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Functional mapping of the 5’LTR has shown that the U3 and the R regions (U3R) contain a cluster of regulatory elements involved in the control of HIV-1 transcription and expression. As the HIV-1 genome is characterized by extensive variability, here we aimed to describe mutations in the U3R from various HIV-1 clades and CRFs in order to highlight strain specific differences that may impact the biological properties of diverse HIV-1 strains. To achieve our purpose, the U3R sequence of plasma derived virus belonging to different clades (A1, B, C, D, F2) and recombinants (CRF02_AG, CRF01_AE and CRF22_01A1) was obtained using Illumina technology. Overall, the R region was very well conserved among and across different strains, while in the U3 region the average inter-strains nucleotide dissimilarity was up to 25%. The TAR hairpin displayed a strain-distinctive cluster of mutations affecting the bulge and the loop, but mostly the stem. Like in previous studies we found a motif in U3 promoter region from the majority of HIV-1 strains and a motif in CRF01_AE; but also in LTRs from CRF22_01A1 isolates. Although LTRs from CRF22_01A1 specimens were assigned CRF01_AE, they contained two NF-kB sites instead of the single TFBS described in CRF01_AE. Also, as previously describe in clade C isolates, we found no C/EBP binding site directly upstream of the enhancer region in CRF22_01A1 specimens. In our study, one-third of CRF02_AG LTRs displayed three NF-kB sites which have been mainly described in clade C isolates. Overall, the number, location and binding patterns of potential regulatory elements found along the U3R might be specific to some HIV-1 strains such as clade F2, CRF02_AG, CRF01_AE and CRF22_01A1. These features may be worth consideration as they may be involved in distinctive regulation of HIV-1 transcription and replication by different and diverse infecting strains. [ABSTRACT FROM AUTHOR]

Objective: Acupuncture has become popular and widely practiced in many countries around the world. Despite the large amount of acupuncture-related literature that has been published, broader trends in the prevalence and scope of acupuncture research remain underexplored. The current study quantitatively analyzes trends in acupuncture research publications in the past 20 years. Methods: A bibliometric approach was used to search PubMed for all acupuncture-related research articles including clinical and animal studies. Inclusion criteria were articles published between 1995 and 2014 with sufficient information for bibliometric analyses. Rates and patterns of acupuncture publication within the 20 year observational period were estimated, and compared with broader publication rates in biomedicine. Identified eligible publications were further analyzed with respect to study type/design, clinical condition addressed, country of origin, and journal impact factor. Results: A total of 13,320 acupuncture-related publications were identified using our search strategy and eligibility criteria. Regression analyses indicated an exponential growth in publications over the past two decades, with a mean annual growth rate of 10.7%. This compares to a mean annual growth rate of 4.5% in biomedicine. A striking trend was an observed increase in the proportion of randomized clinical trials (RCTs), from 7.4% in 1995 to 20.3% in 2014, exceeding the 4.5% proportional growth of RCTs in biomedicine. Over the 20 year period, pain was consistently the most common focus of acupuncture research (37.9% of publications). Other top rankings with respect to medical focus were arthritis, neoplasms/cancer, pregnancy or labor, mood disorders, stroke, nausea/vomiting, sleep, and paralysis/palsy. Acupuncture research was conducted in 60 countries, with the top 3 contributors being China (47.4%), United States (17.5%), and United Kingdom (8.2%). Retrieved articles were published mostly in complementary and alternative medicine (CAM) journals with impact factors ranging between 0.7 and 2.8 in the top 20 journals, followed by journals specializing in neuroscience, pain, anesthesia/analgesia, internal medicine and comprehensive fields. Conclusion: Acupuncture research has grown markedly in the past two decades, with a 2-fold higher growth rate than for biomedical research overall. Both the increases in the proportion of RCTs and the impact factor of journals support that the quality of published research has improved. While pain was a consistently dominant research focus, other topics gained more attention during this time period. These findings provide a context for analyzing strengths and gaps in the current state of acupuncture research, and for informing a comprehensive strategy for further advancing the field. [ABSTRACT FROM AUTHOR]

Aims: Interindividual variability in telomere length is highly heritable. Leukocyte telomere length (LTL) shortening has been shown to be associated with the process of atherosclerosis. But whether the inheritance of LTL is related to stroke is still unclear. The aim of this study was to test if telomere shortening was associated with stroke and whether this association was mainly due to inheritance or acquired cardiovascular risk factors. Methods: Our study was focused on stroke in patients and their siblings. 450 subjects were recruited into this study: 150 patients with ischemic stroke as case group, 150 siblings of patients free of stroke (sibling group) and 150 healthy people as normal control. LTL was measured by real-time Polymerase Chain Reactions. The association between LTL and the cardiovascular risk factors was also determined. Results: A significant decrease of LTL was found in case group when comparing with sibling (0.92±0.77 vs 1.68±1.24, p<0.001) and normal groups (0.92±0.77 vs 1.95±1.07, p<0.001), but no significant difference was found between sibling group and healthy control (p = 0.330). Shorter telomere length was independently associated with hypertension (p = 0.029, OR = 2.189, 95%CI:1.084–4.421), recent social pressure (p = 0.001, OR = 3.121, 95%CI:1.597–6.101), age (p = 0.004, OR = 1.055, 95%CI:1.017–1.093), HDL (p = 0.022, OR = 0.227, 95%CI:0.064–0.810) and diabetes (p = 0.018, OR = 3.174, 95%CI:1.221–8.252). Additionally, shortened length of telomere (p = 0.017, OR = 3.996, 95%CI:1.283–12.774) was an independent risk biomarker for stroke among case and sibling groups. Conclusion: The present study has demonstrated that decreased LTL might be associated with ischemic stroke but unlikely to be causative. [ABSTRACT FROM AUTHOR]

Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms. Mutations in U2AF1 were found in 2.5% (7/275) of AML and 6.3% (6/96) of MDS patients, but in none of 81 CML. All mutations were heterozygous missense mutations affecting codon S34 or Q157. There was no significant association of U2AF1 mutation with blood parameters, FAB subtypes, karyotypes and other gene mutations in AML. The overall survival (OS) of AML patients with U2AF1 mutation (median 3 months) was shorter than those without mutation (median 7 months) (P = 0.035). No difference in the OS was observed between MDS patients with and without U2AF1 mutations. Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS. [ABSTRACT FROM AUTHOR]

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/ 16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS. [ABSTRACT FROM AUTHOR]

Microbes are an important part of the vineyard ecosystem, which significantly influence the quality of grapes. Previously, we identified a bud mutant variety (named 'Fengzao') from 'Kyoho' grapes. The variation of microbial communities in grape and its bud mutant variety has not been studied yet. So, in this study, with the samples of both 'Fengzao' and 'Kyoho', we conducted high-throughput microbiome sequencing and investigated their microbial communities in different tissues. Obvious differences were observed in the microbial communities between 'Fengzao' and 'Kyoho'. The fruit and the stem are the tissues with relatively higher abundance of microbes, while the leaves contained less microbes. The fruit and the stem of 'Kyoho' and the stem of 'Fengzao' had relatively higher species diversity based on the alpha diversity analysis. Proteobacteria, Enterobacteriaceae and Rhodobacteraceae had significantly high abundance in 'Fengzao'. Firmicutes and Pseudomonas were highly abundant in the stems of 'Kyoho', and family of Spirochaetaceae, Anaplasmataceae, Chlorobiaceae, and Sphingomonadaceae, and genera of Spirochaeta, Sphingomonas, Chlorobaculum and Wolbachia were abundant in the fruits of 'Kyoho'. These identified microbes are main components of the microbial communities, and could be important regulators of grapevine growth and development. This study revealed the differences in the microbial compositions between 'Kyoho' and its bud mutant, and these identified microbes will be significant resources for the future researches on the quality regulation and disease control of grapevines. [ABSTRACT FROM AUTHOR]

A major goal of efforts to develop a vaccine to prevent HIV-1 infection is induction of broadly cross-reactive neutralizing antibodies (bcnAb). In previous studies we have demonstrated induction of neutralizing antibodies that did cross-react among multiple primary and laboratory strains of HIV-1, but neutralized with limited potency. In the present study we tested the hypothesis that immunization with multiple HIV-1 envelope glycoproteins (Envs) would result in a more potent and cross-reactive neutralizing response. One Env, CM243(N610Q), was selected on the basis of studies of the effects of single and multiple mutations of the four gp41 glycosylation sites. The other two Envs included R2 (subtype B) and 14/00/4 (subtype F), both of which were obtained from donors with bcnAb. Rhesus monkeys were immunized using a prime boost regimen as in previous studies. Individual groups of monkeys were immunized with either one of the three Envs or all three. The single N610Q and N615Q mutations of CM243 Env did not disrupt protein secretion, processing into, or reactivity with mAbs, unlike other single or multiple deglycosylation mutations. In rabbit studies the N610Q mutation alone or in combination was associated with an enhanced neutralizing response against homologous and heterologous subtype E viruses. In the subsequent monkey study the response induced by the R2 Env regimen was equivalent to the trivalent regimen and superior to the other monovalent regimens against the virus panel used for testing. The 14/00/4 Env induced responses superior to CM243(N610Q). The results indicate that elimination of the glycosylation site near the gp41 loop results in enhanced immunogenicity, but that immunization of monkeys with these three distinct Envs was not more immunogenic than with one. [ABSTRACT FROM AUTHOR]

Despite proposed ecological importance of mucilage in seed dispersal, germination and seedling establishment, little is known about the role of mucilage in seed pre-germination processes. Here we investigated the role of mucilage in assisting achene cells to repair DNA damage during dew deposition in the desert. Artemisia sphaerocephala achenes were first treated c-irradiation to induce DNA damage, and then they were repaired in situ in the desert dew. Dew deposition duration can be as long as 421 min in early mornings. Intact achenes absorbed more water than demucilaged achenes during dew deposition and also carried water for longer time following sunrise. After 4-d dew treatment, DNA damage of irradiated intact and demucilaged achenes was reduced to 24.38% and 46.84%, respectively. The irradiated intact achenes exhibited much higher DNA repair ratio than irradiated demucilaged achenes. Irradiated intact achenes showed an improved germination and decreased nonviable achenes after dew treatment, and significant differences in viability between the two types of achenes were detected after 1020 min of dew treatment. Achene mucilage presumably plays an ecologically important role in the life cycle of A. sphaerocephala by aiding DNA repair of achene cells in genomic-stressful habitats. [ABSTRACT FROM AUTHOR]

