A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

The multiple merger assembly of a hyperluminous obscured quasar at redshift 4.6.

Galaxy mergers and gas accretion from the cosmic web drove the growth of galaxies and their central black holes at early epochs. We report spectroscopic imaging of a multiple merger event in the most luminous known galaxy, WISE J224607.56-052634.9 (W2246-0526), a dust-obscured quasar at redshift 4.6, 1.3 billion years after the Big Bang. Far-infrared dust continuum observations show three galaxy companions around W2246-0526 with disturbed morphologies, connected by streams of dust likely produced by the dynamical interaction. The detection of tidal dusty bridges shows that W2246-0526 is accreting its neighbors, suggesting that merger activity may be a dominant mechanism through which the most luminous galaxies simultaneously obscure and feed their central supermassive black holes.

The role of XRCC6/Ku70 in nasopharyngeal carcinoma.

The association between XRCC6/Ku70, an upstream player in the DNA double-strand break repair system, and the risk of nasopharyngeal carcinoma (NPC) was examined. In this case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with NPC risk were evaluated. NPC tissue samples were also assessed for their XRCC6 mRNA and protein expression by real-time quantitative reverse transcription PCR and Western blotting, respectively. With regard to the XRCC6 promoter T-991C, the TC and CC genotypes were associated with a significantly increased risk of NPC compared with wild-type TT genotype (adjusted odds ratio 2.02 and 3.42, 95% confidence interval 1.21-3.32 and 1.28-8.94, P=0.0072 and 0.0165, respectively). The mRNA and protein expression levels for NPC tissues revealed significantly lower XRCC6 mRNA and protein expression in the NPC samples with TC/CC genotypes compared to those with the TT genotype (P=0.0210 and 0.0164, respectively). These findings suggest that XRCC6 may play an important role in the carcinogenesis of NPC and could serve as a chemotherapeutic target for personalized medicine and therapy.

WWOX suppresses autophagy for inducing apoptosis in methotrexate-treated human squamous cell carcinoma.

Squamous cell carcinoma (SCC) cells refractory to initial chemotherapy frequently develop disease relapse and distant metastasis. We show here that tumor suppressor WW domain-containing oxidoreductase (WWOX) (also named FOR or WOX1) regulates the susceptibility of SCC to methotrexate (MTX) in vitro and cure of SCC in MTX therapy. MTX increased WWOX expression, accompanied by caspase activation and apoptosis, in MTX-sensitive SCC cell lines and tumor biopsies. Suppression by a dominant-negative or small interfering RNA targeting WWOX blocked MTX-mediated cell death in sensitive SCC-15 cells that highly expressed WWOX. In stark contrast, SCC-9 cells expressed minimum amount of WWOX protein and resisted MTX-induced apoptosis. Transiently overexpressed WWOX sensitized SCC-9 cells to apoptosis by MTX. MTX significantly downregulated autophagy-related Beclin-1, Atg12-Atg5 and LC3-II protein expression and autophagosome formation in the sensitive SCC-15, whereas autophagy remained robust in the resistant SCC-9. Mechanistically, WWOX physically interacted with mammalian target of rapamycin (mTOR), which potentiated MTX-increased phosphorylation of mTOR and its downstream substrate p70 S6 kinase, along with dramatic downregulation of the aforementioned proteins in autophagy, in SCC-15. When WWOX was knocked down in SCC-15, MTX-induced mTOR signaling and autophagy inhibition were blocked. Thus, WWOX renders SCC cells susceptible to MTX-induced apoptosis by dampening autophagy, and the failure in inducing WWOX expression leads to chemotherapeutic drug resistance.

