GDF15 promotes weight loss by enhancing energy expenditure in muscle.

Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes1. Despite its effectiveness, in most individuals, weight loss is usually not maintained partly due to physiological adaptations that suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear2,3. Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycaemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake4-7. Here we find that, in addition to suppressing appetite, GDF15 counteracts compensatory reductions in energy expenditure, eliciting greater weight loss and reductions in non-alcoholic fatty liver disease (NAFLD) compared to caloric restriction alone. This effect of GDF15 to maintain energy expenditure during calorie restriction requires a GFRAL-ß-adrenergic-dependent signalling axis that increases fatty acid oxidation and calcium futile cycling in the skeletal muscle of mice. These data indicate that therapeutic targeting of the GDF15-GFRAL pathway may be useful for maintaining energy expenditure in skeletal muscle during caloric restriction.

Brown adipose tissue metabolism in women is dependent on ovarian status.

In rodents, loss of estradiol (E2) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (n = 27; 35 ± 9 yr; body mass index = 26.0 ± 5.3 kg/m2) and postmenopausal (n = 25; 51 ± 8 yr; body mass index = 28.0 ± 5.0 kg/m2) women at room temperature and during acute cold exposure using [11C]acetate with positron emission tomography coupled with computed tomograph. BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18F]fluoro-d-glucose. To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (n = 8; 40 ± 4 yr; BMI = 28.0 ± 7.2 kg/m2) after 6 mo of gonadotropin-releasing hormone agonist therapy to suppress ovarian hormones. At room temperature, there was no difference in BAT oxidative metabolism between premenopausal (0.56 ± 0.31 min-1) and postmenopausal women (0.63 ± 0.28 min-1). During cold exposure, BAT oxidative metabolism (1.28 ± 0.85 vs. 0.91 ± 0.63 min-1, P = 0.03) and net BAT glucose uptake (84.4 ± 82.5 vs. 29.7 ± 31.4 nmol·g-1·min-1, P < 0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent gonadotropin-releasing hormone agonist, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36 ± 0.66 min-1 to 0.91 ± 0.41 min-1) to that observed in postmenopausal women (0.91 ± 0.63 min-1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.NEW & NOTEWORTHY In rodents, loss of estrogen reduces brown adipose tissue (BAT) activity. Whether this is true in humans is not known. We found that BAT oxidative metabolism and glucose uptake were lower in postmenopausal compared to premenopausal women. In premenopausal women who underwent ovarian suppression to reduce circulating estrogen, BAT oxidative metabolism was reduced to postmenopausal levels. Thus the loss of ovarian function in women leads to a reduction in BAT metabolic activity independent of age.

Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate.

Resorcinolic lipids are described as potential examples of selective chemotherapeutic adjuvants that can enhance the effects of cyclophosphamide (CYC) while promoting cell death without causing DNA damage. Therefore, the current study attempted to describe how the resorcinolic lipid methyl 3,5-dimethoxy-2-octanoylbenzoate (AMS35BB) interacted with DNA (DNA docking) and how this compound affected genetic toxicology models and other biological characteristics when combined with CYC. We observed that AMS35BB, used alone (7.5 and 10 mg/kg), increases the frequency of genomic damage (comet assay) but not chromosomal damage (micronuclei assay), lowers phagocytosis, and promotes cell death in Swiss male mice. When used in association with CYC, AMS35BB can reduce the risk of genomic damage by up to 33.8% as well as chromosomal damage, splenic phagocytosis, cell death, and lymphocyte frequency. Molecular docking showed that AMS35BB had a higher affinity than the active metabolite of CYC for binding to the DNA double helix major groove. As a result, AMS35BB has the potential to be both an adjuvant when used in association with CYC and a therapeutic candidate for the development of a selective chemotherapeutic drug.

Design, synthesis and identification of novel molecular hybrids based on naphthoquinone aromatic hydrazides as potential trypanocide and leishmanicidal agents.

In pursuit of potential agents to treat Chagas disease and leishmaniasis, we report the design, synthesis, and identification novel naphthoquinone hydrazide-based molecular hybrids. The compounds were subjected to in vitro trypanocide and leishmanicidal activities. N'-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-3,5-dimethoxybenzohydrazide (13) showed the best performance against Trypanosoma cruzi (IC50 1.83 µM) and Leishmania amazonensis (IC50 9.65 µM). 4-Bromo-N'-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide (16) exhibited leishmanicidal activity (IC50 12.16 µM). Regarding trypanocide activity, compound 13 was low cytotoxic to LLC-MK2 cells (SI = 95.28). Furthermore, through molecular modeling studies, the cysteine proteases cruzain, rhodesain and CPB2.8 were identified as the potential biological targets.

Stacked Polarizing Elements for Controlling Parameters of Surface Relief Gratings Written in Photosensitive Materials.

Photosensitive materials are widely used for the direct fabrication of surface relief gratings (SRGs) without the selective etching of the material. It is known that the interferometric approach makes it possible to fabricate SRGs with submicron and even subwavelength periods. However, to change the period of the written SRGs, it is necessary to change the convergence angle, shift a sample, and readjust the interferometric setup. Recently, it was shown that structured laser beams with predetermined, periodically modulated polarization distributions can also be used to fabricate SRGs. A structured laser beam with the desired polarization distribution can be formed with just one polarizing optical element-for example, the so-called depolarizer, a patterned micro-retarder array. The use of such stacked elements makes it possible to directly control the modulation period of the polarization of the generated laser beam. We show that this approach allows one to fabricate SRGs with submicron periods. Moreover, the addition of q-plates, elements effectively used to generate cylindrical vector beams with polarization singularities, allows the efficient formation of fork polarization gratings (FPGs) and the fabrication of higher-order fork-shaped SRGs. Full control of the parameters of the generated FPGs is possible. We demonstrate the formation of FPGs of higher orders (up to 12) by only adding first- and second-order q-plates and half-wave plates to the depolarizers. In this work, we numerically and experimentally study the parameters of various types of SRGs formed using these stacked polarizing elements and show the significant potential of this method for the laser processing of photosensitive materials, which often also serve as polarization sensors.

A novel approach for vital visualization and studying of neurons containing Ca2+ -permeable AMPA receptors.

Calcium-permeable AMPA receptors (CP-AMPARs) play a pivotal role in brain functioning in health and disease. They are involved in synaptic plasticity, synaptogenesis, and neuronal circuits development. However, the functions of neurons expressing CP-AMPARs and their role in the modulation of network activity remain elusive since reliable and accurate visualization methods are absent. Here we developed an approach allowing the vital identification of neurons containing CP-AMPARs. The proposed method relies on evaluating Ca2+ influx in neurons during activation of AMPARs in the presence of NMDAR and KAR antagonists, and blockers of voltage-gated Ca2+ channels. Using this method, we studied the properties of CP-AMPARs-containing neurons. We showed that the overwhelming majority of neurons containing CP-AMPARs are GABAergic, and they are distinguished by higher amplitudes of the calcium responses to applications of the agonists. Furthermore, about 30% of CP-AMPARs-containing neurons demonstrate the presence of GluK1-containing KARs. Although CP-AMPARs-containing neurons are characterized by more significant Ca2+ influx during the activation of AMPARs than other neurons, AMPAR-mediated Na+ influx is similar in these two groups. We revealed that neurons containing CP-AMPARs demonstrate weak GABA(A)R-mediated inhibition because of the low percentage of GABAergic synapses on the soma of these cells. However, our data show that weak GABA(A)R-mediated inhibition is inherent to all GABAergic neurons in the culture and cannot be considered a unique feature of CP-AMPARs-containing neurons. We believe that the suggested approach will help to understand the role of CP-AMPARs in the mammalian nervous system in more detail.

Incommensurate Antiferromagnetic Order in Weakly Frustrated Two-Dimensional van der Waals Insulator CrPSe3.