Many ecosystems may suffer from both nutrient enrichment and exotic plant invasions simultaneously. Much has been known that nutrient inputs can promote growth and expansion of exotic invasive plants in wetlands, and that allelopathic effects of the exotic invasive plants can inhibit the growth of coexisting native plants, contributing to their invasion success. Thus, we hypothesized that allelopathic effects of exotics on natives in invaded ecosystems can be enhanced by nutrient enrichment. To test this hypothesis, we conducted two greenhouse hydroponic experiments. One is the monoculture experiment in which a widespread exotic invasive perennial Alternanthera philoxeroides and a native perennial Ludwigia peploides subsp. stipulacea in monoculture were subjected to five levels of nutrient supply. The other is the mixture experiment in which the two species in mixture were subjected to five levels of nutrient supply, each with and without activated carbon addition. Both A. philoxeroides and L. peploides grew better under higher level of nutrient availability in monoculture experiment. In the mixture experiment, A. philoxeroides formed less total and root biomass while L. peploides formed more in response to activated carbon addition and all of the responses had larger degree at higher level of nutrient availability, indicating A. philoxeroides had significant allelopathic effects on L. peploides and the effects was significantly enhanced by nutrient enrichment. Such results support our hypothesis and reveal a novel mechanism for exotic plant invasion in eutrophicated and invaded wetlands, i.e. nutrient enhancement of allelopathic effects of exotics on natives. [ABSTRACT FROM AUTHOR]

Although the phylogenetic framework of Davalliaceae is known, the classification of Chinese Davalliaceae is still controversial. In this study, a molecular phylogenetic tree of 60 accessions, including 29 species produced in China, was constructed using five plastid DNA markers—atpB, atpB-rbcL, rbcL, rbcL-accD, and accD. New data on studied specimens, field investigations, and scanning electron microscopy analysis of leaf epidermis and spores were used to reclassify Chinese Davalliaceae. The taxonomic position of Davallia canariensis was confirmed based on new evidence and a new key to sections of Chinese Davalliaceae was proposed. The taxonomically controversial genus Paradavallodes was confirmed as a polyphyletic group, and it was assigned to Davallia sect. Trogostolon and Davallia sect. Davallodes. Further, species endemic to China were delimited, 21 species were admitted to six sections of Davallia, two new combinations were proposed, two new synonyms were defined and a new key to Chinese species of Davalliaceae was presented. [ABSTRACT FROM AUTHOR]

Background: Our prior work on congenital heart disease (CHD) with heterotaxy, a birth defect involving randomized left-right patterning, has shown an association of a high prevalence of airway ciliary dysfunction (CD; 18/43 or 42%) with increased respiratory symptoms. Furthermore, heterotaxy patients with ciliary dysfunction were shown to have more postsurgical pulmonary morbidities. These findings are likely a reflection of the common role of motile cilia in both airway clearance and left-right patterning. As CHD comprising transposition of the great arteries (TGA) is commonly thought to involve disturbance of left-right patterning, especially L-TGA with left-right ventricular inversion, we hypothesize CHD patients with transposition of great arteries (TGA) may have high prevalence of airway CD with increased respiratory symptoms. Methods and results: We recruited 75 CHD patients with isolated TGA, 28% L and 72% D-TGA. Patients were assessed using two tests typically used for evaluating airway ciliary dysfunction in patients with primary ciliary dyskinesia (PCD), a recessive sinopulmonary disease caused by respiratory ciliary dysfunction. This entailed the measurement of nasal nitric oxide (nNO), which is typically low with PCD. We also obtained nasal scrapes and conducted videomicroscopy to assess respiratory ciliary motion (CM). We observed low nNO in 29% of the patients, and abnormal CM in 57%, with 22% showing both low nNO and abnormal CM. No difference was observed for the prevalence of either low nNO or abnormal ciliary motion between patients with D vs. L-TGA. Respiratory symptoms were increased with abnormal CM, but not low nNO. Sequencing analysis showed no compound heterozygous or homozygous mutations in 39 genes known to cause PCD, nor in CFTR, gene causing cystic fibrosis. As both are recessive disorders, these results indicate TGA patients with ciliary dysfunction do not have PCD or cystic fibrosis (which can cause low nNO or abnormal ciliary motion). Conclusions: TGA patients have high prevalence of abnormal CM and low nNO, but ciliary dysfunction was not correlated with TGA type. Differing from PCD, respiratory symptoms were increased with abnormal CM, but not low nNO. Together with the negative findings from exome sequencing analysis, this would suggest TGA patients with ciliary dysfunction do not have PCD but nevertheless may suffer from milder airway clearance deficiency. Further studies are needed to investigate whether such ciliary dysfunction is associated with increased postsurgical complications as previously observed in CHD patients with heterotaxy. [ABSTRACT FROM AUTHOR]

