Exploration of the Polymorphism Distribution of Bovine HMGA2 Gene in Worldwide Breeds and Its Associations with Ovarian Traits.

The high-mobility group AT-hook 2(HMGA2) gene has been widely studied in the context of cancer and animal growth. However, recently, several studies have uncovered its critical role in cell proliferation. A genome-wide association study (GWAS) further suggests that the HMGA2 gene is a candidate gene in fertility, indicating its connection not only to growth traits but also to reproduction, specifically ovarian traits. Thus, this study aimed to analyze the distribution of the HMGA2 gene in 54 bovine breeds worldwide, identify important short fragment variants (indels), and investigate the relationship between HMGA2 and ovarian development. The dataset included genotypic information from a bovine population of 634 individuals (n = 634). After genotyping and analyzing four selected loci, we found that one out of four loci, rs133750033 (P4-D22-bp), was polymorphic. Our results also reveal that this indel of HMGA2 is significantly associated with certain ovarian traits (p < 0.05). Specifically, it has connection with ovarian length (p = 0.004) and ovarian height (p = 0.026) during diestrus. Additionally, we discovered a higher expression of the HMGA2 gene in Asian cattle breeds. In summary, this study suggests that HMGA2 has the potential to serve as an animal fertility testing marker gene. Moreover, these findings contribute to a more promising outlook for the bovine industry.

The OsNAC24-OsNAP protein complex activates OsGBSSI and OsSBEI expression to fine-tune starch biosynthesis in rice endosperm.

Starch accounts for up to 90% of the dry weight of rice endosperm and is a key determinant of grain quality. Although starch biosynthesis enzymes have been comprehensively studied, transcriptional regulation of starch-synthesis enzyme-coding genes (SECGs) is largely unknown. In this study, we explored the role of a NAC transcription factor, OsNAC24, in regulating starch biosynthesis in rice. OsNAC24 is highly expressed in developing endosperm. The endosperm of osnac24 mutants is normal in appearance as is starch granule morphology, while total starch content, amylose content, chain length distribution of amylopectin and the physicochemical properties of the starch are changed. In addition, the expression of several SECGs was altered in osnac24 mutant plants. OsNAC24 is a transcriptional activator that targets the promoters of six SECGs; OsGBSSI, OsSBEI, OsAGPS2, OsSSI, OsSSIIIa and OsSSIVb. Since both the mRNA and protein abundances of OsGBSSI and OsSBEI were decreased in the mutants, OsNAC24 functions to regulate starch synthesis mainly through OsGBSSI and OsSBEI. Furthermore, OsNAC24 binds to the newly identified motifs TTGACAA, AGAAGA and ACAAGA as well as the core NAC-binding motif CACG. Another NAC family member, OsNAP, interacts with OsNAC24 and coactivates target gene expression. Loss-of-function of OsNAP led to altered expression in all tested SECGs and reduced the starch content. These results demonstrate that the OsNAC24-OsNAP complex plays key roles in fine-tuning starch synthesis in rice endosperm and further suggest that manipulating the OsNAC24-OsNAP complex regulatory network could be a potential strategy for breeding rice cultivars with improved cooking and eating quality.

NPM1 promotes nasopharyngeal carcinoma metastasis and stemness by recruiting Mdm2 to induce the ubiquitination-mediated degradation of p53.

Nasopharyngeal carcinoma (NPC) is clinically challenging due to the development of distant metastasis following initial therapy. Therefore, it is necessary to elucidate the mechanisms underlying metastases to develop novel therapeutic strategies. Nucleophosmin 1 (NPM1) has been directly linked to the development of human tumors and may have both tumor-suppressing and oncogenic properties. Although NPM1 is often overexpressed in solid tumors of various histopathological origins, its specific function in mediating the development of NPC is still unknown. Here, we investigated the role of NPM1 in NPC and discovered that NPM1 was elevated in clinical NPC samples and served as a predictor of the worst prognosis in NPC patients. Furthermore, the upregulation of NPM1 promoted the migration and the cancer stemness of NPC both in vitro and in vivo. Mechanistic analyses revealed that the E3 ubiquitin ligase Mdm2 was recruited by NPM1 to induce the ubiquitination-mediated proteasomal degradation of p53. Ultimately, knockdown of NPM1 suppressed the stemness and EMT signals. In summation, this study demonstrated the role and the underlying molecular mechanism of NPM1 in NPC, providing the evidence for the clinical application of NPM1 as a therapeutic target for the treatment of patients with NPC.

