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Balancing selection is frequently invoked as a mechanism that maintains variation within and across populations. However, there are few examples of balancing selection operating on loci underpinning complex traits, which frequently display high levels of variation. We investigated mechanisms that may maintain variation in a focal polymorphism—leaf chemical profiles of a perennial wildflower (Boechera stricta, Brassicaceae)—explicitly interrogating multiple ecological and genetic processes including spatial variation in selection, antagonistic pleiotropy, and frequency-dependent selection. A suite of common garden and greenhouse experiments showed that the alleles underlying variation in chemical profile have contrasting fitness effects across environments, implicating two ecological drivers of selection on chemical profile: herbivory and drought. Phenotype-environment associations and molecular genetic analyses revealed additional evidence of past selection by these drivers. Together, these data are consistent with balancing selection on chemical profile, likely caused by pleiotropic effects of secondary chemical biosynthesis genes on herbivore defense and drought response., Editor’s Summary: Evidence for balancing selection acting on loci that control complex traits is limited. Here, the authors show evidence for past selection on chemical profile in a perennial wildflower by two ecological drivers, herbivory and drought, consistent with balancing selection on this trait.

Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor-normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mutation distributions where certain processes generate mutations in active domains, and others generate mutations in inactive domains. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation-rate variations observed in human cancers.

Tomato (Solanum lycopersicum) is one of the most economically important vegetable crops worldwide. Bacterial wilt (BW), caused by the Ralstonia solanacearum species complex, has been reported as the second most important plant pathogenic bacteria worldwide, and likely the most destructive. Extensive research has identified two major loci, Bwr-6 and Bwr-12, that contribute to resistance to BW in tomato; however, these loci do not completely explain resistance. Segregation of resistance in two populations that were homozygous dominant or heterozygous for all Bwr-6 and Bwr-12 associated molecular markers suggested the action of one or two resistance loci in addition to these two major QTLs. We utilized whole genome sequence data analysis and pairwise comparison of six BW resistant and nine BW susceptible tomato lines to identify candidate genes that, in addition to Bwr-6 and Bwr-12, contributed to resistance. Through this approach we found 27,046 SNPs and 5975 indels specific to the six resistant lines, affecting 385 genes. One sequence variant on chromosome 3 captured by marker Bwr3.2dCAPS located in the Asc (Solyc03g114600.4.1) gene had significant association with resistance, but it did not completely explain the resistance phenotype. The SNP associated with Bwr3.2dCAPS was located within the resistance gene Asc which was inside the previously identified Bwr-3 locus. This study provides a foundation for further investigations into new loci distributed throughout the tomato genome that could contribute to BW resistance and into the role of resistance genes that may act against multiple pathogens.

Objective: To observe the effect of moxibustion on the mRNA and protein expressions of heat-shock protein 70 (HSP70) in gastric cancer-bearing rats. Methods: A total of 40 healthy Sprague-Dawley (SD) rats were adaptively fed for one week. The gastric cancer model was prepared by Walker-256 cancer tissue transplantation. After 7 d, 10 rats were randomly selected to verify the successful modeling, and the remaining 30 rats were divided into a model group, a moxibustion group and an infrared group by the random number table method, with 10 rats in each group. After enrollment, the moxibustion group received suspended moxibustion at Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36), (the first group of acupoints) on the 1st day, and suspended moxibustion at bilateral Pishu (BL 20) and Weishu (BL 21), (the second group of acupoints) on the 2nd day, 20 min each time, once a day. Moxibustion was alternately performed every other day at the two groups of acupoints for 21 d. From the day of enrollment, rats in the infrared group were irradiated with the infrared radiation at the stomach area on the 1st day, and at the T12-T13 interspinous region on the 2nd day, 20 min each time, once a day, and the two locations were alternately irradiated every other day for 21 d. During the treatment, rats in the model group were intervened by grasping and fixation without treatment. At the end of the treatment, blood was collected from the inner eye orbit, and the HSP70 expression in peripheral blood was determined by enzyme linked immunosorbent assay (ELISA). Rats were sacrificed, the tumor volume and growth inhibition rate were measured. The position and changes of HSP70 in gastric cancer were observed by streptavidin-perosidase (SP); HSP70 protein expression was determined by ELISA; HSP70 mRNA expression in cancer tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR) assay. Results: In comparison of the model group, the volume growth of the gastric cancer in the moxibustion group was significantly restricted (P

To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Compared with the blank group, the body weight of the model group decreased significantly after modeling (P

