Discovery of A-type procyanidin dimers in yellow raspberries by untargeted metabolomics and correlation based data analysis

Introduction

Raspberries are becoming increasingly popular due to their reported health beneficial properties. Despite the presence of only trace amounts of anthocyanins, yellow varieties seems to show similar or better effects in comparison to conventional raspberries.

Objectives

The aim of this work is to characterize the metabolic differences between red and yellow berries, focussing on the compounds showing a higher concentration in yellow varieties.

Methods

The metabolomic profile of 13 red and 12 yellow raspberries (of different varieties, locations and collection dates) was determined by UPLC–TOF-MS. A novel approach based on Pearson correlation on the extracted ion chromatograms was implemented to extract the pseudospectra of the most relevant biomarkers from high energy LC–MS runs. The raw data will be made publicly available on MetaboLights (MTBLS333).

Results

Among the metabolites showing higher concentration in yellow raspberries it was possible to identify a series of compounds showing a pseudospectrum similar to that of A-type procyanidin polymers. The annotation of this group of compounds was confirmed by specific MS/MS experiments and performing standard injections.

Conclusions

In berries lacking anthocyanins the polyphenol metabolism might be shifted to the formation of a novel class of A-type procyanidin polymers.

     

Age-related changes in photosensitive melanopsin-expressing retinal ganglion cells correlate with circadian rhythm impairments in sighted and blind rats

The melanopsin system consists of intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (mRGCs). These mRGCs mediate several non-image-forming visual functions, including light entrainment of circadian rhythms. Here we evaluate age-related alterations of the melanopsin system and circadian rhythms in P23H line 1 (P23H-1) rats, a rodent model of retinitis pigmentosa (RP). In homozygous P23H-1 rats and wild-type control rats from the same genetic background (Sprague–Dawley), body temperature and locomotor activity were continuously monitored at 10-min intervals for 7 days, once every 4–5 weeks, between 2 and 24 months of age, using a telemetry transmitter. The distribution and number of mRGCs were assessed in control rats at 12, 18, and 24 months of age and in P23H-1 rats aged 12, 18, 24, and 30 months by immunostaining whole-mount retinas with antibodies against melanopsin. The mean density of mRGCs in control rats showed no significant variations when evaluated at 12 and 18 months of age, and fell by approximately 56% between 18 and 24 months of age. Meanwhile, a significant decrease in the mean number of mRGCs was found in 18-month-old P23H-1 rats as compared to 18-month-old control rats (81% decrease). Parametric and non-parametric analyses of the records showed a gradual age-dependent weakening of body temperature and locomotor activity circadian rhythms robustness in both control and P23H-1 rats from 2 to 24 months of age. However, body temperature and locomotor activity circadian patterns were less robust throughout the experiment in P23H-1 as compared to control rats, with lower amplitude, weaker coupling strength to environmental zeitgebers and higher fragmentation of the rhythms. The present study shows that the degeneration of photoreceptors and inner retinal neurons, characteristic of RP, has age-related degenerative effects on the melanopsin system and is associated with weaker circadian patterns.     

Monitoring population‐level responses of marine mammals to human activities

We provide guidance for monitoring whether human activities affect the physiology or behavior of marine mammals and, if so, whether those effects may lead to changes in survival and reproduction at the population level. We suggest that four elements be included in designing and implementing such a monitoring program. The first is development of a theory of change: a set of mechanistic hypotheses that outline why a given activity might be expected to have one or more measurable effects on individuals and populations, and ideally the magnitude, timing, and duration of the effects. The second element, definition of biologically meaningful effect sizes, ultimately facilitates the development of a monitoring program that can detect those magnitudes of effect with the desired levels of precision. The third element, selection of response variables for monitoring, allows inference to whether observed changes in the status of individuals or populations are attributable to a given activity. Visual observations, passive acoustic and tagging instruments, and direct physical measurements all can provide data that facilitate quantitative hypothesis testing. The fourth element is specification of the temporal sequence of monitoring. These elements also can be used to inform monitoring of the responses of other taxonomic groups to human activities.     

Effectiveness of steam inhalation and nasal irrigation for chronic or recurrent sinus symptoms in primary care: a pragmatic randomized controlled trial