Postnatal thymic epithelial cell (TEC) homeostatic defect- or natural aging-induced thymic atrophy results in a decline in central T-cell tolerance establishment, which is constituted by thymocyte negative selection and cluster of differentiation (CD) 4+ thymic regulatory T (tTreg) cell generation. Emerging evidence shows this decline mainly results from defects in negative selection, but there is insufficient evidence regarding whether tTreg cell generation is also impaired. We mechanistically studied tTreg cell generation in the atrophied thymus by utilizing both postnatal TEC-defective (resulting from FoxN1-floxed conditional knockout [cKO]) and naturally aged mouse models. We found that the capacity of tTreg cell generation was not impaired compared to CD4+ thymic conventional T cells, suggesting thymic atrophy positively influences tTreg cell generation. This is potentially attributed to decreased T cell receptor (TCR) signaling strength due to inefficiency in promiscuous expression of self-antigens or presenting a neo-self-antigen by medullary TECs, displaying decreased negative selection-related marker genes (Nur77 and CD5high) in CD4 single positive (SP) thymocytes. Our results provide evidence that the atrophied thymus attempts to balance the defective negative selection by enhancing tTreg cell generation to maintain central T-cell tolerance in the elderly. Once the balance is broken, age-related diseases could take place. [ABSTRACT FROM AUTHOR]

To reveal the effects of ploidy level and haplotype on photosynthetic traits, we chose 175 genotypes of wild strawberries belonging to two haplotypes at two types of ploidy levels (diploidy and tetraploidy) and measured photosynthetic traits. Our results revealed that ploidy significantly affected the characteristics of light-response curves, CO2-response curves, and leaf gas exchange parameters, except intercellular CO2 concentration (Ci). Tetraploid species had a lower light saturation point (LSP) and CO2 saturation point (CSP), higher light compensation point (LCP), dark respiration (Rd), and CO2 compensation point (CCP) than diploid species. Furthermore, tetraploid species have lower photosynthetic capacity than diploid species, including net photosynthetic rate (Pn), stomatal conductivity (Gs), and transpiration rate (Tr). In addition, haplotype had a significant effect on LSP, CSP, Tr, and Ci as well as a significant interactive effect between ploidy and haplotype on the maximal photosynethic rate of the light-response curve and Rd. Most of the variance existed within haplotypes among individuals. These results suggest that polyploidization was the main driver for the evolution of photosynthesis with increasing ploidy level (i.e. from diploidy to tetraploidy in Fragaria species), while the origin of a chromosome could also affect the photosynthetic traits and the polyploidization effect on photosynthetic traits. [ABSTRACT FROM AUTHOR]

Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery. The antiarrhythmic effects of zacopride (i.v. infusion) were observed in the settings of pre-treatment (zacopride given 3 min prior to coronary occlusion), post-treatment (zacopride given 3 min after coronary occlusion) and therapeutic treatment (zacopride given 30 s after the onset of the first sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) post MI). In all the three treatment modes, zacopride (15 μg/kg) inhibited MI-induced ventricular tachyarrhythmias, as shown by significant decreases in the premature ventricular contraction (PVC) and the duration and incidence of VT or VF. In Langendorff perfused rat hearts, the antiarrhythmic effect of 1 μmol/L zacopride were reversed by 1 μmol/L BaCl2, a blocker of IK1 channel. Patch clamp results in freshly isolated rat ventricular myocytes indicated that zacopride activated the IK1 channel and thereby reversed hypoxia-induced RMP depolarization and action potential duration (APD) prolongation. In addition, zacopride (1 μmol/L) suppressed hypoxia- or isoproterenol- induced delayed afterdepolarizations (DADs). In Kir2.x transfected Chinese hamster ovary (CHO) cells, zacopride activated the Kir2.1 homomeric channel but not the Kir2.2 or Kir2.3 channels. These results support our hypothesis that moderately enhancing IK1/Kir2.1 currents as by zacopride rescues ischemia- and hypoxia- induced RMP depolarization, and thereby prevents and cures acute ischemic arrhythmias. This study brings a new viewpoint to antiarrhythmic theories and provides a promising target for the treatment of acute ischemic arrhythmias. [ABSTRACT FROM AUTHOR]

Mammalian oocytes are arrested at prophase of the first meiotic division in the primordial follicle pool for months, even years, after birth depending on species, and only a limited number of oocytes resume meiosis, complete maturation, and ovulate with each reproductive cycle. We recently reported that protein phosphatase 6 (PP6), a member of the PP2A-like subfamily, which accounts for cellular serine/threonine phosphatase activity, functions in completing the second meiosis. Here, we generated mutant mice with a specific deletion of Ppp6c in oocytes from the primordial follicle stage by crossing Ppp6cF/F mice with Gdf9-Cre mice and found that Ppp6cF/F; GCre+ mice are infertile. Deletion of PP6c caused folliculogenesis defects and germ cell loss independent of the traditional AKT/mTOR pathway, but due to persistent phosphorylation of H2AX (a marker of double strand breaks), increased susceptibility to DNA damage and defective DNA repair, which led to massive oocyte elimination and eventually premature ovarian failure (POF). Our findings uncover an important role for PP6 as an indispensable guardian of genomic integrity of the lengthy prophase I oocyte arrest, maintenance of primordial follicle pool, and thus female fertility. [ABSTRACT FROM AUTHOR]

