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Deltas are deposits directly accumulated by land‐generated gravity flows in a standing body of water. The paradigm of deltaic sedimentation has dramatically changed during recent years, from the popular very simplified ternary models of marine littoral deltas towards more realistic and comprehensive models, considering the importance of sediment‐laden river discharges. Ternary delta models were designed for clean rivers, where a stream flow drags the sediments. Depending on the basin dynamics, these littoral deposits can be modified, forming tidal‐dominated, wave‐dominated or fluvial‐dominated littoral deltas. In recent years, a new classification of delta systems was proposed, based on contrasting the salinity of the receiving water body with the bulk density of the incoming fluvial discharge. Rivers are highly dynamic systems, and their discharges can be very variable in terms of flow duration and sediment concentration. Additionally, the salinity of the receiving water body can exhibit significant variability, especially in closed lakes and epicontinental seas, ranging from freshwater to brines. This scenario allows the distinction of three major delta categories (hypopycnal, homopycnal and hyperpycnal deltas) which can be in turn subdivided, defining seven delta types. Hypopycnal deltas form when the bulk density of the incoming flow is lower than the density of the water in the basin, allowing the definition of three delta types, corresponding to hypersaline littoral deltas, marine littoral deltas and brackish littoral deltas. Homopycnal deltas form when the bulk density of the incoming flow is similar to the density of the water in the basin, defining a delta type termed homopycnal littoral deltas. Hyperpycnal deltas form when the bulk density of the incoming flow is higher than the density of the water in the basin, allowing the definition of three categories termed hyperpycnal littoral deltas, hyperpycnal subaqueous deltas and hyperpycnal fan deltas. [ABSTRACT FROM AUTHOR]

Objectives and scope: Primary mitochondrial diseases (PMDs) are rare genetic disorders resulting from mutations in genes crucial for effective oxidative phosphorylation (OXPHOS) that can affect mitochondrial function. In this review, we examine the bioenergetic alterations and oxidative stress observed in cellular models of primary mitochondrial diseases (PMDs), shedding light on the intricate complexity between mitochondrial dysfunction and cellular pathology. We explore the diverse cellular models utilized to study PMDs, including patient‐derived fibroblasts, induced pluripotent stem cells (iPSCs) and cybrids. Moreover, we also emphasize the connection between oxidative stress and neuroinflammation. Insights: The central nervous system (CNS) is particularly vulnerable to mitochondrial dysfunction due to its dependence on aerobic metabolism and the correct functioning of OXPHOS. Similar to other neurodegenerative diseases affecting the CNS, individuals with PMDs exhibit several neuroinflammatory hallmarks alongside neurodegeneration, a pattern also extensively observed in mouse models of mitochondrial diseases. Based on histopathological analysis of postmortem human brain tissue and findings in mouse models of PMDs, we posit that neuroinflammation is not merely a consequence of neurodegeneration but a potential pathogenic mechanism for disease progression that deserves further investigation. This recognition may pave the way for novel therapeutic strategies for this group of devastating diseases that currently lack effective treatments. Summary: In summary, this review provides a comprehensive overview of bioenergetic alterations and redox imbalance in cellular models of PMDs while underscoring the significance of neuroinflammation as a potential driver in disease progression. [ABSTRACT FROM AUTHOR]

The Mars 2020 Perseverance rover has explored fluvio‐lacustrine sedimentary rocks within Jezero crater. Prior work showed that igneous crater floor Séítah and Máaz formations have mafic mineralogy with alteration phases that indicate multiple episodes of aqueous alteration. In this work, we extend the analyses of hydration to targets in the Jezero western fan delta, using data from the SHERLOC (Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals) Raman spectrometer. Spectral features, for example, sulfate and hydration peak positions and shapes, vary within, and across the crater floor and western fan. The proportion of targets with hydration associated with sulfates was approximately equal in the crater floor and the western fan. All hydrated targets in the crater floor and upper fan showed bimodal hydration peaks at ∼3,200 and ∼3,400 cm−1. The sulfate symmetric stretch at ∼1,000 cm−1 coupled with a hydration peak at ∼3,400 cm−1 indicate that MgSO4·nH2O (2 < n ≤ 5) is a likely hydration carrier phase in all units, perhaps paired with low‐hydration (n ≤ 1) amorphous Mg‐sulfates, indicated by the ∼3,200 cm−1 peak. Low‐hydration MgSO4·nH2O (n = 1–2) are more prevalent in the fan, and hydrated targets in the fan front only had one peak at ∼3,400 cm−1. While anhydrite co‐occurs with hydrated Mg‐sulfates in the crater floor and fan front, hydrated Ca‐sulfates are observed instead at the top of the upper fan. Collectively, the data imply aqueous deposition of sediments with formation of salts from high ionic strength fluids and subsequent aridity to preserve the observed hydration states. Plain Language Summary: The Mars 2020 Perseverance rover has explored a fan delta deposit in the Jezero crater where a lake was present in the past. In this work, we use the SHERLOC (Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals) Raman spectroscopy instrument on the rover to determine the minerals that contain water in the form of H2O and/or OH. These hydrated minerals are indicators of interactions of rock with water and inform us how the environmental conditions and the habitability of Jezero crater evolved over time. Hydrated Mg‐sulfates MgSO4·nH2O (2 < n ≤ 5) are observed in both the crater floor and the western fan. Mg‐sulfates of lower hydration degree (n = 1–2) are more commonly found in the western fan, particularly the fan front. Hydrated Ca‐sulfate is found only close to the top of the fan. These changes in sulfate degree of hydration and/or cations from the floor to the fan are evidence of multiple past fluid events and chemistries at Jezero crater. Key Points: MgSO4·nH2O (2 < n ≤ 5) are found in the Jezero fan and floor while low‐hydration MgSO4·nH2O (n = 1–2) are more commonly found in the fanHydrated Ca‐sulfates are found only in the upper fanThe diverse phases imply salt formation from high ionic strength fluids and subsequent aridity to preserve the observed hydration states [ABSTRACT FROM AUTHOR]

Objective: To evaluate root coverage (RC) in deep single antero‐mandibular RT2 and RT3 gingival recessions (GR) and to investigate the influence of several factors in RC. Materials and Methods: Fifteen single antero‐mandibular GR with a minimum depth of 3 mm were consecutively treated with a new one‐stage technique (laterally positioned flap with a tunnel access and a connective tissue graft). At baseline and at 12‐month follow‐up, the percentage of mean root coverage (%MRC), the recession reduction (RecRed), complete root coverage (CRC) and the gain of keratinized tissue width (KTW) were assessed. Descriptive, intergroup comparative and correlation analyses were performed. Results: At 12 months, a %MRC of 77.29 ± 21.48% with a mean RecRed of 4.10 ± 1.51 mm was achieved. The %MRC was 84.71 ± 21.08% in RT2, and 62.43 ± 14.17% in RT3. The mean gain of KTW was 2.10 ± 0.89 mm, with a mean gain of 2.0 ± 1.03 mm for RT2 and 2.3 ± 0.57 mm for RT3. CRC was observed in six cases, all of them being RT2. A positive association was found between the %MRC and the initial position of the tooth and of both papillae. Conclusions: This technique might be a valuable approach for the treatment of deep single antero‐mandibular RT2 and RT3 recessions, even in malpositioned teeth. Clinical Significance: A combination of different surgical techniques could provide greater vascularization to the CTG especially in malpositioned teeth in sextant V with a large avascular area to be covered. [ABSTRACT FROM AUTHOR]