Deep brain stimulation therapy for Parkinson's disease using frameless stereotaxy: comparison with frame-based surgery.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) surgery has been performed using frame-based stereotaxy traditionally; however, in recent years, it has also been performed using frameless stereotaxy. The purpose of this study was to compare the experience at our centre in performing DBS surgery using frameless surgery for patients with Parkinson's disease with that of using frame-based surgery. METHODS: Twenty-four patients with advanced Parkinson's disease underwent DBS surgery, 12 with frameless and 12 with frame-based stereotaxy. After identifying the subthalamus by microelectrode recording (MER), the DBS electrodes were implanted and connected to an implanted programmable generator in all patients. Programming was started 1 month after the operation and the outcome of the patients was followed up regularly for at least 12 months. RESULTS: After 1 year of follow-up, the patients who received frameless surgery showed no difference in the degree of improvement in clinical motor function compared with the patients who received frame-based surgery (P = 0.819); the average improvement was 60.9% and 56.9%, respectively, in the stimulation alone/medication-off state, as evaluated by the Unified Parkinson's Disease Rating Scale-III motor subscore. However, the frameless group had significantly shorter total MER time (P = 0.0127) and a smaller number of trajectories (P = 0.0096) than the frame-based group. CONCLUSIONS: Our data indicate that frameless DBS surgery has a similar outcome when compared with frame-based surgery; however, frameless surgery can decrease the operation time, MER time, and MER trajectory number.

Transmission of grapevine leafroll-associated virus 3 by the vine mealybug (Planococcus ficus).

Grapevine leafroll disease is caused by grapevine leafroll-associated viruses (GLRaVs). Within this virus complex, GLRaV-3 is the predominant species in the world. Several GLRaVs have been shown to be transmitted from vine to vine by mealybugs although a detailed characterization of transmission biology is lacking. The introduction of the vine mealybug (Planococcus ficus) in California and other regions of the world may result in increasing disease incidence of established GLRaVs. We studied the characteristics of GLRaV-3 transmission by the vine mealybug. Our results indicate that the vine mealybug transmits GLRaV-3 in a semipersistent manner. First instars were more efficient vectors than adult mealybugs. GLRaV-3 transmission lacked a latent period in the vector. Virus transmission occurred with a 1-h acquisition access period (AAP) and peaked with a 24-h AAP. Mealybugs inoculated GLRaV-3 with a 1-h inoculation access period (IAP), and transmission efficiency increased with longer plant access period up to 24 h, after which transmission rate remained constant. After an AAP of 24 h, mealybugs lost GLRaV-3 and infectivity 4 days after virus acquisition. In addition, GLRaV-3 was not transovarially transmitted from infected females to their progeny as detected by reverse transcription polymerase chain reaction. In summary, we systematically analyzed transmission parameters of GLRaV-3 by the vine mealybug and showed that transmission of this virus occurs in a semipersistent manner. This research fills in important gaps in knowledge of leafroll virus transmission, which is critical for development of leafroll disease management practices.

Drosophila melanogaster mounts a unique immune response to the Rhabdovirus sigma virus.

Rhabdoviruses are important pathogens of humans, livestock, and plants that are often vectored by insects. Rhabdovirus particles have a characteristic bullet shape with a lipid envelope and surface-exposed transmembrane glycoproteins. Sigma virus (SIGMAV) is a member of the Rhabdoviridae and is a naturally occurring disease agent of Drosophila melanogaster. The infection is maintained in Drosophila populations through vertical transmission via germ cells. We report here the nature of the Drosophila innate immune response to SIGMAV infection as revealed by quantitative reverse transcription-PCR analysis of differentially expressed genes identified by microarray analysis. We have also compared and contrasted the immune response of the host with respect to two nonenveloped viruses, Drosophila C virus (DCV) and Drosophila X virus (DXV). We determined that SIGMAV infection upregulates expression of the peptidoglycan receptor protein genes PGRP-SB1 and PGRP-SD and the antimicrobial peptide (AMP) genes Diptericin-A, Attacin-A, Attacin-B, Cecropin-A1, and Drosocin. SIGMAV infection did not induce PGRP-SA and the AMP genes Drosomycin-B, Metchnikowin, and Defensin that are upregulated in DCV and/or DXV infections. Expression levels of the Toll and Imd signaling cascade genes are not significantly altered by SIGMAV infection. These results highlight shared and unique aspects of the Drosophila immune response to the three viruses and may shed light on the nature of the interaction with the host and the evolution of these associations.

A double-blind comparison of the efficacy and tolerability of telmisartan 40-80 mg vs. losartan 50-100 mg in Taiwanese hypertensive patients.

