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SARS-CoV-2 is a newly discovered virus which causes COVID-19 (coronavirus disease of 2019), initially documented as a human pathogen in 2019 in the city of Wuhan China, has now quickly spread across the globe with an urgency to develop effective treatments for the virus and emerging variants. Therefore, to identify potential therapeutics, an antiviral catalogue of compounds from the CAS registry, a division of the American Chemical Society was evaluated using a pharmacoinformatics approach. A total of 49,431 compounds were initially recovered. After a biological and chemical curation, only 23,575 remained. A machine learning approach was then used to identify potential compounds as inhibitors of SARS-CoV-2 based on a training dataset of molecular descriptors and fingerprints of known reported compounds to have favorable interactions with SARS-CoV-2. This approach identified 178 compounds, however, a molecular docking analysis revealed only 39 compounds with strong binding to active sites. Downstream molecular analysis of four of these compounds revealed various non-covalent interactions along with simultaneous modulation between ligand and protein active site pockets. The pharmacological profiles of these compounds showed potential drug-likeness properties. Our work provides a list of candidate anti-viral compounds that may be used as a guide for further investigation and therapeutic development against SARS-CoV-2.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers owing to a number of characteristics including difficulty in establishing early diagnosis and the absence of effective therapeutic regimens. A large number of genetic alterations have been ascribed to PDAC with mutations in the KRAS2 proto-oncogene thought to be an early event in the progression of disease. Recent lineage-tracing studies have shown that acinar cells expressing mutant Kras(G12D) are induced to transdifferentiate, generating duct-like cells through a process known as acinar-ductal metaplasia (ADM). ADM lesions then convert to precancerous pancreatic intraepithelial neoplasia (PanIN) that progresses to PDAC over time. Thus, understanding the earliest events involved in ADM/PanIN formation would provide much needed information on the molecular pathways that are instrumental in initiating this disease. As studying the transition of acinar cells to metaplastic ductal cells in vivo is complicated by analysis of the entire organ, an in vitro three dimensional (3D) culture system was used to model ADM outside the animal. Kras(G12D)-expressing acinar cells rapidly underwent ADM in 3D culture, forming ductal cysts that silenced acinar genes and activated duct genes, characteristics associated with in vivo ADM/PanIN lesions. Analysis of downstream KRAS signaling events established a critical importance for the Raf/MEK/ERK pathway in ADM induction. In addition, forced expression of the acinar-restricted transcription factor Mist1, which is critical to acinar cell organization, significantly attenuated Kras(G12D)-induced ADM/PanIN formation. These results suggest that maintaining MIST1 activity in Kras(G12D)-expressing acinar cells can partially mitigate the transformation activity of oncogenic KRAS. Future therapeutics that target both the MAPK pathway and Mist1 transcriptional networks may show promising efficacy in combating this deadly disease.

Salidroside, the 8-O-β-D-glucoside of tyrosol, is the main bioactive component of Rhodiola species and is found mainly in the plant roots. It is well known that glucosylation of tyrosol is the final step in the biosynthesis of salidroside; however, the biosynthetic pathway of tyrosol and its regulation are less well understood. A summary of the results of related studies revealed that the precursor of tyrosol might be tyramine, which is synthesized from tyrosine. In this study, a cDNA clone encoding tyrosine decarboxylase (TyrDC) was isolated from Rhodiola sachalinensis A. Bor using rapid amplification of cDNA ends. The resulting cDNA was designated RsTyrDC. RNA gel-blot analysis revealed that the predominant sites of expression in plants are the roots and high levels of transcripts are also found in callus tissue culture. Functional analysis revealed that tyrosine was best substrate of recombinant RsTyrDC. The over-expression of the sense-RsTyrDC resulted in a marked increase of tyrosol and salidroside content, but the levels of tyrosol and salidroside were 274 and 412%, respectively, lower in the antisense-RsTyrDC transformed lines than those in the controls. The data presented here provide in vitro and in vivo evidence that the RsTyrDC can regulate the tyrosol and salidroside biosynthesis, and the RsTyrDC is most likely to have an important function in the initial reaction of the salidroside biosynthesis pathway in R. sachalinensis.

