Non-enzymatic glycation and diabetic kidney disease.

Chronic diabetes leads to various complications including diabetic kidney disease (DKD). DKD is a major microvascular complication and the leading cause of morbidity and mortality in diabetic patients. Varying degrees of proteinuria and reduced glomerular filtration rate are the cardinal clinical manifestations of DKD that eventually progress into end-stage renal disease. Histopathologically, DKD is characterized by renal hypertrophy, mesangial expansion, podocyte injury, glomerulosclerosis, and tubulointerstitial fibrosis, ultimately leading to renal replacement therapy. Amongst the many mechanisms, hyperglycemia contributes to the pathogenesis of DKD via a mechanism known as non-enzymatic glycation (NEG). NEG is the irreversible conjugation of reducing sugars onto a free amino group of proteins by a series of events, resulting in the formation of initial Schiff's base and an Amadori product and to a variety of advanced glycation end products (AGEs). AGEs interact with cognate receptors and evoke aberrant signaling cascades that execute adverse events such as oxidative stress, inflammation, phenotypic switch, complement activation, and cell death in different kidney cells. Elevated levels of AGEs and their receptors were associated with clinical and morphological manifestations of DKD. In this chapter, we discussed the mechanism of AGEs accumulation, AGEs-induced cellular and molecular events in the kidney and their impact on the pathogenesis of DKD. We have also reflected upon the possible options to curtail the AGEs accumulation and approaches to prevent AGEs mediated adverse renal outcomes.

Neuroblastoma: Emerging trends in pathogenesis, diagnosis, and therapeutic targets.

Neuroblastoma (NB) accounts for about 13% of all pediatric cancer mortality and is the leading cause of pediatric cancer death for children aged 1 to 5 years. NB, a developmental malignancy of neural ganglia, originates from neural crest-derived cells, which undergo a defective sympathetic neuronal differentiation due to genomic and epigenetic aberrations. NB is a complex disease with remarkable biological and genetic variation and clinical heterogeneity, such as spontaneous regression, treatment resistance, and poor survival rates. Depending on its severity, NB is categorized as high-risk, intermediate-risk, and low-risk., whereas high-risk NB accounts for a high infant mortality rate. Several studies revealed that NB cells suppress immune cell activity through diverse signaling pathways, including exosome-based signaling pathways. Exosome signaling has been shown to modulate gene expression in the target immune cells and attenuate the signaling events through non-coding RNAs. Since high-risk NB is characterized by a low survival rate and high clinical heterogeneity with current intensive therapies, it is crucial to unravel the molecular events of pathogenesis and develop novel therapeutic targets in high-risk, relapsed, or recurrent tumors in NB to improve patient survival. This article discusses etiology, pathophysiology, risk assessment, molecular cytogenetics, and the contribution of extracellular vesicles, non-coding RNAs, and cancer stem cells in the tumorigenesis of NB. We also detail the latest developments in NB immunotherapy and nanoparticle-mediated drug delivery treatment options.

Podocyte derived TNF-α mediates monocyte differentiation and contributes to glomerular injury.

Diabetes shortens the life expectancy by more than a decade, and the excess mortality in diabetes is correlated with the incidence of kidney disease. Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Macrophage accumulation predicts the severity of kidney injury in human biopsies and experimental models of DKD. However, the mechanism underlying macrophage recruitment in diabetes glomeruli is unclear. Elevated plasma growth hormone (GH) levels in type I diabetes and acromegalic individuals impaired glomerular biology. In this study, we examined whether GH-stimulated podocytes contribute to macrophage accumulation. RNA-seq analysis revealed elevated TNF-α signaling in GH-treated human podocytes. Conditioned media from GH-treated podocytes (GH-CM) induced differentiation of monocytes to macrophages. On the other hand, neutralization of GH-CM with the TNF-α antibody diminished GH-CM's action on monocytes. The treatment of mice with GH resulted in increased macrophage recruitment, podocyte injury, and proteinuria. Furthermore, we noticed the activation of TNF-α signaling, macrophage accumulation, and fibrosis in DKD patients' kidney biopsies. Our findings suggest that podocytes could secrete TNF-α and contribute to macrophage migration, resulting in DKD-related renal inflammation. Inhibition of either GH action or TNF-α expression in podocytes could be a novel therapeutic approach for DKD treatment.

Silent Sinus Syndrome: A Case Report.

To describe a case of silent sinus syndrome in the perspective of imaging studies, on 2 January 2020 we present this case of a 26-year-old Bangladeshi man with unilateral right facial asymmetry and no sino-nasal symptoms. He was referred to the Ophthalmology Department with complain of right palpebral ptosis and facial asymmetry for 7 months. On physical examination, painless enophthalmos and hypo globus of the right eye was seen. The computed tomography scan of the paranasal air sinuses showed opacification of the right maxillary sinus along with retraction of the walls of the sinus. Regardless of the clinical doubt, the conclusion can only be given by imaging studies, radiologist play a key role here.