StarD7 is a member of the START protein family required for phosphatidylcholine delivery to the mitochondria, thus key to maintain mitochondrial structure. Its deficiency has been associated with an impairment of cellular processes, such as proliferation and migration, and it has also been reported that it is needed in myogenic differentiation. Here, we show that StarD7 deficiency in C2C12 muscle cells results in the accumulation of abnormal mitochondria, a reduced number of mitochondria per cell area and increased glycolysis. In addition, StarD7‐deficient cells undergo an increase in mitochondria‐ER contact sites, reduced connexin 43 expression, and disturbances in lipid handling, evidenced by lipid droplet accumulation and decreased levels in phosphatidylserine synthase 1 and 2 expression. Interestingly, StarD7‐deficient cells showed alterations in mitophagy markers. We observed accumulation of LC3B‐II and BNIP3 proteins in mitochondria‐enriched fractions and accumulation of autophagolysosomal and lysosomal vesicles in StarD7‐deficient cells. Furthermore, live‐cell imaging experiments of StarD7 knockdown cells expressing mitochondria‐targeted mKeima indicated an enhanced mitochondria delivery into lysosomes. Importantly, StarD7 reconstitution in StarD7‐deficient cells restores LC3B‐II expression in mitochondria‐enriched fractions at similar levels to those observed in control cells. Collectively, these findings suggest that StarD7‐deficient C2C12 myoblasts are associated with altered cristae structure, disturbances in neutral lipid accumulation, glucose metabolism, and increased mitophagy flux. The alterations mentioned above allow for the maintenance of mitochondrial function. [ABSTRACT FROM AUTHOR]

The Mars 2020/Mars Sample Return (MSR) Sample Depot Science Community Workshop was held on September 28 and 30, 2022, to assess the Scientifically‐Return Worthy (SRW) value of the full collection of samples acquired by the rover Perseverance at Jezero Crater, and of a proposed subset of samples to be left as a First Depot at a location within Jezero Crater called Three Forks. The primary outcome of the workshop was that the community is in consensus on the following statement: The proposed set of ten sample tubes that includes seven rock samples, one regolith sample, one atmospheric sample, and one witness tube constitutes a SRW collection that: (1) represents the diversity of the explored region around the landing site, (2) covers partially or fully, in a balanced way, all of the International MSR Objectives and Samples Team scientific objectives that are applicable to Jezero Crater, and (3) the analyses of samples in this First Depot on Earth would be of fundamental importance, providing a substantial improvement in our understanding of Mars. At the conclusion of the meeting, there was overall community support for forming the First Depot as described at the workshop and placing it at the Three Forks site. The community also recognized that the diversity of the Rover Cache (the sample collection that remains on the rover after placing the First Depot) will significantly improve with the samples that are planned to be obtained in the future by the Perseverance rover and that the Rover Cache is the primary target for MSR to return to Earth. [ABSTRACT FROM AUTHOR]

The first samples collected by the Mars 2020 mission represent units exposed on the Jezero Crater floor, from the potentially oldest Séítah formation outcrops to the potentially youngest rocks of the heavily cratered Máaz formation. Surface investigations reveal landscape‐to‐microscopic textural, mineralogical, and geochemical evidence for igneous lithologies, some possibly emplaced as lava flows. The samples contain major rock‐forming minerals such as pyroxene, olivine, and feldspar, accessory minerals including oxides and phosphates, and evidence for various degrees of aqueous activity in the form of water‐soluble salt, carbonate, sulfate, iron oxide, and iron silicate minerals. Following sample return, the compositions and ages of these variably altered igneous rocks are expected to reveal the geophysical and geochemical nature of the planet's interior at the time of emplacement, characterize martian magmatism, and place timing constraints on geologic processes, both in Jezero Crater and more widely on Mars. Petrographic observations and geochemical analyses, coupled with geochronology of secondary minerals, can also reveal the timing of aqueous activity as well as constrain the chemical and physical conditions of the environments in which these minerals precipitated, and the nature and composition of organic compounds preserved in association with these phases. Returned samples from these units will help constrain the crater chronology of Mars and the global evolution of the planet's interior, for understanding the processes that formed Jezero Crater floor units, and for constraining the style and duration of aqueous activity in Jezero Crater, past habitability, and cycling of organic elements in Jezero Crater. Plain Language Summary: Here we provide a narrative of sample collection and associated in situ rover observations for the rocks collected by the Perseverance rover to provide a preliminary description of the first samples of the Mars 2020 mission. These rocks collected in Jezero Crater represent the first samples from Mars with a known geologic context, the first collected with the potential to be returned to Earth for laboratory analysis, and the first cores from rock outcrops on another planet. Remote and proximal analyses indicate that all crater floor outcrops investigated are igneous in origin. Laboratory analyses of these rocks will be useful to study the planet's interior at the time of emplacement, characterize martian magmatism, and place timing constraints on geologic processes, both in Jezero Crater and more widely on Mars. All collected rocks have interacted with water and contain secondary geochemical and mineralogical evidence that can be used to understand aqueous environments in the crater and the potential conditions of habitability for ancient life on Mars. Key Points: Nine samples, consisting of four pairs of rock cores and a tube of atmospheric gas, were collected from the floor of Jezero Crater, MarsIn situ observations of crater floor outcrops, used as proxies for the samples, reveal aqueously altered igneous lithologiesPerseverance will leave one sample from each pair at the Three Forks depot and retain a second to be cached with future samples [ABSTRACT FROM AUTHOR]

A multi‐instrument study of the regolith of Jezero crater floor units by the Perseverance rover has identified three types of regolith: fine‐grained, coarse‐grained, and mixed‐type. Mastcam‐Z, Wide Angle Topographic Sensor for Operations and eNgineering, and SuperCam Remote Micro Imager were used to characterize the regolith texture, particle size, and roundedness where possible. Mastcam‐Z multispectral and SuperCam laser‐induced breakdown spectroscopy data were used to constrain the composition of the regolith types. Fine‐grained regolith is found surrounding bedrock and boulders, comprising bedforms, and accumulating on top of rocks in erosional depressions. Spectral and chemical data show it is compositionally consistent with pyroxene and a ferric‐oxide phase. Coarse‐grained regolith consists of 1–2 mm well‐sorted gray grains that are found concentrated around the base of boulders and bedrock, and armoring bedforms. Its chemistry and spectra indicate it is olivine‐bearing, and its spatial distribution and roundedness indicate it has been transported, likely by saltation‐induced creep. Coarse grains share similarities with the olivine grains observed in the Séítah formation bedrock, making that unit a possible source for these grains. Mixed‐type regolith contains fine‐ and coarse‐grained regolith components and larger rock fragments. The rock fragments are texturally and spectrally similar to bedrock within the Máaz and Séítah formations, indicating origins by erosion from those units, although they could also be a lag deposit from erosion of an overlying unit. The fine‐ and coarse‐grained types are compared to their counterparts at other landing sites to inform global, regional, and local inputs to regolith formation within Jezero crater. The regolith characterization presented here informs the regolith sampling efforts underway by Perseverance. Plain Language Summary: We used multiple instruments on the Perseverance rover to describe three populations of loose sediments found on the floor of Jezero crater by their grain sizes and chemical compositions. The smallest population has grains that are small sand‐sized (80–530 μm) and a mixture of minerals commonly found on Mars, including pyroxene that is present in local rocks and airborne dust found globally. These grains are the easiest to move by wind, so could have distal regional sources as well. Larger gray grains that are 1–2 mm in size and rounded contain olivine. These grains move along the surface, pushed by the impacts of smaller grains that are lifted by the wind. Their size and composition are very similar to olivine grains found in nearby in‐place rocks, indicating that they may have a more local source. Finally, there are larger pieces of rocks that have broken down from the erosion of local in‐place rocks over time and mix with the other types of grains. Loose sediments within the Jezero crater described here can be compared to loose sediments studied at other landing sites on Mars to help understand how Jezero sediments are formed and transported. Key Points: Textural, spectroscopic, and chemical analyses of regolith in Jezero crater reveal details of fine, coarse, and mixed grain componentsCompositional information and physical grain characteristics from those analyses inform transport history and possible source materialRegolith components are compared to their counterparts at other landing sites to inform global versus local inputs to regolith formation [ABSTRACT FROM AUTHOR]