Background: Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS) with or without 5q deletion. However whether lenalidomide ultimately improves the overall survival (OS) of lower-risk MDS patients and reduces the progression to AML remains controversial. Method: A meta-analysis was conducted to examine the efficacy and safety of lenalidomide in the treatment of lower-risk MDS. Efficacy was assessed according to erythroid hematologic response (HI-E), cytogenetic response (CyR), OS and AML progression. Safety was evaluated based on the occurrence rates of grades 3–4 adverse events (AEs). Results: Seventeen studies were included consisting of a total of 2160 patients. The analysis indicated that the overall rate of HI-E was 58% with 95% confidence interval (CI) of 43–74%. The pooled estimates for the rates of CyR, complete CyR, and partial CyR were 44% (95% CI 19–68%), 21% (95% CI 13–30%) and 23% (95% CI 15–32%), respectively. The patients with 5q deletion had significantly higher rate of HI-E and CyR than those without 5q deletion (P = 0.002 and 0.001, respectively). The incidences of grades 3–4 neutropenia, thrombocytopenia, leukopenia, anemia, deep vein thrombosis, diarrhea, fatigue and rash were 51% (95% CI 30–73%), 31% (95% CI 20–42%), 9% (95% CI 5–13%), 7% (95% CI 2–12%), 3% (95% CI 2–5%), 3% (95% CI 1–5%), 2% (95% CI 1–4%) and 2% (95% CI 1–3%), respectively. Lenalidomide significantly improved OS (HR: 0.62, 95% CI 0.47–0.83, P = 0.001) and lowered the risk of AML progression in del(5q) patients (RR: 0.61, 95% CI 0.41–0.91, P = 0.014). Conclusions: In spite of the AEs, lenalidomide could be effectively and safely used for the treatment of lower-risk MDS patients with or without 5q deletion. [ABSTRACT FROM AUTHOR]

Plant leaf litter is an important source of soil chemicals that are essential for the ecosystem and changes in leaf litter chemical traits during decomposition will determine the availability of multiple chemical elements recycling in the ecosystem. However, it is unclear whether the changes in litter chemical traits during decomposition and their similarities across species can be predicted, respectively, using other leaf traits or using the phylogenetic relatedness of the litter species. Here we examined the fragmentation levels, mass losses, and the changes of 10 litter chemical traits during 1-yr decomposition under different environmental conditions (within/above surrounding litter layer) for 48 temperate tree species and related them to an important leaf functional trait, i.e. leaf toughness. Leaf toughness could predict the changes well in terms of amounts, but poorly in terms of concentrations. Changes of 7 out of 10 litter chemical traits during decomposition showed a significant phylogenetic signal notably when litter was exposed above surrounding litter. These phylogenetic signals in element dynamics were stronger than those of initial elementary composition. Overall, relatively hard-to-measure ecosystem processes like element dynamics during decomposition could be partly predicted simply from phylogenies and leaf toughness measures. We suggest that the strong phylogenetic signals in chemical ecosystem functioning of species may reflect the concerted control by multiple moderately conserved traits, notably if interacting biota suffer microclimatic stress and spatial isolation from ambient litter. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously. Our research details how BBR protects against gastrointestinal injuries from acute alcohol exposure using both in vivo and in vitro experiments. Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa. Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1β expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions. Alcohol consumption is a popular human social behavior worldwide, and the present study reports a comprehensive mechanism by which BBR protects against gastrointestinal injuries from alcohol stress, providing people with a novel application of BBR. [ABSTRACT FROM AUTHOR]

To screen allelochemical-resistant species of the alien invasive weed Mikania micrantha, we studied the allelopathic inhibition effects of the leaf aqueous extract (LAE) of Mikania on seed germination and seedling growth of the 26 species native or naturalized in the invaded region in South China. Seed germination was more strongly negatively affected by LAE than seedling growth. Responses of seed germination and seed growth to LAE differed differently among the target species. LAE more strongly negatively affected seed germination, but less strongly negatively affected seedling growth, in non-legume species than in legume species. LAE more strongly negatively affected seed germination and seedling growth in native species than naturalized exotic species. Therefore, naturalized exotic non-legume seedlings are more suitable than seeds of native legume species for restoration of Mikania-invaded habitats. [ABSTRACT FROM AUTHOR]

Transplantation of human neural stem/progenitor cells (hNSCs) as a regenerative cell replacement therapy holds great promise. However, the underlying mechanisms remain unclear. We, here, focused on the interaction between hNSCs and allogeneic peripheral blood mononuclear cells (PBMCs) in a co-culture model. We found that hNSCs significantly decrease the CD3+ and CD8+ T cells, reduce the gamma delta T cells and increase the regulatory T cells, along with reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines after co-culture. We also found that PBMCs, in turn, significantly promote the proliferation and differentiation of hNSCs. Our data suggest that hNSCs cross-talk with immune cells. [ABSTRACT FROM AUTHOR]

