Common Response Pattern Research Articles

Exome Sequencing of Aggressive Natural Killer Cell Leukemia and Drug Profiling Highlight Candidate Driver Pathways in Malignant Natural Killer Cells

BackgroundNatural killer (NK) cell malignancies are rare lymphoid neoplasms characterized by aggressive clinical behavior and poor treatment outcomes. Clinically they are classified as extranodal NK/T-cell lymphoma, nasal type (NKTCL) and aggressive NK cell leukemia (ANKL). Both subtypes are almost invariably associated with Epstein-Barr virus (EBV). Recently, genomic studies in NKTCL have identified recurrent somatic mutations in JAK-STAT pathway molecules STAT3 and STAT5b as well as in the RNA helicase gene DDX3X in addition to previously detected chromosomal aberrations. Here, we identified somatic mutations in 4 cases of ANKL in order to understand whether these entities share common alterations at the molecular level. To further establish common patterns of deregulated oncogenic signaling pathways operating in malignant NK cells, we performed drug sensitivity profiling using NK cell lines representing ANKL, NKTCL and other malignant NK cell proliferations. We aimed to identify sensitivities to agents that selectively target components of pathways required for survival of malignant NK cells in an unbiased manner.MethodsExome sequencing was performed on peripheral blood or bone marrow of ANKL patients using the NK cell negative fraction or other healthy tissue as control. Profiling of drug responses was performed with a high-throughput drug sensitivity and resistance testing (DSRT) platform comprising 461 approved and investigational oncology drugs. The NK cell lines KAI3, KHYG-1, NKL, NK-YS, NK-92, SNK-6 and YT and IL-2-stimulated and resting NK cells from healthy donors were used as sample material. All drugs were tested on a 384-well format in 5 different concentrations over a 10,000-fold concentration range for 72 h and cell viability was measured. A Drug Sensitivity Score (DSS) was calculated for each drug using normalized dose response curve values.ResultsThe ANKL patients displayed mutations in genes reported as recurrently mutated in NKTCL, such as FAS, TP53, NRAS, STAT3 and DDX3X. Additionally, novel alterations in genes previously implicated in the pathogenesis of NKTCL were detected. These included an inactivating mutation in INPP5D (SHIP), a negative regulator of the PI3K/mTOR pathway and a missense mutation in PTPRK, a negative regulator of STAT3 activation. Interestingly, the total number of nonsilent somatic mutations in 3 out of 4 ANKL patients (97, 82 and 45) was remarkably high compared to other hematological malignancies analyzed in our variant calling pipeline.Analysis of drug sensitivities in NK cell lines showed a close correlation between all cell lines and a markedly higher correlation with those of IL-2 stimulated than resting healthy NK cells, suggesting that malignant NK cells may share a common drug response pattern. Furthermore, in an unsupervised hierarchical clustering the NK cell lines formed a distinct group from other leukemia cell lines tested (Fig. A). Among pathway-selective compounds (namely, kinase inhibitors and rapalogs), the drugs most selective for malignant NK cells fell into two major categories: PI3K/mTOR inhibitors (e.g. temsirolimus, buparlisib) and inhibitors of aurora and polo-like kinases such as rigosertib and GSK-461364 (Fig. B). JAK inhibitors (e.g. ruxolitinib, gandotinib) and CDK inhibitors (e.g. dinaciclib) showed strong efficacy in both malignant NK cells and IL-2 activated healthy NK cells.ConclusionsOur exome sequencing results suggest that candidate driver alterations affecting similar signaling pathways underlie the pathogenesis of ANKL as has been reported in NKTCL. Drug sensitivity profiling highlights the PI3K/mTOR pathway as a potential major driver of malignant NK cell proliferation, whereas JAK-STAT signaling appears to be essential in both healthy and malignant NK cells. Components of these pathways harbored mutations in our small cohort of ANKL patients and have been shown to be deregulated by mutations or other mechanisms in previous studies, underlining their importance as putative drivers. The systematic large-scale characterization of drug responses also identified these pathways as potential targets for novel therapy strategies in NK cell malignancies. [Display omitted] DisclosuresMustjoki:Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding.