Background & Aims The transition of gastric epithelial mucous neck cells (NCs) to digestive enzyme–secreting zymogenic cells (ZCs) involves an increase in rough endoplasmic reticulum (ER) and formation of many large secretory vesicles. The transcription factor MIST1 is required for granulogenesis of ZCs. The transcription factor XBP1 binds the Mist1 promoter and induces its expression in vitro and expands the ER in other cell types. We investigated whether XBP1 activates Mist1 to regulate ZC differentiation. Methods Xbp1 was inducibly deleted in mice using a tamoxifen/Cre-loxP system; effects on ZC size and structure (ER and granule formation) and gastric differentiation were studied and quantified for up to 13 months after deletion using morphologic, immunofluorescence, quantitative reverse-transcriptase polymerase chain reaction, and immunoblot analyses. Interactions between XBP1 and the Mist1 promoter were studied by chromatin immunoprecipitation from mouse stomach and in XBP1-transfected gastric cell lines. Results Tamoxifen-induced deletion of Xbp1 ( Xbp1Δ ) did not affect survival of ZCs but prevented formation of their structure. Xbp1Δ ZCs shrank 4-fold, compared with those of wild-type mice, with granulogenesis and cell shape abnormalities and disrupted rough ER. XBP1 was required and sufficient for transcriptional activation of MIST1 . ZCs that developed in the absence of XBP1 induced ZC markers (intrinsic factor, pepsinogen C) but showed abnormal retention of progenitor NC markers. Conclusions XBP1 controls the transcriptional regulation of ZC structural development; it expands the lamellar rough ER and induces MIST1 expression to regulate formation of large granules. XBP1 is also required for loss of mucous NC markers as ZCs form.

Previous work demonstrated that methyl palmitate possesses acaricidal activity against Tetranychus viennensis Boisduval (Acari: Tetranychidae) via an unknown mechanism. Here, the symptoms of methyl palmitate toxicity to T. viennensi were studied to determine the acaricidal mechanism of action of this fatty acid methyl ester. Methyl palmitate caused concentration-dependent mortality of T. viennensis, with a moderate concentration (5 mg/ml) eliciting excitement and premature oviposition without spinning shortly after exposure. Tremors of the appendages were subsequently observed, followed by quiescence after approximately 5 h. Mites developed dorsal fluid exosmosis at 15-20 h posttreatment with reduced egg production, followed shortly thereafter by death. Some typical neurotoxic symptoms such as excitement and convulsions were observed in methyl palmitate-exposed mites, suggesting that methyl palmitate may be a neurotoxin. Compared with other neurotoxic acaricides, methyl palmitate poisoning is a slow process in mites. Transmission electron microscopy revealed serious ultrastructural damage in response to 5 mg/ml methyl palmitate exposure. Autolysis of membranous structures was also observed, especially in the mitochondria, suggesting a novel mode of action for methyl palmitate-induced toxicity.

Pancreatic ductal adenocarcinoma (PDAC) is believed to arise through a multistep model comprised of putative precursor lesions known as pancreatic intraepithelial neoplasia (PanIN). Recent genetically engineered mouse models of PDAC demonstrate a comparable morphologic spectrum of murine PanIN (mPanIN) lesions. The histogenesis of PanIN and PDAC in both mice and men remains controversial. The most faithful genetic models activate an oncogenic Kras G12D knockin allele within the pdx1 - or ptf1a/p48 -expression domain of the entire pancreatic anlage during development, thus obscuring the putative cell(s)-of-origin from which subsequent mPanIN lesions arise. In our study, activation of this knockin Kras G12D allele in the Elastase - and Mist1 -expressing mature acinar compartment of adult mice resulted in the spontaneous induction of mPanIN lesions of all histological grades, although invasive carcinomas per se were not seen. We observed no requirement for concomitant chronic exocrine injury in the induction of mPanIN lesions from the mature acinar cell compartment. The acinar cell derivation of the mPanINs was established through lineage tracing in reporter mice, and by microdissection of lesional tissue demonstrating Cre -mediated recombination events. In contrast to the uniformly penetrant mPanIN phenotype observed following developmental activation of Kras G12D in the Pdx1 -expressing progenitor cells, the Pdx1 -expressing population in the mature pancreas (predominantly islet β cells) appears to be relatively resistant to the effects of oncogenic Kras . We conclude that in the appropriate genetic context, the differentiated acinar cell compartment in adult mice retains its susceptibility for spontaneous transformation into mPanIN lesions, a finding with potential relevance vis-à-vis the origins of PDAC.

A number of studies have shown that pancreatic ductal adenocarcinoma develops through precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). PanINs are thought to initiate in the small ducts of the pancreas through activating mutations in the KRAS proto-oncogene. What remains unanswered is the identification of the individual cell type(s) that contributes to pancreatic ductal adenocarcinoma formation. To follow the cellular and molecular changes that occur in acinar and duct cell properties on Kras(G12D) expression, we took advantage of LSL-Kras(G12D/+)/p48(Cre/+) mice, which faithfully mimic the human disease. In young animals (4 weeks), the predominant cellular alteration in the exocrine pancreas was acinar metaplasia in which individual acini consisted of acinar cells and duct-like cells. Metaplastic acinar structures were highly proliferative, expressed Notch target genes, and exhibited mosaic expression patterns for epidermal growth factor receptor, ErbB2, and pErk. This expression pattern paralleled the expression pattern detected in mouse PanINs, suggesting that mouse PanINs and acinar-ductal metaplasia follow similar molecular pathways. Indeed, immunofluorescence studies confirmed the presence of acinar cells within mPanIN lesions, raising the possibility that Kras(G12D)-induced mPanINs develop from acinar cells that undergo acinar-ductal metaplasia. Identification of an acinar contribution to PanIN formation offers new directions for successful targeted therapeutic approaches to combat this disease.