Although magnetic order is suppressed by a strong frustration, it appears in complex forms such as a cycloid or spin density wave in weakly frustrated systems. Herein, we report a weakly magnetically frustrated two-dimensional (2D) van der Waals material CrPSe3. Polycrystalline CrPSe3 was synthesized at an optimized temperature of 700 °C to avoid the formation of any secondary phases (e.g., Cr2Se3). The antiferromagnetic transition appeared at TN ≈ 127 K with a large Curie-Weiss temperature θCW ≈ -301 K via magnetic susceptibility measurements, indicating weak frustration in CrPSe3 with a frustration factor of f (|θCW|/TN) ≈ 2.4. Evidently, the formation of a long-range incommensurate antiferromagnetic order was revealed by neutron diffraction measurements at low temperatures (below 120 K). The monoclinic crystal structure of the C2/m symmetry is preserved over the studied temperature range down to 20 K, as confirmed by Raman spectroscopy measurements. Our findings on the incommensurate antiferromagnetic order in 2D magnetic materials, not previously observed in the MPX3 family, are expected to enrich the physics of magnetism at the 2D limit, thereby opening opportunities for their practical applications in spintronics and quantum devices.

Of the Mechanisms of Paroxysmal Depolarization Shifts: Generation and Maintenance of Bicuculline-Induced Paroxysmal Activity in Rat Hippocampal Cell Cultures.

Abnormal depolarization of neuronal membranes called paroxysmal depolarization shift (PDS) represents a cellular correlate of interictal spikes. The mechanisms underlying the generation of PDSs or PDS clusters remain obscure. This study aimed to investigate the role of ionotropic glutamate receptors (iGluRs) in the generation of PDS and dependence of the PDS pattern on neuronal membrane potential. We have shown that significant depolarization or hyperpolarization (by more than ±50 mV) of a single neuron does not change the number of individual PDSs in the cluster, indicating the involvement of an external stimulus in PDS induction. Based on this data, we have suggested reliable protocols for stimulating single PDS or PDS clusters. Furthermore, we have found that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are necessary for PDS generation since AMPAR antagonist NBQX completely suppresses bicuculline-induced paroxysmal activity. In turn, antagonists of NMDA (N-methyl-D-aspartate) and kainate receptors (D-AP5 and UBP310, respectively) caused a decrease in the amplitude of the first action potential in PDSs and in the amplitude of the oscillations of intracellular Ca2+ concentration occurring alongside the PDS cluster generation. The effects of the NMDAR (NMDA receptor) and KAR (kainate receptor) antagonists indicate that these receptors are involved only in the modulation of paroxysmal activity. We have also shown that agonists of some Gi-coupled receptors, such as A1 adenosine (A1Rs) or cannabinoid receptors (CBRs) (N6-cyclohexyladenosine and WIN 55,212-2, respectively), completely suppressed PDS generation, while the A1R agonist even prevented it. We hypothesized that the dynamics of extracellular glutamate concentration govern paroxysmal activity. Fine-tuning of neuronal activity via action on Gi-coupled receptors or iGluRs paves the way for the development of new approaches for epilepsy pharmacotherapy.

Thermogenic responses to different clamped skin temperatures in cold-exposed men and women.

