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AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.

Mungbean [Vigna radiata (L.) R. Wilczek var. radiata] is an important legume crop for South East Asia. Smallholder farmers rely on this crop to diversify income streams and enrich soils through N-fixation. To produce new varieties that stabilize mungbean productivity under biotic and abiotic stresses, breeders need to take advantage of genomic tools. Genome-Wide Association Studies (GWAS) are an effective strategy to associate agronomic traits with underlying genes. A key factor to avoid false associations in GWAS is a thorough understanding of the population structure. In this study, we analyzed the population structure of the World Vegetable Center’s (WorldVeg) mungbean mini core collection and performed a GWAS to identify loci associated with seed coat luster (SCL) utilizing SNP markers. The mini core collection consisted of 297 most genetically diverse accessions selected from 6700 global accessions held by the WorldVeg genebank. Genotyping by Sequencing (GBS) produced a total of 24,870 Single Nucleotide Polymorphism (SNP) markers. After filtering, 5288 highly polymorphic SNPs were used for analysis. Population structure analysis predicted four sub-populations based on the non-parametric Wilcoxon test. Linkage disequilibrium (LD) was found to decline to half of the maximal r2 value at approximately 350 kb; and a pilot GWAS study investigating seed coat luster (SCL) revealed two loci in chromosome 5 significantly associated with SCL.

Okra (Abelmoschus esculentus) is a heat tolerant vegetable crop with high economic and nutritional importance in parts of Asia, Africa, and America. The okra biodiversity held in gene bank collections could be mined for traits for breeding more stress tolerant and nutritional cultivars. An okra core collection of 166 accessions comprising A. esculentus, A. moschatus, A. caillei, and A. manihot has been assembled from the World Vegetable Center germplasm collection (840 accessions) based on diversity analysis with 20 microsatellite markers. A selection of A. esculentus accessions of the core collection (75 accessions) and 20 breeder-selected genotypes have been screened for variation of their response to flooding stress under field conditions using a high throughput phenotyping system. Growth increment per day and changes of physiological indices were measured before, during, and after application of 9 days of flooding stress. Several accessions showed only a small reduction in daily growth increment during flooding. Across the germplasm panel, maintained growth was correlated with maintained normalized differential vegetation index and was negatively correlated with plant senescence index. Accessions with maintained growth and health under flooding were selected for future further analysis and use in breeding.

Background : Restless legs syndrome (RLS) has been thought to increase the risk of hypertension, cardiovascular events, and all-cause mortality. Periodic limb movements in sleep (PLMS) can be observed in most patients with RLS. Using non-invasive physiologic measurement and analysis, including heart rate variability (HRV) analysis, we aimed to investigate sleep quality and sleep state stability. Method : A total of 53 healthy controls and 15 patients with RLS and PLMS were recruited. Patients with other sleep-related disorders such as obstructive sleep apnea (OSA) and major depressive disorder (MDD) were excluded. Each subject was evaluated using sleep and mood questionnaires and had to undergo polysomnography (PSG). HRV analysis was applied to assess autonomic function and analyze correlations with the severity of periodic leg movements (PLM). The power of different brainwaves was analyzed using electroencephalogram (EEG). Electromyogram (EMG) was also used to explore the temporal correlation between changes in HRV and leg movement events. Results : Compared with healthy controls, PLMS group had not only poorer perceived sleep and mood questionnaires scales but also reductions in parasympathetic-related HRV indices and increases in sympathetic-related HRV parameters. The changes were in proportion to the severity of PLM. Brainwaves and sleep stage which indicate “deep sleep” decreased in the PLMS group. There were no significant temporal correlations between changes in HRV and leg movement events. Conclusions : Our findings suggest that patients with RLS and PLMS have poorer subjective sleep and mood scales. Besides, objective sleep quality including HRV analysis and brainwaves analysis revealed reduced parasympathetic tone, increased sympathetic tone, and sleep disturbance, which reveal the possibility of a higher risk for secondary disease.

Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts. Using wild type D3 and HO-1 knockout ESCs in the 3-dimensional embryoid body (EB) differentiation model, we showed that at an early time point during EB development, an absence of HO-1 led to enhanced ROS level, concomitant with increased expressions of master mesodermal regulator brachyury and endodermal marker GATA6. In addition, critical smooth muscle cell (SMC) transcription factor serum response factor and its coactivator myocardin were enhanced. Furthermore, HO-1 deficiency increased Smad2 in ESCs and EBs, revealing a role of HO-1 in controlling Smad2 level. Smad2 not only mediates mesendoderm differentiation of mouse ESCs but also SMC development. Collectively, loss of HO-1 resulted in higher level of mesodermal and SMC regulators, leading to accelerated and enhanced SMC marker SM α-actin expression. Our results reveal a previously unrecognized function of HO-1 in regulating SMC gene expressions during ESC-EB development. More importantly, our findings may provide a novel strategy in enhancing ESC differentiation toward SMC lineage., Graphical abstract fx1, Highlights • Loss of HO-1 in ESCs promotes adipogenesis but reduces osteogenesis. • During early EB development, loss of HO-1 results in robust induction of brachyury. • During early EB development, lack of HO-1 leads to enhanced ROS level. • Loss of HO-1 increases SMC transcription factor SRF and cofactor myocardin. • HO-1 deficiency promotes mesodermal SMC differentiation during EB development.