The anti-cancer activities of berberine (BBR) have been reported extensively in various cancer cell lines. However, the minimal inhibitory concentrations of BBR varied greatly among different cell lines and very few studies have been devoted to elucidate this aspect. In this study, we employed three cancer cell lines, HepG2, HeLa and SY5Y, to compare the transportation and distribution of BBR. HPLC results demonstrated that BBR was capable of penetrating all the cell lines whereas the cumulative concentrations were significantly different. HepG2 cells accumulated higher level of BBR for longer duration than the other two cell lines. Molecular docking studies revealed the BBR binding site on P-glycoprotein 1 (P-gp). In addition, we elucidated that BBR regulated P-gp at both mRNA and protein levels. BBR induced the transcription and translation of P-gp in HeLa and SY5Y cells, whereas BBR inhibited P-gp expression in HepG2 cells. Further study showed that BBR regulates P-gp expression depending on different mechanisms (or affected by different factors) in different cell lines. To summarize, our study has revealed several mechanistic aspects of BBR regulation on P-gp in different cancer cell lines and might shed some useful insights into the use of BBR in the anti-cancer drug development. [ABSTRACT FROM AUTHOR]

Brazilein, a natural small molecule, shows a variety of pharmacological activities, especially on nervous system and immune system. As a potential multifunctional drug, we studied the distribution and the transport behavior and metabolic behavior of brazilein in vivo and in vitro. Brazilein was found to be able to distribute in the mouse brain and transport into neural cells. A metabolite was found in the brain and in the cells. Positive and negative mode-MS/MS and Q-TOF were used to identify the metabolite. MS/MS fragmentation mechanisms showed the methylation occurred at the10-hydroxyl of brazilein (10-O-methylbrazilein). Further, catechol-O- methyltransferase (COMT) was confirmed as a crucial enzyme correlated with the methylated metabolite generation by molecular docking and pharmacological experiment. [ABSTRACT FROM AUTHOR]

Foraging behavior, one of the adaptive strategies of clonal plants, has stimulated a tremendous amount of research. However, it is a matter of debate whether there is any general pattern in the foraging traits (functional traits related to foraging behavior) of clonal plants in response to diverse environments. We collected data from 97 published papers concerning the relationships between foraging traits (e.g., spacer length, specific spacer length, branch intensity and branch angle) of clonal plants and essential resources (e.g., light, nutrients and water) for plant growth and reproduction. We incorporated the phylogenetic information of 85 plant species to examine the universality of foraging hypotheses using phylogenetic meta-analysis. The trends toward forming longer spacers and fewer branches in shaded environments were detected in clonal plants, but no evidence for a relation between foraging traits and nutrient availability was detected, except that there was a positive correlation between branch intensity and nutrient availability in stoloniferous plants. The response of the foraging traits of clonal plants to water availability was also not obvious. Additionally, our results indicated that the foraging traits of stoloniferous plants were more sensitive to resource availability than those of rhizomatous plants. In consideration of plant phylogeny, these results implied that the foraging traits of clonal plants (notably stoloniferous plants) only responded to light intensity in a general pattern but did not respond to nutrient or water availability. In conclusion, our findings on the effects of the environment on the foraging traits of clonal plants avoided the confounding effects of phylogeny because we incorporated phylogeny into the meta-analysis. [ABSTRACT FROM AUTHOR]

Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02A). Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4), gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L), also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D)) or monomer (gp140-L(M)). Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN) human monoclonal antibodies (mAbs) similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction. [ABSTRACT FROM AUTHOR]

Plant clonality, the ability of a plant species to reproduce itself vegetatively through ramets (shoot-root units), occurs in many plant species and is considered to be more frequent in cold or wet environments. However, a deeper understanding on the clonality-climate relationships along large geographic gradients is still scarce. In this study we revealed the clonality-climate relationships along latitudinal gradient of entire China spanning from tropics to temperate zones using clonality data for 4015 vascular plant species in 545 terrestrial communities. Structural equation modeling (SEM) showed that, in general, the preponderance of clonality increased along the latitudinal gradient towards cold, dry or very wet environments. However, the distribution of clonality in China was significantly but only weakly correlated with latitude and four climatic factors (mean annual temperature, temperature seasonality, mean annual precipitation, precipitation seasonality). Clonality of woody and herbaceous species had opposite responses to climatic variables. More precisely, woody clonality showed higher frequency in wet or climatically stable environments, while herbaceous clonality preferred cold, dry or climatically instable environments. Unexplained variation in clonality may be owed to the influences of other environmental conditions and to different clonal strategies and underlying traits adopted by different growth forms and phylogenetic lineages. Therefore, in-depth research in terms of more detailed clonal growth form, phylogeny and additional environmental variables are encouraged to further understand plant clonality response to climatic and/or edaphic conditions. [ABSTRACT FROM AUTHOR]

Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine. [ABSTRACT FROM AUTHOR]

