The rostromedial tegmental nucleus (RMTg) plays a crucial role in regulating reward-related behavior by exerting inhibitory control over the ventral tegmental area (VTA). This modulation of dopamine ...neuron activity within the VTA is essential for maintaining homeostasis in the reward system. Recently we have shown that activation of RMTg projections to the VTA during the acquisition of cocaine-conditioned place preference (CPP) reduces the rewarding properties of cocaine and decreases VTA dopamine neuron activity. By inhibiting dopamine neurons in the VTA, we hypothesized that RMTg projections hold the potential to restore reward system homeostasis disrupted by repeated cocaine use, and attenuate molecular adaptations in the reward system, including alterations in signaling pathways. Our study demonstrates that enhancing the GABAergic inputs from the RMTg to the VTA can mitigate cocaine-induced molecular changes in key regions, namely the VTA, nucleus accumbens (NAc), and prefrontal cortex (PFC). Specifically, we found that cocaine-induced alteration in the phosphorylation state of ERK (pERK) and GluA1 on serine 845 (S845) and serine 831 (S831), that play a major role in plasticity by controlling the activity and trafficking of AMPA receptors, were significantly reversed following optic stimulation of RMTg afferents to the VTA. These findings highlight the therapeutic potential of targeting the RMTg-VTA circuitry for mitigating cocaine reward. Ultimately, this research may pave the way for novel therapeutic interventions that restore balance in the reward system and alleviate the detrimental effects of cocaine.
Pulpal revascularization is commonly used in the dental clinic to obtain apical closure of immature permanent teeth with thin dentinal walls. Although sometimes successful, stimulating bleeding from ...the periapical area of the tooth can be challenging and in turn may deleteriously affect tooth root maturation. Our objective here was to define reliable methods to regenerate pulp-like tissues in tooth root segments (RSs). G1 RSs were injected with human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) encapsulated in 5% gelatin methacrylate (GelMA) hydrogel. G2 RSs injected with acellular GelMA alone, and G3 empty RSs were used as controls. White mineral trioxide aggregate was used to seal one end of the tooth root segment, while the other was left open. Samples were cultured in vitro in osteogenic media (OM) for 13 d and then implanted subcutaneously in nude rats for 4 and 8 wk. At least 5 sample replicates were used for each experimental group. Analyses of harvested samples found that robust pulp-like tissues formed in G1, GelMA encapsulated hDPSC/HUVEC-filled RSs, and less cellularized host cell–derived pulp-like tissue was observed in the G2 acellular GelMA and G3 empty RS groups. Of importance, only the G1, hDPSC/HUVEC-encapsulated GelMA constructs formed pulp cells that attached to the inner dentin surface of the RS and infiltrated into the dentin tubules. Immunofluorescent (IF) histochemical analysis showed that GelMA supported hDPSC/HUVEC cell attachment and proliferation and also provided attachment for infiltrating host cells. Human cell-seeded GelMA hydrogels promoted the establishment of well-organized neovasculature formation. In contrast, acellular GelMA and empty RS constructs supported the formation of less organized host-derived vasculature formation. Together, these results identify GelMA hydrogel combined with hDPSC/HUVECs as a promising new clinically relevant pulpal revascularization treatment to regenerate human dental pulp tissues.
Primary intestinal lymphangiectasia is an exceedingly rare disorder. Epidemiology is unknown. It usually presents with lower extremity swelling, diarrhea, ascites, and protein-losing enteropathy. ...Since the pathogenesis of edema is usually due to hypoalbuminemia; both extremities are typically involved. The edema can rarely be due to abnormal lymphatic circulation, causing lymphedema, which usually involves both extremities as well. Diagnosis is made by the constellation of clinical, biochemical, endoscopic, and histological findings. Treatment involves dietary modification, to reduce lymphatic dilation in response to dietary fat. Other pharmacologic (e.g., octreotide) and replacement measures may be indicated as well. The most serious long-term complication is intestinal lymphoma. Herein is a case of Primary intestinal lymphangiectasia presenting with unilateral lower limb swelling.
A 4-year-old boy presents with left foot swelling since the age of 4 months, in addition to intermittent diarrhea, and abdominal swelling. The foot swelling had been evaluated by different health care professionals in the past, and was mislabeled as either cellulitis, or congenital hemihyperplasia. Physical examination revealed mild ascites, and a non-pitting foot edema with a positive Stemmer's sign (lymphedema). Blood work revealed hypoalbuminemia (albumin 2 g/dl), and hypogammaglobulinemia. Endoscopy showed dilated lacteals throughout the duodenum. Histopathologic examination revealed massively dilated lamina propria lymphatics in the duodenal biopsies. The patient was diagnosed with primary intestinal lymphangiectasia. He was treated with high-protein and low-fat diet, and supplemental formula high in medium chain triglycerides. On follow-up, the patient's diarrhea completely resolved, and his ascites and edema improved significantly.