Background:Systematic reviews support nasal saline irrigation for chronic or recurrent sinus symptoms, but trials have been small and few in primary care settings. Steam inhalation has also been proposed, but supporting evidence is lacking. We investigated whether brief pragmatic interventions to encourage use of nasal irrigation or steam inhalation would be effective in relieving sinus symptoms.Methods:We conducted a pragmatic randomized controlled trial involving adults (age 18–65 yr) from 72 primary care practices in the United Kingdom who had a history of chronic or recurrent sinusitis and reported a “moderate to severe” impact of sinus symptoms on their quality of life. Participants were recruited between Feb. 11, 2009, and June 30, 2014, and randomly assigned to 1 of 4 advice strategies: usual care, daily nasal saline irrigation supported by a demonstration video, daily steam inhalation, or combined treatment with both interventions. The primary outcome measure was the Rhinosinusitis Disability Index (RSDI). Patients were followed up at 3 and 6 months. We imputed missing data using multiple imputation methods.Results:Of the 961 patients who consented, 871 returned baseline questionnaires (210 usual care, 219 nasal irrigation, 232 steam inhalation and 210 combined treatment). A total of 671 (77.0%) of the 871 participants reported RSDI scores at 3 months. Patients’ RSDI scores improved more with nasal irrigation than without nasal irrigation by 3 months (crude change −7.42 v. −5.23; estimated adjusted mean difference between groups −2.51, 95% confidence interval −4.65 to −0.37). By 6 months, significantly more patients maintained a 10-point clinically important improvement in the RSDI score with nasal irrigation (44.1% v. 36.6%); fewer used over-the-counter medications (59.4% v. 68.0%) or intended to consult a doctor in future episodes. Steam inhalation reduced headache but had no significant effect on other outcomes. The proportion of participants who had adverse effects was the same in both intervention groups.Interpretation:Advice to use steam inhalation for chronic or recurrent sinus symptoms in primary care was not effective. A similar strategy to use nasal irrigation was less effective than prior evidence suggested, but it provided some symptomatic benefit. Trial registration: ISRCTN, no. 88204146.Rhinosinusitis probably affects more than 25 million Americans and 2.5 million Canadians.¹ Quality of life of patients with chronic or recurrent sinusitis has been reported to be similar to congestive heart disease and chronic pulmonary disease.² Antibiotics are prescribed for nearly all patients with sinusitis,³ but the evidence is modest⁴ and an international priority is to contain antibiotic resistance.⁵ Steam inhalation is widely advocated in rhinosinusitis, but a Cochrane review of steam for the “common cold” found equivocal evidence,⁶ and a recent primary care trial found no benefit and some harm (mild thermal injury) for pragmatic advice to inhale steam twice daily for a range of respiratory tract infections.⁷ The Cochrane review of nasal saline irrigation reported benefit.⁸ However, most of the trials were small, mainly from secondary care settings, and the review documented symptom data from only 129 participants, with high heterogeneity. Two small randomized controlled trials included some participants from primary care settings.^9,10 One of the studies compared a gravity-based nasal irrigation device with routine care among 76 participants mainly from primary care settings; it found that symptoms improved very little in the control group (by 1 point on the Rhinosinusitis Disability Index [RSDI] converted to a 100-point scale), as compared with a 14-point improvement in the irrigation group.⁹ The other (published since the Cochrane review) compared a positive-pressure squeeze bottle with saline nasal spray among 121 volunteers from various sources and found an 8.5-point improvement in the control group, as compared with a 15-point improvement in the irrigation group.¹⁰We conducted a large pragmatic randomized controlled trial of the effectiveness of brief advice to use nasal irrigation or steam inhalation in routine primary care for chronic or recurrent sinus symptoms.     

How are nitrogen availability,fine‐root mass,and nitrogen uptake related empirically? Implications for models and theory

Understanding the effects of global change in terrestrial communities requires an understanding of how limiting resources interact with plant traits to affect productivity. Here, we focus on nitrogen and ask whether plant community nitrogen uptake rate is determined (a) by nitrogen availability alone or (b) by the product of nitrogen availability and fine‐root mass. Surprisingly, this is not empirically resolved. We performed controlled microcosm experiments and reanalyzed published pot experiments and field data to determine the relationship between community‐level nitrogen uptake rate, nitrogen availability, and fine‐root mass for 46 unique combinations of species, nitrogen levels, and growing conditions. We found that plant community nitrogen uptake rate was unaffected by fine‐root mass in 63% of cases and saturated with fine‐root mass in 29% of cases (92% in total). In contrast, plant community nitrogen uptake rate was clearly affected by nitrogen availability. The results support the idea that although plants may over‐proliferate fine roots for individual‐level competition, it comes without an increase in community‐level nitrogen uptake. The results have implications for the mechanisms included in coupled carbon‐nitrogen terrestrial biosphere models (CN‐TBMs) and are consistent with CN‐TBMs that operate above the individual scale and omit fine‐root mass in equations of nitrogen uptake rate but inconsistent with the majority of CN‐TBMs, which operate above the individual scale and include fine‐root mass in equations of nitrogen uptake rate. For the much smaller number of CN‐TBMs that explicitly model individual‐based belowground competition for nitrogen, the results suggest that the relative (not absolute) fine‐root mass of competing individuals should be included in the equations that determine individual‐level nitrogen uptake rates. By providing empirical data to support the assumptions used in CN‐TBMs, we put their global climate change predictions on firmer ground.     