A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an audio movie

Here we present a high-resolution functional magnetic resonance (fMRI) dataset – 20 participants recorded at high field strength (7 Tesla) during prolonged stimulation with an auditory feature film (“Forrest Gump”). In addition, a comprehensive set of auxiliary data (T1w, T2w, DTI, susceptibility-weighted image, angiography) as well as measurements to assess technical and physiological noise components have been acquired. An initial analysis confirms that these data can be used to study common and idiosyncratic brain response patterns to complex auditory stimulation. Among the potential uses of this dataset are the study of auditory attention and cognition, language and music perception, and social perception. The auxiliary measurements enable a large variety of additional analysis strategies that relate functional response patterns to structural properties of the brain. Alongside the acquired data, we provide source code and detailed information on all employed procedures – from stimulus creation to data analysis. In order to facilitate replicative and derived works, only free and open-source software was utilized.

VIII. Treatment of chronic lymphocytic leukaemia, where are we heading?

VIII. Treatment of chronic lymphocytic leukaemia, where are we heading?

Cell Wall Metabolism in Response to Abiotic Stress.

This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions.

千岛湖陆桥岛屿鸟类集团对栖息地片段化的敏感性及其季节变化

PDF HTML阅读 XML下载 导出引用 引用提醒 千岛湖陆桥岛屿鸟类集团对栖息地片段化的敏感性及其季节变化 DOI: 10.5846/stxb201406261319 作者: 作者单位: 浙江大学生命科学学院,广东省昆虫研究所 华南濒危动物研究所,浙江大学生命科学学院 作者简介: 通讯作者: 中图分类号: 基金项目: 国家自然科学基金项目(31170397,31210103908) Seasonal changes in sensitivity of bird guilds to habitat fragmentation on land- bridge islands in the Thousand Island Lake, China Author: Affiliation: College of Life Sciences, Zhejiang University,,College of Life Sciences, Zhejiang University Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:为探究千岛湖陆桥岛屿不同鸟类集团对栖息地片段化敏感性的差异和季节变化,于2009年4月-2012年1月鸟类繁殖季(4、5、6月)和冬季(11、12、1月)对千岛湖41个陆桥岛屿鸟类集团进行了研究。结果表明,冬季杂食鸟对片段化敏感性高于食虫鸟,繁殖季时二者无显著差异,繁殖季和冬季时下层鸟对片段化敏感性均高于林冠鸟,冬季留鸟对片段化敏感性高于候鸟,繁殖季则无显著差异。杂食鸟和留鸟对片段化敏感性存在季节差异,而食虫鸟、林冠鸟、下层鸟和候鸟对片段化敏感性均无季节差异。不同鸟类集团对栖息地片段化敏感性的差异和季节变化规律,有助于人们在栖息地管理和保护区设计时采取更有针对性的鸟类保护措施。 Abstract:Habitat loss and fragmentation seriously threaten global species diversity. Understanding the impact on species and communities is a core issue for ecology and conservation biology. A guild acts as a functional unit within a community. Bird guild research can help to analyze relationships among different species and evaluate their responses to habitat fragmentation. Much research has focused on bird guilds in terrestrial fragments, while other fragmented systems, such as land-bridge islands, draw relatively less attention. Because different systems tend to display different geological and ecological patterns, we needed to verify whether terrestrial fragments and land-bridge islands share common patterns of response to habitat fragmentation. The land-bridge islands in the Thousand Island Lake, which were created by dam construction, are an ideal platform for the study of habitat fragmentation. To test bird sensitivity to habitat fragmentation across seasons, we conducted bird guild studies on 41 land-bridge islands in the Thousand Island Lake during the breeding season (April-June) and winter season (November-January) of each year between April 2009, and January 2012. We classified birds into guilds according to dietary type, foraging strata, and migratory status. We used an equation with logarithmic transformation from island biogeography, S=CAz, to clarify the relationship between bird guild species richness and island fragment area. In this equation, S represents species richness of each bird guild, A represents island area, C is a constant, and z is the slope of the species-area curve. This variable can be considered a measurement of sensitivity to habitat fragmentation. The bigger the value of z, the greater the sensitivity of the bird guild. We extracted and compared the slope of each species-area relationship curve (z value) to determine whether there exists significant variation in sensitivity to habitat fragmentation among the different bird guilds. Our research indicated that omnivorous birds were more sensitive to habitat fragmentation than insectivores during the winter season, while no significant difference was found for the breeding season. Understory birds were more sensitive to habitat fragmentation than canopy birds, both in breeding and winter seasons. Resident birds were more sensitive than migrants in winter, while no significant difference between them were observed in the breeding season. Both omnivorous and resident birds showed seasonal changes in their sensitivity to fragmentation. Other guilds, including insectivorous birds, canopy birds, understory birds, and migratory birds, showed no significant seasonal changes. Previous studies conducted in terrestrial fragments support our findings that responses of bird guilds to habitat fragmentation differ and that seasonal changes in the responses to habitat fragmentation do exist. These results may aid in the effective management of bird habitats and in the design of nature reserves. Future studies may focus on other bird guild types and determine if differences in responses to habitat fragmentation occur at a larger temporal scale. 参考文献 相似文献 引证文献