Immunization against inhibin DNA vaccine as an alternative therapeutic for improving follicle development and reproductive performance in beef cattle.

The objective of the present study was to investigate the potential role of immunization against INH on follicular development, serum reproductive hormone (FSH, E2, and P4) concentrations, and reproductive performance in beef cattle. A total of 196 non-lactating female beef cattle (4-5 years old) with identical calving records (3 records) were immunized with 0.5, 1.0, 1.5, or 2.0 mg [(T1, n = 58), (T2, n = 46), (T3, n = 42) and (T4, n = 36), respectively] of the pcISI plasmid. The control (C) group (n = 14) was immunized with 1.0 mL 0.9% saline. At 21d after primary immunization, all beef cattle were boosted with half of the primary immunization dose. On day 10 after primary immunization, the beef cattle immunized with INH DNA vaccine evidently induced anti-INH antibody except for the T1 group. The T3 group had the greatest P/N value peak among all the groups. The anti-INH antibody positive rates in T2, T3 and T4 groups were significantly higher than that in C and T1 groups. RIA results indicated that serum FSH concentration in T2 group increased markedly on day 45 after booster immunization; the E2 amount in T3 group was significantly increased on day 10 after primary immunization, and the levels of E2 also improved in T2 and T3 groups after booster immunization; the P4 concentration in T2 group was significantly improved on day 21 after primary immunization. Ultrasonography results revealed that the follicles with different diameter sizes were increased, meanwhile, the diameter and growth speed of ovulatory follicle were significantly increased. Furthermore, the rates of estrous, ovulation, conception, and twinning rate were also significantly enhanced. These findings clearly illustrated that INH DNA vaccine was capable of promoting the follicle development, thereby improving the behavioral of estrous and ovulation, eventually leading to an augment in the conception rates and twinning rate of beef cattle.

Simultaneously Enhancing the Fire Retardancy and Heat Resistance of Stereo-Complex-Type Polylactic Acid.

Polylactic acid (PLA) is considered to be the material with great application potential in the 21st century which has aroused wide research interest. However, PLA is a highly flammable material and exhibits low heat distortion temperature, which greatly limits its application in many fields. In this work, aluminum diethyl phosphinate (ADP) and poly (d-lactic acid) (PDLA) are used to improve fire retardancy and heat resistance of poly (l-lactic acid) (PLLA). PLLA/PDLA with the presence of 15 wt % ADP exhibited the limiting oxygen index (LOI) value at 26%, and the peak heat release rate (pHRR) and total heat release decreased, respectively, by 14.03 and 24.42% from 500 to 429 kW/m2 and 86 to 65 MJ/m2. The melt dripping phenomenon was suppressed obviously. The addition of ADP realized the flame-retardant effect from both the condensed phase and gas phase. Moreover, the results showed that the addition of ADP promoted the formation of stereo crystals and increased the crystallization temperature to 175 °C. The heat distortion temperature (HDT) of the PLLA/PDLA sample with 15 wt % ADP can be as high as 170.4 °C, which marks significant improvement in the heat resistance of PLA. The mechanical property test results showed that ADP has little effect on the mechanical properties of the composites. This work opens a window to realize the heat-resistant and anti-dripping fire-retardant PLA.

OsNAC129 Regulates Seed Development and Plant Growth and Participates in the Brassinosteroid Signaling Pathway.

Grain size and the endosperm starch content determine grain yield and quality in rice. Although these yield components have been intensively studied, their regulatory mechanisms are still largely unknown. In this study, we show that loss-of-function of OsNAC129, a member of the NAC transcription factor gene family that has its highest expression in the immature seed, greatly increased grain length, grain weight, apparent amylose content (AAC), and plant height. Overexpression of OsNAC129 had the opposite effect, significantly decreasing grain width, grain weight, AAC, and plant height. Cytological observation of the outer epidermal cells of the lemma using a scanning electron microscope (SEM) revealed that increased grain length in the osnac129 mutant was due to increased cell length compared with wild-type (WT) plants. The expression of OsPGL1 and OsPGL2, two positive grain-size regulators that control cell elongation, was consistently upregulated in osnac129 mutant plants but downregulated in OsNAC129 overexpression plants. Furthermore, we also found that several starch synthase-encoding genes, including OsGBSSI, were upregulated in the osnac129 mutant and downregulated in the overexpression plants compared with WT plants, implying a negative regulatory role for OsNAC129 both in grain size and starch biosynthesis. Additionally, we found that the expression of OsNAC129 was induced exclusively by abscisic acid (ABA) in seedlings, but OsNAC129-overexpressing plants displayed reduced sensitivity to exogenous brassinolide (BR). Therefore, the results of our study demonstrate that OsNAC129 negatively regulates seed development and plant growth, and further suggest that OsNAC129 participates in the BR signaling pathway.

Granulosa cell transcriptomic study reveals the differential regulation of lncRNAs and mRNAs related to follicle development in goat.

Mammalian follicle development is a complex biological process regulated by several factors. More than 99% of the follicles in goat ovaries will be atresia and only a few will eventually mature and ovulate. To investigate the potential long non-coding RNAs (lncRNAs) that regulate the expression of genes associated with follicular dominance or atresia, RNA-seq was performed on dominant follicles (DFs) and subordinate follicles (SFs) of granulosa cells from goats at the first follicular wave. A total of 92 differentially expressed lncRNAs and 676 differentially expressed mRNAs were detected in both types of follicles. The qRT-PCR results were consistent with the transcriptome sequencing data. Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed mRNAs revealed that LHR and LDLR are associated with follicle dominance and are involved in the ovarian steroidogenesis pathway. The co-located mRNAs CALM2 and PPP1CA were significantly enriched during oocyte meiosis and in the cAMP and oxytocin signalling pathways. The co-expressed mRNAs were significantly enriched in the oestrogen signalling pathway and in ovarian steroidogenesis and progesterone-mediated oocyte maturation. A co-expression network of lncRNAs, target genes and differentially expressed genes was constructed. Follicle development-related genes, such as LDLR, NOTCH1 and FGF12, were included. These findings expand the lncRNA catalogue and provide a basis for further studies on the mechanism of regulating follicular development in goats.

Cytosine-phosphate-guanine oligodeoxynucleotides regulate the cell cycle, apoptosis, and steroidogenesis of mouse ovarian granulosa cells by targeting inhibin alpha (1 ~ 32) fragments.

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODNs), which exist in vertebrate, bacterial, and viral genomes, are regarded as strong immune adjuvants. To date, the biological activities of CpG-ODNs in reproduction remain unknown. Here, we investigated the effects of CpG-ODNs on the cell cycle, apoptosis, and steroidogenesis in mouse granulosa cells (mGCs), in combination with inhibin alpha (1 ~ 32) fragments. mGCs were transfected with pEGFP (containing green fluorescent protein, as a control), pEGISI (containing inhibin alpha (1 ~ 32) fragments), or pEGISI-CpG-ODNs (containing inhibin alpha (1 ~ 32) fragments and CpG-ODNs motifs) plasmid for 48 h in vitro. Our results showed that the mRNA and protein expression levels of inhibin alpha were downregulated in mGCs transfected with pEGISI-CpG-ODNs, compared to those transfected with pEGISI. Flow cytometry demonstrated that pEGISI-CpG-ODNs transfection promoted cell proliferation (for example, increasing the number of cells in S and G2 phases) and decreased apoptosis, compared to pEGISI transfection. The present study also indicated that the expression of cell cycle-related genes (cyclin D2, cyclin D3, cyclin E1, Cdk2, and Cdk6) was increased, while the expression of apoptosis-related factors (Fas, FasL, caspase-8, and caspase-3) decreased after pEGISI-CpG-ODNs treatment. Additionally, pEGISI-CpG-ODNs reversed the effect of pEGISI on the secretion of estradiol in mGCs, which was further validated by upregulating the levels of its synthesis-related factors (StAR, Cyp11a1, and 17ß-HSD II). Nevertheless, pEGISI-CpG-ODNs or pEGISI did not affect the concentration of progesterone nor changed the expression levels of its synthesis-related factors (3ß-HSD I and Cyp19a1). In conclusion, this study demonstrated that CpG-ODNs may affect the cell cycle, apoptosis, and steroidogenesis by targeting the effects of inhibin alpha (1 ~ 32) fragments, supporting the potential role of CpG-ODNs in the development of granulosa cells.