The Mars 2020 mission rover "Perseverance", launched on 30 July 2020 by NASA, landed successfully 18 February 2021 at Jezero Crater, Mars (Lon. E 77.4509° Lat. N 18.4446°). The landing took place at Mars solar longitude Ls = 5.2°, close to start of the northern spring. Perseverance's payload includes the relative humidity sensor MEDA HS (Mars Environmental Dynamics Analyzer Humidity Sensor), which operations, performance, and the first observations from sol 80 to sol 410 (Ls 44°–210°) of Perseverance's operations we describe. The relative humidity measured by MEDA‐HS is reliable from late night hours to few tens of minutes after sunrise when the measured humidity is greater than 2% (referenced to sensor temperature). Data delivered to the Planetary Data System include relative humidity, sensor temperature, uncertainty of relative humidity, and volume mixing ratio (VMR). VMR is calculated using the MEDA‐PS pressure sensor values. According to observations, nighttime absolute humidity follows a seasonal curve in which release of water vapor from the northern cap with advancing northern spring and summer is visible. At ground level, frost conditions may have been reached a few times during this season (Ls 44°–210°). Volume mixing ratio values show a declining diurnal trend from the midnight toward the morning suggesting adsorption of humidity into the ground. Observations are compared with an adsorptive single‐column model, which complies with observations and confirms adsorption. The model allows estimating daytime VMR levels. Short‐term subhour timescales show large temporal fluctuations in humidity, which suggest vertical and spatial advection. Plain Language Summary: The Mars 2020 mission rover "Perseverance" landed successfully on 18 February 2021 at Jezero Crater, Mars. The rover's payload includes a versatile instrument suite which includes a relative humidity sensor, whose observations for the first 410 Martian days are described here. The observations show how the lowest level of atmosphere is generally dry but still exceeding saturation is feasible because of cold nights. Sensor operations and accuracy estimates are presented. Relative humidity together with MEDA pressure and air temperature observations allow calculating absolute water vapor content of air at the sensor level at nighttime. Humidity observations are also compared with models describing water vapor adsorption and desorption into and out from soil. The results show how atmospheric humidity at the rover's site experiences large subhour variability. Humidity observations help to understand interchange of humidity between the soil and the atmosphere. Water is mandatory for life, such as on earth, thus understanding these water cycle processes better are important for evaluating possibilities of past and current habitability of Mars. Perseverance is also collecting samples which maybe returned to Earth one day. Knowledge of the conditions at the times when samples were collected maybe useful. Key Points: Humidity observations in Mars by M2020 Perseverance rover during the first 410 sols of operation are shown and discussedHumidity sensor MEDA‐HS operations and sensor accuracy are explainedAdsorptive single column model is tested and compared with humidity observations [ABSTRACT FROM AUTHOR]

On Mars, near the equator, much of the terrain in Gale Crater consists of bedrock outcrops separated by relatively smooth, uniform regolith surfaces. In scattered sites, however, distinct patterns—in the form and texture of the ground surface—contrast sharply with the typical terrain and with eolian bedforms. This paper focuses on these diverse, intriguing ground patterns. They include ∼1 to >10 m‐long linear disruptions of uniform regolith surfaces, alignments, and other arrangements of similar‐sized rock fragments and shallow, ∼0.1 m‐wide sandy troughs 1–10 m in length. Similar features were recognized early in the Mars Science Laboratory (MSL) mission, but they received only limited attention until Curiosity, the MSL rover, encountered striking examples in the Glen Torridon region. Herein, the ground patterns are illustrated with rover images. Potential mechanisms are briefly discussed in the context of the bedrock composition and atmospheric conditions documented by Curiosity. The evidence suggests that the patterns are active forms of spontaneous granular organization. It leads to the hypothesis that the patterns arise and develop from miniscule, inferred cyclic expansion and contraction of the bedrock and regolith, likely driven by oscillating transfers of energy and moisture between the atmosphere and the terrain. The hypothesis has significant implications for studies of contemporary processes on Mars on both sides of the atmosphere‐lithosphere interface. The ground patterns, as well as ripples and dunes formed by the wind, constitute remarkable extra‐terrestrial examples of granular self‐organization, complex phenomena well known in diverse systems on Earth. Plain Language Summary: Gale crater, which is near Mars' equator (4.5°S latitude), is generally rocky with sand and rocks scattered between extensive bedrock exposures. However, in a few local sites, distinct natural patterns mark the ground with ∼0.1 m‐wide, sand‐lined troughs and rocks arranged geometrically. We use detailed images from Curiosity, the Mars Science Laboratory rover, to illustrate these intriguing patterns in the Glen Torridon area, where they are widespread. We suggest they are currently active in the dry rock debris at the surface and driven by the sustained shrink‐swell activity of the underlying bedrock. This inferred activity, which likely results from variations in moisture and temperature in the lower Mars atmosphere, could generate these ground patterns, much like vibrations or analogous cyclic disturbances cause patterns to form naturally in diverse settings with granular materials of different sizes and shapes. The inferred cyclic shrink‐swell behavior of the shallow subsurface and underlying transfers of energy and mass may be of broad interest because of their potential implications for studies of processes shaping the Mars landscape and occurring in the lower atmosphere. These ground features, as well as ripples and dunes formed by the wind, are visible examples of extra‐terrestrial self‐organization. Key Points: Near Mars' equator, sandy troughs and organized rock fragments locally form distinct patterns suggestive of active ground deformationUnlike patterned ground on Earth, the ground patterns in Gale Crater form in thin, dry regolith overlying jointed bedrockAtmosphere‐surface exchange of energy and water vapor is inferred to drive self‐organization through cyclic subsurface volume changes [ABSTRACT FROM AUTHOR]

We analysed the steady-state protein levels of CPPED1 (immune system pathway); fibroblast activation protein, FAP (movement, adhesion and projection); and hepatoma-derived growth factor, HDGF (ER stress and unfolded protein response) by western blotting. From this analysis, we observed a total of 231 unique proteins, of which 52 were identified to be differentially secreted (Figure 1A-C); 42 were secreted more by T2D-derived hASCs (81% of all differentially secreted proteins) and 10 were secreted less by T2D-derived hASCs (19%). Diabetes alters the protein secretome of human adipose-derived stem cells and promotes tumorigenesis in hepatic cancer cells (A) Interaction network of the 42 proteins secreted more in the secretome of T2D-hASCs from STRING analysis, showing a high degree of interaction between proteins (protein-protein interaction enrichment p-value < 1.0 × 10-16). [Extracted from the article]

Nek4 is a serine/threonine kinase which has been implicated in primary cilia stabilization, DNA damage response, autophagy and epithelial‐to‐mesenchymal transition. The role of Nek4 in cancer cell survival and chemotherapy resistance has also been shown. However, the precise mechanisms by which Nek4 operates remain to be elucidated. Here, we show that Nek4 overexpression activates mitochondrial respiration coupled to ATP production, which is paralleled by increased mitochondrial membrane potential, and resistance to mitochondrial DNA damage. Congruently, Nek4 depletion reduced mitochondrial respiration and mtDNA integrity. Nek4 deficiency caused mitochondrial elongation, probably via reduced activity of the fission protein DRP1. In Nek4 overexpressing cells, the increase in mitochondrial fission was concomitant to enhanced phosphorylation of DRP1 and Erk1/2 proteins, and the effects on mitochondrial respiration were abolished in the presence of a DRP1 inhibitor. This study shows Nek4 as a novel regulator of mitochondrial function that may explain the joint appearance of high mitochondrial respiration and mitochondrial fragmentation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death globally and more than four out of five cases are due to ischemic events. Cardiac fibroblasts (CF) contribute to normal heart development and function, and produce the post‐ischemic scar. Here, we characterize the biochemical and functional aspects related to CF endurance to ischemia‐like conditions. Expression data mining showed that cultured human CF (HCF) express more BCL2 than pulmonary and dermal fibroblasts. In addition, gene set enrichment analysis showed overrepresentation of genes involved in the response to hypoxia and oxidative stress, respiration and Janus kinase (JAK)/Signal transducer and Activator of Transcription (STAT) signaling pathways in HCF. BCL2 sustained survival and proliferation of cultured rat CF, which also had higher respiration capacity and reactive oxygen species (ROS) production than pulmonary and dermal fibroblasts. This was associated with higher expression of the electron transport chain (ETC) and antioxidant enzymes. CF had high phosphorylation of JAK2 and its effectors STAT3 and STAT5, and their inhibition reduced viability and respiration, impaired ROS control and reduced the expression of BCL2, ETC complexes and antioxidant enzymes. Together, our results identify molecular and biochemical mechanisms conferring survival advantage to experimental ischemia in CF and show their control by the JAK2/STAT signaling pathway. The presented data point to potential targets for the regulation of cardiac fibrosis and also open the possibility of a general mechanism by which somatic cells required to acutely respond to ischemia are constitutively adapted to survive it. [ABSTRACT FROM AUTHOR]