The carmine spider mite, Tetranychus cinnabarinus (Acari: Tetranychidae), is an economically important and extremely polyphagous herbivorous pest, with the title of "resistance champion" among arthropods. Anticholinesterase insecticides such as organophosphate and carbamate account for more than one-third of global insecticide sales. The non-target toxicity and resistance problem of organophosphate and carbamate have become of growing concern, which may be due to the fact that they target the ubiquitous catalytic serine residue of acetylcholinesterase (AChE) in mammals, birds, and beneficial insects. In this study, the structural differences between T. cinnabarinus AChE and human AChE, at or near the catalytic pocket, were illustrated. From the SPECS chemical lead-compound database, 55 AChE inhibitor candidates were screened for high affinity for T. cinnabarinus AChE, but low affinity for human AChE, using the DOCK 6 and AutoDock Vina software. Three of the fifty-five candidates had inhibitory activity greater than that of the reversible AChE inhibitor eserine, with no observed inhibitory activities against human AChE. Two of the three had toxicity to T. cinnabarinus comparable to that of natural insecticidal pyrethrins. However, their potency is low compared with that of etoxazole, and further work is needed to optimize their potency. The selectivity of the three compounds over human and mite AChE may be due to their interaction with the mite-specific residues, as analyzed by Cyscore. The three compounds are potential lead compounds for development of novel acaricides against T. cinnabarinus with reduced toxicity to non-target species and a low propensity for resistance.

The study of microRNAs (miRNAs) became intertwined with cancer biology at an early stage. In one of the first publications reporting altered miRNA expression in cancer, Michael et al. found that loss of miR-143/145 is associated with colorectal cancer.1 This and other seminal studies opened the door to a new field of research, which over the past decade has revealed that miRNA dysregulation is involved in all aspects of malignancy including tumor initiation, progression and metastasis. As one of the most reproducible observations in this vast literature, loss of miR-143/145 has been reported in subsequent studies of colorectal cancer and other epithelial tumor types. Through repression of KRAS, MYC, ERK5 and other oncogenes, overexpression of miR-143/145 inhibits proliferation and survival of cancer cells in cell culture and xenografts.2,3 Therefore, miR-143/145 have been widely accepted as prototypical miRNA tumor suppressors. In a recent study,4 we attempted to complement these reports by examining the endogenous functions of miR-143/145 in mice. We found that loss of miR-143/145 does not lead to any discernable defects in intestinal development or homeostasis. This was not entirely unexpected, as a growing number of studies have reported that miRNAs are dispensable for development but perform important functions under stress conditions.5 Indeed, we found that miR-143/145 were essential for regeneration of epithelial cells following intestinal injury elicited by dextran sulfate sodium (DSS). Adjacent to DSS-induced ulcers, proliferation of wild-type epithelial cells switches from a hierarchical mode restricted to stem cells and transit-amplifying cells to a regenerative mode wherein all cells in the crypts multiply. However, in miR-143/145 null mice, epithelial cells failed to make this transition, resulting in inefficient epithelial repair, sustained inflammation and eventual death of the animals. In the course of investigating the cellular context of this pro-regenerative function, we were surprised to find that miR-143/145 expression is abundant in smooth muscle cells of muscularis mucosae and muscularis externa, myofibroblasts, and other cells of mesenchymal lineages, but completely absent in human and mouse intestinal epithelial cells (Fig. 1). This finding was further corroborated by genetic studies, as mice with mesenchymal deletion of miR-143/145 recapitulated the regenerative defect, while epithelial ablation of miR-143/145 had no discernable effect. Figure 1. miR-143/145 in intestinal regeneration and tumorigenesis. miR-143/145 are abundant in the mesenchymal cells of the intestine, including myofibroblasts and smooth muscle, but completely absent in the epithelium. Although dispensable for development and ... Smooth muscle cells in the GI tract form 2 distinct layers: muscularis mucosae and muscularis externa, which are classic histological structures that, by mechanical contraction, facilitate movement of food along the digestive tract. Previous studies have mainly focused on their mechanical and electrophysiology properties. Given the abundant expression of miR-143/145 in smooth muscle, we deleted the miRNAs specifically within this lineage to determine the contribution of this cell-type to the regenerative defect. Remarkably, smooth muscle-specific miR-143/145 deletion significantly impaired intestinal wound healing, uncovering a previously unrecognized signaling function for this lineage that provides instructive cues during epithelial regeneration. Paracrine signals may be elaborated by smooth muscle cells themselves (Fig. 1). In addition, we showed that within zones of injury, smooth muscle cells adopt a myofibroblast phenotype and migrate into the lamina propria, where they may functionally coordinate epithelial repair. This behavior is reminiscent of smooth muscle cells of the vasculature, which are known to switch between contractile and secretory phenotypes in injury settings.6 We demonstrated that miR-143/145-deficient myofibroblasts secrete an excess of the novel miR-143 target insulin-like growth factor binding protein 5 (IGFBP5), which sequesters IGF ligands and may thereby impair intestinal epithelial proliferation. Further studies are necessary to elucidate the broader signaling program that is dysregulated in miR-143/145-deficient smooth muscle and myofibroblasts. This approach is likely to yield important insights into the mechanisms that govern intestinal wound healing and may reveal new therapeutic strategies for ulcerative colitis, Crohn's disease, and other intestinal diseases. Our findings also have important implications for colorectal cancer. The absence of miR-143/145 in normal and cancerous epithelium clearly rules out a cell autonomous tumor suppressor function for these miRNAs. We suspect that the previously reported loss of miR-143/145 in colorectal cancer simply reflects the distinct cellular composition of normal and neoplastic intestinal tissue. Similar misinterpretations may have occurred in other cancer settings, underscoring the need for careful analyses to resolve the settings wherein these miRNAs may function in a cell autonomous manner to influence cancer cell behavior. Importantly, our findings do not invalidate the reported anti-tumorigenic activity of miR-143/145 in colorectal cancer cells or potential therapeutic strategies based upon delivery of these miRNAs. Nevertheless, the effects of such treatments on mesenchymal cells in target tissues have to be carefully evaluated. Finally, it is tempting to speculate that miR-143/145 could influence colorectal tumorigenesis through their ability to regulate mesenchymal-to-epithelial paracrine signaling (Fig. 1). It has been demonstrated that colorectal tumors exhibit degraded epithelial barrier function, which allows microbial penetration and tumor-promoting inflammation.7 Perhaps loss of miR-143/145 in the mesenchyme, which could impair a compensatory local epithelial regenerative response, exacerbates tumor-associated inflammation and thereby enhances malignant progression. Regardless, these new insights into the natural functions of miR-143/145 serve as yet another reminder that cancer cells do not live in isolation. Stromal components, such as myofibroblasts, vasculature, immune cells, and extracellular matrix, have to be taken into consideration to gain a full understanding of miRNA functions in tumorigenesis.

Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apcmin/+ mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type.

Pyruvate decarboxylase and alcohol dehydrogenase are efficient enzymes for ethanol production in Zymomonas mobilis. These two enzymes were over-expressed in Escherichia coli, a promising candidate for industrial ethanol production, resulting in high ethanol production in the engineered E. coli. To investigate the intracellular changes to the enzyme overexpression for homoethanol production, 2-DE and LC–MS/MS were performed. More than 1,000 protein spots were reproducibly detected in the gel by image analysis. Compared to the wild-type, 99 protein spots showed significant changes in abundance in the recombinant E. coli, in which 46 were down-regulated and 53 were up-regulated. Most proteins related to tricarboxylic acid cycle, glycerol metabolism and other energy metabolism were up-regulated, whereas proteins involved in glycolysis and glyoxylate pathway were down-regulated, indicating the rewired metabolism in the engineered E. coli. As glycolysis is the main pathway for ethanol production, and it was inhibited significantly in engineered E. coli, further efforts should be directed at minimizing the repression of glycolysis to optimize metabolism network for higher yields of ethanol production.

Reproductive potential and daily reproductive rhythms of the tree borer Oemona hirta (F.) were studied in the laboratory. Mean premating periods between emergence from hosts and mating were 3.3 ± 1.9 d (mean ± SD). Preoviposition period averaged 6.1 ± 3.4 d. On average, each female laid 51.3 ± 44.8 eggs and 31.0 ± 20.6 eggs remained in her body upon death. The mean oviposition period was 17.7 ± 9.3 d. Egg hatch rate was 59.5 ± 19.4%. Mean incubation period of eggs was 8.9 ± 1.9 d. Fecundity and longevity were significantly greater in larger females than in smaller ones. Adults were active mainly during scotophase with 66.7% of pair bonds, 72.9% of matings, 97.5% of ovipositions, and 82.2% of feedings taking place during this period. Immediately after scotophase began, feeding activity started and then quickly reached the peak between 2 and 3 h into scotophase. Reproductive activities, including pair bonding, mating, and oviposition occurred later than feeding and reached peaks between 4 and 8 h into scotophase when feeding activity decreased to minimum. Reproductive activities were significantly correlated with 1 another b t not significantly correlated with feeding activity.

SummaryDownregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in the absence of these miRNAs, epithelial regeneration after injury was dramatically impaired. Surprisingly, we found that miR-143/145 are expressed and function exclusively within the mesenchymal compartment of intestine. Defective epithelial regeneration in miR-143/145-deficient mice resulted from the dysfunction of smooth muscle and myofibroblasts and was associated with derepression of the miR-143 target Igfbp5, which impaired IGF signaling after epithelial injury. These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer.

Plant type III polyketide synthase (PKS) generates backbones of a variety of plant secondary metabolites with diverse functions, and has long been models to elucidate the relationship between the three-dimensional structure and function. More than 80 type IIII PKS crystal structures with different functions have been reported in Protein Data Bank, including the crystal structures of the well-studied Chalcone Synthase of plant type III PKS, as well as the 6 other kinds of PKSs in the family, which are critical for understanding the structural basis for diverse starter molecule selectivity, polyketide chain length and the cyclization reaction. Structure-based analysis and site-directed mutagenesis are foundation for the investigation of enzyme engineering, genetic and metabolic engineering. This review summarized 7 plant-specific type III PKS in the aspects of their crystal structures and functions.

We identified acaricidal compounds in Inula japonica Thunberg (Asteraceae) that were effective against carmine spider mite, Tetranychus cinnabarinus (Boisduval). Petroleum-ether extracts from I. japonica were toxic to T. cinnabarinus, with a 50% lethal concentration (LC50) value of 1.18 mg/ml. Silica gel column chromatography was used to separate the acaricidal components. Seventeen of 38 fraction groups had mite mortality rates >50%, nine fraction groups had rates >60%, and three fraction groups had rates >80% at 2 mg/ml. The major volatile compounds in the bioactive fraction groups were identified by gas chromatography-mass spectroscopy, and beta-sitosterol (1), stigmasterol (2), lupeol (3), and alpha-amyrin (4) were identified and determined to have acaricidal activity against T. cinnabarinus in vitro.

Salidroside, the 8-O-β- d -glucoside of tyrosol, is a novel adaptogenic drug extracted from the medicinal plant Rhodiola sachalinensis A. Bor. Due to the scarcity of R. sachalinensis and its low yield of salidroside, there is great interest in enhancing production of salidroside by biotechnological manipulations. In this study, two putative UDP-glycosyltransferase (UGT) cDNAs, UGT72B14 and UGT74R1, were isolated from roots and cultured cells of methyl jasmonate (MeJA)-treated R. sachalinensis, respectively. The level of sequence identity between their deduced amino acid sequences was ca. 20%. RNA gel–blot analysis established that UGT72B14 transcripts were more abundant in roots, and UGT74R1 was highly expressed in the calli, but not in roots. Functional analysis indicated that recombinant UGT72B14 had the highest level of activity for salidroside production, and that the catalytic efficiency (Vmax/Km) of UGT72B14 was 620% higher than that of UGT74R1. The salidroside contents of the UGT72B14 and UGT74R1 transgenic hairy root lines of R. sachalinensis were also ∼420% and ∼50% higher than the controls, respectively. UGT72B14 transcripts were mainly detected in roots, and UGT72B14 had the highest level of activity for salidroside production in vitro and in vivo.

Background & Aims Invasive pancreatic ductal adenocarcinoma is thought to originate from duct-like lesions called pancreatic intraepithelial neoplasia (PanIN). PanINs progress from low grade (PanIN-1) to high grade (PanIN-3) as the cells attain molecular alterations to key regulatory genes, including activating mutations in the KRAS protooncogene. Despite a well-documented progression model, our knowledge of the initiator cells of PanINs and the transcriptional networks and signaling pathways that impact PanIN formation remains incomplete. Methods In this study, we examined the importance of the acinar-restricted transcription factor Mist1 to Kras G12D -induced mouse PanIN (mPanIN) formation in 3 different mouse models of pancreatic cancer. Results In the absence of Mist1 ( Mist1 KO ), Kras G12D -expressing mice exhibited severe exocrine pancreatic defects that were rescued by ectopic expression of Mist1 in acinar cells. mPanIN development was greatly accelerated in Mist1 KO / Kras G12D/+ pancreata, and in vitro assays revealed that Mist1 KO acinar cells were predisposed to convert to a ductal phenotype and activate epidermal growth factor receptor (EGFR) and Notch-signaling pathways. Conclusions We propose that convergence of EGFR, Notch, and Kras pathways in acinar cells lacking Mist1 leads to enhanced mPanIN formation.

