (0.305; 6.313) mg/l at C4 and 2.614 (1.535; 25.812) mg/l at C5 stages of CKD. Regardless of renal dysfunction, the median serum B2M level was clinically significantly higher in females (p>0.05). Single-factor one-way correlation analysis showed statistically highly significant relationship was between serum B2M and creatinine levels both in the subgroup of patients with CKD (r = 0.905; p = 0.001) and in the total sample (r = 0.749; p = 0.001). There was a strong negative relationship between serum B2M levels and estimated glomerular filtration rate (GFR) (r = -0.717; p = 0.001). In individuals without CKD, an increase in serum creatinine was closely associated with an increase in urinary excretion of B2M (r=0.252; p=0.005). Simultaneously, in this category of patients, there was a close correlation between estimated GFR with serum B2M level (r= -0.433; p=0.002) and its urinary excretion (r= -0.247; p=0.005). A direct relationship between an increase in serum B2M and an increase in diastolic blood pressure (r=0.274; p=0.034) among CKD patients was established. In the total sample, a direct relationship between the value of systolic BP and serum B2M level (r= 0.223; p=0.01) was registered, as well as between diastolic BP (r= 0.268; p=0.01) and urinary excretion of B2M.Conclusion. As a result of the study, metabolism of B2M and its relationship with the clinical and laboratory manifestations of CKD were evaluated. The data obtained show high prognostic potential of changes in metabolism of B2M in the population of patients with various forms of socially significant diseases, as well as CKD, which allows to identify among them groups of patients with high and/or very high renal and cardiovascular risk, in order to take timely targeted therapy.

The role of beta- and alpha-adrenergic receptors on alcohol drinking

Alcohol Use Disorders (AUD) is characterized by compulsion-like alcohol drinking (CLAD), where intake despite negative consequences can be a major clinical obstacle. With few treatment options available for AUD, there is a significant need for novel therapies. The noradrenergic system is an important hub for regulating stress responses and maladaptive drives for alcohol. Studies have shown that drugs targeting α1 adrenenergic receptors (ARs) may represent a pharmacological treatment for pathological drinking. However, the involvement of β ARs for treating human drinking has received scant investigation, and thus we sought to provide pre-clinical validation for possible AR utility for CLAD by analyzing whether β AR antagonists propranolol (β1/2), betaxolol (β1), and ICI, 118,551 (β2) impacted CLAD and alcohol-only drinking (AOD) in male Wistar rats. We found that the highest dose of propranolol tested systemically (10 mg/kg) reduced alcohol drinking, while 5 mg/kg propranolol reduced drinking with a trend to impact CLAD more than AOD, and with no effects of 2.5 mg/kg. Betaxolol (2.5 mg/kg) also decreased drinking, while ICI 118.551 had no effects. Also, while AR compounds might have utility for AUD, they can also lead to undesirable side effects. Here, a combination of ineffective doses of propranolol and prazosin reduced both CLAD and AOD. Finally, we investigated the effect of propranolol and betaxolol in two brain areas related to pathological drinking, the anterior insula (aINS) and medial prefrontal cortex (mPFC). Surprisingly, propranolol (1–10 μg) in aINS or mPFC did not affect CLAD or AOD. Together, our findings provide new pharmacological insights into noradrenergic regulation of alcohol consumption, which may inform AUD therapy.

The choline dehydrogenase BetA of Acinetobacter baumannii: a flavoprotein responsible for osmotic stress protection.