To observe the effect of moxibustion on T lymphocyte subsets in peripheral blood of rats with gastric cancer. Sixty healthy Sprague-Dawley (SD) rats were adaptively fed for one week. By the random number table method, 10 rats were randomly selected as a blank group, and 12 rats were randomly selected to simulate the tumor transplantation process; after transplantation, 10 rats were randomly selected as a sham operation group. The remaining 38 rats were used to prepare gastric cancer models by gastric transplantation of the Walker-256 tumor tissue; 8 rats were randomly selected to verify the successful modeling after 7 d; the remaining 30 rats were randomly divided into a model group, a moxibustion group and an infrared group by the random number table method, with 10 rats in each group. From the first day of enrollment, the rats in the moxibustion group received mild moxibustion at Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) (the first group) and bilateral Pishu (BL 20) and Weishu (BL 21) (the second group), and the two groups of acupoints were alternated every other day. The rats in the infrared group received infrared radiation on the stomach area and the area on the back between the T12-T13 spinous processes, the two areas were alternated every other day. Rats in the moxibustion group and the infrared group were treated for 20 min each time, once a day for 21 d. Rats in the blank group, the sham operation group, and the model group were simultaneously grasped and fixed, and no other treatment was performed. After 21 d of intervention, the rats in each group were fasted for 12 h, and blood was collected from the orbits. The numbers of CD3+, CD3+CD4+, CD3+CD8+ T lymphocytes in peripheral blood were determined by flow cytometry, and the ratio of CD3+CD4+/CD3+CD8+ was calculated. The rats were sacrificed and the thymus was dissected under sterile conditions to calculate the thymus index. Compared with the blank group, the thymus index, peripheral blood CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ ratio in the sham operation group did not change significantly (all P>0.05). Compared with the blank group, the thymus index of the model group was increased (P

To observe the effect of electroacupuncture (EA) at Huantiao (GB 30) and Weizhong (BL 40) on thigmesthesia, gait function, and expression levels of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) in rabbits with lumbar intervertebral disc herniation (LIDH). Forty healthy New Zealand rabbits were randomly divided into a blank control group, a model group, an EA at acupoint group and an EA at non-acupoint group, with 10 rabbits in each group. The LIDH pathological model of rabbit was established using the self-made LIDH model maker. The thigmesthesia and gait function of rabbits were recorded by Siegal method. The serum IgG and IgM expression levels were detected by enzyme-linked immunosorbent assay. EA at Huantiao (GB 30) and Weizhong (BL 40) could improve the clinical symptoms of thigmesthesia and gait function, and inhibit the expressions of serum IgG and IgM in the LIDH rabbits, which were significantly different compared with those in the model group and EA at non-acupoint group. EA at Huantiao (GB 30) and Weizhong (BL 40) can improve the clinical symptoms of LIDH rabbits, which is associated with inhibition of the serum IgG and IgM expressions and reduction of the immunoinflammatory factor release. This may be one of the mechanisms of EA at Huantiao (GB 30) and Weizhong (BL 40) in the treatment of LIDH.

To observe the effect of electroacupuncture (EA) on the electrogastrogram and gastric antrum ghrelin in rats with diabetic gastroparesis (DGP). Fifty Sprague-Dawley (SD) rats were randomly divided into group A, group B, group C, group D and group E, 10 rats in each group. Group A was the blank control group without intervention. Group B, Group C, Group D and Group E were treated with single dose intraperitoneal injection of 2% streptozotocin (STZ), combined with 8-week high glucose and high fat diet to establish DGP rat models. Group B was the model group without treatment. Group C was the EA at acupoint group, was treated with EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6). Group D was the EA at non-acupoint group, was treated by EA at the control points of Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6). Rats in the metoclopramide control group received 1.7% metoclopramide solution [10 mL/(kg·bw)] by gavage. Rat’s blood glucose level was measured by blood glucose meter; gastric emptying rate was detected using phenol red as a marker; the electrogastrogram was detected by BL-420F biological function system; the protein level of ghrelin was detected by enzyme-linked immunosorbent assay (ELISA); the expression of ghrelin mRNA was detected by real-time polymerase chain reaction (RT-PCR). Compared with group A, the blood glucose of group B, C, D and E were significantly increased before and after the treatment (all P

To investigate the effect of acupuncture plus mild hypothermia on neurological function impairment score, cerebral infarct size and apoptosis-related factors in cerebral ischemia reperfusion injury (CIRI) rats. Sixty healthy male Sprague-Dawley (SD) rats were routinely reared for 1 week. Ten rats were randomly selected as the sham operation group and 10 rats as the blank control group, while the remaining 40 rats were subjected to preparing the middle cerebral artery occlusion (MCAO) model by modified filament occlusion method. The 40 MCAO rats were further randomly divided into a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group, with 10 rats in each group. Rats in the sham operation group, the blank control group and the model group did not accept treatment except binding; rats in the acupuncture group received acupuncture treatment; rats in the mild hypothermia group received mild hypothermia treatment; rats in the acupuncture plus mild hypothermia group received acupuncture and mild hypothermia treatment. 72 h after the treatment, neurological function impairment score was performed; the infarct area ratio was determined by 2,3,5-tripheyl tetrazolium chloride (TTC) staining; apoptosis of brain cells was observed by TUNEL method; the expressions of Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry. Compared with the blank control group and the sham operation group, the neurological function impairment score, cerebral infarct area ratio, apoptosis, and the expressions of Bax and Caspase-3 in the model group were significantly increased, while the expression of Bcl-2 was significantly decreased, and there were significant between-group differences (all P