A multicentre, randomised, double-blind, double-dummy, parallel-group, dose-titration study was conducted to determine the efficacy and tolerability of telmisartan 40-80 mg once daily compared with losartan 50-100 mg once daily in 180 Taiwanese patients with mild-to-moderate essential hypertension. After an initial 2-week placebo run-in phase, patients were randomised in a double-blind, double-dummy fashion to receive either telmisartan 40 mg or losartan 50 mg. If blood pressure control (diastolic blood pressure [DBP] <90 mmHg or > or = 10 mmHg reduction in DBP) was achieved after 4 weeks, the dose was maintained for the second 4 weeks of the active treatment phase; if not, the dose was doubled to telmisartan 80 mg or losartan 100 mg, respectively, for the second 4 weeks of double-blind treatment. Telmisartan 40-80 mg (n = 86) was as effective as losartan 50-100 mg (n = 90) in reducing trough seated DBP (11.1 vs. 8.7 mmHg, p = 0.144), and was significantly more effective than losartan in reducing trough seated systolic blood pressure (SBP) (22.1 vs. 16.5 mmHg, p = 0.032) and standing SBP (21.0 vs. 16.3 mmHg, p = 0.033). Significantly fewer patients treated with telmisartan than those treated with losartan required uptitration after 4 weeks' treatment (32.6% vs. 61.5%, p = 0.001). Both telmisartan and losartan were well tolerated.

Cell cycle arrest allows centrin translation but not basal body formation during spermiogenesis in Marsilea.

Spermiogenesis in the water fern Marsilea vestita is a rapid process that requires the de novo formation of basal bodies in a cytoplasmic particle known as a blepharoplast. Spermiogenesis is activated by placing dry spores into water and is dependent upon the translation of new proteins from stored mRNAs with little, if any, new transcription. We looked at the necessity of cell division cycles in the gametophyte as a prerequisite for the activation of centrin translation and for the consequent formation of blepharoplasts. Cell cycle arrest was induced by treatments of gametophytes with hydroxyurea, with olomoucine, or after RNAi, employing dsRNA derived from Marsilea cyclin A or cyclin B. In all cases, centrin is translated from stored mRNA at the normal time, approximately 4 hours after imbibition, and it accumulates to maximal levels approximately 6 hours after imbibition. In spite of the fact that centrin is translated at essentially normal times and accumulates to nearly normal levels, no blepharoplasts form in the gametophytes where division cycles have been disrupted. These results provide a clear demonstration that the new translation of centrin, by itself, is insufficient for blepharoplast formation, the de novo formation of basal bodies, and the assembly of a motile apparatus.

Extraction of human DNA for PCR from chewed residues of betel quid using a novel "PVP/CTAB" method.

Residues of chewed betel quid (BQ) are often found on crime scenes in Taiwan and possibly some of the Southeast Asian countries. Although these residues are important biological evidences relating to the suspects, the forensic analysis of BQ evidence has been hindered by failures in extraction of human DNA for PCR analysis. Therefore, it is a prerequisite for relevant forensic casework to establish a reliable method for extracting DNA from chewed BQ residues. Three conventional methods (salt/chloroform, 5% Chelex-100 resin, and QIAamp) were first tested for extraction of human DNA from 33 mock BQ samples, which had been stored for less than two months, and 50 four-year-old forensic BQ samples. PCR amplifications from the HLA-DQA1&PM and the STR loci were then used to test the quality of the extracted DNA. For the mock samples, three observations were made. First, PCR amplification of DNA extracted by using these conventional methods had low success rate. Second, the addition of extra Taq DNA polymerase could compensate the lost enzyme activities due to putative inhibitors and, thus, increase the yield. Third, using the Centricon-100 column to remove putative inhibitors substantially improved the efficiency of PCR. However, for the four-year-old forensic BQ samples, none of the attempts for PCR were successful. In order to solve the problem in PCR analysis of DNA from old BQ samples, we developed a DNA extraction method based on the use of polyvinyl pyrrolidone (PVP) and cetyltrimethylammonium bromide (CTAB), which bind to two common classes of PCR inhibitors in plants, polyphenols, and polysaccharides, respectively. The result showed that this "PVP/CTAB" method is completely successful for the mock BQ samples, and 92% (46 out of 50) successful for the four-year-old forensic BQ samples. To our best knowledge, this is the first report of a reliable method for the extraction of human DNA for PCR from chewed BQ residues. This method should provide a useful means for forensic identification in countries where betel chewing is common.