Despite many decades of research examining thermoregulatory responses under varying cold stresses in humans, very little is known about the variability in metabolic heat production and shivering activity. Here, we used a novel closed-loop mean skin temperature clamping technique with a liquid-conditioned suit to isolate the effects of mean skin temperature on the subjective evaluation of thermal sensation, heat production, shivering responses, and oxidative fuel selection in young, lean, and healthy men (n = 12) and women (n = 12). Our results showed a skin temperature-dependent increase in metabolic heat production (5.2 ± 1.2 kJ/min, 5.9 ± 1.5 kJ/min, and 7.0 ± 1.8 kJ/min with skin temperature maintained at 31 ± 0.1°C, 29 ± 0.2°C, and 27 ± 0.1°C, respectively; P < 0.0001) and shivering intensity in both men and women [0.6 ± 0.1% maximal voluntary contraction (MVC), 1.1 ± 0.4% MVC, and 2.5 ± 0.7% MVC, respectively; P < 0.0001], including sex-dependent differences in heat production at all three temperatures (P < 0.005). Even when controlling for lean body mass and fat mass, sex differences persisted (P = 0.048 and P = 0.004, respectively), whereas controlling for differences in body surface area eliminated these differences. Interestingly, there were no sex differences in the cold-induced change in thermogenesis. Despite clamping skin temperature, there was tremendous variability in the rate of heat production and shivering intensity. Collectively this data suggests that many of the interindividual differences in thermogenesis and shivering may be explained by differences in morphology and body composition.

Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role.

Serine-rich splicing factor 3 (SRSF3) was recently reported as being necessary to preserve RNA stability via an mTOR mechanism in a cardiac mouse model in adulthood. Here, we demonstrate the link between Srsf3 and mitochondrial integrity in an embryonic cardiomyocyte-specific Srsf3 conditional knockout (cKO) mouse model. Fifteen-day-old Srsf3 cKO mice showed dramatically reduced (below 50%) survival and reduced the left ventricular systolic performance, and histological analysis of these hearts revealed a significant increase in cardiomyocyte size, confirming the severe remodeling induced by Srsf3 deletion. RNA-seq analysis of the hearts of 5-day-old Srsf3 cKO mice revealed early changes in expression levels and alternative splicing of several transcripts related to mitochondrial integrity and oxidative phosphorylation. Likewise, the levels of several protein complexes of the electron transport chain decreased, and mitochondrial complex I-driven respiration of permeabilized cardiac muscle fibers from the left ventricle was impaired. Furthermore, transmission electron microscopy analysis showed disordered mitochondrial length and cristae structure. Together with its indispensable role in the physiological maintenance of mouse hearts, these results highlight the previously unrecognized function of Srsf3 in regulating the mitochondrial integrity.

Crystallization Pathways and Evolution of Morphologies and Structural Defects of α-MnO2 under Air Annealing.

Manganese dioxide nanomaterials have wide applications in many areas from catalysis and Li-ion batteries to gas sensing. Understanding the crystallization pathways, morphologies, and formation of defects in their structure is particularly important but still a challenging issue. Herein, we employed an arsenal of X-ray diffraction (XRD), scanning electron microscopy (SEM), neutron diffraction, positron annihilation spectroscopies, and ab initio calculations to investigate the evolution of the morphology and structure of α-MnO2 nanomaterials prepared via reduction of KMnO4 solution with C2H5OH prior to being annealed in air at 200-600 °C. We explored a novel evolution that α-MnO2 nucleation can be formed even at room temperature and gradually developed to α-MnO2 nanorods at above 500 °C. We also found the existence of H+ or K+ ions in the [1 × 1] tunnels of α-MnO2 and observed the simultaneous presence of Mn and O vacancies in α-MnO2 crystals at low temperatures. Increasing the temperature removed these O vacancies, leaving only the Mn vacancies in the samples.

Polarization-Sensitive Patterning of Azopolymer Thin Films Using Multiple Structured Laser Beams.

The polarization sensitivity of azopolymers is well known. Therefore, these materials are actively used in many applications of photonics. Recently, the unique possibilities of processing such materials using a structured laser beam were demonstrated, which revealed the key role of the distribution of polarization and the longitudinal component of light in determining the shape of the nano- and microstructures formed on the surfaces of thin azopolymer films. Here, we present numerical and experimental results demonstrating the high polarization sensitivity of thin azopolymer films to the local polarization state of an illuminating structured laser beam consisting of a set of light spots. To form such arrays of spots with a controlled distribution of polarization, different polarization states of laser beams, both homogeneous and locally inhomogeneous, were used. The results obtained show the possibility of implementing a parallel non-uniform patterning of thin azopolymer films depending on the polarization distribution of the illuminating laser beam. We believe that the demonstrated results will not only make it possible to implement the simultaneous detection of local polarization states of complex-shaped light fields but will also be used for the high-performance fabrication of diffractive optical elements and metasurfaces.