Microwave observations reveal the deep extent and structure of Jupiter's atmospheric vortices.

Jupiter's atmosphere has a system of zones and belts punctuated by small and large vortices, the largest being the Great Red Spot. How these features change with depth is unknown, with theories of their structure ranging from shallow meteorological features to surface expressions of deep-seated convection. We present observations of atmospheric vortices using the Juno spacecraft's Microwave Radiometer. We found vortex roots that extend deeper than the altitude at which water is expected to condense, and we identified density inversion layers. Our results constrain the three-dimensional structure of Jupiter's vortices and their extension below the clouds.

Clusters of cyclones encircling Jupiter's poles.

The familiar axisymmetric zones and belts that characterize Jupiter's weather system at lower latitudes give way to pervasive cyclonic activity at higher latitudes. Two-dimensional turbulence in combination with the Coriolis ß-effect (that is, the large meridionally varying Coriolis force on the giant planets of the Solar System) produces alternating zonal flows. The zonal flows weaken with rising latitude so that a transition between equatorial jets and polar turbulence on Jupiter can occur. Simulations with shallow-water models of giant planets support this transition by producing both alternating flows near the equator and circumpolar cyclones near the poles. Jovian polar regions are not visible from Earth owing to Jupiter's low axial tilt, and were poorly characterized by previous missions because the trajectories of these missions did not venture far from Jupiter's equatorial plane. Here we report that visible and infrared images obtained from above each pole by the Juno spacecraft during its first five orbits reveal persistent polygonal patterns of large cyclones. In the north, eight circumpolar cyclones are observed about a single polar cyclone; in the south, one polar cyclone is encircled by five circumpolar cyclones. Cyclonic circulation is established via time-lapse imagery obtained over intervals ranging from 20 minutes to 4 hours. Although migration of cyclones towards the pole might be expected as a consequence of the Coriolis ß-effect, by which cyclonic vortices naturally drift towards the rotational pole, the configuration of the cyclones is without precedent on other planets (including Saturn's polar hexagonal features). The manner in which the cyclones persist without merging and the process by which they evolve to their current configuration are unknown.

Jupiter's interior and deep atmosphere: The initial pole-to-pole passes with the Juno spacecraft.

On 27 August 2016, the Juno spacecraft acquired science observations of Jupiter, passing less than 5000 kilometers above the equatorial cloud tops. Images of Jupiter's poles show a chaotic scene, unlike Saturn's poles. Microwave sounding reveals weather features at pressures deeper than 100 bars, dominated by an ammonia-rich, narrow low-latitude plume resembling a deeper, wider version of Earth's Hadley cell. Near-infrared mapping reveals the relative humidity within prominent downwelling regions. Juno's measured gravity field differs substantially from the last available estimate and is one order of magnitude more precise. This has implications for the distribution of heavy elements in the interior, including the existence and mass of Jupiter's core. The observed magnetic field exhibits smaller spatial variations than expected, indicative of a rich harmonic content.

Oxidants at the Surface of Mars: A Review in Light of Recent Exploration Results.

In 1976, the Viking landers carried out the most comprehensive search for organics and microbial life in the martian regolith. Their results indicate that Mars' surface is lifeless and, surprisingly, depleted in organics at part-per-billion levels. Several biology experiments on the Viking landers gave controversial results that have since been explained by the presence of oxidizing agents on the surface of Mars. These oxidants may degrade abiotic or biological organics, resulting in their nondetection in the regolith. As several exploration missions currently focus on the detection of organics on Mars (or will do so in the near future), knowledge of the oxidative state of the surface is fundamental. It will allow for determination of the capability of organics to survive on a geological timescale, the most favorable places to seek them, and the best methods to process the samples collected at the surface. With this aim, we review the main oxidants assumed to be present on Mars, their possible formation pathways, and those laboratory studies in which their reactivity with organics under Mars-like conditions has been evaluated. Among the oxidants assumed to be present on Mars, only four have been detected so far: perchlorate ions (ClO4-) in salts, hydrogen peroxide (H2O2) in the atmosphere, and clays and metal oxides composing surface minerals. Clays have been suggested as catalysts for the oxidation of organics but are treated as oxidants in the following to keep the structure of this article straightforward. This work provides an insight into the oxidizing potential of the surface of Mars and an estimate of the stability of organic matter in an oxidizing environment. Key Words: Mars surface-Astrobiology-Oxidant-Chemical reactions. Astrobiology 16, 977-996.

Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars.

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

Mars atmosphere. The imprint of atmospheric evolution in the D/H of Hesperian clay minerals on Mars.

