Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

Deformation-related volcanism in the Pacific Ocean linked to the Hawaiian-Emperor bend

Ocean islands, seamounts and volcanic ridges are thought to form above mantle plumes. Yet, this mechanism cannot explain many volcanic features on the Pacific Ocean floor and some might instead be caused by cracks in the oceanic crust linked to the reorganization of plate motions. A distinctive bend in the Hawaiian–Emperor volcanic chain has been linked to changes in the direction of motion of the Pacific Plate, movement of the Hawaiian plume, or a combination of both. However, these links are uncertain because there is no independent record that precisely dates tectonic events that affected the Pacific Plate. Here we analyse the geochemical characteristics of lava samples collected from the Musicians Ridges, lines of volcanic seamounts formed close to the Hawaiian–Emperor bend. We find that the geochemical signature of these lavas is unlike typical ocean island basalts and instead resembles mid-ocean ridge basalts. We infer that the seamounts are unrelated to mantle plume activity and instead formed in an extensional setting, due to deformation of the Pacific Plate. 40Ar/39Ar dating reveals that the Musicians Ridges formed during two time windows that bracket the time of formation of the Hawaiian–Emperor bend, 53–52 and 48–47 million years ago. We conclude that the Hawaiian–Emperor bend was formed by plate–mantle reorganization, potentially triggered by a series of subduction events at the Pacific Plate margins

Motor Unit Magnetic Resonance Imaging (MUMRI) In Skeletal Muscle

\ua9 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.Magnetic resonance imaging (MRI) is routinely used in the musculoskeletal system to measure skeletal muscle structure and pathology in health and disease. Recently, it has been shown that MRI also has promise for detecting the functional changes, which occur in muscles, commonly associated with a range of neuromuscular disorders. This review focuses on novel adaptations of MRI, which can detect the activity of the functional sub-units of skeletal muscle, the motor units, referred to as “motor unit MRI (MUMRI).” MUMRI utilizes pulsed gradient spin echo, pulsed gradient stimulated echo and phase contrast MRI sequences and has, so far, been used to investigate spontaneous motor unit activity (fasciculation) and used in combination with electrical nerve stimulation to study motor unit morphology and muscle twitch dynamics. Through detection of disease driven changes in motor unit activity, MUMRI shows promise as a tool to aid in both earlier diagnosis of neuromuscular disorders and to help in furthering our understanding of the underlying mechanisms, which proceed gross structural and anatomical changes within diseased muscle. Here, we summarize evidence for the use of MUMRI in neuromuscular disorders and discuss what future research is required to translate MUMRI toward clinical practice. Level of Evidence: 5. Technical Efficacy: Stage 3

Suppression of Lung Adenocarcinoma Progression by Nkx2-1

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limitsmetastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

Whole-body fasciculation detection in amyotrophic lateral sclerosis using motor unit MRI (MUMRI)

\ua9 2024 International Federation of Clinical NeurophysiologyObjective: Compare fasciculation rates between amyotrophic lateral sclerosis (ALS) patients and healthy controls in body regions relevant for diagnosing ALS using motor unit MRI (MUMRI) at baseline and 6 months follow-up, and relate this to single-channel surface EMG (SEMG). Methods: Tongue, biceps brachii, paraspinals and lower legs were assessed with MUMRI and biceps brachii and soleus with SEMG in 10 healthy controls and 10 patients (9 typical ALS, 1 primary lateral sclerosis [PLS]). Results: MUMRI-detected fasciculation rates in typical ALS patients were higher compared to healthy controls for biceps brachii (2.40 \ub1 1.90 cm-3min−1 vs. 0.04 \ub1 0.10 cm-3min−1, p = 0.004), paraspinals (1.14 \ub1 1.61 cm-3min−1 vs. 0.02 \ub1 0.02 cm-3min−1, p = 0.016) and lower legs (1.42 \ub1 1.27 cm-3min−1 vs. 0.13 \ub1 0.10 cm-3min−1, p = 0.004), but not tongue (1.41 \ub1 1.94 cm-3min−1 vs. 0.18 \ub1 0.18 cm-3min−1, p = 0.556). The PLS patient showed no fasciculation. At baseline, 6/9 ALS patients had increased fasciculation rates compared to healthy controls in at least 2 body regions. At follow-up every patient had increased fasciculation rates in at least 2 body regions. The MUMRI-detected fasciculation rate correlated with SEMG-detected fasciculation rates (τ = 0.475, p = 0.006). Conclusion: MUMRI can non-invasively image fasciculation in multiple body regions and appears sensitive to disease progression in individual patients. Significance: MUMRI has potential as diagnostic tool for ALS

The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis

The Triggering Receptors Expressed on Myeloid cells (TREM) are a family of cell-surface molecules that control inflammation, bone homeostasis, neurological development and blood coagulation. TREM-1 and TREM-2, the best-characterized receptors so far, play divergent roles in several infectious diseases. In the intestine, TREM-1 is highly expressed by macrophages, contributing to inflammatory bowel disease (IBD) pathogenesis. Contrary to current understanding, TREM-2 also promotes inflammation in IBD by fueling dendritic cell functions. This review will focus specifically on recent insights into the role of TREM proteins in IBD development, and discuss opportunities for novel treatment approaches

Geographic variation in plant community structure of salt marshes: species, functional and phylogenetic perspectives.

In general, community similarity is thought to decay with distance; however, this view may be complicated by the relative roles of different ecological processes at different geographical scales, and by the compositional perspective (e.g. species, functional group and phylogenetic lineage) used. Coastal salt marshes are widely distributed worldwide, but no studies have explicitly examined variation in salt marsh plant community composition across geographical scales, and from species, functional and phylogenetic perspectives. Based on studies in other ecosystems, we hypothesized that, in coastal salt marshes, community turnover would be more rapid at local versus larger geographical scales; and that community turnover patterns would diverge among compositional perspectives, with a greater distance decay at the species level than at the functional or phylogenetic levels. We tested these hypotheses in salt marshes of two regions: The southern Atlantic and Gulf Coasts of the United States. We examined the characteristics of plant community composition at each salt marsh site, how community similarity decayed with distance within individual salt marshes versus among sites in each region, and how community similarity differed among regions, using species, functional and phylogenetic perspectives. We found that results from the three compositional perspectives generally showed similar patterns: there was strong variation in community composition within individual salt marsh sites across elevation; in contrast, community similarity decayed with distance four to five orders of magnitude more slowly across sites within each region. Overall, community dissimilarity of salt marshes was lowest on the southern Atlantic Coast, intermediate on the Gulf Coast, and highest between the two regions. Our results indicated that local gradients are relatively more important than regional processes in structuring coastal salt marsh communities. Our results also suggested that in ecosystems with low species diversity, functional and phylogenetic approaches may not provide additional insight over a species-based approach