Contribution of perfusion to the 11 C-acetate signal in brown adipose tissue assessed by DCE-MRI and 68 Ga-DOTA PET in a rat model.

PURPOSE: Determine if dynamic contrast enhanced (DCE) -MRI and/or 68 gallium 1,4,7,10-tetraazacyclododecane N, N', N″, N‴-tretraacetic acid (68 Ga-DOTA) positron emission tomography (PET) can assess perfusion in rat brown adipose tissue (BAT). Evaluate changes in perfusion between cold-stimulated and heat-inhibited BAT. Determine if the 11 C-acetate pharmacokinetic model can be constrained with perfusion information to improve assessment of BAT oxidative metabolism. METHODS: Rats were split into three groups. In group 1 (N = 6), DCE-MRI with gadobutrol was compared directly to 68 Ga-DOTA PET following exposure to 10 °C for 48 h. 11 C-Acetate PET was also performed to assess oxidation. In group 2 (N = 4), only 68 Ga-DOTA PET was acquired following exposure to 10 °C for 48 h. Finally, in group 3 (N = 10), perfusion was assessed with DCE-MRI in rats exposed to 10 °C or 30 °C for 48 h, and oxidation was measured with 11 C-acetate. Perfusion was quantified with a two-compartment pharmacokinetic model, while oxidation was assessed by a four-compartment model. RESULTS: DCE-MRI and 68 Ga-DOTA PET provided similar perfusion measures, but a decrease in the perfusion signal was noted with longer imaging sessions. Exposure to 10 °C or 30 °C did not affect the perfusion measures, but the 11 C-acetate signal increased in BAT at 10 °C. Without prior information about blood volume, the 11 C-acetate compartment model overestimated blood volume and underestimated oxidation in 10 °C BAT. CONCLUSION: Precise assessment of oxidation via 11 C-acetate PET requires prior information about blood volume which can be obtained by DCE-MRI or 68 Ga-DOTA PET. Since perfusion can change rapidly, simultaneous PET-MRI would be preferred.

l-Hypaphorine and d-hypaphorine: Specific antiacetylcholinesterase activity in rat brain tissue.

Acetylcholinesterase (AChEis) inhibitors are used to treat neurodegenerative diseases like Alzheimer's disease (AD). l-Hypaphorine (l-HYP) is a natural indole alkaloid that has been shown to have effects on the central nervous system (CNS). The goal of this research was to synthesize l-HYP and d-HYP and test their anticholinesterasic properties in rat brain regions. l-HYP suppressed acetylcholinesterase (AChE) activity only in the cerebellum, whereas d-HYP inhibited AChE activity in all CNS regions studied. No cytotoxic effect on normal human cells (HaCaT) was observed in the case of l-HYP and d-HYP although an increase in cell proliferation. Molecular modeling studies revealed that d-HYP and l-HYP have significant differences in their binding mode positions and interact stereospecifically with AChE's amino acid residues.

Unexpected Polymorphism in Bromoantimonate(III) Complexes and Its Effect on Optical Properties.

Reactions of [SbBr6]3- containing HBr solutions with bromide salts of 1,1'-(1,2-ethanediyl)bis(pyridine) (PyC22+) or 1,1'-(1,2-ethanediyl)bis(3,5-dimethylpyridine) (3,5-MePyC22+) initially result in the formation of the deep orange complexes Cat[SbBr5] (1 and 2), featuring unusual Sb···Br interactions in the solid state. In the mother liquor, 1 transforms into discrete binuclear (C2Py)2[Sb2Br10], which demonstrates polymorphism (triclinic 3 and monoclinic 4), while 2 transforms into polymeric (3,5-MePy){[SbBr4]} (5). DFT calculations reveal that the system of noncovalent Sb···Br contacts may be responsible for the appearance of the observed optical properties (unusual deep orange coloring).