Heterogeneity in signaled active avoidance learning: substantive and methodological relevance of diversity in instrumental defensive responses to threat cues.

Individuals exposed to traumatic stressors follow divergent patterns including resilience and chronic stress. However, researchers utilizing animal models that examine learned or instrumental threat responses thought to have translational relevance for Posttraumatic Stress Disorder (PTSD) and resilience typically use central tendency statistics that assume population homogeneity. This approach potentially overlooks fundamental differences that can explain human diversity in response to traumatic stressors. The current study tests this assumption by identifying and replicating common heterogeneous patterns of response to signaled active avoidance (AA) training. In this paradigm, rats are trained to prevent an aversive outcome (shock) by performing a learned instrumental behavior (shuttling between chambers) during the presentation of a conditioned threat cue (tone). We test the hypothesis that heterogeneous trajectories of threat avoidance provide more accurate model fit compared to a single mean trajectory in two separate studies. Study 1 conducted 3 days of signaled AA training (n = 81 animals) and study 2 conducted 5 days of training (n = 186 animals). We found that four trajectories in both samples provided the strongest model fit. Identified populations included animals that acquired and retained avoidance behavior on the first day (Rapid Avoiders: 22 and 25%); those who never successfully acquired avoidance (Non-Avoiders; 20 and 16%); a modal class who acquired avoidance over 3 days (Modal Avoiders; 37 and 50%); and a population who demonstrated a slow pattern of avoidance, failed to fully acquire avoidance in study 1 and did acquire avoidance on days 4 and 5 in study 2 (Slow Avoiders; 22.0 and 9%). With the exception of the Slow Avoiders in Study 1, populations that acquired demonstrated rapid step-like increases leading to asymptotic levels of avoidance. These findings indicate that avoidance responses are heterogeneous in a way that may be informative for understanding both resilience and PTSD as well as the nature of instrumental behavior acquisition. Characterizing heterogeneous populations based on their response to threat cues would increase the accuracy and translatability of such models and potentially lead to new discoveries that explain diversity in instrumental defensive responses.

Effects of fish farming on microbial planktonic communities in the middle Adriatic sea

The effects of farming on planktonic microbial communities were investigated at the coastal sea bass/sea bream farm in the oligotrophic middle Adriatic Sea. Analyses of nutrients, chlorophyll a, cyanobacteria (Prochlorococcus), heterotrophic bacteria and nanoflagellates (both pigmented and heterotrophic) were carried out on samples taken during six seasonal cruises at different water depths. Farming activity increased the natural concentrations of some nutrients (ammonium, nitrite, phosphate, dissolved inorganic nitrogen) and changed their seasonal pattern. The values still remained typical for oligotrophic environ-ments demonstrating no risk for eutrophication. Enhanced nutrient supply provoked an immediate increase in abundances of both autotrophic and heterotrophic microbial groups (except pigmented nanoflagellates) and chlorophyll a. The effect of farming was more visible for the heterotrophic microbial component. Results from this study reveal a potential common pattern of microbial response to farming in the oligotrophic environments. It also suggests the importance of heterotrophic microbial web in transferring the matter and energy released from the fish farms in nutrient poor environments.

Studies on Rhizosphere-Bacteria mediated Biotic and Abiotic stress tolerance in Chickpea (Cicer arietinumL.)

Rhizospheric bacteria promote plant health and combat with pathogenic microorganisms. Available reports indicate the activity of PGPR are in protection of plant under abiotic stresses. In the present work we have compared the growth promotion and biochemical responses of plants influenced bybacteria isolated from the rhizosphere of different plants. Two Pseudomonas strains S1 (P. putida) and Cgr (P. aeruginosa) were isolated from chickpea and congress grass, respectively, and their antimicrobial activity was tested against Sclerotinia sclerotiorum. Both strains are tested for HCN, IAA and ammonia production. Their surviving ability in salt stress was evaluated and compatibility test was performed. We have got some interesting results that plant defense enzymes and phenolic substances were accumulated in higher concentrations in plants that were treated with the two bacterial strains (Cgr and S1) either individually or in combination when challenged with biotic (Sclerotinia sclerotiorum) and abiotic stress (NaCl salt stress) compared to the non-bacterized plants but exposed to biotic as well as abiotic stresses. These results indicates that the Cgr and S1 have potential to be used as biocontrol agents that can help chickpea to combat attack of S. sclerotiorum as well as thrive under salt stress. Moreover, the results also indicated a common pattern of defense response by chickpea against both the biotic and abiotic stress when they are bacterized by the two bacterial strains.

Attenuated Auditory Event-Related Potentials and Associations with Atypical Sensory Response Patterns in Children with Autism

Neurobiological underpinnings of unusual sensory features in individuals with autism are unknown. Event-related potentials elicited by task-irrelevant sounds were used to elucidate neural correlates of auditory processing and associations with three common sensory response patterns (hyperresponsiveness; hyporesponsiveness; sensory seeking). Twenty-eight children with autism and 39 typically developing children (4-12 year-olds) completed an auditory oddball paradigm. Results revealed marginally attenuated P1 and N2 to standard tones and attenuated P3a to novel sounds in autism versus controls. Exploratory analyses suggested that within the autism group, attenuated N2 and P3a amplitudes were associated with greater sensory seeking behaviors for specific ranges of P1 responses. Findings suggest that attenuated early sensory as well as later attention-orienting neural responses to stimuli may underlie selective sensory features via complex mechanisms.

69. Prenatal diet programs altered expression of immune and epigenetic related genes in the offspring brain

“Bigger is better” is a commonly held belief with regard to infant birthweight, however, epidemiological data support the conclusion that “optimal” birthweight is ideal, as offspring born either small for gestational age (SGA) or large for gestational age (LGA) are at increased risk for adverse neurobehavioral outcomes, including attention deficit hyperactivity disorder and emotional dysregulation. Using mouse models of SGA (maternal low protein diet) and LGA (maternal high fat diet), we have identified a number of behavioral deficits in these offspring, including altered social behavior, executive function deficits (inattention/impulsivity) and hyperresponsivity to stress. In the present study, adult male C57xDBA F1 mice were sacrificed at baseline or 2 h after either restraint or lipopolysaccharide (LPS, ip, 10 μg/mouse) and brains were collected. Gene expression in the hypothalamus was investigated using a custom PCR array (Open Array), with a focus on genes related to epigenetic and immune regulation. Two common response patterns were observed across both domains; (1) baseline elevation in gene expression (e.g., DNMT1, CCR2) in SGA and LGA animals compared to controls and (2) a hyporesponsivity of SGA and LGA animals, seen in response to both LPS and restraint (e.g., DNMT1, CXCL10, CB2). The identification of dysregulation of immune-related genes suggests the possibility that altered neuroinflammation may underlie some of the adverse neurobehavioral outcomes observed in SGA and LGA offspring.

