Ultimate Trigger Research Articles

In 2024, the amyloid-cascade-hypothesis still remains a working hypothesis, no less but certainly no more.

The amyloid-cascade-hypothesis of the pathogenesis of Alzheimer's disease (AD) was introduced 32 years ago, in 1992. From early on, this clear and straight forward hypothesis received a lot of attention, but also a lot of substantial criticism. Foremost, there have always been massive doubts that a complex age-associated disorder of the most intricate organ of the human body, the brain, can be explained by a linear, one-dimensional cause-and-effect model. The amyloid-cascade defines the generation, aggregation, and deposition of the amyloid beta peptide as the central pathogenic mechanism in AD, as the ultimate trigger of the disease, and, consequently, as the key pharmacological target. Certainly, the original 1992 version of this hypothesis has been refined by various means, and the 'formulating fathers' followed up with a few reappraisals and partly very open reflections in 2002, 2006, 2009, and 2016. However, up until today, for the supporters of this hypothesis, the central and initial steps of the cascade are believed to be driven by amyloid beta-even if now displayed somewhat more elaborate. In light of the recently published clinical results achieved with anti-amyloid antibodies, the controversy in the field about (1) the clinical meaningfulness of this approach, (2) the significance of clearance of the amyloid beta peptide, and last but not least (3) the relevance of the amyloid-cascade-hypothesis is gaining momentum. This review addresses the interesting manifestation of the amyloid-cascade-hypothesis as well as its ups and downs over the decades.

Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia.

Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients.

Poleward spawning of Atlantic mackerel (Scomber scombrus) is facilitated by ocean warming but triggered by energetic constraints

Abstract The Northeast Atlantic mackerel is an income breeder with indeterminate fecundity, spawning in multiple batches at optimal temperatures around 11°C in the upper water column during February–July along the continental shelf from 36–62°N. Based on macroscopic staging of gonads (N ∼62000) collected in 2004–2021, we detected an on-going extension of spawning activities into the Norwegian Sea feeding area (62–75°N), reaching stable levels around 2012 onwards. This poleward expansion increased as more fish entered the area, whilst the maximum proportions of spawners concurrently dropped from about 75 to 15% from May to July. Detailed histological examinations in 2018 confirmed the macroscopic results but clarified that 38% of the spawning-capable females in July terminated their spawning by atresia. We suggest that increased access to suitable spawning areas (≥10°C), following ocean warming from 2002 onwards, functions as a proximate cause behind the noticed expansion, whereas the ultimate trigger was the historic drop in body growth and condition about 10 years later. Driven by these energetic constraints, mackerel likely spawn in the direction of high prey concentrations to rebuild body resources and secure the future rather than current reproduction success. The ambient temperature that far north is considered suboptimal for egg and larval survival.

On the Influence of ENSO on Sudden Stratospheric Warmings

AbstractUsing the extended ERA5 reanalysis and three state‐of‐the‐art models, this study explores how El Niño‐Southern Oscillation (ENSO) can influence the total frequency, seasonal cycle and preconditioning of sudden stratospheric warmings (SSWs). Reanalysis data shows that in the last seven decades, winters with SSWs were more common than winters without, regardless El Niño (EN) or La Niña (LN) occurrence or the ENSO/SSW definitions. In agreement with previous studies, our models tend to simulate a linear ENSO‐SSW relationship, with more SSWs for EN, around mid‐winter (January–February) as in reanalysis, and less for LN when compared to neutral conditions. Independently of ENSO, the main tropospheric precursor of SSWs appears to be an anomalous wave‐like pattern over Eurasia, but it is dominated by wavenumber 1 (WN1) for EN and shows an enhanced wavenumber 2 (WN2) for LN. The differences in this Eurasian wave pattern, which is largely internally generated, emerge from the distinct configuration of the background, stationary wave pattern induced by ENSO in the North Pacific, favoring a stronger WN1 (WN2) component during EN (LN). Our results suggest that the ENSO‐forced signal relies on modulating the seasonal‐mean polar vortex strength, becoming weaker and more displaced (stronger and more stable) for EN (LN), while ENSO‐unforced wave activity represents the ultimate trigger of SSWs. This supports the view that ENSO and SSWs are distinct sources of variability of the winter atmospheric circulation operating at different time‐scales and may reconcile previous findings in this context.