Acinetobacter baumannii is outstanding for its ability to cope with low water activities which significantly contributes to its persistence in hospital environments. The vast majority of bacteria are able to prevent loss of cellular water by amassing osmoactive compatible solutes or their precursors into the cytoplasm. One such precursor of an osmoprotectant is choline that is taken up from the environment and oxidized to the compatible solute glycine betaine. Here, we report the identification of the osmotic stress operon betIBA in A. baumannii. This operon encodes the choline oxidation pathway important for the production of the solute glycine betaine. The salt-sensitive phenotype of a betA deletion strain could not be rescued by addition of choline, which is consistent with the role of BetA in choline oxidation. We found that BetA is a choline dehydrogenase but also mediates in vitro the oxidation of glycine betaine aldehyde to glycine betaine. BetA was found to be associated with the membrane and to contain a flavin, indicative for BetA donating electrons into the respiratory chain. The choline dehydrogenase activity was not salt dependent but was stimulated by the compatible solute glutamate.

Neurophysiological Correlates of Dynamic Beat Tracking in Individuals With Williams Syndrome

BackgroundWilliams syndrome (WS) is a neurodevelopmental disorder characterized by hypersociability, heightened auditory sensitivities, attention deficits, and strong musical interests despite differences in musical skills. Behavioral studies have reported that individuals with WS exhibit variable beat and rhythm perception skills. MethodsWe sought to investigate the neural basis of beat tracking in individuals with WS using electroencephalography. Twenty-seven adults with WS and 16 age-matched, typically developing control subjects passively listened to musical rhythms with accents on either the first or second tone of the repeating pattern, leading to distinct beat percepts. ResultsConsistent with the role of beta and gamma oscillations in rhythm processing, individuals with WS and typically developing control subjects showed strong evoked neural activity in both the beta (13–30 Hz) and gamma (31–55 Hz) frequency bands in response to beat onsets. This neural response was somewhat more distributed across the scalp for individuals with WS. Compared with typically developing control subjects, individuals with WS exhibited significantly greater amplitude of auditory evoked potentials (P1-N1-P2 complex) and modulations in evoked alpha (8–12 Hz) activity, reflective of sensory and attentional processes. Individuals with WS also exhibited markedly stable neural responses over the course of the experiment, and these responses were significantly more stable than those of control subjects. ConclusionsThese results provide neurophysiological evidence for dynamic beat tracking in WS and coincide with the atypical auditory phenotype and attentional difficulties seen in this population.

1-LB: Diurnal Regulation of Pancreatic Beta-Cell Proliferation following Massive Ablation

Pancreatic islet cellular oscillators have been recently demonstrated to play a critical role in regulating glucose homeostasis in physiological conditions. However, little is known about changes of molecular clockwork upon islet dysfunction, and its role in beta (b)-cell regeneration. We aimed to assess diurnal regulation of b-cell proliferation and circadian transcriptome of alpha (a)- and b-cells following massive b-cell ablation in rtTA/TET-DTA mouse model. Diurnal proliferation of remnant b-cells was assessed by injecting bromodeoxyuridine (BrdU) before sacrificing in several time-points across 24 h. The role of functional islet oscillators in b-cell regeneration was studies in clock deficient mice. Our data suggest that both absolute levels and diurnal profiles of blood glucose, insulin and glucagon are altered following b-cell ablation. Temporal RNAseq analyses suggest massive changes in b-cell temporal transcriptome landscape, with modest alterations in a-cell transcriptional regulation. Complimentary differential RNAseq analysis of b-cells between intact islets and after ablation showed altered expression of genes involved in hormone secretory pathway, and activation of transcripts responsible for cell proliferation. In line with the circadian rhythmicity of cell-cycle related transcripts, the incorporation of BrdU by residual b-cells exhibited circadian rhythmicity. Moreover, we show that also in young pups, b-cell proliferation follows diurnal pattern. Importantly, the arrhythmic Bmal1 KO mice failed to regenerate b-cells after ablation. To conclude, loss of b-cell mass in rtTA/TET-DTA mice affects gene transcription in residual b-cells, but not in a-cells, while the temporal transcriptome profile is perturbed in both cell types, paralleled with impaired daily secretion of insulin and glucagon. Noteworthy, the key component of molecular clock Bmal1 is required for proper regeneration and functional recovery after massive b-cell ablation. Disclosure V. Petrenko: None. M. Stolovich-Rain: None. B. Vandereycken: None. S. Chera: None. Y. Dor: None. C. Dibner: None. Funding Swiss National Science Foundation (31003A_166700/1, 310030_184708/1)