Sarcopenia is one of the main factors contributing to the disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria (MIT) in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BCL2 interacting protein 3 (BNIP3) plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of Toll‐like receptor 9 (TLR9)‐dependent inflammation and activation of the NLRP3 (nucleotide‐binding oligomerization domain (NOD)‐, leucine‐rich repeat (LRR)‐, and pyrin domain‐containing protein 3) inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age‐induced muscle inflammation in mice and humans. Taken together, our data allow us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key to maintaining muscle health during aging. [ABSTRACT FROM AUTHOR]

Tribocorrosion is a degradation phenomenon of material surfaces subjected to the combined action of mechanical loading and corrosion attack caused by the environment. Although corrosive chemical species such as materials like chloride atoms, chlorides, and perchlorates have been detected on the Martian surface, there is a lack of studies of its impact on materials for landed spacecraft and structures that will support surface operations on Mars. Here, we present a series of experiments on the stainless-steel material of the ExoMars 2020 Rosalind Franklin rover wheels. We show how tribocorrosion induced by brines accelerates wear on the materials of the wheels. Our results do not compromise the nominal ExoMars mission but have implications for future long-term surface operations in support of future human exploration or extended robotic missions on Mars. [ABSTRACT FROM AUTHOR]

In this study, three simulations by the Mars Weather Research and Forecasting Model are compared: two 10 Martian year (MY) 2° × 2° simulations with (i) fully radiatively active dust and (ii) a prescribed dust scenario, and a (iii) 1 MY 0.5° × 0.5° simulation with prescribed dust as in (ii). From comparing (i) and (ii), we found that the impact of dust‐radiation feedback is individually different for any region. The most striking evidence are major dust lifting activities to the south of Chryse Planitia (S‐CP) seen in (i) but not in (ii). By contrast, dust lifting and deposition on the southern slopes and inside the Hellas Basin are similar in both simulations. The latter, in turn, points toward a similar near‐surface atmospheric circulation. In (iii), the total global amount of wind stress lifted dust is by a factor of ∼8 higher than in (ii), with S‐CP being a major lifting region as in (i). Nonetheless, the surface dust lifting by wind stress in (iii) may be also reduced regionally, as seen at the peak of Elysium Mons because of its unique topography. The zonal mean circulation in (i) is generally of a comparable strength to that in (ii), with exceptions in global dust storm years, when it is clearly stronger in (i), in line with a dustier atmosphere. The differences in the zonal mean circulation between (ii) and (iii) are mostly at lower altitudes and may arise because of differences in the representation of the topography. Plain Language Summary: In the Mars atmosphere, the combination of airborne dust and radiation has multiplying effects, which are termed "positive feedbacks." For instance, dust storms intensify when exposed to sun light: temperature differences between warm and cold air are enhanced and winds become stronger, that is, positive feedback. We run a Mars General Circulation Model, or more precisely, the Mars Weather Research and Forecasting Model, with and without such feedbacks. In addition, we refine the spatial resolution of the model from 2° to 0.5° latitude and longitude. Overall, we quantify the impact of feedbacks and spatial resolution on the outcome of model simulations. For that, we compare patterns of dust exchange between the surface and atmosphere between different model simulations. We find that the strength of the positive feedbacks may change considerably from place to place. For the 0.5° resolution, winds are planet wide much more effective in eroding surface dust, including an exception governed by the unique local topography at the Elysium Mons volcano. Key Points: Three MarsWRF model simulations, which differ in the treatment of dust and/or spatial resolution, are comparedDust‐radiation feedback is studied by comparing surface dust lifting between simulations with interactive and prescribed dust treatmentThe highest resolution simulation has increased surface dust lifting by the wind stress globally, but it may be also reduced locally [ABSTRACT FROM AUTHOR]

The MarsWRF model is set up with fully interactive dust at 5° × 5° and 2° × 2 resolution. The latter allows for a better representation of topography and other surface properties. An infinite reservoir of surface dust is assumed for both resolutions. For 5° × 5°, surface dust lifting by wind stress takes place over broad areas, occurring in about 20% of the model's grid cells. For 2° × 2°, it is more spatially restricted, occurring in less than 5% of the grid cells, and somewhat reminiscent of the corridors Acidalia‐Chryse, Utopia‐Isidis, and Arcadia‐West of Tharsis. The onset times of major dust storms—large regional storms or global dust storm events (GDEs)—do not exhibit much interannual variability, typically occurring at around Ls 260°. However, their magnitude does show significant interannual variability—with only small regional storms in some years, large regional storms in others, and some years with GDEs—owing to the interaction between major dust lifting regions at low latitudes. The latter is consistent with observed GDEs having several active dust lifting centers. The agreement between the model's surface dust distribution and observation‐based dust cover index maps is potentially better for 2° × 2°. For the latter, there is also significant surface dust lifting by wind stress in the aphelion season that is largely confined to the Hellas basin. It has a recurring time pattern of 2–7 sols, possibly resulting from the interaction between midlatitude baroclinic systems and local downslope flows. Plain Language Summary: Mars General Circulation Models (MGCMs) simulate the Mars climate and atmosphere for many Martian Years (MYs). A challenge is to configure such models to produce Mars global dust storm events (GDEs) in few but not all MYs. That is because GDEs are known to occur once every few MYs, on average. We set up the MarsWRF MGCM in this way using "interactive dust," meaning the model freely lifts, transports, and deposits surface dust (assuming an inexhaustible amount of available surface dust). We use different horizontal model grid point resolutions and compare their results in terms of dust storm source regions and changes in surface dust loading. For the high‐resolution experiment, we find that GDEs are likely to develop if regional dust storm activity around two equatorial source regions on the planet, namely, south of Chryse Planitia and in the northern Hellas basin, combine with one another. The latter is consistent with knowing from observations that GDEs have several active dust lifting centers. Also, we find that the model's surface dust distribution in the high‐resolution experiment agrees potentially better with observation‐based dust cover maps. Key Points: The MarsWRF model is run with fully interactive dust at 2° × 2° horizontal resolution, assuming an infinite surface dust reservoirThe dust cycle characteristics are clearly different from 5° × 5° resolution in terms of interannual variability and dust source regionsGlobal dust storm events typically occur if dust storm activity at northern Hellas Planitia connects with that south of Chryse Planitia [ABSTRACT FROM AUTHOR]