The deuterium-to-hydrogen (D/H) ratio in strongly bound water or hydroxyl groups in ancient martian clays retains the imprint of the water of formation of these minerals. Curiosity's Sample Analysis at Mars (SAM) experiment measured thermally evolved water and hydrogen gas released between 550° and 950°C from samples of Hesperian-era Gale crater smectite to determine this isotope ratio. The D/H value is 3.0 (±0.2) times the ratio in standard mean ocean water. The D/H ratio in this ~3-billion-year-old mudstone, which is half that of the present martian atmosphere but substantially higher than that expected in very early Mars, indicates an extended history of hydrogen escape and desiccation of the planet.

Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale crater, Mars.

H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.

Volatile, isotope, and organic analysis of martian fines with the Mars Curiosity rover.

Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity's Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.

Complex organic matter in Titan's atmospheric aerosols from in situ pyrolysis and analysis.

Aerosols in Titan's atmosphere play an important role in determining its thermal structure. They also serve as sinks for organic vapours and can act as condensation nuclei for the formation of clouds, where the condensation efficiency will depend on the chemical composition of the aerosols. So far, however, no direct information has been available on the chemical composition of these particles. Here we report an in situ chemical analysis of Titan's aerosols by pyrolysis at 600 degrees C. Ammonia (NH3) and hydrogen cyanide (HCN) have been identified as the main pyrolysis products. This clearly shows that the aerosol particles include a solid organic refractory core. NH3 and HCN are gaseous chemical fingerprints of the complex organics that constitute this core, and their presence demonstrates that carbon and nitrogen are in the aerosols.

The abundances of constituents of Titan's atmosphere from the GCMS instrument on the Huygens probe.

Saturn's largest moon, Titan, remains an enigma, explored only by remote sensing from Earth, and by the Voyager and Cassini spacecraft. The most puzzling aspects include the origin of the molecular nitrogen and methane in its atmosphere, and the mechanism(s) by which methane is maintained in the face of rapid destruction by photolysis. The Huygens probe, launched from the Cassini spacecraft, has made the first direct observations of the satellite's surface and lower atmosphere. Here we report direct atmospheric measurements from the Gas Chromatograph Mass Spectrometer (GCMS), including altitude profiles of the constituents, isotopic ratios and trace species (including organic compounds). The primary constituents were confirmed to be nitrogen and methane. Noble gases other than argon were not detected. The argon includes primordial 36Ar, and the radiogenic isotope 40Ar, providing an important constraint on the outgassing history of Titan. Trace organic species, including cyanogen and ethane, were found in surface measurements.

A low-temperature origin for the planetesimals that formed Jupiter.

The four giant planets in the Solar System have abundances of 'metals' (elements heavier than helium), relative to hydrogen, that are much higher than observed in the Sun. In order to explain this, all models for the formation of these planets rely on an influx of solid planetesimals. It is generally assumed that these planetesimals were similar, if not identical, to the comets from the Oort cloud that we see today. Comets that formed in the region of the giant planets should not have contained much neon, argon and nitrogen, because the temperatures were too high for these volatile gases to be trapped effectively in ice. This means that the abundances of those elements on the giant planets should be approximately solar. Here we show that argon, krypton and xenon in Jupiter's atmosphere are enriched to the same extent as the other heavy elements, which suggests that the planetesimals carrying these elements must have formed at temperatures lower than predicted by present models of giant-planet formation.

A comparison of the atmospheres of Jupiter and Saturn: deep atmospheric composition, cloud structure, vertical mixing, and origin.

We present our current understanding of the composition, vertical mixing, cloud structure and the origin of the atmospheres of Jupiter and Saturn. Available observations point to a much more vigorous vertical mixing in Saturn's middle-upper atmosphere than in Jupiter's. The nearly cloud-free nature of the Galileo probe entry site, a 5-micron hotspot, is consistent with the depletion of condensable volatiles to great depths, which is attributed to local meteorology. Somewhat similar depletion of water may be present in the 5-micron bright regions of Saturn also. The supersolar abundances of heavy elements, particularly C and S in Jupiter's atmosphere and C in Saturn's, as well as the progressive increase of C from Jupiter to Saturn and beyond, tend to support the icy planetesimal model of the formation of the giant planets and their atmospheres. However, much work remains to be done, especially in the area of laboratory studies, including identification of possible new microwave absorbers, and modelling, in order to resolve the controversy surrounding the large discrepancy between Jupiter's global ammonia abundance, hence the nitrogen elemental ratio, derived from the earth-based microwave observations and that inferred from the analysis of the Galileo probe-orbiter radio attenuation data for the hotspot. We look forward to the observations from Cassini-Huygens spacecraft which are expected to result not only in a rich harvest of information for Saturn, but a better understanding of the formation of the giant planets and their atmospheres when these data are combined with those that exist for Jupiter.