Male sterility is of high importance in hybrid seed production of hot and sweet peppers. Genic (or nuclear) male sterility (GMS) is a simply inherited (usually monogenic recessive) and highly stable trait. However, one major disadvantage of using GMS is 1:1 segregation of male sterile to male fertile plants in every subsequent generation. Molecular markers tightly linked to genic male sterility (ms) genes would facilitate an efficient and rapid transfer of ms genes into different genetic backgrounds through marker-assisted backcrossing. The two non-allelic genetic male sterility genes ms3 and msw in hot and sweet pepper backgrounds, respectively, are monogenic recessive. Genotyping by sequencing (GBS) in an F2 population segregating for ms3 gene in hot pepper and in an F6 inbred near-isogenic line (NIL) population segregating for msw gene in sweet pepper yielded 9,713 and 7,453 single nucleotide polymorphism markers, respectively. Four candidate SNPs co-segregating with ms3 gene and one co-segregating with msw were identified by bulk segregant analysis and physically mapped to chromosome 1 and 5, respectively. In hot pepper, two markers (HPGMS2 (CAPS) and HPGMS3 (dCAPS)) located 3.83 cM away from the ms3 gene were developed, while in sweet pepper the dCAPS marker SPGMS1 co-segregated (completely linked) with the msw. These markers will increase the efficacy of male sterility genes for pepper breeding. Markers linked to these genes will be helpful in developing genic male sterile lines in parental inbred lines of commercial hybrids through marker-assisted backcrossing, hybrid seed production and genetic purity testing of hybrid seeds.

Dysfunctional mitochondria have been shown to enhance cancer cell proliferation, reduce apoptosis, and increase chemoresistance. Chemoresistance develops in nearly all patients with colorectal cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. However, the effect of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission on chemoresistance in colorectal cancer is unclear. Here, we found that the release of high-mobility group box 1 protein (HMGB1) in conditioned medium from dying cells by chemotherapeutic drugs and resistant cells, which triggered Drp1 phosphorylation via its receptor for advanced glycation end product (RAGE). RAGE signals ERK1/2 activation to phosphorylate Drp1 at residue S616 triggerring autophagy for chemoresistance and regrowth in the surviving cancer cells. Abolishment of Drp1 phosphorylation by HMGB1 inhibitor and RAGE blocker significantly enhance sensitivity to the chemotherapeutic treatment by suppressing autophagy. Furthermore, patients with high phospho-Drp1Ser616 are associated with high risk on developing tumor relapse, poor 5-year disease-free survival (DFS) and 5-year overall survival (OS) after neoadjuvant chemoradiotherapy (neoCRT) treatment in locally advanced rectal cancer (LARC). Moreover, patients with RAGE-G82S polymorphism (rs2070600) are associated with high phospho-Drp1Ser616 within tumor microenvironment. These findings suggest that the release of HMGB1 from dying cancer cells enhances chemoresistance and regrowth via RAGE-mediated ERK/Drp1 phosphorylation.

Tomato yellow leaf curl disease caused by different begomovirus species leads to substantial tomato production losses worldwide. In Taiwan, the monopartite tomato leaf curl Taiwan virus (ToLCTWV) and bi-partite tomato yellow leaf curl Thailand virus (TYLCTHV) are the predominant begomovirus species causing this disease. Resistance genes are available in wild tomato species and a continuous search for new resistance genes and alternative control methods is required to respond to the rapid evolution of virus strains. RNA interference is an efficient technology to induce resistance against viral pathogens. Six different sections of the ToLCTWV genome were tested in transformed tomato for their capacity to reduce symptoms and inhibit viral DNA accumulation. The two most effective constructs for ToLCTWV infection carried regions of the C1 and C2 genes, and portions of either the C3 or C4 gene of ToLCTWV. A RNAi construct containing fusions of C1, C2 and C3 sections of ToLCTWV and the corresponding sections of the TYLCTHV DNA-A genome were introgressed into tomato line CLN1621L. R1 and R2 families were challenged using viruliferous whiteflies in separate screen houses for ToLCTWV and TYLCTHV. Sixteen and 12 R2 plants derived from one primary transformant remained symptomless until at least 3 weeks after exposure to ToLCTWV and TYLCTHV, respectively, and accumulated only very low titres of viral DNA, as shown by real-time polymerase chain reaction analysis. Our results suggest that expression of bi-viral RNAi constructs in tomato can lead to resistance against two different tomato infecting begomovirus species.