Inhibition of Diacylglycerol O-acyltransferase 1 (DGAT1) has been a mechanism of interest for metabolic disorders. DGAT1 inhibition has been shown to be a key regulator in an array of metabolic pathways; however, based on the DGAT1 KO mouse phenotype the anticipation is that pharmacological inhibition of DGAT1 could potentially lead to skin related adverse effects. One of the aims in developing small molecule DGAT1 inhibitors that target key metabolic tissues is to avoid activity on skin-localized DGAT1 enzyme. In this report we describe a modeling-based approach to identify molecules with physical properties leading to differential exposure distribution. In addition, we demonstrate histological and RNA based biomarker approaches that can detect sebaceous gland atrophy pre-clinically that could be used as potential biomarkers in a clinical setting. [ABSTRACT FROM AUTHOR]

Plant interactions greatly affect plant community structure. Dryland ecosystems are characterized by low amounts of unpredictable precipitation as well as by often having biological soil crusts (BSCs) on the soil surface. In dryland plant communities, plants interact mostly as they compete for water resources, and the direction and intensity of plant interaction varies as a function of the temporal fluctuation in water availability. Since BSCs influence water redistribution to some extent, a greenhouse experiment was conducted to test the hypothesis that the intensity and direction of plant interactions in a dryland plant community can be modified by BSCs. In the experiment, 14 combinations of four plant species (Artemisia ordosica, Artemisia sphaerocephala, Chloris virgata and Setaria viridis) were subjected to three levels of coverage of BSCs and three levels of water supply. The results show that: 1) BSCs affected plant interaction intensity for the four plant species: a 100% coverage of BSCs significantly reduced the intensity of competition between neighboring plants, while it was highest with a 50% coverage of BSCs in combination with the target species of A. sphaerocephala and C. virgata; 2) effects of the coverage of BSCs on plant interactions were modified by water regime when the target species were C. virgata and S. viridis; 3) plant interactions were species-specific. In conclusion, the percent coverage of BSCs affected plant interactions, and the effects were species-specific and could be modified by water regimes. Further studies should focus on effects of the coverage of BSCs on plant-soil hydrological processes. [ABSTRACT FROM AUTHOR]

A considerable number of host-specific biological control agents fail to control invasive plants in the field, and exploring the mechanism underlying this phenomenon is important and helpful for the management of invasive plants. Herbivory and competition are two of the most common biotic stressors encountered by invasive plants in their recipient communities. We predicted that the antagonistic interactive effect between herbivory and competition would weaken the effect of herbivory on invasive plants and result in the failure of herbivory to control invasive plants. To examine this prediction, thus, we conducted an experiment in which both invasive Mikania micrantha and native Coix lacryma-jobi were grown together and subjected to herbivory-mimicking defoliation. Both defoliation and competition had significantly negative effects on the growth of the invader. However, the negative effect of 75% respective defoliation on the above- and below-ground biomass of Mikania micrantha was alleviated by presence of Coix lacryma-jobi. The negative effect of competition on the above- and below-ground biomass was equally compensated at 25%, 50% and 100% defoliation and overcompensated at 75% defoliation. The interactive effect was antagonistic and dependent on the defoliation intensity, with the maximum effect at 75% defoliation. The antagonistic interaction between defoliation and competition appears to be able to release the invader from competition, thus facilitating the invasiveness of Mikania, a situation that might make herbivory fail to inhibit the growth of invasive Mikania in the invaded community. [ABSTRACT FROM AUTHOR]

We previously showed that tanshinone IIA ameliorated the hypoxia-induced pulmonary hypertension (HPH) partially by attenuating pulmonary artery remodeling. The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the major causes for pulmonary arterial remodeling, therefore the present study was performed to explore the effects and underlying mechanism of tanshinone IIA on the hypoxia-induced PASMCs proliferation. PASMCs were isolated from male Sprague-Dawley rats and cultured in normoxic (21%) or hypoxic (3%) condition. Cell proliferation was measured with 3 - (4, 5 - dimethylthiazal - 2 - yl) - 2, 5 - diphenyltetrazoliumbromide assay and cell counting. Cell cycle was measured with flow cytometry. The expression of of p27, Skp-2 and the phosphorylation of Akt were measured using western blot and/or RT-PCR respectively. The results showed that tanshinone IIA significantly inhibited the hypoxia-induced PASMCs proliferation in a concentration-dependent manner and arrested the cells in G1/G0-phase. Tanshinone IIA reversed the hypoxia-induced reduction of p27 protein, a cyclin-dependent kinase inhibitor, in PASMCs by slowing down its degradation. Knockdown of p27 with specific siRNA abolished the anti-proliferation of tanshinone IIA. Moreover, tanshinone IIA inhibited the hypoxia-induced increase of S-phase kinase-associated protein 2 (Skp2) and the phosphorylation of Akt, both of which are involved in the degradation of p27 protein. In vivo tanshinone IIA significantly upregulated the hypoxia-induced p27 protein reduction and downregulated the hypoxia-induced Skp2 increase in pulmonary arteries in HPH rats. Therefore, we propose that the inhibition of tanshinone IIA on hypoxia-induce PASMCs proliferation may be due to arresting the cells in G1/G0-phase by slowing down the hypoxia-induced degradation of p27 via Akt/Skp2-associated pathway. The novel information partially explained the anti-remodeling property of tanshinone IIA on pulmonary artery in HPH. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the effects of berberine (BBR) on thermoregulation in mice exposed to hot (40°C) and cold (4°C) environmental conditions. Four groups of mice were assembled with three different dosages of BBR (0.2, 0.4, and 0.8 mg/kg) and normal saline (control). In room temperature, our largest dosage of BBR (0.8 mg/kg) can reduce rectal temperatures (Tc) of normal mice. In hot conditions, BBR can antagonize the increasing core body temperature and inhibit the expression of HSP70 and TNFα in mice; conversely, in cold conditions, BBR can antagonize the decreasing core body temperature and enhance the expression of TRPM8. This study demonstrates the dual ability of BBR in maintaining thermal balance, which is of great relevance to the regulation of HSP70, TNFα and TRPM8. [ABSTRACT FROM AUTHOR]

