Cross talk between adipose tissue and placenta in obese and gestational diabetes mellitus pregnancies via exosomes

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body’s major energy reservoir. The role of adipose tissue, however, is not restricted to a “bag of fat.” The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue-derived EVs and metabolic syndrome in obesity. In this review, we will discuss the changes in human placenta and adipose tissue in GDM and obesity and summarize the findings regarding the role of adipose tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the contribution of obesity to the development of GDM

Enhanced weathering and erosion of a cohesive shore platform following the experimental removal of mussels

The organisms inhabiting intertidal platforms can affect their weathering and erosion rates. Research on biotic influences on platform integrity has traditionally emphasized the role of bioeroders (i.e., organisms that scrap or bore into platforms via mechanical and chemical means). Yet, recent studies illustrate that covers of sessile organisms on the surfaces of intertidal platforms can have bioprotective effects by reducing the efficacy of physical weathering and erosion agents. Eroding cliffs fronted by cohesive shore platforms are a pervasive feature along the continental Argentinean coastline (37–52°S). In this study, we investigated how mussel (Brachidontes rodriguezii) cover mediates weathering and erosion of a cohesive, consolidated silt platform at Playa Copacabana (5 km north of Miramar, Buenos Aires Province; 38° 14′ S, 57° 46′ W). By means of mussel removal experiments, we found that mussel cover attenuates variations in platform surface temperatures, enhances moisture retention during low tide, reduces rates of salt crystallization within the pores of the platform material, and attenuates hydrodynamic forcing on the platform surface. Mussel removal also led to a 10% decrease in surface hardness and a 2-mm reduction in platform height after 5 months. Collectively, our findings indicate that mussel beds limit substrate breakdown via heating-cooling, wetting-drying, and salt crystallization and provide some of the first experimental field evidence for the direct impacts of biotic cover on platform erosion. As intertidal platforms protect the cliffs behind from the hydraulic impact of waves, which may be enhanced with future sea-level rise, we posit that the protection of platforms by mussels indirectly moderates coastline retreat, especially on soft cohesive shores.Fil: Gonzalez, Juliana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Coombes, Martin A.. University of Oxford; Reino UnidoFil: Palomo, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Isla, Federico Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Soria, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Gutierrez, Jorge Luis Ceferino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentin

Functional asymmetry and chemical reactivity of CsoR family persulfide sensors

CstR is a persulfide-sensing member of the functionally diverse copper-sensitive operon repressor (CsoR) superfamily. While CstR regulates the bacterial response to hydrogen sulfide (H2S) and more oxidized reactive sulfur species (RSS) in Gram-positive pathogens, other dithiol-containing CsoR proteins respond to host derived Cu(I) toxicity, sometimes in the same bacterial cytoplasm, but without regulatory crosstalk in cells. It is not clear what prevents this crosstalk, nor the extent to which RSS sensors exhibit specificity over other oxidants. Here, we report a sequence similarity network (SSN) analysis of the entire CsoR superfamily, which together with the first crystallographic structure of a CstR and comprehensive mass spectrometry-based kinetic profiling experiments, reveal new insights into the molecular basis of RSS specificity in CstRs. We find that the more N-terminal cysteine is the attacking Cys in CstR and is far more nucleophilic than in a CsoR. Moreover, our CstR crystal structure is markedly asymmetric and chemical reactivity experiments reveal the functional impact of this asymmetry. Substitution of the Asn wedge between the resolving and the attacking thiol with Ala significantly decreases asymmetry in the crystal structure and markedly impacts the distribution of species, despite adopting the same global structure as the parent repressor. Companion NMR, SAXS and molecular dynamics simulations reveal that the structural and functional asymmetry can be traced to fast internal dynamics of the tetramer. Furthermore, this asymmetry is preserved in all CstRs and with all oxidants tested, giving rise to markedly distinct distributions of crosslinked products. Our exploration of the sequence, structural, and kinetic features that determine oxidant-specificity suggest that the product distribution upon RSS exposure is determined by internal flexibility.Fil: Fakhoury, Joseph N. Indiana University; Estados UnidosFil: Zhang, Yifan. Indiana University; Estados UnidosFil: Edmonds, Katherine A. Indiana University; Estados UnidosFil: Bringas, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Luebke, Justin L. Indiana University; Estados UnidosFil: Gonzalez Gutierrez, Giovanni. Indiana University; Estados UnidosFil: Capdevila, Daiana Andrea. Indiana University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Giedroc, David Peter. Indiana University; Estados Unido

Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia.

BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. METHODS: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. RESULTS: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. CONCLUSIONS: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia

Beyond the Planar Limit in ABJM

In this article we consider gauge theories with a U(N)X U(N) gauge group. We provide, for the first time, a complete set of operators built from scalar fields that are in the bi fundamental of the two groups. Our operators diagonalize the two point function of the free field theory at all orders in 1/N. We then use this basis to investigate non-planar anomalous dimensions in the ABJM theory. We show that the dilatation operator reduces to a set of decoupled harmonic oscillators, signaling integrability in a nonplanar large N limit.Comment: v2: minor revisison

ABJM Dibaryon Spectroscopy

We extend the proposal for a detailed map between wrapped D-branes in Anti-de Sitter space and baryon-like operators in the associated dual conformal field theory provided in hep-th/0202150 to the recently formulated AdS_4 \times CP^3/ABJM correspondence. In this example, the role of the dibaryon operator of the 3-dimensional CFT is played by a D4-brane wrapping a CP^2 \subset CP^3. This topologically stable D-brane in the AdS_4 \times CP^3 is nothing but one-half of the maximal giant graviton on CP^3.Comment: 26 page

Symbolic dynamics to enhance diagnostic ability of portable oximetry from the Phone Oximeter in the detection of paediatric sleep apnoea

Objective: This study is aimed at assessing symbolic dynamics as a reliable technique to characterize complex fluctuations of portable oximetry in the context of automated detection of childhood obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Approach: Nocturnal oximetry signals from 142 children with suspected OSAHS were acquired using the Phone Oximeter: a portable device that integrates a pulse oximeter with a smartphone. An apnoea-hypopnoea index (AHI) ⩾ 5 events h−1 from simultaneous in-lab polysomnography was used to confirm moderate-to-severe childhood OSAHS. Symbolic dynamics was used to parameterise non-linear changes in the overnight oximetry profile. Conventional indices, anthropometric measures, and time-domain linear statistics were also considered. Forward stepwise logistic regression was used to obtain an optimum feature subset. Logistic regression (LR) was used to identify children with moderate-to-severe OSAHS. Main results: The histogram of 3-symbol words from symbolic dynamics showed significant differences (p < 0.01) between children with AHI < 5 events h−1 and moderate-to-severe patients (AHI ⩾ 5 events h−1). Words representing increasing oximetry values after apnoeic events (re-saturations) showed relevant diagnostic information. Regarding the performance of individual characterization approaches, the LR model composed of features from symbolic dynamics alone reached a maximum performance of 78.4% accuracy (65.2% sensitivity; 86.8% specificity) and 0.83 area under the ROC curve (AUC). The classification performance improved combining all features. The optimum model from feature selection achieved 83.3% accuracy (73.5% sensitivity; 89.5% specificity) and 0.89 AUC, significantly (p <0.01) outperforming the other models. Significance: Symbolic dynamics provides complementary information to conventional oximetry analysis enabling reliable detection of moderate-to-severe paediatric OSAHS from portable oximetry

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA