CARIBBEAN DEMAND OF U.S. AND REST-OF-THE-WORLD STARCHY FOOD (WHEAT, RICE, CORN, AND FRESH POTATOES): A RESTRICTED SOURCE DIFFERENTIATED ALMOST IDEAL DEMAND SYSTEM

This study provides elasticity estimates of the Caribbean demand for U. S. and Rest-of-the-World starchy foods (unmilled wheat and flour, rice, corn and fresh potatoes) using the Restricted Source Differentiated Almost Ideal Demand System (RSDAIDS) model. Caribbean per capita import demand curves for U.S. and Rest-of-the-World (ROW) are own-price unitary elastic for U. S. wheat, and own-price inelastic for U.S. rice and ROW wheat and rice. The implication is that reductions by any means in U. S. or ROW export prices of wheat and rice will increase U.S. or ROW exported quantities in the Caribbean, while at the same time securing food security through import quantity in the Caribbean. Wheat is not produced in the Caribbean. U. S. wheat price policy oriented toward a reduction in the export price of wheat to the Caribbean may increase the U. S. wheat market share in the Caribbean. For wheat and rice, no competition across source exists. Instead, there exists a complementarity relationship across source for each of the two products. In other words, the Caribbean distinguishes between the wheat or rice coming from the U. S. and the wheat or rice coming from the Rest-of-the-World.Caribbean demand, elasticity estimates, food security, price policies, Restricted Source Differentiated Almost Ideal Demand System (RSDAIDS), starchy food, Food Consumption/Nutrition/Food Safety,

Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death

Sensing bacterial products in the cytosol of mammalian cells by NOD-like receptors leads to the activation of caspase-1 inflammasomes, and the production of the pro-inflammatory cytokines interleukin (IL)-18 and IL-1β. In addition, mouse caspase-11 (represented in humans by its orthologs, caspase-4 and caspase-5) detects cytosolic bacterial LPS directly. Activation of caspase-1 and caspase-11 initiates pyroptotic host cell death that releases potentially harmful bacteria from the nutrient-rich host cell cytosol into the extracellular environment. Here we use single cell analysis and time-lapse microscopy to identify a subpopulation of host cells, in which growth of cytosolic Salmonella Typhimurium is inhibited independently or prior to the onset of cell death. The enzymatic activities of caspase-1 and caspase-11 are required for growth inhibition in different cell types. Our results reveal that these proteases have important functions beyond the direct induction of pyroptosis and proinflammatory cytokine secretion in the control of growth and elimination of cytosolic bacteria

The Epstein-Barr Virus Episome Maneuvers between Nuclear Chromatin Compartments during Reactivation.

The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts on the EBV side localize to OriP, the latent origin of replication. This genetic element and the EBNA1 protein that binds there are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts on the human side localize to gene-poor and AT-rich regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of myriad interchromosomal associations also suggests a role for this type of long-range association in gene regulation.IMPORTANCE The human genome is structurally organized in three-dimensional space, and this structure functionally affects transcriptional activity. We set out to investigate whether a double-stranded DNA virus, Epstein-Barr virus (EBV), uses mechanisms similar to those of the human genome to regulate transcription. We found that the EBV genome associates with repressive compartments of the nucleus during latency and with active compartments during reactivation. This study advances our knowledge of the EBV life cycle, adding three-dimensional relocalization as a novel component to the molecular events that occur during reactivation. Furthermore, the data add to our understanding of nuclear compartments, showing that disperse interchromosomal interactions may be important for regulating transcription

Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

A Bound Quantum Particle in a Riemann-Cartan space with Topological Defects and Planar Potential

Starting from a continuum theory of defects, that is the analogous to three-dimensional Einstein-Cartan-Sciama-Kibble gravity, we consider a charged particle with spin 1/2 propagating in a uniform magnetic field coincident with a wedge dispiration of finite extent. We assume the particle is bound in the vicinity of the dispiration by long range attractive (harmonic) and short range (inverse square) repulsive potentials. Moreover, we consider the effects of spin-torsion and spin-magnetic field interactions. Exact expressions for the energy eigenfunctions and eigenvalues are determined. The limit, in which the defect region becomes singular, is considered and comparison with the electromagnetic Aharonov-Bohm effect is made.Comment: 10 page

Homogeneous distribution of Fe isotopes in the early solar nebula

International audienceTo examine the iron (Fe) isotopic heterogeneities of CI and ordinary chondrites, we have analyzed several large chips (approximately 1 g) from three CI chondrites and three ordinary chondrites (LL5, L5, and H5). The Fe isotope compositions of five different samples of Orgueil, one from Ivuna and one from Alais (CI chondrites), are highly homogeneous. This new dataset provides a δ56Fe average of 0.02 ± 0.04‰ (2SE, n = 7), which represents the best available value for the Fe isotopic composition of CI chondrites and probably the best estimate of the bulk solar system. We conclude that the homogeneity of CI chondrites reflects the initial Fe isotopic homogeneity of the well-mixed solar nebula. In contrast, larger (up to 0.26‰ in δ56Fe) isotopic variations have been found between separate approximately 1 g pieces of the same ordinary chondrite sample. The Fe isotope heterogeneities in ordinary chondrites appear to be controlled by the abundances of chondritic components, specifically chondrules, whose Fe isotope compositions have been fractionated by evaporation and recondensation during multiple heating events

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro