A 13-year-old female presented with recurrent, right-sided abdominal pain since the age of 2 years. Examination showed a tender, cylindric mass in the right lower quadrant. Ultrasound and MRI ...revealed an ileocolic intussusception. On laparotomy, there was an ileo-ileal intussusception due to a 3.8-cm polypoid tumor about 40 cm proximal to the ileocoecal valve. Histology showed polypoid heterotopic gastric mucosa with no Meckel's diverticulum. To our knowledge, only 12 cases of intussusception of heterotopic gastric mucosa in the ileum without Meckel's diverticulum have been reported in literature. This case adds to this small list and represents a possible cause of intussusception.
Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with ...autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy.
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•Viruses induce depressive behavior and ISG15 expression at the blood-brain barrier•IFNAR1 expression on neural cells is not involved in IFN-β-induced sickness behavior•IFNAR1 expression on brain endothelial and epithelial cells drives behavioral changes•Brain endothelia- and epithelia-derived CXCL10 inhibits hippocampal synaptic plasticity
Sickness behavior and cognitive dysfunction occur frequently during RNA virus infection by unknown mechanisms. Prinz and colleagues show that virus-induced sickness behavior is induced by interferon receptor chain 1 (IFNAR1) engagement on brain endothelial and epithelial cells that in turn influence neuronal signaling to drive cognitive impairment and depression-like behavior.
Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague ...was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Many intracellular signal-transduction pathways are regulated by specific protein-protein interactions. These interactions are mediated by structural domains within signaling proteins ...that modulate a protein's cellular location, stability or activity. For example, Src-homology 2 (SH2) domains mediate protein-protein interactions through short contiguous amino acid motifs containing phosphotyrosine. As SH2 domains have been recognized as key regulatory molecules in a variety of cellular processes, they have become attractive drug targets.
Results: We have developed a novel mechanism-based cellular assay to monitor specific SH2-domain-dependent protein-protein interactions. The assay is based on a two-hybrid system adapted to function in mammalian cells where the SH2 domain ligand is phosphorylated, and binding to a specific SH2 domain can be induced and easily monitored. As examples, we have generated a series of mammalian cell lines that can be used to monitor SH2-domain-dependent activity of the signaling proteins ZAP-70 and Src. We are utilizing these cell lines to screen for immunosuppressive and anti-osteoclastic compounds, respectively, and demonstrate here the utility of this system for the identification of small-molecule, cell-permeant SH2 domain inhibitors.
Conclusions: A mechanism-based mammalian cell assay has been developed to identify inhibitors of SH2-domain-dependent protein-protein interactions. Mechanism-based assays similar to that described here might have general use as screens for cell-permeant, nontoxic inhibitors of protein-protein interactions.
Among 80 rural Swazi children tested upon entrance to formal schooling, those whose fathers were absent for long periods because of work migration had significantly lower scores on school readiness ...tests than did children with fathers at home. Results were not related to sex of child or family socioeconomic status. (SV)
We present recent results on the use of Chemical Vapor Deposition (CVD) diamond microstrip detectors for charged particle tracking. A series of detectors was fabricated using 1 x 1 cm
2 diamonds. ...Good signal-to-noise ratios were observed using both slow and fast readout electronics. For slow readout electronics, 2 μs shaping time, the most probable signal-to-noise ratio was 50 to 1. For fast readout electronics, 25 ns peaking time, the most probable signal-to-noise ratio was 7 to 1. Using the first 2 x 4 cm
2 diamond from a production CVD reactor with slow readout electronics, the most probable signal-to-noise ratio was 23 to 1. The spatial resolution achieved for the detectors was consistent with the digital resolution expected from the detector pitch.
Identifying the nature and origin of dark matter is one of the major challenges for modern astro and particle physics. Direct dark-matter searches aim at an observation of dark-matter particles ...interacting within detectors. The focus of several such searches is on interactions with nuclei as provided e.g. by weakly interacting massive particles. However, there is a variety of dark-matter candidates favoring interactions with electrons rather than with nuclei. One example are dark photons, i.e., long-lived vector particles with a kinetic mixing to standard-model photons. In this work we present constraints on this kinetic mixing based on data from CRESST-II Phase 2 corresponding to an exposure before cuts of 52 kg-days. These constraints improve the existing ones for dark-photon masses between 0.3 and 0.7 keV/c
2
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Models for light dark matter particles with masses below 1 GeV/c
2
are a natural and well-motivated alternative to so-far unobserved weakly interacting massive particles. Gram-scale cryogenic ...calorimeters provide the required detector performance to detect these particles and extend the direct dark matter search program of CRESST. A prototype 0.5 g sapphire detector developed for the
ν
-cleus experiment has achieved an energy threshold of
E
t
h
=
(
19.7
±
0.9
)
eV. This is one order of magnitude lower than for previous devices and independent of the type of particle interaction. The result presented here is obtained in a setup above ground without significant shielding against ambient and cosmogenic radiation. Although operated in a high-background environment, the detector probes a new range of light-mass dark matter particles previously not accessible by direct searches. We report the first limit on the spin-independent dark matter particle-nucleon cross section for masses between 140 and 500 MeV/c
2
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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