The presence of unilateral lower limb edema should not preclude the diagnosis of systemic disorders, and a high index of suspicion is required in atypical presentations. A good knowledge about Primary intestinal lymphangiectasia manifestations, and physical examination skills to differentiate edema or lymphedema from tissue overgrowth can significantly aid in the diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mars Science Laboratory Curiosity rover observations of the 2018/Mars year 34 global/planet-encircling dust storm represent the first in situ measurements of a global dust storm with dedicated ...meteorological sensors since the Viking Landers. The Mars Science Laboratory team planned and executed a science campaign lasting approximately 100 Martian sols to study the storm involving an enhanced cadence of environmental monitoring using the rover's meteorological sensors, cameras, and spectrometers. Mast Camera 880-nanometer optical depth reached 8.5, and Rover Environmental Monitoring Station measurements indicated a 97 percent reduction in incident total ultraviolet solar radiation at the surface, 30 degrees Kelvin reduction in diurnal range of air temperature, and an increase in the semidiurnal pressure tide amplitude to 40 pascals. No active dust-lifting sites were detected within Gale Crater, and global and local atmospheric dynamics were drastically altered during the storm. This work presents an overview of the mission's storm observations and initial results.
The hyperarid mangrove in the Middle East is characterised by the absence of rivers or freshwater inputs and is one of the most extreme settings of this ecosystem on Earth. Endemic to Qatar's ...hyperarid mangroves, a Palaemon shrimp is uniquely confined to a sole mangrove site in the Arabian Gulf. Within these mangrove channels, we unveiled brine groundwater sources exceeding 70 ppt salinity, contrasting the local marine standard of 42 ppt. Concurrently, a mysid species typically linked to salt pans and groundwater coexists. Stable isotopic analysis implied the existence of a predator-prey dynamic between this mysid species and the studied shrimp. Then, investigating the endemic shrimp's adaptation to extreme salinity, we conducted osmolarity experiments and phylogenetic studies. Our findings demonstrate that this shrimp transitions from hypo- to hyper-osmoregulation, tolerating salinities from 18 to 68 ppt-an unprecedented osmoregulatory capacity among caridean shrimps. This speciation pattern likely arises from the species osmolarity adaptation, as suggested for other Palaemon congeners. Phylogenetic analysis of the studied Palaemon, along with the mangrove's geological history, suggests a profound evolutionary interplay between the ecosystem and the shrimp since the Eocene. This study proposes the hyperarid mangrove enclave as an Athalassic mangrove oasis-a distinctive, isolated ecosystem within the desert landscape.
A simple and efficient numerical procedure using a singularity cancellation scheme is presented for evaluating singular and near-singular potential integrals with 1/R singularities. The procedure not ...only has several advantages over singularity subtraction methods, but also improves on some aspects of other singularity cancellation methods such as polar and Duffy transformations. A theoretical analysis is presented for triangles, quadrilaterals, tetrahedrons, bricks, and prisms, and numerical results are presented for triangles and prisms.
Of all the myosin filaments in muscle, the most important in terms of human health, and so far the least studied, are those in the human heart. Here we report a 3D single-particle analysis of ...electron micrograph images of negatively stained myosin filaments isolated from human cardiac muscle in the normal (undiseased) relaxed state. The resulting 28-Å resolution 3D reconstruction shows axial and azimuthal (no radial) myosin head perturbations within the 429-Å axial repeat, with rotations between successive 132 Å-, 148 Å-, and 149 Å-spaced crowns of heads close to 60°, 35°, and 25° (all would be 40° in an unperturbed three-stranded helix). We have defined the myosin head atomic arrangements within the three crown levels and have modeled the organization of myosin subfragment 2 and the possible locations of the 39 Å-spaced domains of titin and the cardiac isoform of myosin-binding protein-C on the surface of the myosin filament backbone. Best fits were obtained with head conformations on all crowns close to the structure of the two-headed myosin molecule of vertebrate chicken smooth muscle in the dephosphorylated relaxed state. Individual crowns show differences in head-pair tilts and subfragment 2 orientations, which, together with the observed perturbations, result in different intercrown head interactions, including one not reported before. Analysis of the interactions between the myosin heads, the cardiac isoform of myosin-binding protein-C, and titin will aid in understanding of the structural effects of mutations in these proteins known to be associated with human cardiomyopathies.
► A comprehensive search for organics and trace species on Mars. ► For most of the targeted species we derived the most stringent upper limits ever obtained. ► We sampled the same regions where ...plumes of methane have been recently observed.
Is Mars actively releasing organic and other minor gases into the atmosphere? We present a comprehensive search for trace species on Mars, targeting multiple volatile organic species (CH4, CH3OH, H2CO, C2H6, C2H2, C2H4), hydroperoxyl (HO2), several nitrogen compounds (N2O, NH3, HCN), and two chlorine species (HCl, CH3Cl) through their rovibrational spectra in the 2.8–3.7μm spectral region. The data were acquired over a period of 4years (2006–2010) using powerful infrared high-resolution spectrometers (CRIRES, NIRSPEC, CSHELL) at high-altitude observatories (VLT, Keck-2, NASA-IRTF), and span a broad range of seasons, Doppler shifts and spatial coverage. Here, we present results from a selection of high-quality spectra obtained on four separate dates, representing a fraction of our search space. For most of these species we derived the most stringent upper limits ever obtained, and because the targeted gases have substantially different resident lifetimes in the Martian atmosphere (from hours to centuries), our measurements not only test for current release but also provide stringent limits on the quiescent levels. In particular, we sampled the same regions where plumes of methane have been recently observed (e.g., Syrtis Major and Valles Marineris), allowing us to test for seasonal and temporal variability.
The Nadir and Occultation for MArs Discovery (NOMAD)/UV‐visible (UVIS) spectrometer on the ExoMars Trace Gas Orbiter provided observations of ozone (O3) and water vapor in the global dust storm of ...2018. Here we show in detail, using advanced data filtering and chemical modeling, how Martian O3 in the middle atmosphere was destroyed during the dust storm. In data taken exactly 1 year later when no dust storm occurred, the normal situation had been reestablished. The model simulates how water vapor is transported to high altitudes and latitudes in the storm, where it photolyzes to form odd hydrogen species that catalyze O3. O3 destruction is simulated at all latitudes and up to 100 km, except near the surface where it increases. The simulations also predict a strong increase in the photochemical production of atomic hydrogen in the middle atmosphere, consistent with the enhanced hydrogen escape observed in the upper atmosphere during global dust storms.
Plain Language Summary
Global dust storms are rare but impactful events on Mars, occurring about once in a decade. Previous investigations found how water vapor is redistributed throughout the entire atmosphere in a dust storm. Photolysis of water vapor by sunlight produces highly reactive species that destroy ozone (O3). Here we present O3 measurements taken by the NOMAD/UVIS instrument on the ExoMars Trace Gas Orbiter in the 2018 global dust storm. After advanced data filtering, they demonstrate how O3 in the middle atmosphere was much reduced compared to one Mars year later when no dust storm occurred. 3D atmospheric model simulations of atmospheric chemistry in the global dust storm confirm this planet‐wide O3 destruction, and help to understand the involved processes. The simulations also predict a strong increase in production of atomic hydrogen in the middle atmosphere, that can explain the observed increased hydrogen atmospheric escape during global dust storms.
Key Points
NOMAD ozone (O3) data filtering during the 2018 global dust storm shows strong O3 destruction compared to one year later with no dust storm
3D simulations of atmospheric chemistry in the 2018 global dust storm are presented to understand impact on odd hydrogen and odd oxygen
The model confirms middle‐atmospheric O3 destruction in the dust storm and predicts increased photochemical production of hydrogen
Bifacial solar cells are receiving increased attention in the PV market due to their higher energy yield compared to conventional monofacial modules thanks to additional light conversion through ...their back surface. This additional rear side energy gain creates a potential for significant reduction of the overall levelized cost of energy (LCOE). Despite this fact, wide deployment of bifacial PV modules is very limited because of the high unpredictability of their power output due to various factors such as ground reflectance, module elevation angle, orientation and tilt angle. Due to this complexity, modelling of bifacial modules and systems is currently not developed at the same level of maturity as monofacial ones, where established commercial tools have been developed for PV system designers. In this regard, a customized 2D device model has been developed to simulate bifacial PV structures based on the numerical solution of the transport equations by the finite element method. The model was used to simulate actual PV performance and energy yield based on measured outdoor environmental parameters including solar radiation spectrum and temperature. Bifacial device output was also compared with a monofacial one based on the industrial standard Al-BSF structure. Simulated results were also compared and validated with outdoor experimental data based on IV measurements of monofacial and bifacial modules installed at various tilt angles at a location near the Western coast of Saudi Arabia.
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•A new customized 2D device simulator is developed.•Simulations of monofacial and bifacial PV structures are presented.•Climate characteristics of Middle East were taken into account in simulations.•Frequent hazy days in the Middle East favour bifacial devices over monofacial ones.•Bifacial device shows a gain of 10% and 15% when compared to the monofacial one.
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