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Aim: Recently, substantial studies have been accumulated to indicate the important role of gut microbiota in diabetic kidney disease (DKD). The abnormal change of bacterial‐derived products could imply specific injuries or play beneficial or harmful roles in DKD progression. In this study, we examined the presence and contribution of the Klebsiella oxytoca gene in the circulation of patients with DKD. Method: We enrolled a total of 16 healthy participants, 17 patients with DKD, 5 patients with DKD requiring haemodialysis (HD), and 7 patients with CKD without diabetes. Bacterial‐derived DNA (16S rDNA and a specific K. oxytoca gene) in the blood was detected using droplet digital PCR, then investigated the relationship with clinical characteristics. Results: We identified an increase in K. oxytoca genes in the blood of DKD patients. Interestingly, blood K. oxytoca copies and K. oxytoca/ 16S DNA ratio correlated with higher blood creatinine and BUN levels together with lower eGFR in DKD patients. K. oxytoca levels were also associated with higher neutrophil percentage, lower lymphocyte frequency, and increased neutrophil‐to‐lymphocyte ratio. Conclusion: Collectively, the presence of the K. oxytoca gene in the circulation could serve as a biomarker reflecting reduced renal function in DKD patients. [ABSTRACT FROM AUTHOR]

Objectives Reportedly, patients with LN and low-level proteinuria have favourable short-term renal outcomes. We aimed to clarify the long-term renal outcomes and overall survival of these patients, and the significance of renal biopsy in the early phase with low-level proteinuria. Methods We included 144 Japanese patients with biopsy-proven LN from 10 hospitals. Low-level proteinuria was defined by a urine protein:creatinine ratio (UPCR) of ≤1 g/gCr based on previous reports. The outcomes were end-stage renal disease (ESRD) and death. Results Compared with patients with high-level proteinuria (UPCR >1 g/gCr), those with low-level proteinuria [ n  = 67 (46.5%)] had significantly improved renal function at the time of renal biopsy, and low activity index and chronicity index while the frequency of class III/IV was similar (79.1% vs 84.4%, P  = 0.409). In patients with low-level proteinuria, CYC usage was less, and the incidences of ESRD (3.0% vs 13.0%, P  = 0.036) and death (3.0% vs 16.9%, P  = 0.006) during the total observation period (median, 72 months) were low. Kaplan–Meier analysis showed significant differences in the incidence of ESRD and death between the groups. Multivariate Cox regression analysis revealed that the significant risk factors for ESRD were high chronicity index and hypertension, whereas those for death were increased age and high-level proteinuria. Conclusion Patients with LN and low-level proteinuria had favourable long-term renal and life outcomes. As these patients have substantial active pathological lesions, renal biopsy in the early phase with low-level proteinuria could enable early diagnosis and treatment and thus improve prognosis. [ABSTRACT FROM AUTHOR]

Complications of diabetes affect tissues throughout the body, including the central nervous system. Epidemiological studies show that diabetic patients have an increased risk of depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in the brain or on hypothalamic neurons display an array of metabolic abnormalities; however, the role of insulin action on astrocytes and neurobehaviors remains less well studied. Here, we demonstrate that astrocytes are a direct insulin target in the brain and that knockout of IR on astrocytes causes increased anxiety- and depressive-like behaviors in mice. This can be reproduced in part by deletion of IR on astrocytes in the nucleus accumbens. At a molecular level, loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c. This led to decreased exocytosis of ATP from astrocytes, resulting in decreased purinergic signaling on dopaminergic neurons. These reductions contributed to decreased dopamine release from brain slices. Central administration of ATP analogs could reverse depressive-like behaviors in mice with astrocyte IR knockout. Thus, astrocytic insulin signaling plays an important role in dopaminergic signaling, providing a potential mechanism by which astrocytic insulin action may contribute to increased rates of depression in people with diabetes, obesity, and other insulin-resistant states., Introduction Over the past decade it has become clear that the brain is an insulin-sensitive organ. Insulin receptors (IRs) are widely distributed in the brain (1). Intracerebroventricular insulin infusion reduces [...]