In semiarid drylands water shortage and trampling by large herbivores are two factors limiting plant growth and distribution. Trampling can strongly affect plant performance, but little is known about responses of morphological and mechanical traits of woody plants to trampling and their possible interaction with water availability. Seedlings of four shrubs (Caragana intermedia, Cynanchum komarovi, Hedysarum laeve and Hippophae rhamnoides) common in the semiarid Mu Us Sandland were grown at 4% and 10% soil water content and exposed to either simulated trampling or not. Growth, morphological and mechanical traits were measured. Trampling decreased vertical height and increased basal diameter and stem resistance to bending and rupture (as indicated by the increased minimum bend and break force) in all species. Increasing water availability increased biomass, stem length, basal diameter, leaf thickness and rigidity of stems in all species except C. komarovii. However, there were no interactive effects of trampling and water content on any of these traits among species except for minimum bend force and the ratio between stem resistance to rupture and bending. Overall shrub species have a high degree of trampling resistance by morphological and mechanical modifications, and the effects of trampling do not depend on water availability. However, the increasing water availability can also affect trade-off between stem strength and flexibility caused by trampling, which differs among species. Water plays an important role not only in growth but also in trampling adaptation in drylands. [ABSTRACT FROM AUTHOR]

Aging increases susceptibility to infection, in part because thymic involution culminates in reduced naïve T-lymphocyte output. Thymic epithelial cells (TECs) are critical to ensure normal maturation of thymocytes and production of peripheral T cells. The forkhead-class transcription factor, encoded by FoxN1, regulates development, differentiation, and function of TECs, both in the prenatal and postnatal thymus. We recently showed that expression of FoxN1, by keratin 14 (K14)- expressing epithelial cells is essential for maintenance of thymic medullary architecture, and deletion of FoxN1 in K14 promoter-driven TECs inhibited development of mature TECs and reduced the number of total thymocytes. These findings are reminiscent of changes observed during normal thymic aging. In the current report, we compared the effects of K14- driven FoxN1 deletion on peripheral T cell function in response to influenza virus infection with those associated with normal aging in a mouse model. FoxN1-deleted mice had reduced numbers of peripheral CD62L+CD44- naïve T-cells. In addition, during influenza infection, these animals had reduced antigen-specific CD8+ T-cell and IgG responses to influenza virus, combined with increased lung injury, weight loss and mortality. These findings paralleled those observed in aged wild type mice, providing the first evidence that K14-mediated FoxN1 deletion causes changes in T-cell function that mimic those in aging during an immune response to challenge with an infectious agent. [ABSTRACT FROM AUTHOR]

Background:The Mongolian steppe is one of the most important grasslands in the world but suffers from aridization and damage from anthropogenic activities. Understanding structure and function of this community is important for the ecological conservation, but has seldom been investigated. Methodology/Principal Findings:In this study, a total of 324 quadrats located on the three main types of Mongolian steppes were surveyed. Early-season perennial forbs (37% of total importance value), late-season annual forbs (33%) and late-season perennial forbs (44%) were dominant in meadow, typical and desert steppes, respectively. Species richness, diversity and plant functional type (PFT) richness decreased from the meadow, via typical to desert steppes, but evenness increased; PFT diversity in the desert and meadow steppes was higher than that in typical steppe. However, above-ground net primary productivity (ANPP) was far lower in desert steppe than in the other two steppes. In addition, the slope of the relationship between species richness and PFT richness increased from the meadow, via typical to desert steppes. Similarly, with an increase in species diversity, PFT diversity increased more quickly in both the desert and typical steppes than that in meadow steppe. Random resampling suggested that this coordination was partly due to a sampling effect of diversity. Conclusions/Significance:These results indicate that desert steppe should be strictly protected because of its limited functional redundancy, which its ecological functioning is sensitive to species loss. In contrast, despite high potential forage production shared by the meadow and typical steppes, management of these two types of steppes should be different: meadow steppe should be preserved due to its higher conservation value characterized by more species redundancy and higher spatial heterogeneity, while typical steppe could be utilized moderately because its dominant grass genus Stipa is resistant to herbivory and drought. [ABSTRACT FROM AUTHOR]