Risk Factors for Post-operative Planned Reintubation in Patients After General Anesthesia: A Systematic Review and Meta-Analysis.

Background: The occurrence of postoperative reintubation (POR) in patients after general anesthesia (GA) is often synonymous with a poor prognosis in patients. This is the first review analyzing scientific literature to identify risk factors of POR after general anesthesia. The purpose of this study was to collect currently published studies to determine the most common and consistent risk factors associated with POR after GA. Methods: We have retrieved all relevant research published before April 2021 from PubMed, Embase, Web of Science, and the Cochrane Library electronic databases. These studies were selected according to the inclusion and exclusion criteria. The Z test determined the combined odds ratio (OR) of risk factors. We used OR and its corresponding 95% confidence interval (CI) to identify significant differences in risk factors. The quality of the study was evaluated with the NOS scale, and meta-analysis was carried out with Cochrane Collaboration's Revman 5.0 software. Results: A total of 10 studies were included, with a total of 7,789 recipients of POR. We identified 7 risk factors related to POR after GA: ASA ≥ 3 (OR = 3.58), COPD (OR = 2.09), thoracic surgery (OR = 17.09), airway surgery (OR = 9.93), head-and-neck surgery (OR = 3.49), sepsis (OR = 3.50), DVT (OR = 4.94). Conclusion: Our meta-analysis showed that ASA ≥ 3, COPD, thoracic surgery, airway surgery, head-and-neck surgery, sepsis and DVT were associated with POR after GA. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, Identifier: CRD42021252466.

Traditional Chinese herbal medicine complex supplementation improves reproductive performance, serum biochemical parameters, and anti-oxidative capacity in periparturient dairy cows.

This study was conducted to investigate the effects of a traditional Chinese herbal medicine complex (TCHMC) on the productive performance of periparturient dairy cows. Eighteen non-lactating pregnant Holstein dairy cows with similar body conditions with 1 to 2 parity were randomly divided into three groups (n = 6), receiving a basal diet with 0 (CON group), 200 (T-200 group), and 300 (T-300 group) g TCHMC per day from 14 to 9 days prepartum. The results demonstrated that TCHMC treatments decreased the days of gestation, calving to first service, and calving to first visible estrus. Compared with CON at specific time points, TCHMC treatments increased the concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), whereas progesterone (P4) and E2 concentrations decreased. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) concentrations were downregulated, whereas that of globulin (GLB) and immunoglobulin G (IgG) were upregulated by TCHMC treatments around the time of calving. Compared with CON and T-200 treatments, the T-300 treatment increased the serum concentrations of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) and decreased the malondialdehyde (MDA) concentration from 7 d prepartum to 21 d postpartum when. In addition, although TCHMC treatment had no effect on average birth weight, heart rate, respiratory rate, and body temperature of calves, the T-300 treatment increased serum albumin (ALB) and IgG concentrations in calves from 3 to 14 days postpartum. The addition of TCHMC used in the present study could serve as a potential effective strategy to improve the health and productive performance of periparturient dairy cows, and the optimal dose should be set at 300 g per day.

High-resolution quantitative trait locus mapping for rice grain quality traits using genotyping by sequencing.

Rice is a major food crop that sustains approximately half of the world population. Recent worldwide improvements in the standard of living have increased the demand for high-quality rice. Accurate identification of quantitative trait loci (QTLs) for rice grain quality traits will facilitate rice quality breeding and improvement. In the present study, we performed high-resolution QTL mapping for rice grain quality traits using a genotyping-by-sequencing approach. An F2 population derived from a cross between an elite japonica variety, Koshihikari, and an indica variety, Nona Bokra, was used to construct a high-density genetic map. A total of 3,830 single nucleotide polymorphism markers were mapped to 12 linkage groups spanning a total length of 2,456.4 cM, with an average genetic distance of 0.82 cM. Seven grain quality traits-the percentage of whole grain, percentage of head rice, percentage of area of head rice, transparency, percentage of chalky rice, percentage of chalkiness area, and degree of chalkiness-of the F2 population were investigated. In total, 15 QTLs with logarithm of the odds (LOD) scores >4 were identified, which mapped to chromosomes 6, 7, and 9. These loci include four QTLs for transparency, four for percentage of chalky rice, four for percentage of chalkiness area, and three for degree of chalkiness, accounting for 0.01%-61.64% of the total phenotypic variation. Of these QTLs, only one overlapped with previously reported QTLs, and the others were novel. By comparing the major QTL regions in the rice genome, several key candidate genes reported to play crucial roles in grain quality traits were identified. These findings will expedite the fine mapping of these QTLs and QTL pyramiding, which will facilitate the genetic improvement of rice grain quality.

