Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis

Disrupted in schizophrenia 1 (DISC1) is a risk factor for a spectrum of neuropsychiatric illnesses including schizophrenia, bipolar disorder, and major depressive disorder. Here we use two missense Disc1 mouse mutants, described previously with distinct behavioural phenotypes, to demonstrate that Disc1 variation exerts differing effects on the formation of newly generated neurons in the adult hippocampus. Disc1 mice carrying a homozygous Q31L mutation, and displaying depressive-like phenotypes, have fewer proliferating cells while Disc1 mice with a homozygous L100P mutation that induces schizophrenia-like phenotypes, show changes in the generation, placement and maturation of newly generated neurons in the hippocampal dentate gyrus. Our results demonstrate Disc1 allele specific effects in the adult hippocampus, and suggest that the divergence in behavioural phenotypes may in part stem from changes in specific cell populations in the brain.     

An analysis of class I antigens of man and other species by one-dimensional IEF and immunoblotting

A procedure for the molecular identification of MHC class I products based on 1-D IEF and subsequent immunoblotting is described. Optimal conditions for 1-D IEF, the electrophoretic transfer of proteins out of denaturing, nonionic detergent-containing gels to nitrocellulose, and the requisite antibodies, both polyclonal and monoclonal, for the visualization of class I heavy chains have been established. Cross-reactivity of antibodies has enabled the biochemical analysis of class I heavy chains in the dog. The procedure reported here requires modest amounts of cells and allows a rapid molecular characterization of class I heavy chain polymorphisms in man and other species without the need for radiochemical methods.Abbreviations used in this paper FCS fetal calf serum - MHC major histocompatibility complex - NP-40 Nonidet P-40 - PBL peripheral blood lymphocytes - PHA phytohemagglutinin - RaHC rabbit anti-heavy chain serum - TX-114 Triton X-114 - 1-D IEF one-dimensional isoelectric focusing     

Hepatitis C Virus Induced miR200c Down Modulates FAP-1, a Negative Regulator of Src Signaling and Promotes Hepatic Fibrosis

Hepatitis C virus (HCV) induced liver disease is the leading indication for liver transplantation (LTx). Reinfection and accelerated development of fibrosis is a universal phenomenon following LTx. The molecular events that lead to fibrosis following HCV infection still remains poorly defined. In this study, we determined microRNA (miRNA) and mRNA expression profiles in livers from chronic HCV patients and normals using microarrays. Using Genego software and pathway finder we performed an interactive analysis to identify target genes that are modulated by miRNAs. 22 miRNAs were up regulated (>2 fold) and 35 miRNAs were down regulated (>2fold) compared to controls. Liver from HCV patients demonstrated increased expression of 306 genes (>3 fold) and reduced expression of 133 genes (>3 fold). Combinatorial analysis of the networks modulated by the miRNAs identified regulation of the phospholipase C pathway (miR200c, miR20b, and miR31through cellular proto-oncogene tyrosine-protein kinase Src (cSrc)), response to growth factors and hormones (miR141, miR107 and miR200c through peroxisome proliferator-activated receptor alpha and extracellular-signal-regulated kinases, and regulation of cellular proliferation (miR20b, miR10b, and miR141 through cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 p21). Real time PCR (RT-PCR) validation of the miRNA in HCV infected livers demonstrated a 3.3 ±0.9 fold increase in miR200c. In vitro transfection of fibroblasts with miR200c resulted in a 2.2 fold reduction in expression of tyrosine-protein phosphatase non-receptor type 13 or FAS associated phosphatase 1 (FAP-1) and 2.3 fold increase in expression of cSrc. miR200c transfection resulted in significant increases in expression of collagen and fibroblast growth factor (2.8 and 3.4 fold, p<0.05). Therefore, we propose that HCV induced increased expression of miR200c can down modulate the expression of FAP1, a critical regulator of Src and MAP kinase pathway that play an important role in the production of fibrogenic growth factors and development of fibrosis.     

