Role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice

Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(−/−) or A1(+/−) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2−/−, but not A1+/−, mice. Additionally, A2−/− HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of PGC-1α, PPAR-γ, and adiponectin. A2 deletion blunted these effects, increased levels of active AMPK-α, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2−/− mice, but more prominently maintained in A1+/− mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction

On spectral minimal partitions II, the case of the rectangle

In continuation of \cite{HHOT}, we discuss the question of spectral minimal 3-partitions for the rectangle $]-\frac a2,\frac a2[\times ] -\frac b2,\frac b2[$, with $0< a\leq b$. It has been observed in \cite{HHOT} that when $0<\frac ab < \sqrt{\frac 38}$ the minimal 3-partition is obtained by the three nodal domains of the third eigenfunction corresponding to the three rectangles $]-\frac a2,\frac a2[\times ] -\frac b2,-\frac b6[$, $]-\frac a2,\frac a2[\times ] -\frac b6,\frac b6[$ and $]-\frac a2,\frac a2[\times ] \frac b6, \frac b2[$. We will describe a possible mechanism of transition for increasing $\frac ab$ between these nodal minimal 3-partitions and non nodal minimal 3-partitions at the value $\sqrt{\frac 38}$ and discuss the existence of symmetric candidates for giving minimal 3-partitions when $\sqrt{\frac 38}<\frac ab \leq 1$. Numerical analysis leads very naturally to nice questions of isospectrality which are solved by introducing Aharonov-Bohm Hamiltonians or by going on the double covering of the punctured rectangle

Strongly intersecting integer partitions

We call a sum a1+a2+• • •+ak a partition of n of length k if a1, a2, . . . , ak and n are positive integers such that a1 ≤ a2 ≤ • • • ≤ ak and n = a1 + a2 + • • • + ak. For i = 1, 2, . . . , k, we call ai the ith part of the sum a1 + a2 + • • • + ak. Let Pn,k be the set of all partitions of n of length k. We say that two partitions a1+a2+• • •+ak and b1+b2+• • •+bk strongly intersect if ai = bi for some i. We call a subset A of Pn,k strongly intersecting if every two partitions in A strongly intersect. Let Pn,k(1) be the set of all partitions in Pn,k whose first part is 1. We prove that if 2 ≤ k ≤ n, then Pn,k(1) is a largest strongly intersecting subset of Pn,k, and uniquely so if and only if k ≥ 4 or k = 3 ≤ n ̸∈ {6, 7, 8} or k = 2 ≤ n ≤ 3.peer-reviewe

PG 1115+080: variations of the A2/A1 flux ratio and new values of the time delays

We report the results of our multicolor observations of PG 1115+080 with the 1.5-m telescope of the Maidanak Observatory (Uzbekistan, Central Asia) in 2001-2006. Monitoring data in filter R spanning the 2004, 2005 and 2006 seasons (76 data points) demonstrate distinct brightness variations of the source quasar with the total amplitude of almost 0.4 mag. Our R light curves have shown image C leading B by 16.4d and image (A1+A2) by 12d that is inconsistent with the previous estimates obtained by Schechter et al. in 1997 - 24.7d between B and C and 9.4d between (A1+A2) and C. The new values of time delays in PG 1115+080 must result in larger values for the Hubble constant, thus reducing difference between its estimates taken from the gravitational lenses and with other methods. Also, we analyzed variability of the A2/A1 flux ratio, as well as color changes in the archetypal "fold" lens PG 1115+080. We found the A1/A2 flux ratio to grow during 2001-2006 and to be larger at longer wavelengths. In particular, the A2/A1 flux ratio reached 0.85 in filter I in 2006. We also present evidence that both the A1 and A2 images might have undergone microlensing during 2001-2006, with the descending phase for A1 and initial phase for A2. We find that the A2/A1 flux ratio anomaly in PG 1115 can be well explained both by microlensing and by finite distance of the source quasar from the caustic fold.Comment: 14 pages, 7 figures, 8 tables, Accepted for publication in MNRA

Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes.