PERGERAKAN HARGA SAHAM SEKTOR PROPERTI BURSA EFEK JAKARTA BERDASARKAN KONDISI PROFITABILITAS, SUKU BUNGA DAN BETA SAHAM

Understanding the empirical description of stock prices movement on the economical setting, firm’s perform, and the behavior of its beta is fundamental to portfolio risk management. This study evaluates the effect of three factors: firm’s profitability, interest rate, and beta, toward the stock prices movement of 32 property stocks listing at Jakarta Stock Exchange (BEJ). Path analytical model was designed with interest and return on asset (ROA) profitability as the exogenous, stock beta became an intervening variable and average rate of stock prices movement became an endogenous variable. Daily prices for the stocks, BEJ Composite Index, profitability, and interest rate were obtained from BEJ and Bank Indonesia tapes for January 2000 to December 2004 period. This analysis indicated that the stock prices movement was the most dominant influenced by beta followed by interest rate (negative) and firm’s profitability. This study also found that beta would become an effective intervening variable for transmitting both ROA and interest effect toward the stock prices movements, and hence the role of beta could be adopted as investor strategy. Structurally, the average rate of stocks prices movement would be up about: 0.37 standard units if beta was force up about one standard unit (of increasing on ROA or decreasing on interest or both together), 0.24 standard units if interest rate was lead to set down about one standard unit of ceteris paribus, and 0.19 standard units if ROA was grow about one standard unit of ceteris paribus. Furthermore, the stock prices movement of BEJ property stocks by forcing of the investor strategy was higher than leading the economical setting which it was higher than its firm’s fundamental perform growing.

Nocturnal asthma is affected by genetic interactions between RORA and NPSR1.

Neuropeptide S Receptor 1 ( NPSR1) and Retinoid Acid Receptor-Related Orphan Receptor Alpha (RORA ) interact biologically, are both known candidate genes for asthma, and are involved in controlling circadian rhythm. Thus, we assessed (1) whether interactions between RORA and NPSR1 specifically affect the nocturnal asthma phenotype and (2) how this may differ from other asthma phenotypes. Interaction effects between 24 single-nucleotide polymorphisms (SNPs) in RORA and 35 SNPs in NPSR1 on asthma and nocturnal asthma symptoms were determined in 1432 subjects (763 asthmatics [192 with nocturnal asthma symptoms]; 669 controls) from the Multicenter Asthma Genetic in Childhood/International Study of Asthma and Allergies in Childhood studies. The results were validated and extended in children from the Manchester Asthma and Allergy Study (N = 723) and the Children Allergy Milieu Stockholm and Epidemiological cohort (N = 1646). RORA* NPSR1 interactions seemed to affect both asthma and nocturnal asthma. In stratified analyses, however, interactions mainly affected nocturnal asthma and less so asthma without nocturnal symptoms or asthma severity. Results were replicated in two independent cohorts and seemed to remain constant over time throughout youth. RORA* NPSR1 interactions appear to be involved in mechanisms specific for nocturnal asthma. In contrast to previous studies focusing on the role of beta 2 receptor polymorphisms in nocturnal asthma as a feature of asthma control or severity in general, our data suggest that changes in circadian rhythm control are associated with nighttime asthma symptoms.

Antioxidant Role of Beta Carotene: Protection against Cadmium Induced Testicular Toxicity

system. The purpose of present study was to investigate the protective role of Beta carotene on cadmium induced testicular damage. Materials and Methods: The present study was conducted following approval from Institutional Bioethical Committee and strict internationally accepted guidelines, for the usage of animals in experimental study were. Rats were divided into four groups with 8 rats in each.The Gr. I rats were administered with the single dose of normal saline intraperitoneally. Group II received Beta carotene (10 mg/kg bw) orally for 30 days. Group III received a single dose of 1 mg/kg bw cadmium chloride and Group IV received Beta carotene for 30 days prior to cadmium administration. After the desired protocol, rats were sacrificed and both the testes were removed for biochemical and histopathological evaluation. One testis was fixed in Bouvins fluid and processed or histopathological studies. The levels of lipid peroxides (LPO) and glutathione (GSH) and superoxide dismutase (SOD) were detected in the tissue homogenates of other testis. Results: In the present study, the level of lipid peroxidation (LPO) was significantly high and GSH and SOD (P<0.001) were low in cadmium treated rats compared to normal control. Pre-treatment with beta carotene showed a protective effect by decreasing LPO and increasing GS Hand SOD level (P<0.001). The morphological changes like atrophy of tubules, edema and decreased spermatogenesis in the testis of rats exposed to cadmium chloride. But, antioxidant showed the normal architecture of the testis. Conclusion: Results of the present study showed the antioxidative role of beta carotene in protecting the testis from cadmium induced toxicity.

The Difference δ-Cells Make in Glucose Control.

The role of beta and α-cells to glucose control are established, but the physiological role of δ-cells is poorly understood. Delta-cells are ideally positioned within pancreatic islets to modulate insulin and glucagon secretion at their source. We review the evidence for a negative feedback loop between delta and β-cells that determines the blood glucose set point and suggest that local δ-cell-mediated feedback stabilizes glycemic control.

High-gamma oscillations in the motor cortex during visuo-motor coordination: A tACS interferential study.

While the role of beta (∼20Hz), theta (∼5Hz) and alpha (∼10Hz) oscillations in the motor areas have been repeatedly associated with defined properties of motor performance, the investigation of gamma (∼40-90Hz) oscillatory activity is a more recent and still not fully understood component of motor control physiology, despite its potential clinical relevance for motor disorders. We have implemented an online neuromodulation paradigm based on transcranial alternating current stimulation (tACS) of the dominant motor cortex during a visuo-motor coordination task. This approach would allow a better understanding of the role of gamma activity, as well as that of other oscillatory bands, and their chronometry throughout the task. We tested the effects of 5Hz, 20Hz, 60Hz (mid-gamma) 80Hz (high-gamma) and sham tACS on the performance of a sample of right-handed healthy volunteers, during a custom-made unimanual tracking task addressing several randomly occurring components of visuo-motor coordination (i.e., constant velocity or acceleration pursuits, turns, loops). Data showed a significant enhancement of motor performance during high-gamma stimulation - as well as a trending effect for mid-gamma - with the effect being prominent between 200 and 500ms after rapid changes in tracking trajectory. No other effects during acceleration or steady pursuit were found. Our findings posit a role for high-frequency motor cortex gamma oscillations during complex visuo-motor tasks involving the sudden rearrangement of motor plan/execution. Such a "prokinetic" effect of high-gamma stimulation might be worth to be tested in motor disorders, like Parkinson's disease, where the switching between different motor programs is impaired.

Characterization of the BETA1 gene, which might play a role inBeta vulgaris subsp. maritima salt tolerance

Salinity stress has a negative impact on plant growth, which affects homeostasis and productivity. The uptake of nonessential salt ions changes the osmotic balance of the cell and causes dehydration. Higher plants develop salt tolerance mechanisms to avoid dehydration. Sea beet (Beta vulgaris subsp. maritima) is a halophytic ancestor of cultivated sugar beet that displays salt stress tolerance. In this study, we screened a B. vulgaris subsp. maritima cDNA library in Saccharomyces cerevisiae strain Ab11c (ena1Δ, nha1/4Δ, nhx1Δ), which is deficient in sodium transport, to find sodium-detoxifying genes. We identified a cDNA construct, named BETA1, providing salt tolerance to yeast cells. This gene had no previously described function. Intracellular sodium measurements demonstrated no significant differences between yeast cells expressing BETA1 or a sham vector, suggesting that sodium was not effluxed in BETA1-expressing cells. Transcriptionally, BETA1 mRNA levels were induced immediately in leaves and later in the root system in response to the salt stress. Our results suggest that the BETA1 gene is part of the salt tolerance network in B. vulgaris subsp. maritima.