By using community structural characteristic indices and principal component analysis, this paper studied the community structure and its dynamics of predatory arthropod in the jujube orchards intercropped with Astrugalus complanatus, Trifolium repen, Lotus comiculotus, and Medicago sativa. The results showed that in all test jujube orchards, spider and predatory insects were the predominant components of the predatory arthropod community, and their relative abundances were 48.3% - 52.7% and 38.8% - 44.4% , respectively. There were significant differences (P0.05) in the mean density, diversity, and evenness of the most common predatory arthropod groups in the jujube orchards intercropped with different herbage species, with the sequence of intercropped with Lotus comiculotusMedicago sativaAstrugalus complanatuTrifolium repens, but for dominant concentration index, the sequence was intercropped with Trifolium repensAstrugalus complanatuMedicago sativaLotus comiculotus. The average density of predatory spiders was significant higher (P0.05) than that of predatory insects in all test jujube orchards. The individuals of Coccinellidae, Pentatomidae, inoccllidae, Chrysopidae, Thomisidae, Araneidae and Phytoseiidae played the dominant role in the community.

To effectively control the scale insects in jujube orchards, a field study was made on the population structure and niche of Pseudococcus comstock Kuwane, Ceroplastes japonicus Green and Quadraspidiotus perniciosus Comstock in the jujube orchards intercropped with wheat in Taigu area of Shanxi Province. The results showed that at the early development stage of jujube trees, these three kinds of scale insects mainly distributed on the southeast direction of the lower and central parts of the tree crown, and P. comstock was the dominant species, with a wider breadth of two-dimensional temporal-spatial niche than the other two scale insects. At the mid-stage of jujube trees development, these scale insects mainly distributed on the northwest direction of the upper part of the tree crown, C. japonicus had a wider breadth of two-dimensional temporal-spatial niche than the other two scale insects, and the niche proportional similarity and interspecific competition of the three kinds of scale insects were not obvious. At the later stage of jujube trees development, there was no significant difference (P0.05) in the population structure of the three kinds of scale insects on the different parts and directions of tree crown, but the density of Q. perniciosus was bigger, and C. japonicus had a wider breadth of two-dimensional temporal-spatial niche. The average values of niche proportional similarity and interspecific competition of the three kinds of scale insects were smaller (P0.05) at the later development stage of jujube trees. Therefore, P. comstock should be controlled at the early development stage of jujube trees, all the three kinds of scale insects should be controlled selectively at the mid-stage of jujube trees development, and their overwinterings should be decreased by all means at the later development stage of jujube trees.

In this paper, an investigation was made on the temporal-spatial dynamics of the functional groups of natural enemies in the jujube orchard 2.5 km west of Taigu (112 degrees 8'E, 38 degrees 9'N, 780 m elevation), Shanxi Province in 2002, aimed to work out an effective strategy to control the pests there. In this orchard, four management modes were applied, i. e., intercropping herbage combined with integrated pest management (IPM), intercropping combined with conventional pest management (CM), intercropping with no pest management (NM), and non- intercropping (CK). The results indicated that the total number of natural enemies in IPM, CM and NM was 187.99%, 151.82% and 210.03% higher than CK, respectively, and the recovery and reconstruction rates as well as the average breadth and overlap indices of two dimensional temporal-spatial niches of the functional groups were higher in intercropping modes than in CK. The average diversity index of the functional groups in intercropping modes was significantly bigger than that in CK, but the fluctuation of the diversity standard error of the functional groups was significantly smaller (P0.05). The fluctuation trends of the dominance, diversity, and evenness of functional groups had a significant correlation (P0.01) with those of species. These results showed that intercropping herbage in jujube orchard was favorable to the conservation, proliferation, and making use of natural enemies. The natural enemy's community in jujube orchard intercropped with herbage was more stable than that without intercropping, and the numbers and functions of the functional groups were differed with different management modes and different stages. Among the functional groups of natural enemies, ladybirds had a stronger ability of recovery, while spiders and parasitoids were weaker. It was feasible to use functional groups instead of species to study the natural enemy's community in jujube orchard.

An investigation on the insects in the jujube ecosystem in Taigu District of Shanxi Province, Northern China showed that more species and individual numbers of pest, predatory and neutral insects were found on the tree than on the ground. The ratio of the species and individual numbers of predatory and neutral insects to those of pest insects fluctuated from year to year. Homoptera, Coleoptera and Lepidoptera were the dominant groups of pest insects, while those of predatory insects were Coleopteran, Hemiptera, Diptera and Hymenoptera. The vertical distribution of the community structure of the same or different subcommunity was different in different seasons, as was the case of the same or different subcommunity in the same season. The diversity indexes of pest, predatory and neutral insects fluctuated with seasons, and the populations of predatory and neutral insects had a significant correlation (r = 0.9833, P0.05) with the fluctuation of pest insects. There was also a significant correlation between the pest, predatory and neutral insects in different stratums of tree canopy, especially in the middle stratum of tree canopy (r = 0.9887, P0.01).

