Adaptive Immunity Alters Distinct Host Feeding Pathways during Nematode Induced Inflammation,a Novel Mechanism in Parasite Expulsion

Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.     

Fragmented Perception: Slower Space-Based but Faster Object-Based Attention in Recent-Onset Psychosis with and without Schizophrenia

Background

Schizophrenia is associated with impairments of the perception of objects, but how this affects higher cognitive functions, whether this impairment is already present after recent onset of psychosis, and whether it is specific for schizophrenia related psychosis, is not clear. We therefore tested the hypothesis that because schizophrenia is associated with impaired object perception, schizophrenia patients should differ in shifting attention between objects compared to healthy controls. To test this hypothesis, a task was used that allowed us to separately observe space-based and object-based covert orienting of attention. To examine whether impairment of object-based visual attention is related to higher order cognitive functions, standard neuropsychological tests were also administered.

Method

Patients with recent onset psychosis and normal controls performed the attention task, in which space- and object-based attention shifts were induced by cue-target sequences that required reorienting of attention within an object, or reorienting attention between objects.

Results

Patients with and without schizophrenia showed slower than normal spatial attention shifts, but the object-based component of attention shifts in patients was smaller than normal. Schizophrenia was specifically associated with slowed right-to-left attention shifts. Reorienting speed was significantly correlated with verbal memory scores in controls, and with visual attention scores in patients, but not with speed-of-processing scores in either group.

Conclusions

deficits of object-perception and spatial attention shifting are not only associated with schizophrenia, but are common to all psychosis patients. Schizophrenia patients only differed by having abnormally slow right-to-left visual field reorienting. Deficits of object-perception and spatial attention shifting are already present after recent onset of psychosis. Studies investigating visual spatial attention should take into account the separable effects of space-based and object-based shifting of attention. Impaired reorienting in patients was related to impaired visual attention, but not to deficits of processing speed and verbal memory.     

The Oxytricha trifallax Macronuclear Genome: A Complex Eukaryotic Genome with 16,000 Tiny Chromosomes

The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction (∼5%) of its precursor “silent” germline micronuclear genome by a process of “unscrambling” and fragmentation. The tiny macronuclear “nanochromosomes” typically encode single, protein-coding genes (a small portion, 10%, encode 2–8 genes), have minimal noncoding regions, and are differentially amplified to an average of ∼2,000 copies. We report the high-quality genome assembly of ∼16,000 complete nanochromosomes (∼50 Mb haploid genome size) that vary from 469 bp to 66 kb long (mean ∼3.2 kb) and encode ∼18,500 genes. Alternative DNA fragmentation processes ∼10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is ∼4.0%), suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb) suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing studies of rearrangements arising during evolution and disease.     

Comparative effects of cytokines and cytokine combinations on complement component C3 secretion by HepG2 cells

The mechanisms that control complement protein synthesis are incompletely understood. Recent evidence suggests that cytokines are involved in the regulation of hepatic synthesis of circulating complement components. Therefore, we compared the effects of human recombinant IL-1alpha, IL-1beta, IL-6, IFN-gamma, and TNF-alpha individually or in combination, on HepG2 secretion of complement component C3, the major opsonic protein of the complement system. HepG2 cells were incubated with each cytokine alone and with various combinations of the cytokines. At 24, 48, 72, and 96 h of incubation, the C3 and albumin secreted by the HepG2 cells were quantified by a sandwich ELISA. IL-1alpha and IFN-gamma significantly enhanced C3 secretion by the cells (P<0.02 vs. control cells). IL-1beta when combined with either IL-6 or IFN-gamma also increased C3 secretion (P<0.03 vs. control cells). The stimulatory effect on HepG2 cells by the IL-1beta/IL-6 combination was synergistic. With the exception of IL-1alpha, which increased albumin secretion, HepG2 secretion of albumin was not affected by incubation with individual cytokines or the cytokine combinations. Therefore, IL-1alpha, IFN-gamma, and the combination of IL-1beta with IL-6 or IFN-gamma specifically enhanced C3 secretion by HepG2 cells. The greatest magnitude of C3 secretion was induced by the combination of IL-1beta and IL-6.     