The Sample Analysis at Mars (SAM) instrument onboard the Mars Science Laboratory Curiosity rover measures the chemical composition of major atmospheric species (CO2, N2, 40Ar, O2, and CO) through a dedicated atmospheric inlet. We report here measurements of volume mixing ratios in Gale Crater using the SAM quadrupole mass spectrometer, obtained over a period of nearly 5 years (3 Mars years) from landing. The observation period spans the northern summer of MY 31 and solar longitude (LS) of 175° through spring of MY 34, LS = 12°. This work expands upon prior reports of the mixing ratios measured by SAM QMS in the first 105 sols of the mission. The SAM QMS atmospheric measurements were taken periodically, with a cumulative coverage of four or five experiments per season on Mars. Major observations include the seasonal cycle of CO2, N2, and Ar, which lags approximately 20–40° of LS behind the pressure cycle driven by CO2 condensation and sublimation from the winter poles. This seasonal cycle indicates that transport occurs on faster timescales than mixing. The mixing ratio of O2 shows significant seasonal and interannual variability, suggesting an unknown atmospheric or surface process at work. The O2 measurements are compared to several parameters, including dust optical depth and trace CH4 measurements by Curiosity. We derive annual mean volume mixing ratios for the atmosphere in Gale Crater: CO2 = 0.951 (±0.003), N2 = 0.0259 (±0.0006), 40Ar = 0.0194 (±0.0004), O2 = 1.61 (±0.09) x 10‐3, and CO = 5.8 (±0.8) x 10‐4. Plain Language Summary: The atmosphere of Mars is made up of primarily carbon dioxide, and during the Martian year, the barometric pressure is known to cycle up and down substantially as this carbon dioxide freezes out and then is rereleased from polar caps. The Mars Science Laboratory Curiosity rover has now acquired atmospheric composition measurements at the ground over multiple years, capturing the variations in the major gases over several seasonal cycles for the first time. With the Sample Analysis at Mars instrument, the annual average composition in Gale Crater was measured as 95.1% carbon dioxide, 2.59% nitrogen, 1.94% argon, 0.161% oxygen, and 0.058% carbon monoxide. However, the abundances of some of these gases were observed to vary up to 40% throughout the year due to the seasonal cycle. Nitrogen and argon follow the pressure changes but with a delay, indicating that transport of the atmosphere from pole to pole occurs on faster timescales than mixing of the components. Oxygen has been observed to show significant seasonal and year‐to‐year variability, suggesting an unknown atmospheric or surface process at work. These data can be used to better understand how the surface and atmosphere interact as we search for signs of habitability. Key Points: First multiyear in situ measurements of the major components of the Mars atmosphere have been obtained by the MSL/SAM investigationSeasonal variation of CO2, N2, and Ar reveals differences in atmospheric transport and mixing timescalesOxygen varies seasonally and interannually, independently from Ar and N2, on timescales too fast to be explained by known chemistry [ABSTRACT FROM AUTHOR]

Introduction: A new technique was performed for the removal of an amalgam tattoo (AT), consisting in mucoabrasion combined with a free connective tissue graft (FCTG). Case Presentation: A 59‐year‐old female presented with a large AT involving the alveolar mucosa and gingiva between teeth #7 and #8, where endodontic treatment and apicoectomy was performed 21 years ago. To avoid compromising esthetics, the lesion was managed with a new technique including mucoabrasion and an FCTG. At the 53‐month follow‐up, the patient exhibited a naturally appearing soft tissue with no evidence of the AT. Conclusion: When performing a one‐stage treatment of removing ATs in areas of high esthetic demand, it is possible to achieve good results and ideal gingival color. [ABSTRACT FROM AUTHOR]

In this paper we use the Mars implementation of the Planet Weather Research and Forecasting model, MarsWRF, to simulate the Entry, Descent and Landing (EDL) vertical profiles from six past missions: Pathfinder, Mars Exploration Rovers Opportunity and Spirit, Phoenix, Mars Science Laboratory Curiosity rover, and ExoMars 2016 (Schiaparelli), and compare the results with observed data. In order to investigate the sensitivity of the model predictions to the atmospheric dust distribution, MarsWRF is run with two prescribed dust scenarios. It is concluded that the MarsWRF EDL predictions can be used for guidance into the design and planning stage of future missions to the planet, as it generally captures the observed EDL profiles, although it has a tendency to underestimate the temperature and overestimate the density for heights above 15 km. This could be attributed to an incorrect representation of the observed dust loading. We have used the model to predict the EDL conditions that may be encountered by two future missions: ExoMars 2020 and Mars 2020. When run for Oxia Planum and Jezero Crater for the expected landing time, MarsWRF predicts a large sensitivity to the dust loading in particular for the horizontal wind speed above 10‐15 km with maximum differences of up to ±30 m/s for the former and ±15 m/s for the latter site. For both sites, the best time for EDL, that is, when the wind speed is generally the weakest with smaller shifts in direction, is predicted to be in the late morning and early afternoon. Plain Language Summary: One of the most critical stages of a mission to another planet is the Entry, Descent and Landing (EDL) stage. If not successful, the entire mission will be deemed a failure. The thin atmosphere, unpredictable winds, variable dust content, and rough terrain make an EDL on Mars particularly challenging. In this paper, a simplified Martian mesoscale model is used to simulate the EDL conditions encountered by six past missions to the planet with the model predictions evaluated against the observed measurements. By and large, the model successfully captures the observed density, temperature, pressure, and horizontal wind vertical profiles in the lowest 30 km, where the most critical phase of the EDL takes place. The main discrepancy with respect to the observed profiles is for heights above 15 km and is probably due to an incorrect representation of the vertical profile of atmospheric dust, which strongly affects heating rates and hence other variables. The model is subsequently run for the proposed landing sites of ExoMars 2020 (Oxia Planum) and Mars 2020 (Jezero Crater) missions and for the expected time of EDL. For both sites, the model predictions indicate a strong sensitivity to the dust loading, with the most favorable time for the EDL, that is, when the horizontal wind speed is generally the weakest with smaller shifts in wind direction, being the late morning and early afternoon. Key Points: MarsWRF reproduces well the observed EDL vertical profiles from six past missions to the planetMarsWRF EDL predictions can be used for guidance into the design and planning stage of future missions to the planetFor ExoMars 2020 and Mars rover 2020 missions, the best time for EDL seems to be in the late morning and early afternoon [ABSTRACT FROM AUTHOR]

Good knowledge of the environmental conditions of deserts on Earth is relevant for climate studies. The Atacama Desert is of particular interest as it is considered to be the driest region on Earth. We have performed simulations using the Weather Research and Forecasting (WRF) model over the Atacama Desert for two week‐long periods in the austral winter season coincident with surface temperature and relative humidity in‐situ observations at three sites. We found that the WRF model generally overestimates the daytime surface temperature, with biases of up to 11°C, despite giving a good simulation of the relative humidity. In order to improve the agreement with observed measurements, we conducted sensitivity experiments in which the surface albedo, soil moisture content and five tuneable parameters in the Noah Land Surface Model (namely soil porosity, soil suction, saturated soil hydraulic conductivity, the b parameter used in hydraulic functions and the quartz fraction) are perturbed. We concluded that an accurate simulation is not possible, most likely because the Noah Land Surface Model does not have a groundwater table that may be shallow in desert regions. The WRF‐predicted land surface temperature is also evaluated against that estimated from the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument. While at night the satellite‐derived and ground‐based measurements are generally in agreement, during the day MODIS estimates are typically lower by as much as 17°C. This is attributed to the large uncertainty in the MODIS‐estimated land surface temperatures in arid and semi‐arid regions. The findings of this work highlight the need for ground‐based observational networks in remote regions such as the Atacama Desert where satellite‐derived and model products may not be very accurate. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the clinical outcomes of a nonsurgical treatment protocol for peri‐implantitis and to evaluate the influence that some factors could have on the results of this treatment. Material and methods: In this retrospective case series, patients with at least one implant with peri‐implantitis, treated with a nonsurgical protocol and with a one‐year follow‐up, were included. Clinical parameters (probing depth, recession, bleeding, and/or suppuration on probing) were collected at baseline, 6 weeks, 3, 6, and 12 months. Radiographic bone levels were assessed in periapical radiographs taken at baseline and 12 months. An analysis of the factors significantly associated with marginal bone level changes was performed. Descriptive and analytic statistics were carried out at the patient and at the implant level, as well as a multiple linear regression analysis. Results: Data from 37 patients with 70 implants were analyzed. There was a general and consistent improvement from baseline compared to all follow‐up points in the clinical variables. A significant radiographic bone gain of 0.91 mm was observed. The factors significantly associated were baseline plaque index, sex, and age at patient level, and type of prosthesis and implant location at implant level. Conclusions: Within the limitations of this study, this nonsurgical treatment protocol might be considered as a first treatment option for peri‐implantitis. More studies are needed, with larger sample sizes and longer follow‐ups, to confirm these outcomes and their long‐term stability. [ABSTRACT FROM AUTHOR]

Slope streaks are prevalent and intriguing dark albedo surface features on contemporary Mars. Slope streaks are readily observed in the equatorial and subequatorial dusty regolith regions with low thermal inertia. They gradually fade over decadal timescales. The proposed mechanisms for their formation vary widely based on several physicochemical and geomorphological explanations. The scientific community is divided in proposing both dry and wet mechanisms for the formation of slope streaks. Here we perform a systematic evaluation of the literature for these wet and dry mechanisms. We discuss the probable constraints on the various proposed mechanisms and provide perspectives on the plausible process driving global‐scale slope streak formation on contemporary Mars. Although per our understanding, a thorough consideration of the global distribution of slope streaks, their morphology and topography, flow characteristics, physicochemical and atmospheric coincidences, and terrestrial analogies weighs more in favor of several wet mechanisms, we acknowledge that such wet mechanisms cannot explain all the reported morphological and terrain variations of slope streaks. Thus, we suggest that explanations considering both dry and wet processes can more holistically describe all the observed morphological variations among slope streaks. We further acknowledge the constraints on the resolutions of remote sensing data and on our understanding of the Martian mineralogy, climate, and atmosphere and recommend continuous investigations in this direction using future remote sensing acquisitions and simulations. In this regard, finding more wet and dry terrestrial analogs for Martian slope streaks and studying them at high spatiotemporal resolutions can greatly improve our understanding. Plain Language Summary: Slope streaks are prevalent surface features on contemporary Mars. They have dark albedo and are abundant in the equatorial and subequatorial latitudes. The exact mechanisms behind their formation and development are still unknown, and several hypotheses have been proposed based on the physicochemical and geomorphological properties of slope streaks. These features generate a common interest because several hypotheses have linked them with transiently flowing liquid water on the Martian surface. Such probable linkages with Martian liquid water can have wide implications for understanding habitability conditions and ongoing water cycles on Mars and for evolving planetary protection policies to prevent possible contamination of Martian surface during future missions. Therefore, here we perform a systematic evaluation of the literature covering morphological and flow characteristics of slope streaks for water‐driven or dry dust avalanche mechanisms. We discuss the probable limitations of the various proposed models for slope streak development and provide perspectives on the plausible processes driving global‐scale slope streak formations on Mars. Continuously improving satellite and rover observations of Martian surface, topography, climate, and minerals are bound to improve our understanding of slope streaks in the coming years. Key Points: We provide a systematic survey and evaluation of the literature covering morphological characteristics of slope streaksWe present a novel analog environment, Salar de Uyuni in the Bolivian Altiplano, where slope streaks are formed solely by deliquescenceWe offer perspectives on the probable mechanisms driving global‐scale slope streak formation on contemporary Mars [ABSTRACT FROM AUTHOR]

Abstract: We create a vertically coarse, but complete, profile of dust mixing ratio from the surface to the upper atmosphere over Gale Crater, Mars, using the frequent joint atmospheric observations of the orbiting Mars Climate Sounder (MCS) and the Mars Science Laboratory Curiosity rover. Using these data and an estimate of planetary boundary layer (PBL) depth from the MarsWRF general circulation model, we divide the vertical column into three regions. The first region is the Gale Crater PBL, the second is the MCS‐sampled region, and the third is between these first two. We solve for a well‐mixed dust mixing ratio within this third (middle) layer of atmosphere to complete the profile. We identify a unique seasonal cycle of dust within each atmospheric layer. Within the Gale PBL, dust mixing ratio maximizes near southern hemisphere summer solstice (Ls = 270°) and minimizes near winter solstice (Ls = 90–100°) with a smooth sinusoidal transition between them. However, the layer above Gale Crater and below the MCS‐sampled region more closely follows the global opacity cycle and has a maximum in opacity near Ls = 240° and exhibits a local minimum (associated with the “solsticial pause” in dust storm activity) near Ls = 270°. With knowledge of the complete vertical dust profile, we can also assess the frequency of high‐altitude dust layers over Gale. We determine that 36% of MCS profiles near Gale Crater contain an “absolute” high‐altitude dust layer wherein the dust mixing ratio is the maximum in the entire vertical column. [ABSTRACT FROM AUTHOR]

Mitochondrial fusion and fission events, collectively known as mitochondrial dynamics, act as quality control mechanisms to ensure mitochondrial function and fine-tune cellular bioenergetics. Defective mitofusin 2 (Mfn2) expression and enhanced mitochondrial fission in skeletal muscle are hallmarks of insulin-resistant states. Interestingly, Mfn2 is highly expressed in brown adipose tissue ( BAT), yet its role remains unexplored. Using adipose-specific Mfn2 knockout (Mfn2-ad KO) mice, we demonstrate that Mfn2, but not Mfn1, deficiency in BAT leads to a profound BAT dysfunction, associated with impaired respiratory capacity and a blunted response to adrenergic stimuli. Importantly, Mfn2 directly interacts with perilipin 1, facilitating the interaction between the mitochondria and the lipid droplet in response to adrenergic stimulation. Surprisingly, Mfn2-ad KO mice were protected from high-fat diet-induced insulin resistance and hepatic steatosis. Altogether, these results demonstrate that Mfn2 is a mediator of mitochondria to lipid droplet interactions, influencing lipolytic processes and whole-body energy homeostasis. [ABSTRACT FROM AUTHOR]

We model the fluids involved in the alteration processes recorded in the Sheepbed Member mudstones of Yellowknife Bay ( YKB), Gale crater, Mars, as revealed by the Mars Science Laboratory Curiosity rover investigations. We compare the Gale crater waters with fluids modeled for shergottites, nakhlites, and the ancient meteorite ALH 84001, as well as rocks analyzed by the Mars Exploration rovers, and with terrestrial ground and surface waters. The aqueous solution present during sediment alteration associated with phyllosilicate formation at Gale was high in Na, K, and Si; had low Mg, Fe, and Al concentrations-relative to terrestrial groundwaters such as the Deccan Traps and other modeled Mars fluids; and had near neutral to alkaline pH. Ca and S species were present in the 10−3 to 10−2 concentration range. A fluid local to Gale crater strata produced the alteration products observed by Curiosity and subsequent evaporation of this groundwater-type fluid formed impure sulfate- and silica-rich deposits-veins or horizons. In a second, separate stage of alteration, partial dissolution of this sulfate-rich layer in Yellowknife Bay, or beyond, led to the pure sulfate veins observed in YKB. This scenario is analogous to similar processes identified at a terrestrial site in Triassic sediments with gypsum veins of the Mercia Mudstone Group in Watchet Bay, UK. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. [ABSTRACT FROM AUTHOR]

Objectives To describe the status of implants in periodontally compromised patients who regularly receive supportive periodontal therapy ( SPT) and to determine the factors associated to peri-implant inflammatory disease in those patients. Material and methods Clinical and radiographic data of implants in periodontal patients who, after being treated and included in a SPT programme, wore implant prostheses for at least 6 months were recorded. The implants were classified according to the criteria of the 6th European Workshop on Periodontology in health, mucositis and peri-implantitis. Logistic regression analysis was performed to analyse the individual and adjusted effects of each study variable on mucositis or peri-implantitis, using SUDAAN to account for clustering (multiple implants within the patient). Results A total of 786 implants were placed in 239 patients. At patient level, 60.3%, 24.7% and 15.1% were classified as healthy, mucositis and peri-implantitis patients, respectively. At implant level, the respective percentages were 77.4%, 12.8% and 9.8%. For mucositis, at implant level, the adjusted ORs indicate a significant association with plaque index ( P = 0.050), type of periodontitis ( P = 0.030) and location ( P = 0.045). For peri-implantitis, the adjusted ORs indicate a significant association with plaque index ( P < 0.001) and location ( P = 0.002). Conclusions The prevalence of peri-implant inflammatory disease in periodontal patients who regularly undergo SPT is clinically significant. The factors associated with peri-implant inflammatory disease were plaque index and implant location, and mucositis was also affected by the type of periodontitis the patient had. [ABSTRACT FROM AUTHOR]