Global profiling of lncRNAs-miRNAs-mRNAs reveals differential expression of coding genes and non-coding RNAs in the lung of beagle dogs at different stages of Toxocara canis infection.

The roundworm Toxocara canis causes toxocariasis in dogs and larval migrans in humans. Better understanding of the lung response to T. canis infection could explain why T. canis must migrate to and undergoes part of its development inside the lung of the definitive host. In this study, we profiled the expression patterns of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in the lungs of Beagle dogs infected by T. canis, using high throughput RNA sequencing. At 24 h p.i., 1,012 lncRNAs, 393 mRNAs and 10 miRNAs were differentially expressed (DE). We also identified 883 DElncRNAs, 264 DEmRNAs and 20 DEmiRNAs at 96 h p.i., and 996 DElncRNAs, 342 DEmRNAs and eight DEmiRNAs at 36 days p.i., between infected and control dogs. Significant changes in the levels of expression of transcripts related to immune response and inflammation were associated with the antiparasitic response of the lung to T. canis. The remarkable increase in the expression of scgb1a1 at all time points after infection suggests the need for consistent moderation of the excessive inflammatory response. Also, upregulation of foxj1 at 24 h p.i., and downregulation of IL-1ß and IL-21 at 96 h p.i., suggest an attenuation of the humoral immunity of infected dogs. These results indicate that T. canis pathogenesis in the lung is mediated through contributions from both pro-inflammatory and anti-inflammatory mechanisms. Competing endogenous RNA (ceRNA) network analysis revealed significant interactions between DElncRNAs, DEmiRNAs and DEmRNAs, and improved our understanding of the ceRNA regulatory mechanisms in the context of T. canis infection. These data provide comprehensive understanding of the regulatory networks that govern the lung response to T. canis infection and reveal new mechanistic insights into the interaction between the host and parasite during the course of T. canis infection in the canine.

Alterations in vaginal temperature during the estrous cycle in dairy cows detected by a new intravaginal device-a pilot study.

Estrus identification is important in dairy cow production. At present, estrus identification is automated with a pedometer or accelerometer and the results remain unsatisfactory. It was previously reported that body temperature changes during estrus. In the present study, dairy cow vaginal temperature (VT) was monitored during various seasons, and an increase in VT of 0.3 °C was suggested for the onset of estrus, using an automated VT monitoring system developed in-house. Natural and synchronized estrus were measured simultaneously. The VT was determined to be in circadian rhythm and significantly higher in summer than in either autumn or winter (P < 0.05). VT difference (between estrus VT and average VT 7 days earlier) gradually increased, reached a peak of 0.56 °C ± 0.17 at 4 h before the end of estrus, and then decreased to the normal. The VT of cows in estrus and the duration of their estrus were significantly affected by seasons and estrus types (P < 0.05). VT gradually decreased in response to prostaglandin (PG) injection and was significantly lower (0.15-0.35 °C) from 9 to 33 h after the drug administration than the average VT at the same time 7 days earlier (P < 0.05). Changes in circadian and seasonal VT and in the estrous cycle can be monitored to assess the physiological status of cows and will help in developing an effective automated estrus identification technique. Results of this pilot study should be validated in further studies.

Early pregnancy diagnoses based on physiological indexes of dairy cattle: a review.

With the development of standardization and scaling in the dairy farming industry, timely and accurate pregnancy diagnosis is required to improve the benefits of breeding by shortening the calving interval. However, the current pregnancy diagnostic methods cannot meet the requirements of the industry. Here, we review changes in the physiological indexes and in the function and morphological status of the reproductive organs of dairy cows at the early stages of pregnancy. In addition, the corresponding pregnancy diagnostic methods based on certain indexes are well development, and the pregnancy diagnostic approaches based on remote sensing and automation technology have become inevitable trends in the industry. These applications will reveal physiological regularities in pregnancy and benefit the detailed management of dairy cows during early pregnancy.