Claspin-Dependent and -Independent Chk1 Activation by a Panel of Biological Stresses.

Replication stress has been suggested to be an ultimate trigger of carcinogenesis. Oncogenic signal, such as overexpression of CyclinE, has been shown to induce replication stress. Here, we show that various biological stresses, including heat, oxidative stress, osmotic stress, LPS, hypoxia, and arsenate induce activation of Chk1, a key effector kinase for replication checkpoint. Some of these stresses indeed reduce the fork rate, inhibiting DNA replication. Analyses of Chk1 activation in the cell population with Western analyses showed that Chk1 activation by these stresses is largely dependent on Claspin. On the other hand, single cell analyses with Fucci cells indicated that while Chk1 activation during S phase is dependent on Claspin, that in G1 is mostly independent of Claspin. We propose that various biological stresses activate Chk1 either directly by stalling DNA replication fork or by some other mechanism that does not involve replication inhibition. The former pathway predominantly occurs in S phase and depends on Claspin, while the latter pathway, which may occur throughout the cell cycle, is largely independent of Claspin. Our findings provide evidence for novel links between replication stress checkpoint and other biological stresses and point to the presence of replication-independent mechanisms of Chk1 activation in mammalian cells.

Assessment of lipid peroxidation in irradiated cells.

Lipid peroxidation occurs under conditions where reactive oxygen species (ROS) readily react with vulnerable lipids on cell membranes. Polyunsaturated fatty acids (PUFAs) are highly susceptible to lipid peroxidation because of their unstable double bonds. Because the cell membrane is particularly rich in PUFAs, it is often the site at which many lipid peroxidation chain reactions occur. Lipid peroxidation is considered the ultimate trigger of ferroptosis, an iron-dependent form of non-apoptotic cell death. Radiotherapy is a common cancer treatment that uses high-energy ionizing radiation to kill cancer cells, and radiation-induced cell death is partially attributed to lipid peroxidation-driven ferroptosis. Here, we describe methods to assess lipid peroxidation in irradiated cells. The same techniques can be applied to a variety of lipid peroxidation measurements under different treatment conditions.

BrGDGTs-based temperature and hydrological reconstruction from fluvio-lacustrine sediments in the monsoonal North China Plain since 31 kyr BP

Knowledge of glacial-interglacial changes in the East Asian summer monsoon (EASM) can potentially provide insights into future hydrological changes in its region of influence, caused by ongoing global warming. Here, we present temperature and hydrological (soil moisture and pH) reconstructions based on records of branched glycerol dialkyl glycerol tetraethers from fluvio-lacustrine sediments in the monsoonal North China Plain (NCP) for the past 31 kyr. The results show that the air temperature in the NCP was ∼8–9 °C warmer during the mid-Holocene than during the Last Glacial Maximum, and that soil pH is negatively correlated with soil moisture but with a lag of 2–4 kyr due to the buffering effect of carbonates. By contrast, soil moisture increased synchronously with temperature, suggesting that EASM precipitation will increase in the near future as global warming continues. Additionally, the initial increase in land and sea temperature during the last deglaciation lagged summer insolation at northern high latitudes, indicating that insolation was the ultimate trigger of the last deglacial warming.

Perspectival factors and pro-drop: A corpus study of speaker/addressee pronouns with creer ‘think/ believe’ and saber ‘know’ in spoken Spanish

This paper examines overt and covert speaker/addressee pronouns with the cognitive verbs creer ‘think/believe’ and saber ‘know’ in a corpus of spoken peninsular Spanish – the Madrid and Alcalá samples of PRESEEA (2014– ) – with a focus on 1st person singular (yo) creo que ‘(I) think that’. Departing from the observation made in the literature that overt pronouns are highly frequent with creer and that topic shift cannot account for all of them, it will be argued that perspectival factors related to evidentiality/epistemicity and subjectivity influence overt pronoun realization. A corpus study was conducted to investigate whether (i) [person] and [polarity] and (ii) the type of complement affect overt pronoun realization with the cognitive verbs creer and saber. The results indicate that the type of belief expressed in the embedded clause should be taken into account, as well as person and polarity. The ultimate trigger for phonetic realization of speaker/addressee pronouns will be argued to be the notion of contrast: cognitive verbs whose embedded complement encodes evaluations and non-visual, abstract information have high frequencies of overt pronoun realization because these contexts favor the evoking of alternative perspective holders. Overt pronouns will be analyzed as the result of a [+contrast] feature which is assigned to the specifier of a functional category encoding perspective in the split IP.