Interactions of diet, gut microbiota, and host genetics play important roles in the development of obesity and insulin resistance. Here, we have investigated the molecular links between gut microbiota, insulin resistance, and glucose metabolism in 3 inbred mouse strains with differing susceptibilities to metabolic syndrome using diet and antibiotic treatment. Antibiotic treatment altered intestinal microbiota, decreased tissue inflammation, improved insulin signaling in basal and stimulated states, and improved glucose metabolism in obesity- and diabetes-prone C57BL/6J mice on a high-fat diet (HFD). Many of these changes were reproduced by the transfer of gut microbiota from antibiotic-treated donors to germ-free or germ-depleted mice. These physiological changes closely correlated with changes in serum bile acids and levels of the antiinflammatory bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) and were partially recapitulated by treatment with a TGR5 agonist. In contrast, antibiotic treatment of HFD-fed, obesity- resistant 129S1 and obesity-prone 129S6 mice did not improve metabolism, despite changes in microbiota and bile acids. These mice also failed to show a reduction in inflammatory gene expression in response to the TGR5 agonist. Thus, changes in bile acid and inflammatory signaling, insulin resistance, and glucose metabolism driven by an HFD can be modified by antibiotic- induced changes in gut microbiota; however, these effects depend on important interactions with the host's genetic background and inflammatory potential., Introduction Gut microbiota affect the host's energy balance, glucose and lipid metabolism, and the immune response (1). Obesity, type 2 diabetes, and metabolic syndrome are all associated with changes in [...]

This article examines the folkloric protest and popular political culture during the anti‐Corn Law agitation. It offers a new analysis of the role of customary demonstration based on moral economy in supporting free importation of foreign corn. It examines previously unstudied bread processions during the 1841 general election and effigy burnings of Sir Robert Peel that occurred simultaneously against his minor revision of the Corn Laws in 1842. It argues that the practice of these traditional protests offered a basis on which plebeians understood the emerging idea of Free Trade. While the protesters and more moderate reformers represented by the Anti‐Corn Law League shared a common cause of Corn Law repeal, there was a potential conflict over respectability. Moreover, Chartists could appropriate this popular custom for promoting the People's Charter rather than Free Trade. This article contributes to understanding the relationship between popular custom and radical politics in the wider context of the emergence of Free Trade Britain in the early Victorian period. [ABSTRACT FROM AUTHOR]

Systemic salt loading has been reported to facilitate operant heat-escape/cold-seeking behavior. In the present study, we hypothesized that the median preoptic nucleus (MnPO) would be involved in this mechanism. Rats were divided into two groups (n = 6 each): one group had the MnPO lesion with ibotenic acid (4.0 [micro]g) and the other was the vehicle control. After subcutaneous injection (10 ml/kg) of either isotonic- (154 mM) or hypertonic-saline (2,500 mM), each rat was placed in a behavior box, where the ambient temperature was changed to 26[degrees]C, 35[degrees]C, and 40[degrees]C every 1 h. The position of a rat in the box and the body core temperature ([T.sub.core]) were monitored. A rat could trigger 0[degrees]C air for 45 s in the 35[degrees]C and 40[degrees]C heat when moved in a specific area in the box (operant behavior). In the control group, counts of the operant behavior were greater (P < 0.05) in the hypertonic- than in the isotonic-saline injection (17 [+ or -] 2 and 10 [+ or -] 2 at 35[degrees]C, 24 [+ or -] 2 and 18 [+ or -] 1 at 40[degrees]C). [T.sub.core] remained unchanged throughout the exposure, although the level was lower (P < 0.05) in the hypertonic- than in the isotonic-saline trial (36.6 [+ or -] 0.2[degrees]C and 37.4 [+ or -] 0.1[degrees]C at 26[degrees]C and 36.9 [+ or -] 0.2[degrees]C and 37.4 [+ or -] 0.1[degrees]C at 40[degrees]C, respectively). However, in the MnPO-lesion group, counts of the behavior were similar between the hypertonic- and isotonic-saline injection trials (10 [+ or -] 2 and 8 [+ or -] 1 at 35[degrees]C, and 17 [+ or -] 1 and 16 [+ or -] 1 at 40[degrees]C, respectively). [T.sub.core] increased (P < 0.05) in the heat in both trials (36.8 [+ or -] 0.1[degrees]C and 37.4 [+ or -] 0.1[degrees]C at 26[degrees]C and 37.4 [+ or -] 0.2[degrees]C and 37.8 [+ or -] 0.2[degrees]C at 40[degrees]C in the hypertonicand isotonic-saline injection trials, respectively). These results may suggest that, at least in part, the MnPO is involved in the facilitation of heat-escape/cold-seeking behavior during osmotic stimulation. osmolality; body temperature; operant behavior; lesion

The criptochrome genes (Cry1 and Cry2) are involved in the molecular mechanism that controls the circadian clock, and mice lacking these genes ([Cry1.sup.-/-]/ [Cry2.sup.-/-]) are behaviorally arrhythmic. It has been speculated that the circadian clock modulates the characteristics of thermoregulation, resulting in body temperature ([T.sub.b]) rhythm. However, there is no direct evidence proving this speculation. We show here that Tb and heat production in [Cry1.sup.-/-]/[Cry2.sup.-/-] mice are arrhythmic under constant darkness. In contrast, both rhythms occur under a light-dark cycle and/or periodical food restriction linked with spontaneous activity and/or eating, although they are not robust as those in wild-type mice. The relationship between heat production and [T.sub.b] in [Cry1.sup.-/-]/[Cry2.sup.-/-] mice is linear and identical under any conditions, indicating that their [T.sub.b] rhythm is determined by heat production rhythm associated with activity and eating. However, [T.sub.b] in wild-type mice is maintained at a relatively higher level in the active phase than the inactive phase regardless of the heat production level. These results indicate that the thermoregulatory responses are modulated according to the circadian phase, and the Cry genes are involved in this mechanism. circadian clock; thermoregulation; metabolism

Maruyama, Megumi, Maiko Nishi, Masahiro Konishi, Yuko Takashige, Kei Nagashima, Toshikazu Kiyohara, and Kazuyuki Kanosue. Brain regions expressing Fos during thermoregulatory behavior in rats. Am J Physiol Regul Integr Comp Physiol 285: R1116-R1123, 2003. First published July 31, 2003; 10.1152/ajpregu.00166.2002.--We surveyed the neural substrata for behavioral thermoregulation with immunohistochemical analysis of the expression of Fos protein in the rat brain. We used an operant system in which a rat exposed to heat (40[degrees]C) could get cold air (0[degrees]C) for 30 s when it moved into the reward area. Rats moved in and out of the reward area of the system periodically and thus maintained their body temperature at a normal level. In the rats performing heat escape behavior (active group), strong Fos immunoreactivity (Fos-IR) was found in the median preoptic nucleus (MnPO), parastrial nucleus (PS), and dorsomedial hypothalamus (DMH) compared with the controls. Another group of rats (passive group) were given the same temperature changes, regardless of the rat's movement, as those obtained by rats of the active group. Fos-IR in the MnPO was also seen in this group. The present results suggest that the PS and DMH play an important role in the genesis of thermoregulatory behavior, whereas the MnPO may be important for detecting changes in ambient and/or body temperatures. preoptic area; dorsomedial hypothalamus; operant behavior

To investigate the mechanism involved in the reduction of body core temperature ([T.sub.core]) during fasting in rats, which is selective in the light phase, we measured [T.sub.core], surface temperature, and oxygen consumption rate in fed control animals and in fasted animals on day 3 of fasting and day 4 of recovery at an ambient temperature ([T.sub.a]) of 23[degrees]C by biotelemetry, infrared thermography, and indirect calorimetry, respectively. On the fasting day, 1) [T.sub.core] in the light phase decreased (P < 0.05) from the control; however, [T.sub.core] in the dark phase was unchanged, 2) tail temperature fell from the control (P < 0.05, from 30.7 [+ or -] 0.1 to 23.9 [+ or -] 0.1[degrees]C in the dark phase and from 29.4 [+ or -] 0.1 to 25.2 [+ or -] 0.2[degrees]C in the light phase), 3) oxygen consumption rate decreased from the control (P < 0.05, from 24.37 [+ or -] 1.06 to 16.24 [+ or -] 0.69 ml*[min.sup.-1]* kg body [wt.sup.-0.75] in the dark phase and from 18.91 [+ or -] 0.64 to 14.00 [+ or -] 0.41 ml*[min.sup.-1]*kg body [wt.sup.-0.75] in the light phase). All these values returned to the control levels on the recovery day. The results suggest that, in the fasting condition, [T. sub.core] in the dark phase was maintained by suppression of the heat loss mechanism, despite the reduction of metabolic heat production. In contrast, the response was weakened in the light phase, decreasing [T.sub.core] greatly. Moreover, the change in the regulation of tail blood flow was a likely mechanism to suppress heat loss. core temperature; oxygen consumption; heat loss mechanism