Evaluation of Serum Beta-2 Microglobulin as a Diagnostic and Prognostic Marker in Oral Squamous Cell Carcinoma and Leukoplakia

Background: The disfiguring defects, functional loss and thus the mortality rate in oral squamous cell carcinoma (OSCC) can be significantly reduced by its early diagnosis. Tumour markers are being studied which could aid in screening, diagnosis, study prognosis and monitor the response to treatment. This research was conducted to study the role of Beta - 2 microglobulin (B2M), a tumour marker in OSCC and leukoplakia. Method: Serum from 30 cases of OSCC and leukoplakia each and 20 controls was studied Materials and methods: IMMULITE/ IMMULITE 1000 kit was used to assess the B2M levels. Findings: B2M levels in various stages and were higher degree of differentiation of OSCC (p<0.001) and as the stages (p<0.05) and grades of dysplasia (p<0.001) increased in leukoplakia. Conclusion: Serum B2M levels were higher in OSCC and leukoplakia than controls. So B2M can be considered as a diagnostic and prognostic marker.

Cortical entrainment to music and its modulation by expertise

Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta-theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.

Genetics of Type 2 Diabetes: Advances and Future Prospect

Type 2 diabetes (T2D) is a complex metabolic disorder with an increasing incidence worldwide. The disease is characterized by a combination of impairment in insulin secretion from pancreatic beta cells and insulin resistance of peripheral tissues, especially muscle and liver, resulting from interaction between multiple environmental and genetic factors. Life-style changes and obesity are the major causes for the current epidemic of T2D. The rapidly increasing prevalence of Type 2 diabetes makes it a major healthcare problem worldwide. In the developing nations this poses a serious health care burden. In recent years there has been a swing in the onset to younger age group. To date, Genome-Wide Association Scan (GWAS) studies have identified more than 65 common genetic variants associated with T2D or glucose/insulin levels. The recently discovered genes by GWAS suggest a shift from genes involved in insulin action to those involved in insulin secretion, indicating pivotal role of beta- cell dysfunction in the pathogenesis of T2D. However, in most cases the causal variants are not known. Also, the molecular mechanism of the patho-physiology of the disease is still obscure. Functional studies will be required to identify the mechanisms by which the associated signals impair islet function and increase risk of T2D. Understanding the pathophysiology of T2D will provide new and useful information(s) for prevention of the disease and development of new drugs for the treatment of T2D. Pharmacogenetics is another promising clinical application of the genetic findings for T2D. Also, efforts are being made to understand the genetic basis of differences in disease susceptibility by studying the genetic variations among different populations, an area that is important for the future of medicine.

Role of Beta 3 Adrenergic Receptor in Facultative Thermogenesis

Obesity, characterized by an increase in body fat, is related to a defect in facultative thermogenesis (FT). Brown adipose tissue (BAT) is the main site of this FT and is activated by Sympathetic Nervous System through the release of norepinephrine (NE) that binds to Beta adrenergic receptors (B‐ADR). Our goal was to evaluate the role of B3 isoform of B‐ADR in diet and cold‐induced FT. B3 knockout mice (KOB3) kept their body temperature normal when exposed to cold (4°C) and BAT thermogenic capacity was also normal when stimulated by NE i.v. infusion. In spite of a normal BAT activity, the absence of B3 receptor worsens diet‐induced obesity, with body weight gain significantly higher in KOB3 when compared to wild‐type (WT) mice (16g ± 1,4 vs. 12g ± 3,7) and larger epididymal adipocytes area (13079,81μm2 ± 10611,7 vs. 4501,55μm2 ± 1996,61). Also, a significant macrophages and neutrophils infiltration was observed in white adipose tissue (WAT), indicating inflammatory process in this tissue. Our results suggest that B3 receptor is not important in cold induced FT but it is fundamental to regulation of the body weight. It also indicates that this isoform mediates NE induced lipolysis since its absence results in very large adipocytes and inflammation in WAT.Supported by CAPES.