Through investigation and by the methods of optimal partitioning, principal component analysis, and one-or two-dimensional ordination, this paper analyzed the main groups and succession trends of the pest and natural enemy communities at a jujube orchard of Taigu area. The results showed that the communities had more obvious dominant factors and temporal succession pattern. The first three principal components of the communities had a bigger variation, with an obvious follow effects. The community succession was temporally divided into four stages, i. e., in the periods of pre-budding, leaf expanding and blooming, fruiting, and maturing. The dominant species of pests and their natural enemies were demonstrated.

Auxin is central to many aspects of plant development; accordingly, plants have evolved several mechanisms to regulate auxin levels, including de novo auxin biosynthesis, degradation, and conjugation to sugars and amino acids. Here, we report the characterization of an Arabidopsis thaliana mutant, IAA carboxyl methyltransferase1-dominant (iamt1-D), which displayed dramatic hyponastic leaf phenotypes caused by increased expression levels of the IAMT1 gene. IAMT1 encodes an indole-3-acetic acid (IAA) carboxyl methyltransferase that converts IAA to methyl-IAA ester (MeIAA) in vitro, suggesting that methylation of IAA plays an important role in regulating plant development and auxin homeostasis. Whereas both exogenous IAA and MeIAA inhibited primary root and hypocotyl elongation, MeIAA was much more potent than IAA in a hypocotyl elongation assay, indicating that IAA activities could be effectively regulated by methylation. IAMT1 was spatially and temporally regulated during the development of both rosette and cauline leaves. Changing expression patterns and/or levels of IAMT1 often led to dramatic leaf curvature phenotypes. In iamt1-D, the decreased expression levels of TCP genes, which are known to regulate leaf curvature, may partially account for the curly leaf phenotype. The identification of IAMT1 and the elucidation of its role in Arabidopsis leaf development have broad implications for auxin-regulated developmental process.

Extracts of a perennial and poisonous weed, Stellera chamaejasme L. (Thymelaeaceae) were bioassayed to determine their acaricidal activities against Tetranychus viennensis Zacher (Acari: Tetranychidae) in the laboratory. Extracts had both contact and systemic toxicity to the mite. After liquid chromatography and thin layer chromatography, the extract was further concentrated, separated, and bioassayed. This study is the first to report the acaricidal property of S. chamaejasme and its potential as a botanical pest control agent.

Oemona hirta (F.) is a New Zealand native longicorn beetle, whose larvae bore into the wood of branches and stems of living trees and vines, causing serious damage. To explore effective methods for maintaining laboratory colonies and biology of immature stages of this species we evaluated four laboratory rearing methods with both natural and artificial diets and compared biological parameters of laboratory colonies with those of field-collected insects. On an artificial diet, approximately 40% of neonate and 70% of autumn- and 11% of winter-collected larvae reached adulthood. Neonate larvae could not complete their development in cut poplar (Populus nigra variety italica Koehne) twigs; however, when twigs were standing in water46% of neonate larvae survived to adulthood. Mean larval development time ranged from approximately150 to almost 300 d, depending on rearing methods. Mean pupal stage ranged from 15 to 19 d. Adult females were significantly heavier than males. Although adult females from field-collected twigs and reared on the artificial diet had similar mean body weight, which was significantly greater than that of other rearing colonies, the potential fecundity was the highest in the former (83.1 +/- 29.4 eggs) and the lowest in the latter (33.5 +/- 9.1 eggs). In all laboratory-reared and field-collected insects, the total number of eggs produced (eggs laid + eggs that remained in dead female body) by females was positively correlated with their body weight. When larvae fed on the artificial diet, there was no positive correlation between the number of eggs successfully laid and female body weight. However, when larvae lived on natural food, a positive correlation was found. In laboratory colonies, mean longevity of females (36 to 52 d) was slightly greater than that of males (30 to 50 d) without significant difference between sexes but in the adults from field-collected twigs, males (52 d) lived significantly longer than females (33 d). In terms of time, labor, and the number of resulting adults, collecting larvae in the field in autumn and then transferring them onto artificial diet is the most effective method for maintaining a laboratory colony.

Background & Aims Gastric cancer evolves in the setting of a pathologic mucosal milieu characterized by both loss of acid-secreting parietal cells and mucous cell metaplasias. Indeed, mucous cell metaplasia is considered the critical preneoplastic lesion for gastric cancer. Previous investigations have shown that infection of mice with Helicobacter felis or induction of acute parietal cell loss with the drug DMP-777 leads to the emergence of a type of metaplasia designated spasmolytic polypeptide-expressing metaplasia (SPEM). We have hypothesized that SPEM arises from proliferating cells in gland bases, either from a cryptic progenitor cell or by transdifferentiation of mature chief cells. Methods Taking advantage of the chief cell-restricted expression of Mist1-Cre-ER T2 , we used lineage mapping to examine whether SPEM lineages were derived from chief cells in 3 independent models of induction by DMP-777 treatment, L-635 treatment, or H felis infection. Results Treatment of mice with L-635 for 3 days led to rapid parietal cell loss, induction of a prominent inflammatory infiltrate, and emergence of SPEM. In all 3 models, SPEM developed, at least in part, from transdifferentiation of chief cells. We further found that acute parietal cell loss in the setting of inflammation (L-635 treatment) led to more rapid induction and expansion of SPEM derived from transdifferentiation of chief cells. Conclusions These studies provide direct evidence by lineage tracing that SPEM evolves from differentiated chief cells. Thus, mature gastric chief cells have the ability to act as cryptic progenitors and reacquire proliferative capacity within the context of mucosal injury and inflammation.