To observe the effect of electroacupuncture (EA) at Zusanli (ST 36) on the gastrointestinal motility and the ultrastructures of pacemaker cells [the interstitial cells of Cajal (ICC)] in diabetic gastroparesis (DGP) rats and explore the mechanism of EA for DGP. A total of 50 Sprague-Dawley (SD) rats were randomly divided into group A, group B, group C, group D and group E, with 10 rats in each group. Group A was the blank control; a single intraperitoneal injection of 2% streptozotocin (STZ) was performed in rats of group B, group C, group D and group E, with high glucose and high fat diet for 8 weeks to establish the DGP rat models. Group B was the model group and the rats did not receive any treatment; group C was EA at acupoint group and the rats received EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); group D was EA at non-acupoint group and the rats received EA at the control points of Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); group E was metoclopramide group and the rats were treated by intragastric administration of metoclopramide. Blood glucose was detected using ONE TOUCH blood glucose meter; gastric emptying rate and small intestine migration rate were measured using intragastric phenol red; ultrastructures of gastric antrum ICC were detected by transmission electron microscopy. The differences of blood glucose between group B, group C, group D, group E versus that of group A were statistically significant after modeling (P

To explore the action mechanism of electroacupuncture (EA) in improving the gastric motility of rats with diabetic gastroparesis (DGP). Forty-eight healthy Sprague-Dawley (SD) rats were randomly assigned into four groups: a normal group (group A), a model group (group B), a group of EA at acupoints (group C), and a group of EA at non-acupoints (group D), 12 rats in each group. The animal model of DGP was established by intraperitoneal injection of streptozotocin (STZ) plus high glucose and fat diet. The blood glucose, urine glucose and gastric emptying rate (GER) were observed. The content of insulin (INS) in serum and ghrelin in gastric antrum tissue were detected by enzyme linked immunoassay (ELISA). The expression of growth hormone secretagogue receptor mRNA (GHSR mRNA) in gastric antrum tissue was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). Compared with group A, blood glucose and urine glucose increased significantly (P

To investigate the effects of electroacupuncture (EA) at Neiguan (PC 6) and Baihui (GV 20) by observing the changes of CCAAT/enhancer-binding protein(C/EBP) homologous protein (CHOP) and caspase-12 gene expressions in rats after cerebral ischemia-reperfusion injury (IRI), and explore whether the apoptosis pathway of endoplasmic reticulum stress (ERS) is involved in the protective mechanisms of EA. Sixty rats were randomly assigned to five groups (12 in each group): a normal control group (group A), a sham-operation group (group B), an operation group (group C), an Edaravone group (group D) and an EA group (group E). The cerebral IRI rat model was induced by middle cerebral artery occlusion (MCAO) using intraluminal monofilament. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was adopted in the measurement of cerebral infarction volume. Real-time polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of CHOP and caspase-12. Compared with group A and group B, the volume of cerebral infarction and mRNA expressions of CHOP and caspase-12 in group C, group D and group E were increased, with statistical significances (P 0.05). EA at Neiguan (PC 6) and Baihui (GV 20) can effectively suppress the volume of cerebral infarction. Furthermore, the underlying mechanism of EA at Neiguan (PC 6) and Baihui (GV 20) is possibly related to the down-regulation of CHOP and caspase-12 mRNA expressions, so as to decrease cell apoptosis.

A super-peer semantic network defines the semantic groups that client peers and their super peers use to connect with each other according to the semantic similarity of shared documents in peers. This will result in a query that can be evaluated locally thus reducing query process time and the amount of communication required to obtain related data. In this study, new algorithms are proposed to arrange shared documents in peers into hierarchical cluster tree structures, and links will be set up to connect semantically related super peers. During query evaluation, only related peers will be searched thus the complexity of computing is significantly reduced. Consideration is also given to automatically deciding the threshold for clustering and the construction and other essential operations for hierarchical cluster trees. The experiment results illustrate the features of the approach developed in this study.

Objective To observe the effects of moxibustion pretreatment on Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), and Malondialchehyche (MDA) in gastric mucosa of rats with stress ulcer, and to investigate the mechanism of moxibustion pretreatment preventing the oxidized injury of gastric mucosa.

There were many contradictory evaluation criteria to select next-hop in the delay-disruption tolerance networks (DTN). To solve this problem, an attribute hierarchical model was proposed, in which the predefined criteria were summarized as static identity attributes, forwarding desire attributes and delivery capability attributes (IDC). Based on this model, a novel multi-attributes congestion aware routing (MACAR) scheme with uncertain information for next-hop selection was presented, by adopting an decision theory to aggregate attributes with belief structure and computing partial ordering relations. The simulation results show that MACAR presents higher successful delivery rate, lower average delay and effectively alleviate congestion.