OP05 Cystathionine γ-lyase deficiency protects mice from galactosamine/lipopolysaccharide-induced acute liver failure

Background Acute liver failure (ALF) is a fatal syndrome attributed to massive hepatocyte death. Although a variety of insults including viral infection and drugs can cause ALF, the resulting clinical picture is remarkably similar across the different etiologies, reflecting common patterns of response of the innate immune system and the resulting inflammatory response. Hydrogen sulfide (H 2 S) has been reported to exert cytoprotective or cytotoxic effects. We have recently reported that breathing low concentration of H 2 S prevents lethal endotoxemia and inflammatory liver injury in mice at least in part by increasing thiosulfate, an oxidative metabolite of H 2 S [1] . Nonetheless, role of endogenously produced H 2 S in inflammatory organ injury remains incompletely defined. Here, we examined the role of cystathionine γ -lyase (CSE) in the ALF induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS) in mice. Methods Wild-type C57BL6J (WT) and CSE-deficient mice [2] on C57BL6J background were challenged with saline or GalN (300 mg/kg)/LPS (1 μg/kg). Impact of CSE deficiency on LPS-induced tumor necrosis factor- α (TNF- α ) production by macrophages and GalN/TNF- α -induced hepatocyte death was examined in primary culture. Plasma and liver levels of sulfide metabolites were measured by HPLC after derivatization with monobromobimane. Results WT mice exhibited high mortality rate, prominent liver injury, and increased plasma alanine aminotransferase (ALT) levels after GalN/LPS challenge. Congenital deficiency or chemical inhibition of CSE by DL-propargylglycine (PAG) attenuated GalN/LPS-induced liver injury. CSE-deficiency markedly improved survival rate and attenuated GalN/LPS-induced up-regulation of inflammatory cytokines and activation of caspase 3 and PARP in the liver. CSE-deficiency protected primary hepatocytes from GalN/TNF- α -induced cell death without affecting LPS-induced TNF- α production from primary peritoneal macrophages. CSE-deficient mice exhibited up-regulated NF-E2 p45-related factor 2 (Nrf2) and Nrf2-dependent antioxidant proteins, activated Akt-dependent anti-apoptotic signaling, and markedly attenuated GalN/LPS-induced JNK phosphorylation in the liver. Beneficial effects of CSE-deficiency and administration of PAG were associated with markedly elevated homocysteine and thiosulfate levels in the liver and plasma. Finally, administration of sodium thiosulfate (STS) markedly attenuated GalN/LPS-induced liver injury via activation of Akt- and Nrf2-dependent signaling and inhibition of GalN/LPS-induced JNK phosphorylation in WT mice. Conclusion Using CSE-deficient mice and primary hepatocytes, we unexpectedly revealed cytoprotective effects of CSE deficiency against inflammatory acute liver failure. Our results also showed a profound impact of CSE deficiency on sulfide metabolism that triggered several cytoprotective mechanisms including Akt- and Nrf2-dependent signaling and augmentation of thiosulfate levels. Lastly, we confirmed the robust cytoprotective effects of sodium thiosulfate against inflammatory liver failure, suggesting an important translational potential of our findings.

Herbage accumulation and grazing losses on Mulato grass subjected to strategies of rotational stocking management

Grazing management strategies affect not only herbage accumulation but also the efficiency of grazing. This study aimed to evaluate herbage accumulation (leaf, stem and dead material), grazing efficiency and losses of mulato grass (a Brachiaria ruziziensis × Brachiaria brizantha cv. Marandu hybrid) subjected to strategies of rotational stocking management. Treatments consisted of combinations between two post-grazing heights (15 and 20 cm) and two pre-grazing conditions (95 % and maximum canopy light interception (LI)) assigned to experimental units (1200-m² paddocks) according to a 2 × 2 factorial arrangement and a randomized complete block design, with four replications. The experiment was carried out from Jan 2008 to Mar 2009. Season of the year influenced almost all studied variables, resulting in a common pattern of response that was determined by pre- and post-grazing management targets. Herbage accumulation was greater on swards managed at 95 %, with higher accumulation of leaves and lower accumulation of stem and dead material in relation to those managed at maximum LI (99 %) during the entire experimental period. On the other hand, herbage removal by grazing was larger on swards managed at 99 % LI, which was compensated for by the smaller number of grazing cycles and larger losses due to grazing under those circumstances. Under rotational stocking, the pre-grazing LI of 95 % and post-grazing height of 20 cm resulted in efficient grazing and high producing leafy pastures, highlighting the potential of Mulato grass pastures for animal production.

Study on Citrus Response to Huanglongbing Highlights a Down-Regulation of Defense-Related Proteins in Lemon Plants Upon ‘Ca. Liberibacter asiaticus’ Infection

Citrus huanglongbing (HLB) is a highly destructive disease of citrus presumably caused by ‘ Candidatus Liberibacter asiaticus ’ (Las), a gram-negative, insect-transmitted, phloem-limited α-proteobacterium. Although almost all citrus plants are susceptible to HLB, reports have shown reduced susceptibility to Las infection in lemon ( Citrus limon ) plants. The aim of this study is to identify intra-species specific molecular mechanisms associated with Las-induced responses in lemon plants. To achieve this, comparative 2-DE and mass spectrometry, in addition to Inductively Coupled Plasma Spectroscopy (ICPS) analyses, were applied to investigate differences in protein accumulation and the concentrations of cationic elements in leaves of healthy and Las-infected lemon plants. Results showed a differential accumulation of 27 proteins, including an increase in accumulation of starch synthase but decrease in the production of photosynthesis-related proteins in Las-infected lemon plants compared to healthy plants. Furthermore, there was a 6% increase (P > 0.05) in K concentration in leaves of lemon plants upon Las infection, which support results from previous studies and might represent a common response pattern of citrus plants to Las infection. Interestingly, contrary to reports from prior studies, this study showed a general reduction in the production of defense-related pathogen-response proteins but a 128% increase in Zn concentration in lemon plants in response to Las infection. Taken together, this study sheds light on general and intra-species specific responses associated with the response of citrus plants to Las.

Ability of phytoplankton trait sensitivity to highlight anthropogenic pressures in Mediterranean lagoons: A size spectra sensitivity index (ISS-phyto)

Size spectra exhibit common patterns of variation and predictable responses to pressures across ecosystem types, functional guilds and taxonomic groups. Here, we extend the size spectra approach to phytoplankton ecological status assessment in transitional waters by developing, testing and validating a multi-metric index of size spectra sensitivity (ISS-phyto), which integrates size structure metrics with others such as phytoplankton diversity, biomass and sensitivity of size classes to anthropogenic disturbance. The ability of various theoretical models of size spectra sensitivity to discriminate between disturbed and undisturbed ecosystems and levels of anthropogenic stress was evaluated. We used data on phytoplankton samples collected in 14 Mediterranean and Black sea transitional water ecosystems (coastal lagoons) from Italy, Albania, Greece, Bulgaria and Romania, and compared the models’ efficiency by looking at their pressure–impact response along salinity and enrichment gradients, the latter quantified as variations in dissolved inorganic nitrogen (DIN) and dissolved inorganic phosphorus (DIP). Data from a fifteenth Mediterranean lagoon was used for external validation purposes. Right asymmetric models of size class sensitivity, implying higher sensitivity of smaller cell size classes, were found to contribute to the ISS-phyto multimetric tool more effectively than symmetric and left asymmetric models, distinguishing disturbed from undisturbed lagoons and disturbed from undisturbed stations within the same lagoon. When based on right asymmetric sensitivity models, i.e., those that were most efficient in identifying anthropogenic impacts, ISS-phyto also showed the best fit of pressure–response relationships along the salinity and enrichment gradients; at low to high levels of impact ISS response was driven by size class sensitivity and at very high impacts by phytoplankton biomass. A scheme for the classification of Ecological Quality Status based on ISS-phyto is proposed and validated. The validation procedure found that ISS-phyto is an effective and sensitive monitoring tool, robust, easy to apply and to inter-calibrate among laboratories.