Serum metabolomic alterations in Beagle dogs experimentally infected with Toxocara canis.

BACKGROUND: Toxocara canis, a globally distributed roundworm, can cause debilitating disease in dogs and humans; however, little is known about the metabolomic response of the hosts to T. canis infection. There is an increasing need to understand the metabolic mechanisms underlying the pathogenesis of T. canis infection in dogs. Here, we examined the metabolomic changes in Beagle dogs' serum following T. canis infection using LC-MS/MS. RESULTS: The metabolic profiles of Beagle dogs' serum were determined at 12 h, 24 h, 10 d and 36 d after oral infection with 300 infectious T. canis eggs by LC-MS/MS. We tested whether the T. canis-associated differentially abundant metabolites could distinguish the serum of infected dogs from controls, as measured by the area under the receiver operating characteristic (ROC) curve (AUC). The differentially expressed metabolites were further evaluated by principal components analysis and pathway enrichment analysis. A total of 5756 and 5299 ions were detected in ESI+ and ESI- mode, respectively. ROC curve analysis revealed nine and five metabolite markers, at 12 hpi and 24 hpi to 36 dpi, respectively, with potential diagnostic value for toxocariasis. The levels of taurocholate, estradiol, prostaglandins and leukotriene were significantly changed. Primary bile acid biosynthesis pathway, steroid hormone biosynthesis pathway and biosynthesis of unsaturated fatty acids pathway were significantly altered by T. canis infection. CONCLUSIONS: These findings show that T. canis infection can induce several changes in the dog serum metabolome and that the metabolic signature associated with T. canis infection in dogs has potential for toxocariasis diagnosis.

Molecular Detection and Genotyping of Toxoplasma gondii in Edward's Long-Tailed Rats (Leopoldamys edwardsi).

Toxoplasma gondii is an important zoonotic parasite infecting humans and various animals with a worldwide distribution. However, limited information is available on T. gondii infection in wild rats. The present study aimed to examine the prevalence and characterize the genotypes of T. gondii in wild rats in two regions of China. Brain tissues were collected from 111 Edward's long-tailed rats (Leopoldamys edwardsi) and 117 Bower's white-toothed rats (Berylmys bowersi) between November 2017 and January 2018. Genomic DNA was extracted and amplified by PCR targeting the T. gondii B1 gene. B1 gene-positive samples were genotyped at 10 genetic markers (SAG1, SAG2 [5', 3'] and [alternative], SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using multilocus nested polymerase chain reaction/restriction fragment length polymorphism. Six (5.41%, 6/111) Edward's long-tailed rats from Chongqing Municipality were positive for T. gondii B1 gene, whereas no T. gondii infection was detected in Bower's white-toothed rats (n = 117) from Guangdong province. T. gondii prevalence in female and male rats was 1.77% (2/113) and 3.48 (4/115), respectively. Four of the six positive DNA samples were completely genotyped at 10 genetic loci and were identified as ToxoDB#20. The present study revealed the occurrence of T. gondii infection in Edward's long-tailed rats. These findings raised public health concerning about T. gondii infection in wild rats. These results provide reference data for understanding the distribution of T. gondii genotypes in wild rats in China.

Insufficient PINX1 expression stimulates telomerase activation by direct inhibition of EBV LMP1-NF-κB axis during nasopharyngeal carcinoma development.