Use of teledermatology by dermatology hospitalists is effective in the diagnosis and management of inpatient disease.

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

Mechanism and kinetics of the oxidation of 1,3-butadien-1-yl (n-C4H5): a theoretical study.

Ab initio CCSD(T)-F12/cc-pVTZ-f12//B3LYP/6-311G(d,p) calculations of the C4H5O2 potential energy surface have been combined with Rice-Ramsperger-Kassel-Marcus Master Equation (RRKM-ME) calculations of temperature- and pressure-dependent rate constants and product branching ratios to unravel the mechanism and kinetics of the n-C4H5 + O2 reaction. The results indicate that the reaction is fast, with the total rate constant being in the range of 3.4-5.6 × 10-11 cm3 molecule-1 s-1. The main products include 1-oxo-n-butadienyl + O and acrolein + HCO, with their cumulative yield exceeding 90% at temperatures above 1500 K. Two conformers of 1-oxo-n-butadienyl + O are formed via a simple mechanism of O2 addition to the radical site of n-C4H5 followed by the cleavage of the O-O bond proceeding via a van der Waals C4H5OO complex. Alternatively, the pathways leading to acrolein + HCO involve significant reorganization of the heavy-atom skeleton either via formal migration of one O atom to the opposite end of the molecule or its insertion into the C1-C2 bond. Not counting thermal stabilization of the initial peroxy adducts, which prevails at low temperatures and high pressures, all other products share a minor yield of under 5%. Rate constants for the significant reaction channels have been fitted to modified Arrhenius expressions and are proposed for kinetic modeling of the oxidation of aromatic molecules and 1,3-butadiene. As a secondary reaction, n-C4H5 + O2 can be a source for the formation of acrolein observed experimentally in oxidation of the phenyl radical at low combustion temperatures, whereas another significant (secondary) product of the C6H5 + O2 reaction, furan, could be formed through unimolecular decomposition of 1-oxo-n-butadienyl. Both the n-C4H5 + O2 reaction and unimolecular decomposition of its 1-oxo-n-butadienyl primary product are shown not to be a substantial source of ketene.

Functional characterization of human brown adipose tissue metabolism.

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Straightforward synthesis of cytosporone analogs AMS35AA and AMS35BB.

Cytosporones, a class of octaketide resorcinolic lipids, have drawn the attention of researchers for exhibiting a number of notable biological properties. Herein, we describe routes to synthesize the bioactive synthetic resorcinolic lipids AMS35AA and AMS35BB with excellent overall yields using 3,5-dimethoxybenzoic acid as the starting material. The methods proved remarkably efficient to achieve the target compounds and comprise the synthesis of AMS35AA catalyzed by ascorbic acid (vitamin C).

Superficial Granulomatous Pyoderma Gangrenosum Involving the Face: A Case Series of Five Patients and a Review of the Literature [Formula: see text].

BACKGROUND: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful and ulcerating lesions on the skin. It rarely involves the face and is often difficult to diagnose. There are few cases reported in the literature of PG involving the face. AIM: To share our experience with 5 patients in whom the final diagnosis was PG involving the face, and to review the literature. METHODS: We report a series of 5 patients with a final diagnosis of PG involving the face and reviewed relevant literature. We searched through PubMed andEMBASE using keywords such as "face" and "pyoderma gangrenosum," "blastomycosis-like pyoderma gangrenosum, vegetative pyoderma gangrenosum and granulomatous pyoderma gangrenosum." RESULTS: We report 5 patients (4 females) with pyoderma gangrenosum involving the face. All 5 had a final diagnosis of superficial granulomatous PG. All cases presented with nonhealing facial ulcer most commonly on cheeks and a common histopathology of mixed inflammatory infiltrates, multinucleated giant cells, and plasma cells with some granulomatous inflammation. CONCLUSIONS: PG can involve the face, and all 5 of our patients had the superficial granulomatous as the most common form.