The formation of massive stars in dense and cold molecular clouds is a fundamental problem in star formation. In this work, we studied three compact massive star-forming regions, M8E, RAFGL 6366S, and IRAS 18317−0513, to investigate the environment of massive star formation, specifically the possibility of a local feedback process. Our new mid-infrared observations using miniTAO/MAX38 at 31 and 37 μm resolved individual objects in each region and allowed us to obtain their individual luminosities and masses. Together with existence/absence of ultra-compact H  ii regions, it is suggested that less-massive objects are more evolved than the more-massive objects in two out of the three regions. Because the objects that are more massive evolve faster, those that are less massive form earlier. This formation trend of local mass-sequential star was first suggested in 0.1 pc-scale massive star-forming regions. Therefore, feedback, such as outflows, jets, or radiative heating, from previously formed lower-mass young stellar objects might affect the environment of parental clouds and lead to next-generation massive young stellar objects. [ABSTRACT FROM AUTHOR]

The brain is now recognized as an insulin-sensitive tissue; however, the role of changing insulin concentrations in the peripheral circulation in gene expression in the brain is largely unknown. Here, we performed a hyperinsulinemic-euglycemic clamp on 3-month-old male C57BL/6 mice for 3 h. We show that, in comparison with results in saline-infused controls, increases in peripheral insulin within the physiological range regulate expression of a broad network of genes in the brain. Insulin regulates distinct pathways in the hypothalamus (HTM), hippocampus, and nucleus accumbens. Insulin shows its most robust effect in the HTM and regulates multiple genes involved in neurotransmission, including upregulating expression of multiple subunits of GABA-A receptors, Na+ and K+ channels, and SNARE proteins; differentially modulating glutamate receptors; and suppressing multiple neuropeptides. Insulin also strongly modulates metabolic genes in the HTM, suppressing genes in the glycolysis and pentose phosphate pathways, while increasing expression of genes regulating pyruvate dehydrogenase and long-chain fatty acyl-CoA and cholesterol biosynthesis, thereby rerouting of carbon substrates from glucose metabolism to lipid metabolism required for the biogenesis of membranes for neuronal and glial function and synaptic remodeling. Furthermore, based on the transcriptional signatures, these changes in gene expression involve neurons, astrocytes, oligodendrocytes, microglia, and endothelial cells. Thus, peripheral insulin acutely and potently regulates expression of a broad network of genes involved in neurotransmission and brain metabolism. Dysregulation of these pathways could have dramatic effects in normal physiology and diabetes. [ABSTRACT FROM AUTHOR]

Author(s): Thomas Thomou; Marcelo A. Mori; Jonathan M. Dreyfuss; Masahiro Konishi; Masaji Sakaguchi; Christian Wolfrum; Tata Nageswara Rao; Jonathon N. Winnay; Ruben Garcia-Martin; Steven K. Grinspoon; Phillip Gorden; C. Ronald [...]

Nagashima, Kei, Sadamu Nakai, Masahiro Konishi, Liu Su, and Kazuyuki Kanosue. Increased heat-escape/ cold-seeking behavior following hypertonic saline injection in rats. Am J Physiol Regulatory Integrative Comp Physiol 280: R1031-R1036, 2001.--We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40 [degrees] C heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaC1) injection (1 ml/100 g body wt). The rats received a 0 [degrees] C air for 30 s when they entered a specific area in an experimental box. Core temperature ([T.sub.c]) surpassed 40 [degrees] C in both conditions when 0 [degrees] C air was not available. Hypertonic saline injection produced a lower baseline [T.sub.c] than control [36.9 [+ or -] 0.2 and 37.9 [+ or -] 0.2 [degrees] C (means [+ or -] SE), P [is less than] 0.05] and a greater number of 0 [degrees] C air rewards during the 2-h heat with lower [T.sub.c] at the end (48 [+ or -] 1 and 34 [+ or -] 2, 37.6 [+ or -] 0.1, and 37.3 [+ or -] 0.1 [degrees] C in the control and hypertonic saline injection trial, respectively, P [is less than] 0.05, n = 6). However, Tc was similar (37.7 [+ or -] 0.2 and 37.6 [+ or -] 0.4 [degrees] C in the control and hypertonic saline injection trial, n = 5) when 0 [degrees] C air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline [T.sub.c] and increasing heat-escape/coldseeking behavior. hyperosmolality; operant behavior; desalivation

