Cystic kidney disease is a leading cause of morbidity in patients with tuberous sclerosis complex (TSC). We characterize the misregulated metabolic pathways using cell lines, a TSC mouse model, and human kidney sections. Our study reveals a substantial perturbation in the arginine biosynthesis pathway in TSC models with overexpression of argininosuccinate synthetase 1 (ASS1). The rise in ASS1 expression is dependent on the mechanistic target of rapamycin complex 1 (mTORC1) activity. Arginine depletion prevents mTORC1 hyperactivation and cell cycle progression and averts cystogenic signaling overexpression of c-Myc and P65. Accordingly, an arginine-depleted diet substantially reduces the TSC cystic load in mice, indicating the potential therapeutic effects of arginine deprivation for the treatment of TSC-associated kidney disease.
Deciphering aspect-related hillslope asymmetry can enhance our understanding of the influence of climate on Earth’s surface morphology and the linkage between topographic morphology and erosion processes. Although hillslope asymmetry is documented worldwide, the role of microclimatic factors in the evolution of dryland cliffs has received little attention. Here, we address this gap by quantifying aspect-dependent bedrock weathering, slope-rill morphology, and subcliff clast transport rates in the hyperarid Negev desert, Israel, based on light detection and ranging (LiDAR)-derived topography, clast-size measurements, and cosmogenic 10Be concentrations. Cliff retreat rates were evaluated using extrapolated profiles from dated talus flatirons and 10Be measurements from the cliff face and sub-cliff sediments. We document systematic, aspect-dependent patterns of south-facing slopes being less steep and finer-grained relative to east and north-facing aspects. In addition, cliff retreat and clast transport rates on slopes of the south-facing aspect are faster compared to the other aspects. Our data demonstrate that bedrock weathering of the cliff face and the corresponding grain size of cliff-derived clasts delivered to the slopes constitute a first-order control on cliff retreat and sediment transport rates. We demonstrate that the morphology of the cliff and the pattern of bedrock weathering co-vary with the solar radiation flux and hence that cliff evolution in hyperarid regions is modulated by aspectdependent solar radiation. These results help to better understand interactions between climate and dryland surface processes.
Deciphering aspect-related hillslope asymmetry can enhance our understanding of the influence of climate on Earth's surface morphology and the linkage between topographic morphology and erosion processes. Although hillslope asymmetry is documented worldwide, the role of microclimatic factors in the evolution of dryland cliffs has received little attention. Here, we address this gap by quantifying aspect-dependent bedrock weathering, slope-rill morphology, and subcliff clast transport rates in the hyperarid Negev desert, Israel, based on light detection and ranging (LiDAR)-derived topography, clast-size measurements, and cosmogenic 10Be concentrations. Cliff retreat rates were evaluated using extrapolated profiles from dated talus flatirons and 10Be measurements from the cliff face and sub-cliff sediments. We document systematic, aspect-dependent patterns of south-facing slopes being less steep and finer-grained relative to east and north-facing aspects. In addition, cliff retreat and clast transport rates on slopes of the south-facing aspect are faster compared to the other aspects. Our data demonstrate that bedrock weathering of the cliff face and the corresponding grain size of cliff-derived clasts delivered to the slopes constitute a first-order control on cliff retreat and sediment transport rates. We demonstrate that the morphology of the cliff and the pattern of bedrock weathering co-vary with the solar radiation flux and hence that cliff evolution in hyperarid regions is modulated by aspectdependent solar radiation. These results help to better understand interactions between climate and dryland surface processes.
Fragile X mental retardation protein (FMRP) binds a selected set of mRNAs and proteins to guide neural circuit assembly and regulate synaptic plasticity. Loss of FMRP is responsible for Fragile X syndrome, a neuropsychiatric disorder characterized with auditory processing problems and social difficulty. FMRP actions in synaptic formation, maturation, and plasticity are site-specific among the four compartments of a synapse: presynaptic and postsynaptic neurons, astrocytes, and extracellular matrix. This review summarizes advancements in understanding FMRP localization, signals, and functional roles in axons and presynaptic terminals.
Nigerian playwright and Nobel laureate Wole Soyinka wrote the Jero plays (The Trials of Brother Jero and Jero’s Metamorphosis) thirteen years apart, and they shed light on the distresses of a society in transition from colony to postcolony. Philosopher Achille Mbembe describes the postcolony as a site of high levels of corruption and appropriation of wealth by a ruling elite, a place where colonial rules linger and disrupt the workings of the state. Characterized by a distinctive style of political improvisation defined by excess and a lack of proportion, in the postcolony, regimes of violence are prone to celebrating their own grandeur through macabre public events such as executions. Soyinka satirizes the protagonist of the Jero plays, a Machiavellian con artist who wraps himself in the cloak of Pentecostal Born-Again Christianity, for using blackmail and grift to secure a profitable spiritual monopoly on Bar Beach (to say prayers before and after each execution, to administer last rites, and to preach on the evils of crime). Through depictions of venality at every level of society, the Jero plays illustrate the difficulty of eradicating colonial legacies and demonstrate the deleterious effects of entrenched social and political corruption on daily life in the postcolony.
March 2023: Mark S. Ferrara is associate professor of English at State University of New York and author of six books including Palace of Ashes, Sacred Bliss, and American Community. He has taught for universities in South Korea, China, and on a Fulbright scholarship in Turkey.
The East Mediterranean Sea (EMS) circulation has previously been characterized as dominated by gyres, mesoscale eddies, and disjoint boundary currents. We develop nested high resolution EMS numerical simulations to examine circulation variability spectrum with emphasis on the yet unexplored EMS submesoscale. It is identified in model and altimetry data that there is a continuous cyclonic boundary current (BC) encircling the Levantine basin, rather than several disjoint currents. This EMS BC advects eddy chains downstream and is identified as a principle source of regional mesoscale and submesoscale variability. During the seasonal fall to winter mixed layer deepening, energetic submesoscale (O(10 km)) eddies, fronts, and filaments emerge throughout the basin, characterized by O(1) Rossby numbers.
We identify the EMS submesoscale temporal scales as ~1-5 days through spatio-temoral spectral analysis. Mooring data confirms the EMS winter energization of submesoscales with the model-identified times scales. The submesoscale is associated with a ~ k-2 kinetic energy (KE) wavenumber (k) spectral slope, shallower than the quasigeostrophic-like ~ k-3 slope diagnosed at summer. The shallowness of the winter spectrum is shown to be due to divergent subinertial motions, consistent with the Boyd 1992 theoretical model rather than surface quasigeostrophy. Using coarse graining, we diagnose a seasonal inverse (forward) KE cascade above (below) 30 km scales due to rotational (divergent) motions, and show that these commence after completion of the fall submesosacle energization. We also show via coarse graining that at scales larger than several 100 kms, the spectrum becomes near constant and a weak forward cascade occurs (from gyre scales) to mesoscales.
The ties that bind the Greco-Roman and Hebrew cultures together are strong and convoluted, from as early as their beginnings in ancient times. This chapter deals with the encounter of modern Hebrew poetry with the Greco-Roman classical tradition, situating it in the polarized relations between the two cultures, as well as in their close and symbiotic interactions. Complex historical residues played a role in the relatively belated reception of Greco-Roman classical elements in modern Hebrew literature. And while Greco-Roman elements contributed to the shaping of Hebrew literature as part of modern European culture, they were not integrated deeply into it. It was only after the Second World War that a window of opportunity for a common cross-cultural destiny opened up, when Hebrew writers saw the shared platform of the two cultures as a bulwark against fascism. At the same time, the belatedness in the reception of elements of the Greco-Roman classical tradition in Hebrew poetry prevented them from being “eroded”, as it were, by the Biblical corpus (the main point of reference of Hebrew literature) – by becoming, for example, objects of irony or parody.
IntroductionBeta-glucans are known as biological response modifiers due to their ability to activate the immune system. This research aimed to determine the efficacy and safety of feeding beta-glucans from various sources on the immune status and intestinal morphology of chickens.MethodsTo this end we used in vitro and in vivo set-ups. In the in vitro set-up the chicken macrophage cell line HD-11 was used to measure the response of the chicken immune cells to beta-glucans extracted from algae and mushrooms on immune-related gene expression and associated activities. Additionally, we conducted two in vivo experiments using either beta-glucans extracted from yeast or mix of yeast and mushrooms beta-glucans as part of the chicks feed in order to test their effects on the chick intestinal morphology.ResultsIn the in vitro set-up exposure of HD-11 cells to a concentration of 1 mg/ml of algae and mushroom beta-glucans resulted in significantly higher expression of 6 genes (TNFα, IL4, IL6, IL8, IL10, and iNOS2) compared to control. The release of nitrite oxide (NO) to the medium after exposure of HD-11 cells to mushrooms or algae beta-glucans was significantly increased compared to control. Additionally, significantly increased phagocytosis activity was found after exposure of the cells to algae and mushroom beta-glucans. In the in vivo set-up we observed that the length of the villi and the number of goblet cells in the ileum and the jejunum in the beta-glucan fed chicks were significantly augmented compared to control, when the chicks were fed with either yeast or yeast and mushroom beta-glucans mix.DiscussionIn conclusion, dietary supplementation of poultry with beta-glucan exerts significant and positive effects on immune activity and the intestinal morphology in poultry.
In this paper, we propose a new strategy for classifying evaluations in large text corpora, using supervised machine learning (SML). Departing from a conceptual and methodological critique of the use of sentiment measures to recognize object-specific evaluations, we argue that a key challenge consists in determining whether a semantic relationship exists between evaluative expressions and evaluated objects. Regarding sentiment terms as merely potentially evaluative expressions, we thus use a SML classifier to decide whether recognized terms have an evaluative function in relation to the evaluated object. We train and test our classifier on a corpus of 10,004 segments of election coverage from 16 major U.S. news outlets and Tweets by 10 prominent U.S. politicians and journalists. Specifically, we focus on evaluations of political predictions about the outcomes and implications of the 2016 and 2020 U.S. presidential elections. We show that our classifier consistently outperforms both off-the-shelf sentiment tools and a pre-trained transformer-based sentiment classifier. Critically, our classifier correctly discards numerous non-evaluative uses of common sentiment terms, whose inclusion in conventional analyses generates large amounts of false positives. We discuss contributions of our approach to the measurement of object-specific evaluations and highlight challenges for future research.