DACH1 inhibits transforming growth factor-beta signaling through binding Smad4

The vertebrate homologues of Drosophila dachsund, DACH1 and DACH2, have been implicated as important regulatory genes in development. DACH1 plays a role in retinal and pituitary precursor cell proliferation and DACH2 plays a specific role in myogenesis. DACH proteins contain a domain (DS domain) that is conserved with the proto-oncogenes Ski and Sno. Since the Ski/Sno proto-oncogenes repress AP-1 and SMAD signaling, we hypothesized that DACH1 might play a similar cellular function. Herein, DACH1 was found to be expressed in breast cancer cell lines and to inhibit transforming growth factor-beta (TGF-beta)-induced apoptosis. DACH1 repressed TGF-beta induction of AP-1 and Smad signaling in gene reporter assays and repressed endogenous TGF-beta-responsive genes by microarray analyses. DACH1 bound to endogenous NCoR and Smad4 in cultured cells and DACH1 co-localized with NCoR in nuclear dotlike structures. NCoR enhanced DACH1 repression, and the repression of TGF-beta-induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain. The DS domain of DACH was sufficient for NCoR binding at a Smad4-binding site. Smad4 was required for DACH1 repression of Smad signaling. In Smad4 null HTB-134 cells, DACH1 inhibited the activation of SBE-4 reporter activity induced by Smad2 or Smad3 only in the presence of Smad4. DACH1 participates in the negative regulation of TGF-beta signaling by interacting with NCoR and Smad4.     

Hyperscums and the population dynamics of Microcystis aeruginosa

Conceptual models, based on 7 years of data, are constructedto simulate the annual cycle and population dynamics of Microcystisaeruginosa in hypertrophic, warm monomictic Hartbees-poort Dam,South Africa in order to assess the role of hyperscum formation.In Hartbeespoort Dam the large summer planktonic population(mean epilimnion biovolumes of 20–50 mm³ I^–1) andthe low wind speed resulted in the formation of hyperscums (thick,crusted accumulations of floating cyanobacteria at wind-protectedsites) containing up to 50% of the total standing crop for 2–3months in 4 out of 5 years. In years in which hyperscums formedthe post-maximal summer population maintained itself throughoutautumn and into late winter before declining to the annual nadir(>1000 cells ml^–1). When hyperscums did not form, orwere artificially removed, the population fell to similarlylow levels as early as May (autumn) and remained small untilthe spring growth phase began. Microcystis cells decompose inthe upper layers of a hyperscum, but this is not a major lossto the planktonic population. Hyperscums are refuges which helpmaintain large planktonic standing crops during winter whengrowth is not possible but have no effect on the long-term (perennial)survival of Microcystis.     

Untargeted metabolomics reveals differences between commercial and non-commercial Camellia sinensis cultivars used in black tea production

Journal of Plant Biochemistry and Biotechnology - Tea (Camellia sinensis) has enthralled both consumers and researchers, due to its taste, aroma and its medicinal attributes. Tea consumers concern...     

Chlamydosporol,a new metabolite from Fusarium chlamydosporum

Extracts of rice on which an isolate of Fusarium chlamydosporum had been cultured were toxic to brine shrimps. The toxic fraction was purified by flash chromatography to give two compounds which were identified by UV, IR, NMR and mass spectroscopy at the 6 and 6 isomers of 5-hydroxy-4-methoxy-6, 8a-dimethyl-6,7-dihydro-2H,8aH-pyrano[2,3-b]pyran-2-one. These lactones for which the name chlamydosporol is proposed have not been reported previously. When tested in brine shrimp and HeLa cell assays, the LC₅₀ concentration for a mixture of the isomers was approximately 400 g/ml in both systems.