In order to investigate populations of massive stars in massive star clusters, we have constructed a near-infrared image set: narrow bands of 1.87 and 2.07 $$\mu$$ m and the K s standard band with miniTAO, a 1-m infrared telescope at Atacama. First, we observed the well-known three massive star clusters near the Galactic Centre. Colour–colour diagrams made from the set of images show clear excess in 1.87 μm for WN-type Wolf–Rayet stars, luminous blue variables and Ofpe stars, and also clear excess in 2.07 μm for WC-type Wolf–Rayet stars. Our detection in 1.87 μm agrees well with the 1.87-μm detection with the Hubble Space Telescope by Dong et al. The 1.87-μm excess of WN stars seems to have a clear correlation to the K s magnitude. The correlation suggests that the 1.87-μm excess originates in recombination line emission of H and He, and the K s magnitude includes free–free radiation. Moreover, the K s magnitude of WN-late stars, excluding the component of the free–free emission, seems to have nearly a common K s magnitude. However, the colour–colour diagrams also enable us to find the extinction for each star and thus to draw extinction maps. Furthermore, almost all Mira variables reported by Matsunaga et al. are detected in our images. By using the extinction maps, several tens of extremely red sources except for Mira variables are detected. These are considered to be possibly low-temperature (T < 1000 K) objects. [ABSTRACT FROM AUTHOR]

Systemic salt loading has been reported to facilitate operant heat-escape/cold-seeking behavior. In the present study, we hypothesized that the median preoptic nucleus (MnPO) would be involved in this mechanism. Rats were divided into two groups (n = 6 each): one group had the MnPO lesion with ibotenic acid (4.0 μg) and the other was the vehicle control. After subcutaneous injection (10 ml/kg) of either isotonic- (154 mM) or hypertonic-saline (2,500 mM), each rat was placed in a behavior box, where the ambient temperature was changed to 26°C, 35°C, and 40°C every 1 h. The position of a rat in the box and the body core temperature (Tcore) were monitored. A rat could trigger 0°C air for 45 s in the 35°C and 40°C heat when moved in a specific area in the box (operant behavior). In the control group, counts of the operant behavior were greater (P < 0.05) in the hypertonic- than in the isotonic-saline injection (17 ± 2 and 10 ± 2 at 35°C, 24 ± 2 and 18 ± 1 at 40°C). Tcore remained unchanged throughout the exposure, although the level was lower (P < 0.05) in the hypertonic- than in the isotonic-saline trial (36.6 ± 0.2°C and 37.4 ± 0.1°C at 26°C and 36.9 ± 0.2°C and 37.4 ± 0.1°C at 40°C, respectively). However, in the MnPO-lesion group, counts of the behavior were similar between the hypertonic- and isotonic-saline injection trials (10 ± 2 and 8 ± 1 at 35°C, and 17 ± 1 and 16 ± 1 at 40°C, respectively). Tcore increased (P < 0.05) in the heat in both trials (36.8 ± 0.1°C and 37.4 ± 0.1°C at 26°C and 37.4 ± 0.2°C and 37.8 ± 0.2°C at 40°C in the hypertonic- and isotonic-saline injection trials, respectively). These results may suggest that, at least in part, the MnPO is involved in the facilitation of heat-escape/cold-seeking behavior during osmotic stimulation. [ABSTRACT FROM AUTHOR]