Oxidative stress effect before fermentation to bioethanol and alcoholic beverages production

During ethanol and alcoholic beverages production, yeast cells are affected by several stress conditions that are adverse to growth (oxidative, osmotic and ethanol stress among others) and they should detect and respond to these conditions, otherwise alcoholic fermentation can be negatively affected. In this work we have analyzed the fermentative behavior of four commercial and non‐commercial strains in synthetic musts. The yeast used were two Saccharomyces cerevisiae and two Kluyveromyces marxianus, isolated from mezcal processes in México. According to the data, indicate that common patterns of stress response are found among all the strains and can been classified into three groups depending on whether or not alcoholic fermentation was completed. The oxidative stress with H2O2 decreased the specific growth rate during the fermentation more than the stress induced by menadione, but the ethanol production at the end of the fermentation, not showed a significant difference between the H2O2 and the menadione. Our results indicate a clear relationship between stress resistance and fermentative behavior and this opens up the possibility of using this information as a criterion for the future selection of bioethanol and alcoholic beverages yeasts.

Heterogeneity of Responses to Real-Time Continuous Glucose Monitoring (RT-CGM) in Patients With Type 2 Diabetes and Its Implications for Application

OBJECTIVETo characterize glucose response patterns of people who wore a real-time continuous glucose monitor (RT-CGM) as an intervention to improve glycemic control. Participants had type 2 diabetes, were not taking prandial insulin, and interpreted the RT-CGM data independently.RESEARCH DESIGN AND METHODSData were from the first 12 weeks of a 52-week, prospective, randomized trial comparing RT-CGM (n = 50) with self-monitoring of blood glucose (n = 50). RT-CGM was used in 8 of the first 12 weeks. A1C was collected at baseline and quarterly. This analysis included 45 participants who wore the RT-CGM ≥4 weeks. Analyses examined the RT-CGM data for common response patterns—a novel approach in this area of research. It then used multilevel models for longitudinal data, regression, and nonparametric methods to compare the patterns of A1C, mean glucose, glycemic variability, and views per day of the RT-CGM device.RESULTSThere were five patterns. For four patterns, mean glucose was lower than expected as of the first RT-CGM cycle of use given participants’ baseline A1C. We named them favorable response but with high and variable glucose (n = 7); tight control (n = 14); worsening glycemia (n = 6); and incremental improvement (n = 11). The fifth was no response (n = 7). A1C, mean glucose, glycemic variability, and views per day differed across patterns at baseline and longitudinally.CONCLUSIONSThe patterns identified suggest that targeting people with higher starting A1Cs, using it short-term (e.g., 2 weeks), and monitoring for worsening glycemia that might be the result of burnout may be the best approach to using RT-CGM in people with type 2 diabetes not taking prandial insulin.

Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation

Since the inaugural description in 1959 by Prinzmetal,1 coronary artery spasm and abnormal coronary artery vasomotion have been extensively studied both clinically and scientifically. There is no doubt that abnormal...

Strong Concordance Between Transcriptomic Patterns of Spleen and Peripheral Blood Leukocytes in Response to Avian Pathogenic Escherichia coli Infection

Avian pathogenic Escherichia coli (APEC) causes morbidity in chickens and exhibits zoonotic potential. Understanding host transcriptional responses to infection aids the understanding of protective mechanisms and serves to inform future colibacillosis control strategies. Transcriptomes of spleen and peripheral blood leukocytes (PBLs) of the same individual birds in response to APEC infection were compared to identify common response patterns and connecting pathways. More than 100 genes in three contrasts examining pathology and infection status were significantly differentially expressed in both tissues and similarly regulated. Tissue-specific differences in catalytic activity, however, appear between birds with mild and severe pathology responses. Early expression differences, between birds with severe pathology and uninfected controls, in the mitogen-activated protein kinase pathway in PBLs precede spleen responses in the p53 and cytokine-cytokine receptor pathways. Tissue bianalysis is useful in identifying genes and pathways important to the response to APEC, whose role might otherwise be underestimated in importance.

