Summary
Despite a much higher proportion of intragenic heterochromatin‐containing genes in crop genomes, the importance of intragenic heterochromatin in crop development remains unclear. Intragenic ...heterochromatin can be recognised by a protein complex, ASI1–AIPP1–EDM2 (AAE) complex, to regulate alternative polyadenylation.
Here, we investigated the impact of rice ASI1 on global poly(A) site usage through poly(A) sequencing and ASI1‐dependent regulation on rice development.
We found that OsASI1 is essential for rice pollen development and flowering. OsASI1 dysfunction has an important impact on global poly(A) site usage, which is closely related to heterochromatin marks. Intriguingly, OsASI1 interacts with the intronic heterochromatin of OsXRNL, a nuclear XRN family exonuclease gene involved in the processing of an miRNA precursor, to promote the processing of full‐length OsXRNL and regulate miRNA abundance. We found that OsASI1‐mediated regulation of pollen development partially depends on OsXRNL. Finally, we characterised the rice AAE complex and its involvement in alternative polyadenylation and pollen development.
Our findings help to elucidate an epigenetic mechanism governing miRNA abundance and rice development, and provide a valuable resource for studying the epigenetic mechanisms of many important processes in crops.
In this paper, we used the data set of domain names Global Top 1M provided by Alexa to analyze the effectiveness of Fallback in ECN. For the same test server, we first negotiate a connection with ...Not-ECN-Capable, and then negotiate a connection with ECN-Capable, if the sender does not receive the response to ECN-Capable negotiation from the receiver by the end of retransmission timeout, it will enter the Fallback state, and switch to negotiating a connection with Not-ECN-Capable. By extracting the header fields of the TCP/IP packets, we confirmed that in most regions, connectivity will be slightly improved after Fallback is enabled and Fallback has a positive effect on the total time of the whole access process. Meanwhile, we provided the updated information about the characteristics related to ECN with Fallback in different regions by considering the geographical region distribution of all targeted servers.
Analysis of the State of ECN on the Internet CHEN, Chun-Xiang; NAGAOKA, Kenichi
IEICE Transactions on Information and Systems,
05/2019, Letnik:
E102.D, Številka:
5
Journal Article
Recenzirano
Odprti dostop
ECN, as a decisive approach for TCP congestion control, has been proposed for many years. However, its deployment on the Internet is much slower than expected. In this paper, we investigate the state ...of the deployment of ECN (Explicit Congestion Notification) on the Internet from a different viewpoint. We use the data set of web domains published by Alexa as the hosts to be tested. We negotiate an ECN-Capable and a Not ECN-Capable connections with each host and collect all packets belonging to the connections. By analyzing the header fields of the TCP/IP packets, we dig out the deployment rate, connectivity, variation of round-trip time and time to live between the Not ECN-Capable and ECN-Capable connections as well as the rate of IPv6-Capable web servers. Especially, it is clear that the connectivity is different from the domains (regions on the Internet). We hope that the findings acquired from this study would incentivize ISPs and administrators to enable ECN in their network systems.
Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1‐AIPP1‐EDM2 (AAE) complex, ...participates in polyadenylation regulation of several intronic heterochromatin‐containing genes. However, the genome‐wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome‐wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin‐containing genes, including not only intronic heterochromatin‐containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin‐overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin‐containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation.
Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. In Arabidopsis, the AAE complex (ANTI‐SILENCING1 ASI1, ASI1‐IMMUNOPRECIPITATED PROTEIN1, and ENHANCED DOWNY MILDEW2) preferentially interacts with genic heterochromatin to control alternative RNA processing and contributes to the epigenetic silencing of transposable elements.
The
mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the
-specific inhibitor AMG510 showed ...promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the
mutation in Chinese NSCLC patients are rarely reported.
Next-generation sequencing was used to confirm the
mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort).
In the mCohort, 3998 patients (9.8%) were confirmed to harbor a
mutation, of whom 1179 (29.5%) had the
subtype. In the iCohort, 130 NSCLC patients (8.9%) had a
mutation and 42 (32.3%) had the
subtype. The
subgroup included more male patients (85.2% vs 67.4%,
< 0.0001) and more smokers (76.2% vs 53.4%,
= 0.02) than did the non-
subgroup. Both the
mutation group and
mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio HR
= 1.50,
= 0.002; 18.3 vs 26.7 months, HR
= 1.66,
= 0.007). In Cox regression analysis, smoking (HR = 1.39,
= 0.05) and stage IV disease (HR = 2.72,
< 0.001) remained as independent predictors of shorter OS. Both the
mutation (HR = 1.30,
= 0.07) and
mutation (HR = 1.47,
= 0.07) reached borderline significance.
In the largest sample used thus for, our study found that approximately 10% of Chinese NSCLC patients had
mutations. Of these, nearly 30% harbored the
mutation subtype, which was most common in male smokers. The
mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by
-specific inhibitors in the future.(296 words).
Background
In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) has been ...controversial. The potential reasons for these inconsistent findings were unknown.
