ANGUSTIFOLIA3 Signaling Coordinates Proliferation between Clonally Distinct Cells in Leaves

SummaryCoordinated proliferation between clonally distinct cells via inter-cell-layer signaling largely determines the size and shape of plant organs [1–4]. Nonetheless, the signaling mechanism underlying this coordination in leaves remains elusive because of a lack of understanding of the signaling molecule (or molecules) involved. ANGUSTIFOLIA3 (AN3, also called GRF-INTERACTING FACTOR1) encodes a putative transcriptional coactivator with homology to human synovial sarcoma translocation protein [5–7]. AN3 transcripts accumulate in mesophyll cells but are not detectable in leaf epidermal cells [8]. However, we found here that in addition to mesophyll cells [5, 6], epidermal cells of an3 leaves show defective proliferation. This spatial difference between the accumulation pattern of AN3 transcripts and an3 leaf phenotype is explained by AN3 protein movement across cell layers. AN3 moves into epidermal cells after being synthesized within mesophyll cells and helps control epidermal cell proliferation. Interference with AN3 movement results in abnormal leaf size and shape, indicating that AN3 signaling is indispensable for normal leaf development. AN3 movement does not require type II chaperonin activity, which is needed for movement of some mobile proteins [9]. Taking these findings together, we present a novel model emphasizing the role of mesophyll cells as a signaling source coordinating proliferation between clonally independent leaf cells

IgG4-related chronic rhinosinusitis: A new clinical entity of nasal disease

Conclusion: IgG4-related disease involves nasal manifestations with chronic rhinosinusitis (CRS). This type of sinusitis is a new clinical entity of nasal disease associated with a high level of serum IgG4 for which steroid therapy is effective. Objectives. To confirm whether IgG4-related disease has distinctive chronic rhinosinusitis. Methods: We compared serum IgG4 levels as well as nasal computed tomography (CT) and clinicopathological findings before and after glucocorticoid treatment in 31 patients diagnosed as having IgG4-related disease with nasal manifestations. To evaluate immunohistochemical findings of nasal mucosa, we compared them with IgG4-related CRS and common CRS. Results: All patients had levels of high serum IgG4. Ten of the 31 patients had nasal obstruction, nasal discharge, postnasal discharge, hyposmia, and dull headache. They also demonstrated sinus lesions on radiological findings. After glucocorticoid treatment, serum IgG and IgG4 levels were markedly decreased and along with improvement of the symptoms, nasal sinus CT findings also revealed improvement of the sinus opacification. In immunohistochemical examination, the magnitude of IgG4-positive plasma cell infiltration in common CRS was almost the same as in the IgG4-related CRS group. Therefore, in nasal mucosa immunocytochemical positive staining for IgG4 is not specific for definition of IgG4-related disease.ArticleACTA OTO-LARYNGOLOGICA. 131(5):518-526 (2011)journal articl

Combined Gastrectomy with Adjacent Organs in T4 Gastric Cancer : Therapeutic Results and Indication

The postoperative morbidity, mortality and survival of 244 T4 gastric cancer patients were examined to assess the therapeutic results and to clarify the indication for combined gastrectomy with adjacent (T4) organs. A total of 190 combined and 54 simple gastrectomies were performed during the 25-year period between 1969 and 1994. Fourteen (7.4%) and 7 (13.0%) patients died of the complications after combined and simple gastrectomies respectively. No statistical significant difference was found in the mortality rates between the gastrectomies. The histological examination of 190 resected specimens by the combined gastrectomy with T4 organs revealed that gastric resections with conclusive curability A, B and C were performed in 33 (17.4%), 84 (44.2%) and 73 (38.4%) cases respectively. Significant differences (P < 0.01) among 3 survival curves of the patients with curability A, B and C were found, and the 5-year survival rates were 65.5%, 35.4% and 9.2% respectively. The survival curve of 176 patients with combined gastrectomy was significantly (P < 0.01) higher than that of 47 patients with simple gastrectomy, and the 5-year survival rates were 31.3% and 4.3%. However, the survival curve and the 5-year survival rate of the patients with simple gastrectomy were not statistically different from those of the patients with curability C. These results suggest that combined gastrectomy with T4 organs in T4 gastric cancer may be indicated for the patients with surgical curability B, but not surgical curability C

Enzyme systems involved in glucosinolate metabolism in Companilactobacillus farciminis KB1089

Cruciferous vegetables are rich sources of glucosinolates (GSLs). GSLs are degraded into isothiocyanates, which are potent anticarcinogens, by human gut bacteria. However, the mechanisms and enzymes involved in gut bacteria-mediated GSL metabolism are currently unclear. This study aimed to elucidate the enzymes involved in GSL metabolism in lactic acid bacteria, a type of gut bacteria. Companilactobacillus farciminis KB1089 was selected as a lactic acid bacteria strain model that metabolizes sinigrin, which is a GSL, into allylisothiocyanate. The sinigrin-metabolizing activity of this strain is induced under glucose-absent and sinigrin-present conditions. A quantitative comparative proteomic analysis was conducted and a total of 20 proteins that were specifically expressed in the induced cells were identified. Three candidate proteins, β-glucoside-specific IIB, IIC, IIA phosphotransferase system (PTS) components (CfPttS), 6-phospho-β-glucosidase (CfPbgS) and a hypothetical protein (CfNukS), were suspected to be involved in sinigrin-metabolism and were thus investigated further. We hypothesize a pathway for sinigrin degradation, wherein sinigrin is taken up and phosphorylated by CfPttS, and subsequently, the phosphorylated entity is degraded by CfPbgS. As expression of both pttS and pbgS genes clearly gave Escherichia coli host strain sinigrin converting activity, these genes were suggested to be responsible for sinigrin degradation. Furthermore, heterologous expression analysis using Lactococcus lactis suggested that CfPttS was important for sinigrin degradation and CfPbgS degraded phosphorylated sinigrin

Active Hippocampal Networks Undergo Spontaneous Synaptic Modification

The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial) stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone

The Role of c-fos in Cell Death and Regeneration of Retinal Ganglion Cells

PURPOSE. To investigate the effect of c-fos on apoptotic cell death and regeneration of damaged retinal ganglion cells (RGCs) in tissue culture of retinal explants. METHODS. Retinas from transgenic mice carrying the exogenous c-fos gene under the control of the interferon (IFN)-␣/␤ inducible Mx-promoter (Mx-c-fos), c-fos-deficient mice, and littermate control mice were dissected and cultured in a threedimensional collagen gel culture system, followed by an analysis of TdT-dUTP terminal nick-end labeling (TUNEL) staining and measurement of neurites that emerged from explants. RESULTS. Compared with littermate control mice, Mx-c-fos transgenic animals showed a higher ratio of TUNEL positivity in the RGC layer from early in the culture period that correlated with the small number of regenerating neurites. In contrast, the c-fos-null mutated mice showed a still-lower ratio of TUNEL-positive cells. Nevertheless, the number of regenerating neurites was significantly lower in the initial phase, although the drastic increase in density of neurite regeneration was observed in the late period of culture. CONCLUSIONS. These findings suggest that c-fos is involved in both apoptotic cell death and regeneration of damaged RGCs. Elucidation of the precise c-fos-mediated cascade involved in RGC apoptosis and regeneration is significant in realizing neuronal survival and regeneration. (Invest Ophthalmol Vis Sci