Clopidogrel resistance in North Indian patients of coronary artery disease and lack of its association with platelet ADP receptors P2Y1 and P2Y12 gene polymorphisms

Aspirin and Clopidogrel are used in prophylaxis of patients undergoing percutaneous coronary intervention and long-term prevention of cardiovascular and cerebrovascular events. Clopidogrel resistance has been attributed to P2Y1 and P2Y12 adenosine diphosphate (ADP) receptor polymorphisms. This study enrolled 100 patients of coronary artery disease (CAD) who were on the maintenance dose of clopidogrel (75 mg OD) with or without aspirin. In addition, 10 received loading dose (300 mg) prior to percutaneous coronary intervention. Relevant clinical and drug history were elicited. ADP-induced platelet aggregation study and PCR-RFLP for P2Y1 (1622A > G) and P2Y12 (i-T744C) polymorphisms were performed. Two groups of controls were used for defining cut-off for platelet aggregation response. Follow-up data, wherever available was recorded. The most common pattern of aggregation response was disaggregation, either complete (46.4%) or partial (53.6%). A frequency of 13% clopidogrel non-responders and 19% semi-responders was found. All the cases were H1/H1 haplotype for P2Y12 gene polymorphism and 28 (29.2%) patients carried P2Y1 1622A > G (21(21.9%) AG and 7(7.3%) GG) gene polymorphism, the frequency being greater in clopidogrel responders compared to semi/non-responders but difference was not statistically significant. There was no statistically significant difference between responders and semi/non-responders in terms of the history of risk factor for CAD, concurrent atorvastatin use or past history of an acute vascular event. On follow up, the two patients who developed myocardial infarction/acute coronary syndromes (MI/ACS) were clopidogrel semi- and non-responder, respectively. Variability in clopidogrel response with 13% non-responders and 19% semi-responders was seen in this study with adverse outcome (MI/ACS) on follow up seen in two patients. Hence, poor response to clopidogrel may be related to increased likelihood of adverse long-term coronary event that may benefit from additional or alternative anti-platelet therapy. Clopidogrel resistance was not associated with ADP receptor P2Y1 and P2Y12 gene polymorphisms. Hence, it is postulated that clopidogrel resistance in CAD patients is multifactorial and not caused by single-gene polymorphisms.

Common bacterial responses in six ecosystems exposed to 10 years of elevated atmospheric carbon dioxide

Six terrestrial ecosystems in the USA were exposed to elevated atmospheric CO(2) in single or multifactorial experiments for more than a decade to assess potential impacts. We retrospectively assessed soil bacterial community responses in all six-field experiments and found ecosystem-specific and common patterns of soil bacterial community response to elevated CO(2) . Soil bacterial composition differed greatly across the six ecosystems. No common effect of elevated atmospheric CO(2) on bacterial biomass, richness and community composition across all of the ecosystems was identified, although significant responses were detected in individual ecosystems. The most striking common trend across the sites was a decrease of up to 3.5-fold in the relative abundance of Acidobacteria Group 1 bacteria in soils exposed to elevated CO(2) or other climate factors. The Acidobacteria Group 1 response observed in exploratory 16S rRNA gene clone library surveys was validated in one ecosystem by 100-fold deeper sequencing and semi-quantitative PCR assays. Collectively, the 16S rRNA gene sequencing approach revealed influences of elevated CO(2) on multiple ecosystems. Although few common trends across the ecosystems were detected in the small surveys, the trends may be harbingers of more substantive changes in less abundant, more sensitive taxa that can only be detected by deeper surveys. Representative bacterial 16S rRNA gene clone sequences were deposited in GenBank with Accession No. JQ366086–JQ387568.