Nitrogen-containing bisphosphonates (N-BPs) are the most widely used anti-resorptive agents in the treatment of bone-related diseases. N-BPs inhibit bone resorption by specifically targeting osteoclasts, bone-resorbing cells. However, soft tissue toxicity, such as oral or gastrointestinal (GI) ulcerations has frequently been reported in N-BP users, suggesting that N-BPs may also directly target cells other than osteoclasts. Previously, we reported that BPs inhibit proliferation without inducing the apoptosis of normal human oral keratinocytes (NHOKs). However, the molecular mechanisms through which N-BPs inhibit the proliferation of NHOKs are not yet fully understood. In this study, we performed gene expression profiling in N-BP-treated NHOKs and identified cyclin A2 as one of the most commonly downregulated genes. When the NHOKs were treated with N-BPs, we found that the level of cyclin A2 was suppressed in a dose- and time-dependent manner. In addition, the protein level of cyclin A2 was also significantly lower in oral epithelial cells in N-BP-treated oral mucosal tissue constructs. Cyclin A2 promoter reporter assay revealed that N-BPs inhibited the luciferase activity, indicating that the inhibition of cyclin A2 expression occurs at the transcriptional level. Furthermore, N-BPs did not alter the expression of cyclin A2 in normal human oral fibroblasts (NHOFs), suggesting that the effect of N-BPs on cyclin A2 expression may be cell-type specific. Thus, the findings of our study demonstrate that the inhibition of NHOK proliferation by N-BPs is mediated, at least in part, by the suppression of cyclin A2 expression at the transcriptional level, which may explain the underlying mechanisms of soft tissue toxicity by N-BPs

PCR Based Genotyping of Lulu Cattle of Nepal for A1, A2 Type Beta-caseins

Lulu is an indigenous breed of cattle (Bos taurus) found in high altitude regions of western Nepal. Population of Lulu cattle has been declining due to introgression with other exotic breeds to increase milk productivity. Here we aimed at finding potential approach for conserving Lulu cattle and its assets by studying the milk contents and investigating which variant of beta-casein protein is present in this breed. Beta caseins are an abundant protein in cow milk with A1 and A2 being the most common genetic variants of this protein. Consumption of A1 type of milk has numerous health-related complications whereas A2 type of milk has numerous human health promoting factors. We used restriction fragment length polymorphism (RFLP) for determining the A1 and A2 variant of beta casein in Lulu cattle. For performing DNA extraction, we collected (n = 18) blood samples of Lulu from Mustang and (n=17) Nepal Agriculture research council farm. The amplified fragments in 3% agarose at 251bp and 213bp respectively confirmed the presence of both A1 and A2 gene in Lulu; however, A2 was of greater abundance. Our study indicated that Lulu has A2 variant of beta-casein predominantly. The gene frequency of A1A1 is 0, A1A2 is 0.06 and A2A2 is 0.94. We further found that the allele frequency of A1 and A2 is 0.03 and 0.97 respectively. We designed special primer for sequencing CSN2 genes since A2 type beta casein gene was predominantly seen on Lulu. The sequencing result further supports our RFLP result as most of our samples have “C” nucleotide SNP in amplified CSN2 gene sequence. The Chi-square value of the current study is 0.04 which supports Hardy-Weinberg equilibrium inferring that Lulu cattle are still in the pure state, where there is no genetic introgression with the exotic breed for the sake of improvement of productivity

Dimeric procyanidins as modulators of airway inflammation in the context of allergic asthma : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Human Physiology at Massey University, Manawatū, Palmerston North, New Zealand