To investigate the mechanism involved in the reduction of body core temperature (T[sub core]) during fasting in rats, which is selective in the light phase, we measured T[sub core], surface temperature, and oxygen consumption rate in fed control animals and in fasted animals on day 3 of fasting and day 4 of recovery at an ambient temperature (T[sub a]) of 23°C by biotelemetry, infrared thermography, and indirect calorimetry, respectively. On the fasting day, 1) T[sub core] in the light phase decreased (P < 0.05) from the control; however, T[sub core] in the dark phase was unchanged, 2) tail temperature fell from the control (P < 0.05, from 30.7 ± 0.1 to 23.9 ± 0.1°C in the dark phase and from 29.4 ± 0.1 to 25.2 ± 0.2°C in the light phase), 3) oxygen consumption rate decreased from the control (P < 0.05, from 24.37 ± 1.06 to 16.24 ± 0.69 ml·min[sup -1]·kg body wt[sup -0.75] in the dark phase and from 18.91 ± 0.64 to 14.00 ± 0.41 ml·min[sup -1]·kg body wt[sup -0.75] in the light phase). All these values returned to the control levels on the recovery day. The results suggest that, in the fasting condition, T[sub core] in the dark phase was maintained by suppression of the heat loss mechanism, despite the reduction of metabolic heat production. In contrast, the response was weakened in the light phase, decreasing T[sub core] greatly. Moreover, the change in the regulation of tail blood flow was a likely mechanism to suppress heat loss. [ABSTRACT FROM AUTHOR]

An extended version of cross-bar type addressing technique is developed for three-port electrostatic micro shutters arranged in an arrayed format. A microelectromechanical systems (MEMS) shutter blade suspended by a pair of torsion beams works as a movable electrode that is either attracted upwards to the cover plate to close the aperture or retracted downwards into the through-hole to open it. Tri-state positioning of the shutter—i.e., open, rest, and close—is controlled by the hysteresis loop of the electrostatic pull-in and release behavior using the combination of the voltages applied to the shutter, the cover, and the substrate. Random access addressing of the shutters is demonstrated by a control system composed of MATLAB-coded Arduino electronics. The shutter array developed in this work is for a sub-cluster of a reconfigurable shutter array under development for a multi-object galactic astronomy. [ABSTRACT FROM AUTHOR]

Using a prototype of the Tomo-e Gozen wide-field CMOS mosaic camera, we acquire wide-field optical images at a cadence of |$2\:$| Hz and search them for transient sources of duration 1.5 to |$11.5\:$| s. Over the course of eight nights, our survey encompasses the equivalent of roughly two days on one square degree, to a fluence equivalent to a limiting magnitude of about |$V = 15.6$| in a 1-s exposure. After examining by-eye the candidates identified by a software pipeline, we find no sources which meet all our criteria. We compute upper limits to the rate of optical transients consistent with our survey, and compare those to the rates expected and observed for representative sources of ephemeral optical light. [ABSTRACT FROM AUTHOR]

Impaired insulin signaling in brain leads to both metabolic and behavioral abnormalities. To understand the role of insulin on gene expression in the brain, we performed hyperinsulinemic-euglycemic clamps using physiological doses of insulin in C57BL/6 mice, and after 3 hours collected different brain regions and analyzed their transcriptomes by RNA Seq. In response to peripheral insulin, 1851 genes were up- or down-regulated in the hypothalamus by at least 50% (all P < 0.01). Other regions showed different responses with 205 genes significantly regulated by ≥ 50% in hippocampus and 131 regulated in nucleus accumbens. Insulin upregulated the pathway for very long chain fatty acyl-CoA synthesis in all three regions, but most insulin responsive genes were region specific. Thus, in hypothalamus, insulin modulated metabolism by suppressing the glycolysis and pentose phosphate pathway, while increasing expression of genes in the pyruvate dehydrogenase complex and cholesterol biosynthesis. Conversely, mice with streptozotocin diabetes displayed decreased expression of genes involved in the regulation of pyruvate dehydrogenase complex, very long-chain fatty acyl-CoA and cholesterol biosynthesis in hypothalamus, all of which were normalized by exogenous insulin. In addition, insulin regulated many genes in the hypothalamus involved in neurotransmission, including enhancing the expression of multiple GABA-A receptor subunits and suppressing many neuropeptides. Based on the transcriptional signature, changes in gene expression by insulin involve neurons, astrocytes, oligodendrocytes, microglia and endothelial cells. In summary, peripherally administered insulin rapidly and potently regulates expression of genes involved in neurotransmission, neuromodulation and brain metabolism, especially in the hypothalamus. This helps reroute substrate carbons to the biogenesis of plasma membrane for neuronal and glial function and synaptic remodeling. Disclosure: W. Cai: None. T.M. Batista: None. R. Garcia Martin: None. A. Ramirez: None. M. Konishi: None. B.T. O'Neill: None. J.K. Kim: None. C. Kahn: Advisory Panel; Self; MedImmune. Board Member; Self; Kaleido Biosciences. Consultant; Self; AntriaBio, Inc., Cobalt Therapeutics, Flagship Pioneering. Research Support; Self; Alnylam. [ABSTRACT FROM AUTHOR]

Highlights from the article: That star-forming galaxies with classical bulges have compact star-forming regions con- Key words: HII regions - galaxies: interactions - galaxies: star formation - galaxies: starburst - infrared: Thus selected 20 non-irregular galaxies out of 38 galaxies A Seyfert 1 galaxy whose concentrated Pa emission may HII regions, galaxies: interactions, galaxies: star formation, galaxies: starburst, infrared: galaxies.

We have developed a near-infrared camera called ANIR (Atacama Near-InfraRed camera) for the University of Tokyo Atacama Observatory 1.0 m telescope (miniTAO) installed at the summit of Cerro Chajnantor (5640 m above sea level) in the north of Chile. The camera provides a field of view of 5${^{\prime}_{.}}$1 × 5${^{\prime}_{.}}$1 with a spatial resolution of 0${^{\prime\prime}_{.}}$298 pixel−1 in the wavelength range of 0.95 to 2.4 μm, using Offner relay optics and a PACE HAWAII-2 focal plane array. Taking advantage of the dry site, the camera is capable of narrow-band imaging observations at the hydrogen Paschen-α (Paα, λ = 1.8751 μm in air) wavelength ground-based observations of which have been quite difficult due to deep atmospheric absorption, mainly from water vapor. We have been successfully obtaining Paα images of Galactic objects and nearby galaxies since the first-light observation in 2009 with ANIR. The throughputs at the narrow-band filters (N1875, N191) including the atmospheric absorption show larger dispersion (∼ 10%) than those at broad-band filters (a few percent), indicating that they are affected by temporal fluctuations in precipitable water vapor (PWV) above the site. We evaluate the PWV content via the atmospheric transmittance at the narrow-band filters, and deduce that the median and the dispersion of the distribution of the PWV are 0.40 ± 0.30 and 0.37 ± 0.21 mm, for the N1875 and N191 data respectively, which are remarkably smaller (49% ± 38% for N1875 and 59% ± 26% for N191) than radiometry measurements at the base of Cerro Chajnantor (an altitude of 5100 m). The decrease in PWV can be explained by the altitude of the site when we assume that the vertical distribution of the water vapor is approximated at an exponential profile with scale heights within 0.3–1.9 km (previously observed values at night). We thus conclude that miniTAO/ANIR at the summit of Cerro Chajnantor indeed provides us an excellent capability for a ground-based Paα observation. [ABSTRACT FROM PUBLISHER]

In response to increased core temperature, mammals initiate evaporative cooling responses (e.g. sweating, punting). These responses result in dehydration and plasma hypertonicity if the fluid losses are not replaced. The aim of the present study was to determine whether osmoreceptors in the lamina terminalis (LT) may exert an inhibitory influence on evaporative thermoregulatory cooling responses. We studied the effect of infusions of either hypertonic 1.65M NaCl or 3M sorbitol in 0.15M NaCl at 1.6 ml/min for 10 min into a carotid artery, on the rate of punting of 4 conscious sheep exposed to an ambient temperature of 39°C for 1,-2 hours. Both intracarotid (IC) 1.65M NaCl or 3M sorbitol caused rapid and large reduction in punting (127 ± 18 to 65 ± 15 and 110 ± 15 to 76 ± 24 breaths/rain respectively) that reversed immediately infusions ended. Control IC infusion of isotonic saline did not inhibit panting during heat exposure. In 3 sheep in which the osmoregulatory region of the lamina term±nails had been ablated, IC infusion of 1.65M NaCl or 3M sorbitol did not reduce punting. Drinking in response to IC hypertonic saline was also abolished in these 3 sheep with LT lesions. We propose that osmoreceptors in the region of the lamina terminal±s, probably located in the organum vaseulosum laminae term±nails and/or subfornical organ, may exert inhibitory osmoregulatory influences on evaporative cooling mechanisms. [ABSTRACT FROM AUTHOR]