OBJECTIVE: Early malignant transformation of nasopharyngeal carcinoma(NPC) is associated with Epstein-Barr virus(EBV) infection and telomerase activation. The EBV latent membrane protein 1(LMP1) regulates expression of various genes by triggering NF-κB signaling pathway. PINX1 is a well-identified tumor suppressor gene by inhibiting telomerase activity and cancer cell growth. However, whether and how EBV inhibit PINX1 expression and activate telomerase in NPC is still incompletely elucidated. METHODS: Immunohistochemistry, real-time PCR and Western blotting were utilized to explore the expression of PINX1. Chromatin immunoprecipitation(ChIP) and Dual-luciferase reporter assay were used to elucidate the regulatory mechanism between NF-κB and PINX1. TRAP-SYBR Green assay and Southern blotting were utilized to detect telomerase activity and telomere length. CCK8 and EdU tests were conducted to measure proliferation ability. RESULTS: We demonstrated that PINX1 is down-regulated in NPC for the first time. Mechanistically, we found that LMP1 could inhibit the transcriptional activity of PINX1 by promoting the binding of p65 to three specific sites in PINX1 promoter, significantly, two(-1698/-1689, tgcaatttcc; -206/-197, cgggctttac) of which have not been reported. In addition, we also observed that LMP1 overexpression resulted in increased telomerase activity, prolonged telomere length and enhanced proliferation. CONCLUSION: We first discovered EBV led to reduced PINX1 expression through LMP1-NF-κB-PINX1 axis, which up-regulated telomerase activity in NPC. And hence, the tumor cells acquired the ability to proliferate more exuberantly. This signaling pathway illustrates the relationship between EBV latent infection and telomerase activation, and further provides new thinking for early diagnosis and treatment in NPC.

New Insights on Water Buffalo Genomic Diversity and Post-Domestication Migration Routes From Medium Density SNP Chip Data.

The domestic water buffalo is native to the Asian continent but through historical migrations and recent importations, nowadays has a worldwide distribution. The two types of water buffalo, i.e., river and swamp, display distinct morphological and behavioral traits, different karyotypes and also have different purposes and geographical distributions. River buffaloes from Pakistan, Iran, Turkey, Egypt, Romania, Bulgaria, Italy, Mozambique, Brazil and Colombia, and swamp buffaloes from China, Thailand, Philippines, Indonesia and Brazil were genotyped with a species-specific medium-density 90K SNP panel. We estimated the levels of molecular diversity and described population structure, which revealed historical relationships between populations and migration events. Three distinct gene pools were identified in pure river as well as in pure swamp buffalo populations. Genomic admixture was seen in the Philippines and in Brazil, resulting from importations of animals for breed improvement. Our results were largely consistent with previous archeological, historical and molecular-based evidence for two independent domestication events for river- and swamp-type buffaloes, which occurred in the Indo-Pakistani region and close to the China/Indochina border, respectively. Based on a geographical analysis of the distribution of diversity, our evidence also indicated that the water buffalo spread out of the domestication centers followed two major divergent migration directions: river buffaloes migrated west from the Indian sub-continent while swamp buffaloes migrated from northern Indochina via an east-south-eastern route. These data suggest that the current distribution of water buffalo diversity has been shaped by the combined effects of multiple migration events occurred at different stages of the post-domestication history of the species.

Effect of a DNA vaccine harboring two copies of inhibin α (1-32) fragments on immune response, hormone concentrations and reproductive performance in rats.

The objective was to investigate the effects of a novel DNA vaccine (pcISI) harboring two copies of inhibin α (1-32) fragments on immune response, hormone concentrations and reproductive performance in rats. Female Wistar rats (n=18 per group) were immunized (twice, 4 wk apart) with 10, 50, or 100 µg (T1, T2 and T3, respectively), of the pcISI plasmid. At 4 wk after the second immunization, plasma antibody titers were higher (P<0.05) in T3 than in either T1 or T2 (0.341±0.123, 0.236±0.068, and 0.251±0.077, respectively, mean±SD). Concurrrently, plasma concentrations of FSH and estradiol were highest (P<0.05) in T3, and were higher (P<0.05) in T1 and T2 than in control groups. For antibody-positive rats, there was a correlation (P<0.01) between antibody titer and FSH concentrations after two pcISI immunizations. The number of mature follicles in the T3 group (46.00±4.65) was higher (P<0.05) than in two control groups (29.25±3.72 and 27.92±3.48), and also higher (P<0.05) than in T1 and T2 (37.17±4.99 and 38.75±7.09). Antibody-positive rats had more mature ovarian follicles than negative rats (46.75±4.23 vs. 35.60±3.38, P<0.05). Moreover, litter size and number of placentas were increased (P<0.05) in the pcISI immunization groups, except for the T1 group, compared to the control groups. In conclusion, the pcISI DNA vaccine successfully induced a humoral immune response, improved reproductive hormone concentrations, stimulated follicular development, and increased number of placentas and litter size. Furthermore, 100 µg yielded the best immune response.