Protein Disorder and Short Conserved Motifs in Disordered Regions Are Enriched near the Cytoplasmic Side of Single-Pass Transmembrane Proteins

Intracellular juxtamembrane regions of transmembrane proteins play pivotal roles in cell signalling, mediated by protein-protein interactions. Disordered protein regions, and short conserved motifs within them, are emerging as key determinants of many such interactions. Here, we investigated whether disorder and conserved motifs are enriched in the juxtamembrane area of human single-pass transmembrane proteins. Conserved motifs were defined as short disordered regions that were much more conserved than the adjacent disordered residues. Human single-pass proteins had higher mean disorder in their cytoplasmic segments than their extracellular parts. Some, but not all, of this effect reflected the shorter length of the cytoplasmic tail. A peak of cytoplasmic disorder was seen at around 30 residues from the membrane. We noted a significant increase in the incidence of conserved motifs within the disordered regions at the same location, even after correcting for the extent of disorder. We conclude that elevated disorder within the cytoplasmic tail of many transmembrane proteins is likely to be associated with enrichment for signalling interactions mediated by conserved short motifs.     

The need for co-product allocation in the life cycle assessment of agricultural systems—is “biophysical” allocation progress?

Purpose

Several new “biophysical” co-product allocation methodologies have been developed for LCA studies of agricultural systems based on proposed physical or causal relationships between inputs and outputs (i.e. co-products). These methodologies are thus meant to be preferable to established allocation methodologies such as economic allocation under the ISO 14044 standard. The aim here was to examine whether these methodologies really represent underlying physical relationships between the material and energy flows and the co-products in such systems, and hence are of value.

Methods

Two key components of agricultural LCAs which involve co-product allocation were used to provide examples of the methodological challenges which arise from adopting biophysical allocation in agricultural LCA: (1) the crop production chain and (2) the multiple co-products produced by animals. The actual “causal” relationships in these two systems were illustrated, the energy flows within them detailed, and the existing biophysical allocation methods, as found in literature, were critically evaluated in the context of such relationships.

Results and discussion

The premise of many biophysical allocation methodologies has been to define relationships which describe how the energy input to agricultural systems is partitioned between co-products. However, we described why none of the functional outputs from animal or crop production can be considered independently from the rest on the basis of the inputs to the system. Using the example of manure in livestock systems, we also showed why biophysical allocation methodologies are still sensitive to whether a system output has economic value or not. This sensitivity is a longstanding criticism of economic allocation which is not resolved by adopting a biophysical approach.

Conclusions

The biophysical allocation methodologies for various aspects of agricultural systems proposed to date have not adequately explained how the physical parameters chosen in each case represent causal physical mechanisms in these systems. Allocation methodologies which are based on shared (but not causal) physical properties between co-products are not preferable to allocation based on non-physical properties within the ISO hierarchy on allocation methodologies and should not be presented as such.

     

Effects of gibberellic acid and prohexadione-calcium on growth,chlorophyll fluorescence and quality of okra plant

The experiment was conducted to identify the response of three cultivars of okra [Abelmoschus esculentus (L.) Moench] to exogenous hormones [gibberellic acid-(GA₃) and prohexadione-Ca] applied as foliar spray. Stem and leaf dry masses and stem length were significantly enhanced by the application of exogenous GA₃, but prohexadione-Ca inhibited growth. Control and prohexadione-Ca treated okra plants took more time to bloom than did GA₃ treated plants. In the fruits of all the cultivars a decrease in fructose content was observed, while protein content remained almost unchanged after the application of the two growth regulators. The small changes in chlorophyll a fluorescence characteristics observed under prohexadione-Ca suggested a weakening of the photochemical processes near the photosystem 2 reaction centre. The lowering of ratio between maximum time to reach maximum fluorescence, F_m (T_max) and Area (sum of F_m-F_t for t = 0 to t = T_max) caused by GA₃ was probably due to the increase of Area rather than to changes in T_max.