The principal phenolic compounds and methylglyoxal were analysed in New Zealand
Leptospermum scoparium (manuka) and
Kunzea ericoides (kanuka) honeys. These honeys shared six phenolic acids as primary ...components and differentiation was possible as relative proportions varied. Manuka honey contained an elevated concentration of a trimethoxybenzoic acid and methylglyoxal; and 2-methoxybenzoic acid and methylglyoxal concentrations were linearly correlated in fresh manuka honey. Kanuka honey contained an elevated concentration of methoxyphenyllactic acid. The concentration of the phenolic components increased with maturation in both honey types; and this profile development, along with a corresponding increase of methylglyoxal concentration, was linear in manuka honey. Nectar analysed from the plant species contained the same phenolic components as the honeys. These results demonstrated the phenolic profile could be used to differentiate the honey types, heat treatment of honey could be identified, and the presence of these components may contribute to the efficacy of these honeys in therapeutic uses.
The maximum entropy (ME) method is a recently-developed approach for estimating local false discovery rates (LFDR) that incorporates external information allowing assignment of a subset of tests to a ...category with a different prior probability of following the null hypothesis. Using this ME method, we have reanalyzed the findings from a recent large genome-wide association study of coronary artery disease (CAD), incorporating biologic annotations. Our revised LFDR estimates show many large reductions in LFDR, particularly among the genetic variants belonging to annotation categories that were known to be of particular interest for CAD. However, among SNPs with rare minor allele frequencies, the reductions in LFDR were modest in size.
The prevailing models of stress induced Programmed Cell Death (PCD) posit that excess extracellular chemicals interact with or enter cells and disrupts cellular homeostasis. This activates signalling ...cascades involving the mitochondria, an increase in the steady state levels of Reactive Oxygen Species (ROS) as well as the activation of Bax and caspases. Further, the increased ROS also causes cellular damage that triggers or enhances PCD responses. The models have been modified in a number of ways, for example to include the existence of caspase and Bax independent forms of PCD. More recently, the ubiquity of ROS has also been challenged in part based on the failure of anti-oxidants to protect from diseases with increased intensity of oxidative stress. Here we focus on a number of other, often overlooked, observations regarding stress mediated responses that may further increase our mechanistic understanding of PCD. These include the concept of the “milieu intérieur” which suggests that cells actively protect themselves (adaptive homeostasis) in part by limiting entry to most extracellular chemicals. Of similar importance, stress also increases the levels of other stress inducible second messengers including ceramide, iron and calcium. This review focuses on the concept that stress is an agonist that conveys information that is transduced into the cell to activate the appropriate genetically encoded cell death and survival responses.
•Extracellular stress disrupts homeostasis.•Maintaining the “milieu intérieur” is critical for understanding the mechanisms by which cells respond to stress.•Cells respond to stress as if it were an agonist that induces appropriate intracellular processes.
The exceptionally well-preserved holotype of the armoured dinosaur Borealopelta markmitchelli (Ornithischia; Nodosauridae) from the Early Cretaceous (Clearwater Formation) of northern Alberta ...preserves a distinct mass within the abdominal cavity. Fourteen independent criteria (including: co-allochthony, anatomical position, gastroliths) support the interpretation of this mass as ingested stomach contents—a cololite. Palynomorphs in the cololite are a subset of the more diverse external sample. Analysis of the cololite documents well-preserved plant material dominated by leaf tissue (88%), including intact sporangia, leaf cross-sections and cuticle, but also including stems, wood and charcoal. The leaf fraction is dominated (85%) by leptosporangiate ferns (subclass Polypodiidae), with low cycad–cycadophyte (3%) and trace conifer foliage. These data represent the most well-supported and detailed direct evidence of diet in an herbivorous dinosaur. Details of the dietary palaeoecology of this nodosaur are revealed, including: selective feeding on ferns; preferential ingestion of leptosporangiate ferns to the exclusion of Osmundaceae and eusporangiate ferns such as Marattiaceae; and incidental consumption of cycad–cycadophyte and conifer leaves. The presence of significant (6%) charcoal may represent the dietary use of recently burned conifer forest undergoing fern succession, early evidence of a fire succession ecology, as is associated with many modern large herbivores.
Early Eocene global climate was warmer than much of the Cenozoic and was punctuated by a series of transient warming events or ‘hyperthermals’ associated with carbon isotope excursions when ...temperature increased by 4–8 °C. The Paleocene-Eocene Thermal Maximum (PETM, ~55 Ma) and Eocene Thermal Maximum 2 (ETM2, 53.5 Ma) hyperthermals were of short duration (<200 kyr) and dramatically restructured terrestrial vegetation and mammalian faunas at mid-latitudes. Data on the character and magnitude of change in terrestrial vegetation and climate during and after the PETM and ETM2 at high northern latitudes, however, are limited to a small number of stratigraphically restricted records. The Arctic Coring Expedition (ACEX) marine sediment core from the Lomonosov Ridge in the Arctic Basin provides a stratigraphically expanded early Eocene record of Arctic terrestrial vegetation and climates. Using pollen/spore assemblages, palynofacies data, bioclimatic analyses (Nearest Living Relative, or NLR), and lipid biomarker paleothermometry, we present evidence for expansion of mesothermal (Mean Annual Temperatures 13–20 °C) forests to the Arctic during the PETM and ETM2. Our data indicate that PETM mean annual temperatures were ~2° to 3.5 °C warmer than those of the Late Paleocene. Mean winter temperatures in the PETM reached ≥5 °C (~2 °C warmer than the late Paleocene), based on pollen-based bioclimatic reconstructions and the presence of palm and Bombacoideae pollen. Increased runoff of water and nutrients to the ocean during both hyperthermals resulted in greater salinity stratification and hypoxia/anoxia, based on marked increases in concentration of massive Amorphous Organic Matter (AOM) and dominance of low-salinity dinocysts. During the PETM recovery, taxodioid Cupressaceae-dominated swamp forests were important elements of the landscape, representing intermediate climate conditions between the early Eocene hyperthermals and background conditions of the late Paleocene.
•Arctic vegetation in the PETM and ETM2 included broadleaf forests, palms, and subtropical taxa.•Taxodioid swamp forests dominated Arctic landmasses during the PETM recovery.•Mixed conifer-broadleaf forests occupied Arctic sites during non-hyperthermals.•Proxy data indicate increased runoff and hypoxia during Eocene hyperthermals.•Bioclimatic and brGDGT indicators show ~2–3.5 °C warming during hyperthermals.
Antibody-drug conjugates containing peroxide-cleavable arylboronic acid linkers are described, which target the high levels of reactive oxygen species (ROS) in cancer. The arylboronic acid linkers ...rapidly release a payload in the presence of hydrogen peroxide, but remain stable in plasma. Anti-HER2 and PD-L1 peroxide-cleavable ADCs exhibited potent cytotoxicity
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The amyloid precursor protein (APP) is a cell surface protein of uncertain function that is notable for being the parent protein of beta-amyloid. Research around this protein has focussed heavily on ...the link to Alzheimer's disease and neurodegeneration. However, there is increasing evidence that APP may be linked to neuronal loss through mechanisms independent of beta-amyloid. FoxO3a is a transcription factor associated with neuronal longevity and apoptosis. In neurons, FoxO3a is associated with cell death through pathways that include BIM, a BCL-2 family member. In this study we have shown that APP overexpression increased the cellular levels and activity of FoxO3a. This increased expression and activity is not a result of decreased phosphorylation but is more likely a result of increased nuclear stability due to increased levels of FANCD2, a binding partner of FoxO3a. The changes caused by APP overexpression were shown to be due to the AICD fragment of APP possibly directly inducing transcription increase in FANCD2. These findings strengthen the link between APP metabolism and FoxO3a neuronal activity. This link may be crucial in better understanding the cellular role of APP and its link to neurodegeneration and aging.