Primary structure and developmental expression of zebrafish sodium channel Na(v)1.6 during neurogenesis.

A zebrafish sodium channel cDNA encoding a 1949-amino acid polypeptide, Na(v)1.6, was isolated. Two transcripts were detected in zebrafish adult brain but not in cardiac or skeletal muscle. The RNase protection analysis confirmed the neural specificity of zebrafish Na(v)1.6 24 hours postfertilization (hpf) Na(v)1.6 was expressed in the trigeminal ganglion, anterior and posterior lateral line ganglia, rhombomeres, and Rohon-Beard neurons. This preferential localization suggests that Na(v)1.6 plays an important role in tactile sensitivity. The abundance of zebrafish Na(v) 1.6 mRNA in the central and peripheral nervous systems increased markedly between 48 and 72 hpf, during the maturation of the nervous system.

Dietary fat and garlic oil independently regulate hepatic cytochrome p(450) 2B1 and the placental form of glutathione S-transferase expression in rats.

The individual and combined effects of dietary fat and garlic oil on two drug-metabolizing enzymes, cytochrome P(450) 2B1 and the placental form of glutathione (GSH) S-transferase (PGST), in rat liver were examined in this study. Rats were fed a low corn oil, high corn oil or high fish oil diet and received various amount of garlic oil (0, 30, 80, 200 mg/kg body) orally three times per week for 6 wk. The fat energy in the low and high fat diets accounted for 11.6 and 45.7% of total energy, respectively. Final body weights did not differ among the three dietary fat groups and were not affected by garlic oil treatment. The fatty acid profile in hepatic phospholipids revealed higher eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)] levels in the fish oil-fed group than in the low and high corn oil-fed groups (P < 0.05). In contrast, the corn oil-fed groups had greater hepatic phospholipid arachidonic acid [20:4(n-6)] levels (P < 0.05). Both dietary fat and garlic oil significantly affected hepatic cytochrome 7-pentoxyresorufin O-dealkylase (PROD) activity and GST activity toward ethacrynic acid. Rats fed the high fish oil diet had 85 and 51% higher PROD activity compared with those fed the low or the high corn oil diet, respectively (P < 0.05). The GST activity in the high fish oil and the high corn oil groups was 33 and 18% higher than that in the low corn oil group (P < 0.05), respectively, and the GST activity in rats fed the high fish oil diet was higher than in those fed the high corn oil diet (P < 0.05). Garlic oil dose-dependently increased GST activity. No interaction between dietary fat and garlic oil on PROD or GST activity was noted. Northern and Western blot analysis revealed that dietary fish oil increased both cytochrome P(450) 2B1 and PGST mRNA and protein levels. Cytochrome P(450) 2B1 and PGST mRNA and protein levels were also dose-dependently increased by garlic oil treatment. The effects of garlic oil and dietary fat on P(450) 2B1 and PGST mRNA and protein expression were independent. These results indicate that dietary fat and garlic oil independently modulate P(450) 2B1 and PGST expression at transcriptional and/or post-transcriptional stages.

Analysis of specific adaptation to a domicile habitat: a comparative study of two closely related cockroach species.

The German cockroach, Blattella germanica (L.), and the closely related species B. bisignata (Brunner) belong to the germanica species group. They are similar in appearance, life history, reproductive cycle, and courtship behavior. The most significant difference is habitat preferences: B. germanica is a household species and lives in crowded conditions, whereas the feral B. bisignata lives outdoors in a solitary manner. Nevertheless, B. bisignata has recently been found in households. A comparison between the two species has shown that B. germanica displays gregarious behavior and produces an aggregation pheromone, whereas both characters are absent in B. bisignata. Mate preference experiments have revealed that B. germanica females accepted only conspecific males, whereas B. bisignata females mated with males from both species, provided that long distance calling was bypassed. In addition, the high reproductive potential of B. germanica outcompeted the other species: when 10 pairs of B. germanica and of B. bisignata were kept together in crowded conditions during 3 mo, B. bisignata was driven into extinction. It is concluded that the chances of B. bisignata becoming a new household species are remote.