The Role of Beta−Adrenergic Receptor Blockers in Autism

β-adrenergic receptor blockade has been demonstrated to benefit individuals with autism. Genetic studies have identified numerous factors linking β-adrenergic receptor blockade to autism spectrum disorder (ASD), including β-adrenergic receptor variants, human leukocyte antigen genes, apoptotics factor caspase-3, glycogen synthetase kinase-3β, and the reduced form of nicotinamide adenine dinucleotide phosphate. β-adrenergic receptor blockade has also been implicated in ASD via its effects on myelin basic protein, prostaglandins, cyclooxygenase-2, and nitric oxide synthase. β-adrenergic receptor blockade may have a significant role in ASD.Therefore, the characterization of β-adrenergic receptor blockade in individuals with ASD is needed.

The role of beta 1 adrenergic receptor in Non‐Alcoholic Fat Liver Disease development

Non‐Alcoholic Fat Liver Disease (NAFLD) is characterized by the development of macrovesicular steatosis in the absence of significant consumption of alcohol, which can progress to nonalcoholic steato‐hepatitis (NASH). β1 adrenergic receptor may be related to development of NAFLD, since knockout mice for the β1adrenergic receptor (β1KO) are obese when placed on high fat diet. Thus, the aim of this study is to determine the role of β1 adrenergic receptor in NAFLD development. For that we treated β1KO with high fat diet (40%) for 8 weeks. The β1KO mice were significantly more obese than the WT animals (21.8±3.4g β1KO vs. 17.4±3.37g WT, p&lt;0.05) and have higher white adipocyte area (10.8±0.34 β1KO; 6.20±2.06 WT; p&lt;0.001). The liver of β1KO mice showed severe steatosis and fibrosis. The expression of LDL‐R protein was increase in β1KO when compared to WT treated with high fat diet (1307±130 β1KO vs. 627±33 WT, p&lt;0.05). The expression of MTTP protein in β1KO was significantly reduced (568±6 β1KO vs. 837±22 WT; p&lt;0.05). In conclusion, the results showed that the β1 adrenergic receptor are involved in lipid metabolism in liver and has direct influence on expression of proteins related to lipid metabolism.

Tactile exploration of virtual objects for blind and sighted people: the role of beta 1 EEG band in sensory substitution and supramodal mental mapping

The neural correlates of exploration and cognitive mapping in blindness remain elusive. The role of visuo-spatial pathways in blind vs. sighted subjects is still under debate. In this preliminary study, we investigate, as a possible estimation of the activity in the visuo-spatial pathways, the EEG patterns of blind and blindfolded-sighted subjects during the active tactile construction of cognitive maps from virtual objects compared with rest and passive tactile stimulation. Ten blind and ten matched, blindfolded-sighted subjects participated in the study. Events were defined as moments when the finger was only stimulated (passive stimulation) or the contour of a virtual object was touched (during active exploration). Event-related spectral power and coherence perturbations were evaluated within the beta 1 band (14-18 Hz). They were then related to a subjective cognitive-load estimation required by the explorations [namely, perceived levels of difficulty (PLD)]. We found complementary cues for sensory substitution and spatial processing in both groups: both blind and sighted subjects showed, while exploring, late power decreases and early power increases, potentially associated with motor programming and touch, respectively. The latter involved occipital areas only for blind subjects (long-term plasticity) and only during active exploration, thus supporting tactile-to-visual sensory substitution. In both groups, coherences emerged among the fronto-central, centro-parietal, and occipito-temporal derivations associated with visuo-spatial processing. This seems in accordance with mental map construction involving spatial processing, sensory-motor processing, and working memory. The observed involvement of the occipital regions suggests that a substitution process also occurs in sighted subjects. Only during explorations did coherence correlate positively with PLD for both groups and in derivations, which can be related to visuo-spatial processing, supporting the existence of supramodal spatial processing independently of vision capabilities.