Oxidative stress-induced growth inhibitor 1 (OSGIN1), a tumor suppressor, inhibits cell proliferation and induces cell death. N-6 and n-3 PUFAs protect against breast cancer, but the molecular mechanisms of this effect are not clear. We investigated the effect of n-6 and n-3 PUFAs on OSGIN1 expression and whether OSGIN1 is involved in PUFA-induced apoptosis in breast cancer cells. We used 100 μM of n-6 PUFAs including arachidonic acid, linoleic acid, and gamma-linolenic acid and n-3 PUFAs including alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). Only DHA significantly induced OSGIN1 protein and mRNA expression. DHA triggered reactive oxygen species (ROS) generation and nuclear translocation of Nrf2. LY294002, a PI3K inhibitor, suppressed DHA-induced OSGIN1 protein expression and nuclear accumulation of Nrf2. Nrf2 knockdown attenuated DHA-induced OSGIN1 expression. N-Acetyl-l-cysteine, a ROS scavenger, abrogated the DHA-induced increases in Akt phosphorylation, Nrf2 nuclear accumulation, and OSGIN1 expression. DHA induced the Bax/Bcl-2 ratio, mitochondrial accumulation of OSGIN1 and p53, and cytochrome c release; knockdown of OSGIN1 diminished these effects. In conclusion, induction of OSGIN1 by DHA is at least partially associated with increased ROS production, which activates PI3K/Akt/Nrf2 signaling. Induction of OSGIN1 may be involved in DHA-induced apoptosis in breast cancer cells.

Background Bruchid beetles are an important storage pest of grain legumes. Callosobruchus sp. infect mungbean (Vigna radiata) at low levels in the field, multiply during grain storage and can destroy seed stocks in a few months. Resistance against bruchid beetles has been found in wild mungbean V. radiata var. sublobata TC1966 and in cultivated mungbean line V2802. Results Bruchid resistance data were obtained from recombinant inbred line populations TC1966 (V. radiata var. sublobata) × NM92 (F12) and V2802 (V. radiata) × NM94 (F7). More than 6,000 single nucleotide polymorphic markers were generated through genotyping by sequencing (GBS) for each of these populations and were used to map bruchid resistance genes. One highly significant quantitative trait locus (QTL) associated with bruchid resistance was mapped to chromosome 5 on genetic maps of both populations, suggesting that TC1966 and V2802 contain the same resistance locus. Co-segregation of all markers associated with resistance indicated the presence of only one major resistance QTL on chromosome 5, while QTL analysis based on physical map positions of the markers suggested the presence of multiple QTLs on different chromosomes. The diagnostic capacity of the identified molecular markers located in the QTL to correctly predict resistance was up to 100 %. Conclusions Molecular markers tightly linked to bruchid resistance loci of two different mungbean resistance sources were developed and validated. These markers are highly useful for developing resistant lines. Electronic supplementary material The online version of this article (doi:10.1186/s12870-016-0847-8) contains supplementary material, which is available to authorized users.

From 1989 to 1996, we treated 18 cases (10 males, eight females; average age 48.2 years) of failed ankle arthrodesis by revision of ankle arthrodesis and followed their progress for at least two years. The average time interval between original surgery and revision was 17.3 months. Revisions were needed due to infection in one case, nonunion in 10 cases, and malalignment in seven cases. The salvage operations included debridement in the infected case, refreshed pseudoarthrosis in nonunion cases, and corrective osteotomy in malalignment cases. Sixteen cases were fixed by crossed screws with internal compression, one infected case was fixed by an external fixator, and one case with bone loss was fixed with buttress plate. The average follow-up period was 40.4 months. There was one nonunion and two delayed unions, with an ultimate fusion rate of 94%. The average AOFAS ankle-hindfoot score was 70.9 at final follow up. There was one excellent result (5.6%), five good results (27.8%), 11 fair results (61%), and one poor result (5.6%), and the overall results were poorer compared with our series of primary arthrodesis. The time to fusion also took longer in the revision cases (average 2.7 months in primary cases and 4.8 months in revision cases). Fusion techniques that ensure solid union in a functional position are essential. If an ankle arthrodesis fails, however, revision is a salvage procedure that can achieve an acceptable result.