We report herein the synthesis and structure-activity relationships (SAR) of a series of pyridazine derivatives with the activation of glucose transporter type 4 (GLUT4) translocation. Through a cell-based phenotype screening in L6-GLUT4-myc myoblasts and functional glucose uptake assays, lead compound 1a was identified as a functional small molecule. After further derivatization, the thienopyridazine scaffold as the central ring (B-part) was revealed to have potent GLUT4 translocation activities. Consequently, we obtained promising compound 26b , which showed a significant blood glucose lowering effect in the severe diabetic mice model (10-week aged db / db mice) after oral dosing even at 10 mg/kg, implying that our pyridazine derivatives have potential to become novel therapeutic agents for diabetes mellitus. [ABSTRACT FROM AUTHOR]

Complications of diabetes affect tissues throughout the body, including the central nervous system. Epidemiological studies show that diabetic patients have an increased risk of depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in the brain or on hypothalamic neurons display an array of metabolic abnormalities; however, the role of insulin action on astrocytes and neurobehaviors remains less well studied. Here, we demonstrate that astrocytes are a direct insulin target in the brain and that knockout of IR on astrocytes causes increased anxiety- and depressive-like behaviors in mice. This can be reproduced in part by deletion of IR on astrocytes in the nucleus accumbens. At a molecular level, loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c. This led to decreased exocytosis of ATP from astrocytes, resulting in decreased purinergic signaling on dopaminergic neurons. These reductions contributed to decreased dopamine release from brain slices. Central administration of ATP analogs could reverse depressive-like behaviors in mice with astrocyte IR knockout. Thus, astrocytic insulin signaling plays an important role in dopaminergic signaling, providing a potential mechanism by which astrocytic insulin action may contribute to increased rates of depression in people with diabetes, obesity, and other insulin-resistant states. [ABSTRACT FROM AUTHOR]

Interactions of diet, gut microbiota, and host genetics play important roles in the development of obesity and insulin resistance. Here, we have investigated the molecular links between gut microbiota, insulin resistance, and glucose metabolism in 3 inbred mouse strains with differing susceptibilities to metabolic syndrome using diet and antibiotic treatment. Antibiotic treatment altered intestinal microbiota, decreased tissue inflammation, improved insulin signaling in basal and stimulated states, and improved glucose metabolism in obesity- and diabetes-prone C57BL/6J mice on a high-fat diet (HFD). Many of these changes were reproduced by the transfer of gut microbiota from antibiotic-treated donors to germ-free or germ-depleted mice. These physiological changes closely correlated with changes in serum bile acids and levels of the antiinflammatory bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) and were partially recapitulated by treatment with a TGR5 agonist. In contrast, antibiotic treatment of HFD-fed, obesity-resistant 129S1 and obesity-prone 129S6 mice did not improve metabolism, despite changes in microbiota and bile acids. These mice also failed to show a reduction in inflammatory gene expression in response to the TGR5 agonist. Thus, changes in bile acid and inflammatory signaling, insulin resistance, and glucose metabolism driven by an HFD can be modified by antibiotic-induced changes in gut microbiota; however, these effects depend on important interactions with the host's genetic background and inflammatory potential. [ABSTRACT FROM AUTHOR]

Novel compounds based on 1a were synthesized with the focus of obtaining agonists acting upon peripheral BRS-3. To identify potent anti-obesity compounds without adverse effects on the central nervous system (CNS), a carboxylic acid moiety and a labile carboxylic ester with an antedrug functionality were introduced. Through the extensive synthetic exploration and the pharmacokinetic studies of intravenous administration in mice, the ester 2b was selected owing to its most suitable pharmacological profile. In the evaluation of food intake suppression in C57BL/6N mice, 2b showed significant in vivo efficacy and no clear adverse effects on blood pressure change in dogs administered the compound by intravenous infusion. [ABSTRACT FROM AUTHOR]