Procyanidins are polyphenolic compounds that have come to be known as biologically active in the context of promoting human health. Epidemiological evidence suggests that populations that consume diets rich in procyanidins are less susceptible to inflammatory diseases. Allergic asthma is an inflammatory lung disease with an estimated 100 million affected individuals worldwide, with New Zealand having the world’s second highest rate. Inflammation at the airway epithelium and infiltration of immune cells, specifically eosinophils, into the lung tissue are two central characteristics of allergic asthma. Thymic stromal lymphopoietin (TSLP) and eotaxin isoforms, eotaxin-1 (CCL11) and eotaxin-3 (CCL26), are three biomarkers of airway inflammation produced by the epithelium. Cell culture models were successfully optimized for CCL11 and CCL26 production in A549 cells. Investigation of procyanidins effect on epithelial TSLP production was not possible because TSLP production in A549 cells was undetectable. Data suggests that dimeric A-type linked procyanidin A2, but not B-type linked procyanidin B1 or B2, is capable of inhibiting IL-4-induced CCL11 production when incubated on A549 cells prior to an inflammatory insult. Co-incubation of A549 cells with procyanidin A2 and procyanidin B2 demonstrated no evidence of a synergistic relationship for inhibiting cytokine- induced CCL11 production. Similarly, A549 cells exposed to procyanidin A2, and to a lesser extent procyanidin B2, had reduced production of cytokine-induced CCL26 production. An inhibition time course demonstrated procyanidin A2 had greatest inhibition efficacy on cytokine-induced CCL26 production when incubated for 2 h prior to an inflammatory insult. Comparison of procyanidin A2 inhibition to the known CCL26 inhibitor, IFN , demonstrated that procyanidin A2 and IFN did not share the same temporal inhibition patterns. Furthermore, experiments investigating concomitant incubation of procyanidin A2 and IFN demonstrated that procyanidin A2 could interfere with IFN –mediated CCL26 inhibition. Two possible mechanisms responsible for the procyanidin A–mediated inhibition of cytokine-induced CCL11 and CCL26 were investigated: the modulation of cytokine receptor expression, and modulation of plasma membrane fluidity. However, there was no evidence to support either of these modes of action. The data presented in this thesis collectively demonstrate the ability of procyanidin A2 to inhibit cytokine-induced eotaxin production from the lung epithelium in vitro and support further investigation of procyanidin A2 as a preventative approach for managing airway inflammation

Complex organics in IRAS 4A revisited with ALMA and PdBI: Striking contrast between two neighbouring protostellar cores

We used the Atacama Large (sub-)Millimeter Array (ALMA) and the IRAM Plateau de Bure Interferometer (PdBI) to image, with an angular resolution of 0.5$''$ (120 au) and 1$''$ (235 au), respectively, the emission from 11 different organic molecules in the protostellar binary NGC1333 IRAS 4A. We clearly disentangled A1 and A2, the two protostellar cores present. For the first time, we were able to derive the column densities and fractional abundances simultaneously for the two objects, allowing us to analyse the chemical differences between them. Molecular emission from organic molecules is concentrated exclusively in A2 even though A1 is the strongest continuum emitter. The protostellar core A2 displays typical hot corino abundances and its deconvolved size is 70 au. In contrast, the upper limits we placed on molecular abundances for A1 are extremely low, lying about one order of magnitude below prestellar values. The difference in the amount of organic molecules present in A1 and A2 ranges between one and two orders of magnitude. Our results suggest that the optical depth of dust emission at these wavelengths is unlikely to be sufficiently high to completely hide a hot corino in A1 similar in size to that in A2. Thus, the significant contrast in molecular richness found between the two sources is most probably real. We estimate that the size of a hypothetical hot corino in A1 should be less than 12 au. Our results favour a scenario in which the protostar in A2 is either more massive and/or subject to a higher accretion rate than A1, as a result of inhomogeneous fragmentation of the parental molecular clump. This naturally explains the smaller current envelope mass in A2 with respect to A1 along with its molecular richness.Comment: Accepted in Astronomy and Astrophysic

On the structure of Ammann A2 tilings

We establish a structure theorem for the family of Ammann A2 tilings of the plane. Using that theorem we show that every Ammann A2 tiling is self-similar in the sense of [B. Solomyak, Nonperiodicity implies unique composition for self-similar translationally finite tilings, Discrete and Computational Geometry 20 (1998) 265-279]. By the same techniques we show that Ammann A2 tilings are not robust in the sense of [B. Durand, A. Romashchenko, A. Shen. Fixed-point tile sets and their applications, Journal of Computer and System Sciences, 78:3 (2012) 731--764]