Our studies are focused on the identification and prevention of the initial transformation events associated with pancreatic ductal adenocarcinoma (PDA) development, an extremely lethal malignancy with poor prognosis and ineffective treatments. PDA initiates through activating mutations in the KRAS proto-oncogene (KrasG12D) and recent studies from our laboratory have determined that targeted expression of an endogenous KrasG12D allele in pancreatic acinar cells is sufficient to produce PDA precursor lesions (PanINs). These results suggest that PDA arises via acinar cells undergoing a process of acinar-to-ductal metaplasia (ADM) which is characterized by a loss of acinar cell properties with the acquisition of duct-like characteristics. Several studies indicate that the process of ADM requires inactivation of the acinar-specific transcription factor Mist1, since Mist1 null (Mist1KO) mice display accelerated ADM and PanIN formation upon KrasG12D expression. Additionally, acinar cell polarity is disrupted in Mist1KO mice with diffuse zymogen granule organization and mis-localization of nuclei. These results suggest that Mist1 has a key role in suppressing PDA formation by maintaining the acinar cell differentiation program. To identify the downstream genes affected by the absence of Mist1, we have generated an inducible Mist1 transgenic mouse line (LSL-Mist1myc) in which constitutive Mist1 expression is activated through Cre-mediated recombination. When LSL-Mist1myc mice are crossed to Mist1Cre-ER mice, Mist1myc expression can be induced in acinar cells upon Tamoxifen (TM) addition. Analysis of Mist1Cre-ER/Cre-ER; LSL-Mist1myc mice confirmed that exogenous Mist1myc expression is detected as early as 6 hours post-TM. Time course studies in a Mist1KO background revealed that nuclear and zymogen granule organization can be restored within 24 hours of Cre activation. We conclude that Mist1 actively controls pancreatic acinar cell organization and that induction of Mist1 in Mist1KO mice leads to complete reorganization of pancreatic tissues. Our current efforts are focused on establishing how Mist1 negatively regulates ADM and PanIN formation and to identify Mist1 targets that negatively regulate Kras-induced pancreas metaplasia and transformation. Citation Information: Cancer Res 2009;69(23 Suppl):A76.

Significance: Pancreatic ductal adenocarcinoma (PDA) is one of the most fatal malignancies, partially due to the lack of early detection methods. Background: Efforts to understand the early stages of PDA progression have led to identification of Kras mutations as the initiating event and pancreatic intraepithelial neoplasias (PanINs) as one of the cellular precursors of PDA. Recently, several labs have demonstrated that PanINs can be generated from pancreatic acinar cells upon expression of Kras mutants in mouse models. This dramatic shift from differentiated acinar cells to duct-like PanIN cells, generally termed acinar-ductal metaplasia (ADM), is accelerated by loss of Mist1, an acinar-restricted basic helix-loop-helix transcription factor. Despite this recent progress, the transcription and signaling networks that regulate ADM remain largely unknown. Results: To study these networks, we employed a collagen-based 3-dimensional (3D) culture model of ADM, where primary acinar cells can be transformed into duct-like cysts when treated with transforming growth factor-alpha (TGF-α). A similar acinar-to-ductal conversion was observed with primary acinar cells that express the KrasG12D mutant. Initial characterization of the ADM process revealed that the MAPK pathway is required in both settings. However, EGFR activity is required for TGF-α-induced conversion but not for KrasG12D-induced conversion. Consistent with previous data generated from mouse models, loss of Mist1 accelerates KrasG12D-induced conversion to ductal cysts in vitro. This accelerated ADM formation can be reversed by inhibition of EGFR, without affecting the basal level conversion induced by KrasG12D, suggesting that loss of Mist1 promotes transformation through an EGFR-dependent pathway. Further investigation has revealed that Mist1 directly activates transcription of the epidermal growth factor (EGF) gene, which encodes a classic ligand of EGFR. Conclusion: These data suggest that EGFR has a complex role in this ADM model. EGFR activity either promotes maintenance of acinar differentiation, or cooperates with KrasG12D-induced transformation, possibly depending on the functional specificity of different ligands. Citation Information: Cancer Res 2009;69(23 Suppl):A71.