Chemical composition measurements of the atmosphere of Jupiter with the Galileo Probe mass spectrometer.

The Galileo Probe entered the atmosphere of Jupiter on December 7, 1995. Measurements of the chemical and isotopic composition of the Jovian atmosphere were obtained by the mass spectrometer during the descent over the 0.5 to 21 bar pressure region over a time period of approximately 1 hour. The sampling was either of atmospheric gases directly introduced into the ion source of the mass spectrometer through capillary leaks or of gas, which had been chemically processed to enhance the sensitivity of the measurement to trace species or noble gases. The analysis of this data set continues to be refined based on supporting laboratory studies on an engineering unit. The mixing ratios of the major constituents of the atmosphere hydrogen and helium have been determined as well as mixing ratios or upper limits for several less abundant species including: methane, water, ammonia, ethane, ethylene, propane, hydrogen sulfide, neon, argon, krypton, and xenon. Analysis also suggests the presence of trace levels of other 3 and 4 carbon hydrocarbons, or carbon and nitrogen containing species, phosphine, hydrogen chloride, and of benzene. The data set also allows upper limits to be set for many species of interest which were not detected. Isotope ratios were measured for 3He/4He, D/H, 13C/12C, 20Ne/22Ne, 38Ar/36Ar and for isotopes of both Kr and Xe.

The composition of the Jovian atmosphere as determined by the Galileo probe mass spectrometer.

The Galileo probe mass spectrometer determined the composition of the Jovian atmosphere for species with masses between 2 and 150 amu from 0.5 to 21.1 bars. This paper presents the results of analysis of some of the constituents detected: H2, He, Ne, Ar, Kr, Xe, CH4, NH3, H2O, H2S, C2 and C3 nonmethane hydrocarbons, and possibly PH3 and Cl. 4He/H2 in the Jovian atmosphere was measured to be 0.157 +/- 0.030. 13C/C12 was found to be 0.0108 +/- 0.0005, and D/H and 3He/4He were measured. Ne was depleted, < or = 0.13 times solar, Ar < or = 1.7 solar, Kr < or = 5 solar, and Xe < or = 5 solar. CH4 has a constant mixing ratio of (2.1 +/- 0.4) x 10(-3) (12C, 2.9 solar), where the mixing ratio is relative to H2. Upper limits to the H2O mixing ratio rose from 8 x 10(-7) at pressures <3.8 bars to (5.6 +/- 2.5) x 10(-5) (16O, 0.033 +/- 0.015 solar) at 11.7 bars and, provisionally, about an order of magnitude larger at 18.7 bars. The mixing ratio of H2S was <10(-6) at pressures less than 3.8 bars but rose from about 0.7 x 10(-5) at 8.7 bars to about 7.7 x 10(-5) (32S, 2.5 solar) above 15 bars. Only very large upper limits to the NH3 mixing ratio have been set at present. If PH3 and Cl were present, their mixing ratios also increased with pressure. Species were detected at mass peaks appropriate for C2 and C3 hydrocarbons. It is not yet clear which of these were atmospheric constituents and which were instrumentally generated. These measurements imply (1) fractionation of 4He, (2) a local, altitude-dependent depletion of condensables, probably because the probe entered the descending arm of a circulation cell, (3) that icy planetesimals made significant contributions to the volatile inventory, and (4) a moderate decrease in D/H but no detectable change in (D + 3He)/H in this part of the galaxy during the past 4.6 Gyr.

The Galileo probe mass spectrometer: composition of Jupiter's atmosphere.

The composition of the jovian atmosphere from 0.5 to 21 bars along the descent trajectory was determined by a quadrupole mass spectrometer on the Galileo probe. The mixing ratio of He (helium) to H2 (hydrogen), 0.156, is close to the solar ratio. The abundances of methane, water, argon, neon, and hydrogen sulfide were measured; krypton and xenon were detected. As measured in the jovian atmosphere, the amount of carbon is 2.9 times the solar abundance relative to H2, the amount of sulfur is greater than the solar abundance, and the amount of oxygen is much less than the solar abundance. The neon abundance compared with that of hydrogen is about an order of magnitude less than the solar abundance. Isotopic ratios of carbon and the noble gases are consistent with solar values. The measured ratio of deuterium to hydrogen (D/H) of (5 +/- 2) x 10(-5) indicates that this ratio is greater in solar-system hydrogen than in local interstellar hydrogen, and the 3He/4He ratio of (1.1 +/- 0.2) x 10(-4) provides a new value for protosolar (solar nebula) helium isotopes. Together, the D/H and 3He/4He ratios are consistent with conversion in the sun of protosolar deuterium to present-day 3He.