Origin of Fish Biomass in a Diverse Subtropical River: An Allochthonic-Supported Biomass Increase Following Flood Pulses

Ecosystems - The origin of resources supporting metazoan biomass in rivers has long been a subject of debate. The river wave concept (RWC) postulates that the energetic basis of food webs varies...     

Female Social Feedback Reveals Non-imitative Mechanisms of Vocal Learning in Zebra Finches

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Streptococcal dTDP‐L‐rhamnose biosynthesis enzymes: functional characterization and lead compound identification

Biosynthesis of the nucleotide sugar precursor dTDP‐L‐rhamnose is critical for the viability and virulence of many human pathogenic bacteria, including Streptococcus pyogenes (Group A Streptococcus; GAS), Streptococcus mutans and Mycobacterium tuberculosis. Streptococcal pathogens require dTDP‐L‐rhamnose for the production of structurally similar rhamnose polysaccharides in their cell wall. Via heterologous expression in S. mutans, we confirmed that GAS RmlB and RmlC are critical for dTDP‐L‐rhamnose biosynthesis through their action as dTDP‐glucose‐4,6‐dehydratase and dTDP‐4‐keto‐6‐deoxyglucose‐3,5‐epimerase enzymes respectively. Complementation with GAS RmlB and RmlC containing specific point mutations corroborated the conservation of previous identified catalytic residues. Bio‐layer interferometry was used to identify and confirm inhibitory lead compounds that bind to GAS dTDP‐rhamnose biosynthesis enzymes RmlB, RmlC and GacA. One of the identified compounds, Ri03, inhibited growth of GAS, other rhamnose‐dependent streptococcal pathogens as well as M. tuberculosis with an IC₅₀ of 120–410 µM. Importantly, we confirmed that Ri03 inhibited dTDP‐L‐rhamnose formation in a concentration‐dependent manner through a biochemical assay with recombinant rhamnose biosynthesis enzymes. We therefore conclude that inhibitors of dTDP‐L‐rhamnose biosynthesis, such as Ri03, affect streptococcal and mycobacterial viability and can serve as lead compounds for the development of a new class of antibiotics that targets dTDP‐rhamnose biosynthesis in pathogenic bacteria.     

Spatial memory shapes migration and its benefits: evidence from a large herbivore

From fine‐scale foraging to broad‐scale migration, animal movement is shaped by the distribution of resources. There is mounting evidence, however, that learning and memory also guide movement. Although migratory mammals commonly track resource waves, how resource tracking and memory guide long‐distance migration has not been reconciled. We examined these hypotheses using movement data from four populations of migratory mule deer (n = 91). Spatial memory had an extraordinary influence on migration, affecting movement 2–28 times more strongly than tracking spring green‐up or autumn snow depth. Importantly, with only an ability to track resources, simulated deer were unable to recreate empirical migratory routes. In contrast, simulated deer with memory of empirical routes used those routes and obtained higher foraging benefits. For migratory terrestrial mammals, spatial memory provides knowledge of where seasonal ranges and migratory routes exist, whereas resource tracking determines when to beneficially move within those areas.     

A risk‐based inventory of invasive plant species of Queensland,Australia: Regional,ecological and floristic insights

Invasive alien plant species threaten agriculture and biodiversity globally and require ongoing management to minimise impacts. However, the large number of invasive species means that a risk‐based approach to prioritisation is needed, taking into account the spatial scale of management decisions and myriad of available information. Here, we developed a risk‐based inventory of invasive plants in Queensland, Australia, using both current species distribution/abundance and the severity of their impacts. Our assessment followed a comprehensive data collection process including a scoping of local government pest management plans, herbarium records, the published literature and structured elicitation of expert knowledge during a series of regional stakeholder workshops. From ~300 plant species that were identified as established and/or emerging invaders in the State, only one‐third were considered by practitioners to pose significant risks across regions to be considered management priorities. We aggregated regional species lists into a statewide priority list and analysed the data set (107 species) for historical, geographical, floristic and ecological patterns. Regions on the mainland eastern seaboard of the State share similar invasive plant communities, suggesting that these regions may form a single management unit, unlike the western/inland and the extreme far north (Torres Strait Islands) regions, which share fewer invasive plant species. Positive correlations were detected between invasiveness and time since introduction for some but not all plant life forms. Stakeholders identified research and management priorities for the invasive plant list, including biological control options, public awareness/education, effective herbicide use, ecology/taxonomy and risk analysis. In the course of the exercise, a statewide invasive plant priority list of high‐, medium‐ and low‐impact scores for policy, research and management was compiled. Finally, our approach to invasive plant species prioritisation highlighted that planning and policy documents are not necessarily reflected at the grass‐root level in terms of species identity and management priorities.