Methods
Data from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR‐mutant non‐small cell lung cancer (NSCLC) patients treated with first‐ and second‐generation EGFR‐TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty‐eight patients were treated with third‐generation EGFR‐TKIs in the GLCI cohort. The BIM gene status was examined by next‐generation sequencing.
Results
The frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first‐ and second‐generation EGFR‐TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild‐type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression‐free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third‐generation EGFR‐TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR‐TKIs, but not BIM deletion.
Conclusions
The presence of BIM deletion showed no relation to an impaired response to first‐, second‐, and third‐generation EGFR‐TKIs in NSCLC patients. The factors influencing the response of EGFR‐TKIs were concomitant genetic alterations, but not BIM deletion.
In this paper, we propose an adaptive Go-Back-N (GBN) ARQ protocol over two parallel channels with slow state transition. This proposed protocol sophisticatedly determines the order of priority of ...the channel usage for sending packets, by using the channel-state feedback information. We exactly analyze the throughput efficiency of the protocol and obtain its closed-form expression under the assumption that the time-varying channel is modeled by a two-state Markov chain, which is characterized by packet error rate and the decay factor. The analytical results and numerical examples show that, for a given round-trip time, the throughput efficiency depends on both the average packet-error rate and the decay factor. Furthermore, it is shown that the throughput efficiency of the proposed protocol is superior to that of the non-adaptive Go-Back-N protocol using the two channels in a fixed order in the case of slow state transition (i.e. the decay factor is positively large).
In the island of Hainan, the great majority of malaria cases occur in mountain worker populations. Using the behavioral change communication (BCC) strategy, an interventional study was conducted to ...promote mountain worker malaria prevention at a test site. This study found the methods and measures that are suitable for malaria prevention among mountain worker populations.
During the Plasmodium falciparum elimination stage in Hainan, a representative sampling method was used to establish testing and control sites in areas of Hainan that were both affected by malaria and had a relatively high density of mountain workers. Two different methods were used: a BCC strategy and a conventional strategy as a control. Before and after the intervention, house visits, core group discussions, and structural surveys were utilized to collect qualitative and quantitative data regarding mountain worker populations (including knowledge, attitudes, and practices KAPs; infection status; and serological data), and these data from the testing and control areas were compared to evaluate the effectiveness of BCC strategies in the prevention of malaria.
In the BCC malaria prevention strategy testing areas, the accuracy rates of malaria-related KAP were significantly improved among mountain worker populations. The accuracy rates in the 3 aspects of malaria-related KAP increased from 37.73%, 37.00%, and 43.04% to 89.01%, 91.53%, and 92.25%, respectively. The changes in all 3 aspects of KAP were statistically significant (p < 0.01). In the control sites, the changes in the indices were not as marked as in the testing areas, and the change was not statistically significant (p > 0.05). Furthermore, in the testing areas, both the percentage testing positive in the serum malaria indirect fluorescent antibody test (IFAT) and the number of people inflicted decreased more significantly than in the control sites (p < 0.01).
The use of the BCC strategy significantly improved the ability of mountain workers in Hainan to avoid malarial infection. Educational and promotional materials and measures were developed and selected in the process, and hands-on experience was gained that will help achieve the goal of total malaria elimination in Hainan.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim： Caveolin-1 （cav-1） is a major multifunctional scaffolding protein of caveolae. Cav-1 is primarily expressed in mesangial cells, renal proximal tubule cells and podocytes in kidneys. Recent ...evidence shows that the functional connections between cav-1 and ROS play a key role in many diseases. In this study we investigated whether regulating the functional connections between cav-1 and ROS in kidneys contributed to the beneficial effects of curcumin in treating diabetic nephropathy in vitro and in vivo. Methods： Cultured mouse podocytes （mpc5） were incubated in a high glucose （HG, 30 mmol/L） medium for 24, 48 or 72 h. Male rats were injected with STZ （60 mg/kg, ip） to induce diabetes. ROS generation, SOD activity, MDA content and caspase-3 activity in the cultured cells and kidney cortex homogenate were determined. Apoptotic proteins and cav-1 phosphorylation were analyzed using Western blot analyses. Results： Incubation in HG-containing medium time-dependently increased ROS production, oxidative stress, apoptosis, and cav-1 phosphorylation in podocytes. Pretreatment with curcumin （1, 5, and 10 pmol/L） dose-dependently attenuated these abnormalities in HG-treated podocytes. Furthermore, in HG-containing medium, the podocytes transfected with a recombinant plasmid GFP-cav-1 Y14F （mutation at a cav-1 phosphorylation site） exhibited significantly decreased ROS production and apoptosis compared with the cells transfected with empty vector. In diabetic rats, administration of curcumin （100 or 200 mg/kg body weight per day, ig, for 8 weeks） not only significantly improved the renal function, but also suppressed ROS levels, oxidative stress, apoptosis and cav-1 phosphorylation in the kidneys.Conclusion： Curcumin attenuates high glucose-induced podocyte apoptosis in vitro and diabetic nephropathy in vivo partly through regulating the functional connections between cav-1 phosphorylation and ROS.
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