•APP is a key protein in the understanding of Alzheimer's disease.•APP overexpression caused increase in active FoxO3a. a protein associated with aging and cell death.•The increase in FoxO3a was linked to increased expression of the AICD fragment of APP.•Increased AICD levels cause increased expression of FANCD2 associated with increased nuclear stabilisation of FoxO3a.
Premise of research. Fossil fan palm fronds are well known from Eocene sites in the United States; however, although they are also known from the Paleogene Huntingdon Formation of British Columbia ...for over 100 years, these are poorly studied. There are early anecdotal reports of Eocene “Sabal” or Sabalites leaves from the Vancouver area, pollen from Vancouver and the interior of British Columbia, and a single megafossil palm described from the Princeton Chert, indicating past warm climates in the region. Leaves of coryphoid palms (Arecaceae) from British Columbia are described formally here for the first time.
Methodology. We analyze morphologically the Eocene palm frond fossils from the Vancouver area (Huntingdon Formation) and the Ashcroft area in British Columbia.
Pivotal results. The Sabalites fossil fronds from the Vancouver area represent fan palms (subfamily Coryphoideae, cf. tribe Sabaleae) and are assigned to the new taxon Sabalites dawsonii. These and other Eocene palm fossils from the Pacific Northwest demonstrate that—based on prior paleoclimate analyses—coryphoid palms were growing under paleotemperatures close to their modern cold limits. Palm fossils reported from near Ashcroft are not Arecaceae, as key diagnostic characters are absent.
Conclusions. These and comparable palm fossil records, coupled with analyses of paleoclimate, corroborate an early Paleogene origin of temperate climate adaptation by Coryphoideae, likely as part of the initial Sabaleae and Trachycarpeae diversifications.
A human cDNA encoding the LIM domain containing 194 amino acid cysteine and glycine rich protein 3 (CSRP3) was identified as a BAX suppressor in yeast and a pro-survival sequence that abrogated ...copper mediated regulated cell death (RCD). Yeast lacks a CSRP3 orthologue but it has four LIM sequences, namely RGA1, RGA2, LRG1 and PXL1. These are known regulators of stress responses yet their roles in RCD remain unknown. Given that LIMs interact with other LIMs, we ruled out the possibility that overexpressed yeast LIMs alone could prevent RCD and that CSRP3 functions by acting as a dominant regulator of yeast LIMs. Of interest was the discovery that even though yeast cells lacking the LIM encoding PXL1 had no overt growth defect, it was nevertheless supersensitive to the effects of sublethal levels of copper. Heterologous expression of human CSPR3 as well as the pro-survival 14-3-3 sequence corrected this copper supersensitivity. These results show that the pxl1∆-copper synthetic lethality is likely due to the induction of RCD. This differs from the prevailing model in which synthetic lethality occurs because of specific defects generated by the combined loss of two overlapping but non-essential functions.
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•Human LIM domain containing CSRP3 acts as a Bax suppressor and pro-survival protein when heterologously expressed in yeast•All four yeast LIM containing sequences are not involved in modulating programmed cell death responses•The loss of the LIM containing PXL1 gene in yeast is synthetically lethal with sublethal levels of copper•PXL1-copper synthetically lethality is reversed by general pro-survival sequences
The genus Trichoderma contains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, ...comprehensive overview of the genomic content of these species for "hot topic" research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism in T. reesei, T. atroviride, and T. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of each Trichoderma species discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved in N-linked glycosylation was detected, as were indications for the ability of Trichoderma spp. to generate hybrid galactose-containing N-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique to Trichoderma, and these warrant further investigation. We found interesting expansions in the Trichoderma genus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique to T. atroviride is the duplication of the alternative sulfur amino acid synthesis pathway.
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