The skeleton acts as an endocrine organ that regulates energy metabolism and calcium and phosphorous homeostasis through the secretion of osteocalcin (Oc) and fibroblast growth factor 23 (FGF23). However, evidence suggests that osteoblasts secrete additional unknown factors that contribute to the endocrine function of bone. To search for these additional factors, we generated mice with a conditional osteoblast-specific deletion of p38a MAPK known to display profound defects in bone homeostasis. Herein, we show that impaired osteoblast function is associated with a strong decrease in body weight and adiposity (P< 0.01). The differences in adiposity were not associated with diminished caloric intake, but rather reflected 20% increased energy expenditure and the up-regulation of uncoupling protein-1 (Ucp1) in white adipose tissue (WAT) and brown adipose tissue (BAT) (P< 0.05). These alterations in lipid metabolism and energy expenditure were correlated with a decrease in the blood levels of neuropeptide Y (NPY) (40% lower) rather than changes in the serum levels of insulin, Oc, or FGF23. Among all Npy-expressing tissues, only bone and primary osteoblasts showed a decline in Npy expression (P< 0.01). Moreover, the intraperitoneal administration of recombinant NPY partially restored the WAT weight and adipocyte size of p38a-deficient mice (P < 0.05). Altogether, these results further suggest that, in addition to Oc, other bone-derived signals affect WAT and energy expenditure contributing to the regulation of energy metabolism. [ABSTRACT FROM AUTHOR]

Introduction: The Mars 2020 mission is to investigate regional geology, evaluate past habitability, seek signs of ancient life, and assemble a returnable cache of samples as the Perseverance rover explores Jezero Crater, a Noachian crater on the edge of the Isidis basin that contains a deltaic system. The Perseverance rover recently completed a traverse of the floor of Jezero crater, characterizing and collecting samples from two units informally named the Máaz and Séítah formations (Cf-Fr and Cf-F1 in [1]). The Máaz fm makes up the current Jezero Floor surface, appearing to overlie the Séítah strata. Eight rock samples were collected and stored in the rover, along with proximity science observations using the rover's onboard payload about the composition, mineralogy, and texture of the sampled rocks. Seitah samples: The Séítah fm outcrops across the crater floor to the southeast of the delta. Orbital data suggested that Séítah contains olivine- and carbonate-bearing lithologies [2, 3] that may have formed by igneous, volcaniclastic, or sedimentary processes (e.g., [4-7]). Samples were collected from Brac (topographically high, within the Séítah bondaries) and Issole (topographically low, near the contact with the Máaz fm). Natural surfaces of both Brac and Issole exhibited horizontal layering at the cm- to dm-scale. They comprise densely packed, relatively coarse (1-2 mm) dark gray grains variably surrounded by lighter-toned interstitial materials. Their mineralogy is (ultra)mafic, dominated by olivine and pyroxene, with large olivine grains protruding from some natural rock surfaces. Minor (several volume %) secondary phases, including carbonates, silica phases, Mg-sulphates and Na-perchlorates, were present; ongoing work will assess the abundance of organic molecules, potentially associated with secondary mineral phases. The Seitah rocks are interpreted as olivine cumulates, extensively altered by fluids [8, 9]. Maaz samples: The Máaz fm was inferred to be volcanic because of the remote detection of olivine and pyroxene in the unit, its lobate margins, and embayment relationships [5, 10-12]; however, volcanoclastic and/or sedimentary origins were also posited [13, 14]. Three rocks in the area were sampled: Roubion, Rochette, and Sid. Roubion is in a topographically low area of flat-lying, polygonally jointed material. Rochette is located along the feature named Artuby Ridge, a resistant ledge that can be traced from near the Roubion site along the southern edge of the Séítah fm boundary. Sid represents the stratigraphically capping member of the Máaz fm, expressed as massive, blocky rocks that appear to cover much of the Jezero Crater surface. The three Máaz fm rocks are fine-to-medium grained, holocrystalline rocks dominated by pyroxene and feldspar, with an overall alkalic nature in contrast to the basaltic nature of martian meteorites (e.g., [15, 16], see also Udry et al. this conference). The mafic grain size appeared to be smallest in Roubion and coarsened upward to Sid, where several-mm, euhedral feldspar grains are visible. Roubion was pervasively altered with abundant secondary phases, Rochette and Sid contained only minor secondary phases. Mechanical competence corroborated the degree of weathering. Together, these observations imply that the Máaz fm is an igneous rock package that has experienced variable degrees of fluid interaction. Future work: The suite of the Séítah and Máaz fm samples represents a powerful outcome of the Perseverance Crater Floor campaign that will address several important objectives of the Mars Sample Return campaign [17], including magmatic history, water-rock interactions, environmental conduciveness to life, and isotopic ages for geologic events. Perseverance is now beginning its exploration of the delta facies and will place one of the returnable sample caches near the delta in the upcoming year for Mars Sample Return in the 2030s (see also Herd et al., this conference). [ABSTRACT FROM AUTHOR]

Introduction: A primary goal of the NASA Mars 2020 Perseverance rover mission is to select, acquire, and document a scientifically return-worthy collection of martian samples for return to Earth by future missions [1]. Perseverance is currently exploring Noachian-aged Jezero Crater, once the site of a delta-lake system with a high potential for habitability. Perseverance carries 38 identical sample tubes designed for rock core or regolith, and five "witness tubes" for characterizing contamination from the rover. As of the completion of the Crater Floor Campaign in mid-March, 2022, Perseverance has sealed 10 tubes: 8 rock cores, one tube in which inadvertently no core was acquired but which does include a serendipitous sample of ~5 µmol of ambient atmosphere (Table 1), and one witness tube. Here we provide an overview of the characterization and documentation acquired during each sample collection. The Sampling and Caching Subsystem (SCS) is fully decribed by [2]. The "STOP: List: During mission operations, a standardized set of required activities and observations are undertaken to fully document a sample, once the sampling target has been identified. These activities are called the Standardized Observation Protocol, or STOP list. The STOP list includes imagery at multiple scales along with chemical and mineralogical analyses of the outcrop surface. Because rock surfaces are frequently coated with dust or other materials, an ~1 cm deep and 5 cm diameter Abrasion Target is acquired within a few tens of cm of the sample target within the same lithology (Table 1). In this "sample proxy" patch, high-resolution images and detailed maps of elemental composition, mineralogy and potential organic matter are obtained. After coring, an image is taken of the sample in the tube, the amount of sample is estimated, and the tube is hermetically sealed [2]. Unique serial numbers are readily visible on the tube and seal exteriors to ensure confident identification even decades after acquisition. Sample documentation: Each sample is documented by the following products: Sample Dossier: Contains all observations from the STOP list, along with relevant rover data (e.g., temperatures, rover location, rover arm position and actions, etc). Uploaded to the NASA Planetary Data System (PDS) on a regular cadence, the Sample Dossier primarily consists of pointers to instrument-specific and engineering data products. These data are independently delivered to the PDS, and thus the dossier acts as a "one stop shop" for sample-specific results. Initial Report: A description of each sample in a standardized narrative format is written by the Science Team within three weeks of sample acquisition to capture the reasons for sampling and describe the interpretations available at the time of sampling and the completion of the STOP list. The Initial Report can be thought of as a set of field notes associated with each sample. Initial Reports are archived in the NASA PDS as an element of each Sample Dossier. The first volume of the Mars 2020 Initial Reports has been delivered to the NASA PDS; this volume includes the first four tubes collected during the Crater Floor Campaign: specifically, the Bit Carousel Witness Tube (see [2] for details); and the tubes containing Roubion, Montdenier and Montagnac (Table 1). Like field notes, the Initial Reports do not include extensive assessment and interpretation of the collected samples; these are reported elsewhere. The mineralogy, petrology and geochemistry of the first several samples collected during the Crater Floor Campaign, as well as the stratigraphy of crater floor units, can be found in [3,4]. Implications for Returned Sample Science are provided by [5]; comparisons with martian meteorite lithologies are provided by [6, 7]. [ABSTRACT FROM AUTHOR]

Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented, but the mechanism underlying this process is poorly understood. Here, we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis, and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. We found that transcription factor MEF2 regulates basal Mfn2 expression in neurons and that excitotoxicity-dependent degradation of MEF2 causes Mfn2 downregulation. Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective For a long time Aquaporin-7 has been the only aquaporin associated with the adipose tissue, and its dysregulation has been linked to the underlying mechanisms of obesity. However, the presence of alternative glycerol channels within the adipose tissue has been postulated, which has prompted us to the search of alternate glycerol transport routes in adipocytes. In view of this, it is hypothesized that Aquaporin-11 (AQP11) would have a role in adipocyte cell biology. Methods The expression, the localization and the function of human AQP11 (hAQP11) in cultured differentiated adipocytes were investigated. Results Gene expression analysis revealed the presence of AQP11 in both subcutaneous and visceral human mature adipocytes. It is found that hAQP11 is primarily located intracellularly in human adipocytes and partially colocalizes with perilipin, pointing towards AQP11 preferential location in the vicinity of lipid droplets. Overexpression of hAQP11 in 3T3-L1 adipocytes enabled to validate its function as a water channel and reveal its glycerol permeation activity. Conclusions hAQP11 permeates both water and glycerol, localizing in the vicinity of lipid droplets in human adipocytes. [ABSTRACT FROM AUTHOR]

Mitofusin 2 (Mfn2) is a key protein in mitochondrial fusion and it participates in the bridging of mitochondria to the endoplasmic reticulum (ER). Recent data indicate that Mfn2 ablation leads to ER stress. Here we report on the mechanisms by which Mfn2 modulates cellular responses to ER stress. Induction of ER stress in Mfn2-deficient cells caused massive ER expansion and excessive activation of all three Unfolded Protein Response (UPR) branches (PERK, XBP-1, and ATF6). In spite of an enhanced UPR, these cells showed reduced activation of apoptosis and autophagy during ER stress. Silencing of PERK increased the apoptosis of Mfn2-ablated cells in response to ER stress. XBP-1 loss-of-function ameliorated autophagic activity of these cells upon ER stress. Mfn2 physically interacts with PERK, and Mfn2-ablated cells showed sustained activation of this protein kinase under basal conditions. Unexpectedly, PERK silencing in these cells reduced ROS production, normalized mitochondrial calcium, and improved mitochondrial morphology. In summary, our data indicate that Mfn2 is an upstream modulator of PERK. Furthermore, Mfn2 loss-of-function reveals that PERK is a key regulator of mitochondrial morphology and function. [ABSTRACT FROM AUTHOR]

Abstract: DOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress–response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption. [Copyright &y& Elsevier]

Mitochondria are dynamic subcellular organelles that convert nutrient intermediates into readily available energy equivalents. Optimal mitochondrial function is ensured by a highly evolved quality control system, coordinated by protein machinery that regulates a process of continual fusion and fission. In this work, we provide in vivo evidence that the ATP-independent metalloprotease OMA1 plays an essential role in the proteolytic inactivation of the dynamin-related GTPase OPA1 (optic atrophy 1). We also show that OMA1 deficiency causes a profound perturbation of the mitochondrial fusion-fission equilibrium that has important implications for metabolic homeostasis. Thus, ablation of OMA1 in mice results in marked transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters. Additionally, Oma1-mutant mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis. These alterations are especially significant under metabolic stress conditions, indicating that an intact OMA1-OPA1 system is essential for developing the appropriate adaptive response to different metabolic stressors such as a high-fat diet or cold-shock. This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function. [ABSTRACT FROM AUTHOR]

The regulation of autophagy in metazoans is only partly understood, and there is a need to identify the proteins that control this process. The diabetes- and obesity-regulated gene (DOR), a recently reported nuclear cofactor of thyroid hormone receptors, is expressed abundantly in metabolically active tissues such as muscle. Here, we show that DOR shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation. We demonstrate that DOR interacts physically with autophagic proteins Golgi-associated ATPase enhancer of 16 kDa (GATE16) and microtubule-associated protein 1A/1B-light chain 3. Gain-of-function and loss-of-function studies indicate that DOR stimulates autophagosome formation and accelerates the degradation of stable proteins. CG11347, the DOR Drosophila homologue, has been predicted to interact with the Drosophila Atg8 homologues, which suggests functional conservation in autophagy. Flies lacking CG11347 show reduced autophagy in the fat body during pupal development. All together, our data indicate that DOR regulates autophagosome formation and protein degradation in mammalian and Drosophila cells. [ABSTRACT FROM AUTHOR]

The aims of this work were to evaluate thyroid hormone receptor-α (TRα), TRα1, and TRα2 mRNA gene expression and TRα1:TRα2 ratio, identified as candidate factors for explaining regional differences between human adipose tissue depots. TRα, TRα1, and TRα2 mRNA levels, and the gene expressions of arginine–serine-rich, splicing factor 2 (SF2), heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), and Spot 14 (S14) were evaluated in 76 paired adipose tissue samples obtained from a population of 38 women who varied widely in terms of obesity and body fat distribution. Gene expression for these factors was also studied in stromal-vascular cells (SVCs) and mature adipocytes (MAs) from eight paired fat depots. TRα gene and TRα1 mRNA expression were increased 1.46-fold (P = 0.006) and 1.80-fold (P < 0.0001), respectively, in subcutaneous (SC) vs. visceral fat. These differences in gene expression levels were most significant in the obese group, in which the TRα1:TRα2 ratio was 2.24-fold (P < 0.0001) higher in SC vs. visceral fat. S14 gene expression was also increased by 2.42-fold (P < 0.0001) and correlated significantly with TRα and TRα1 gene expression and with the TRα1:TRα2 ratio. In agreement with these findings, hnRNP A1:SF2 ratio was decreased by 1.39-fold (P = 0.001). TRα and S14 levels were 2.1-fold (P < 0.0001) and 112.4-fold (P < 0.0001), respectively, higher in MAs than in SVCs from both fat depots. In summary, genes for TR-α, their upstream regulators, and downstream effectors were differentially expressed in SC vs. omental (OM) adipose tissue. Our findings suggest that TRα1 could contribute to SC adipose tissue expandability in obese subjects. [ABSTRACT FROM AUTHOR]

Objective The amplified in breast cancer-3 protein (AIB3) is a nuclear coactivator involved in proliferation, apoptosis and development. AIB3 loss of function causes deficient insulin secretion in mice, indicating that AIB3 participates in β-cell regulation. Our objective was to evaluate genetic variants located on AIB3 associated with β-cell function in children and to analyse the effect of AIB3 overexpression on gene expression in insulin 1 (INS-1) β-pancreatic cells. Design Polymorphisms from AIB3 were genotyped in 148 children with normal or low birthweights for gestational age. The effect of AIB3 overexpression on gene expression was analysed by real-time polymerase chain reaction (PCR) in INS-1 cells. Results AIB3 variants were associated with homeostasis model assessment of β-cell function (HOMA-β-cell) in children with normal or low birthweights for gestational age, but not with HOMA of insulin resistance (HOMA-IR), or with birthweight. AIB3 overexpression increased the expression of genes involved in signalling, such as IRS-1, IRS-2, IGF-II receptor or Foxo1, or of genes that control insulin secretion, such as Cplx2, Glut2 or Kv3·1 in INS-1 cells. Conclusions Our results suggest that AIB3 contributes to the maintenance of β-cell function in nondiabetic children and regulates gene expression in INS-1 cells. [ABSTRACT FROM AUTHOR]