Genetics of Hypertension and Cardiovascular Disease

With the force something like a tsunami wave, a surge of genome-wide association studies (GWASs) in common complex diseases has flooded the recent literature and left us awash with data regarding the identification of causative genetic risk factors for cardiovascular disease such as hypertension. Nevertheless, the more slowly moving tide of the classical candidate gene approach also makes steady progress to clarify the interaction between gene function and pathogenesis of hypertension. Like most other common conditions the estimated effects of each genetic variant on blood pressure and the predisposition to hypertension is quite small, yet the delineation of genetic contribution could reveal new targets for risk reduction in cardiovascular disease. The main focus of this special issue is to highlight the genetic basis of hypertension and cardiovascular disease and outline recent progress in genomics. In addition, several successful investigations in common diseases are introduced as good examples of the potential for better understanding of hypertension using genomic approaches. In the first part of this issue, two papers provide clear reviews of the recent progress in the GWAS approach for hypertension and coronary artery disease. These papers elucidate not only the common findings in studies that, to a certain extent, disparate but also interprete these findings in the context of the advantages and limitations of GWAS. This context includes the contrast between the very strong (genome-wide) significance of associations and the relatively small phenotypic effects of each SNP. In terms of discovery potential, unexpected candidate genes obtained from GWAS provide fresh perspectives in hypertension research. But the genomic picture is for more complex than isolated SNPs. It involves the ways in which the sophisticated organization of the operational elements of the genome interdigitates to provide tissue and development stage-specific regulation and integration of gene expression. It also aligns these factors with phenotypic changes that can result. Two subsequent review articles illustrate these principles by showcasing a new cutting edge of cardiovascular research in the form of microRNAs (miRNAs) and scavenger receptors. Both papers disclose the potentials of these newcomers as therapeutic targets of cardiovascular disease. In a more focused review of candidate genes, the next 2 papers focus on gene polymorphisms of adrenergic receptors. K. Masuo examines the critical role of beta2- and beta3-adrenoceptors gene polymorphisms on hypertension or metabolic syndrome unequivocally. K. B. Bostrom et al. report that a polymorphism (Arg389Gly) of beta1-adrenoceptor gene is significantly associated with increased risk of obstructive sleep apnea (OSA) with hypertension. In the research using candidate gene approach, precise and appropriate phenotyping is important to identify small but significant genetic effect. G. D. Kitsios and E. Zintzaras reveal the protective effect of a haplotype of endothelial nitric oxide synthase gene (NOS3) for predisposition to hypertension. K. Sugimoto et al. point out that a polymorphism in the promoter region of regulator of G protein signaling-2 (RGS2) gene affects the difference of antihypertensive medication in a clinical trial. The last two papers extend the consideration of novel and unexpected concepts for cardiovascular research. A recent topic is the awareness of shared physiological mechanisms between osteoporosis and cardiovascular disease. F. Marini and M. L. Brandi elegantly review the genetic aspects of osteoporosis and touch on the shared mechanisms. The last manuscript by G. Mertens offers a unique perspective on these issues by zooming out to take an evolutionary view. To consider the underlying mechanisms of atherosclerosis, we have to take a larger view without becoming lost in details of the immediate. We hope that this special issue is useful for your research and is conducive to the incorporation of new concepts and methods in your own laboratory. Tomohiro Katsuya Stephen B. Harrap Toshio Ogihara