On the Generation of Weddell Sea Polynyas in a High-Resolution Earth System Model

AbstractLarger Weddell Sea polynyas (WSPs), differentiated in this study from the smaller Maud Rise Polynyas (MRPs) that form to the east of the prime meridian in the proximity of the Maud Rise seamount, have last been observed in the 1970s. We investigate WSPs that grow realistically out of MRPs in a high-resolution preindustrial simulation with the Energy Exascale Earth System Model, version 0.1. The formation of MRPs requires high resolution to simulate the detailed flow around Maud Rise, whereas the realistic formation of WSPs requires a model to produce MRPs. Furthermore, WSPs tend to follow periods of a prolonged buildup of a heat reservoir at depth and weakly negative wind stress curl in association with the core of the Southern Hemisphere westerlies at an anomalously northern position. While this scenario also leads to drier conditions over the central Weddell Sea, which some literature claims to be a necessary condition for the formation of WSPs, our model results indicate that open-ocean polynyas do not occur during periods of weakly negative wind stress curl despite drier atmospheric conditions. Our study supports the hypothesis noted in earlier studies that a shift from a weakly negative to a strongly negative wind stress curl over the Weddell Sea is a prerequisite for WSPs to form, together with a large heat reservoir at depth. However, the ultimate trigger is a pronounced MRP, whose associated convection creates high surface salinity anomalies that propagate westward with the flow of the Weddell Gyre. If large enough, these anomalies trigger the formation of a WSP and a pulse of newly formed Antarctic Bottom Water.

Failures of Feeling: Insensibility and the Novel by Wendy Anne Lee

Reviewed by: Failures of Feeling: Insensibility and the Novel by Wendy Anne Lee Scott R. Mackenzie LEE, WENDY ANNE. Failures of Feeling: Insensibility and the Novel. Stanford: Stanford University Press, 2020. $55.00 hardcover; $26.00 paperback. Wendy Anne Lee's Failures of Feeling identifies and investigates a "dilemma in fiction" of which Melville's Bartleby is the "culmination": his "unfeeling combined with inaction" (1) and "unnerving oscillation between impassivity (no feeling) and contempt (bad feeling)" disrupt "the novel's promise to deliver the goods of human interiority at the same time that [his insensibility] foments that very mission" (2). Lee calls characters who embody this dilemma "insensibles" and her examples include the Princesse de Cleves, Clarissa, Oliver Goldsmith's Tony Lumpkin, Gwendolen Harleth, and King Charles I. They belong to a "genealogy of insensibles" (126) and, while an insensible is not exactly a stock character, Lee's case studies also include Clarissa's typological forebear, the prude, and the folkloric figure Puck, of whom Tony Lumpkin is an avatar. Insensibility functions narratologically as well as characterologically. It may, for instance, elucidate Jane Austen's narratorial strategy in Sense and [in] Sensibility, which Lee winningly dubs "the Elinor doctrine": "screening [the narrative's] subjects from the torments of self-awareness" (158). It upsets "protocols of fictionality" [End Page 314] (126) and induces "narrative failure" (66), but in the same motion (which presents as immobility) it is "oddly galvanizing" (46) to those who encounter it, and "the ultimate trigger" for compensatory engagement and narration. This paradox is best exemplified by a question that John Harlowe asks his niece, Clarissa: "How can you be so unmoved yourself, yet be so able to move everybody else?" (qtd. in Lee 60). Insensibility is not strictly determined by either internal or external impulses. It tends to have the formal trappings of choice or intent ("I prefer not to"), but at the same time to undermine the sense that affects or acts are produced by feelings or volition. This disarticulation of internal states from external expressions generates Lee's principle of simultaneous narrative obstruction and incitement: "writing is not a relay between feeling and action but…some third thing" (48). The insensible is a kind of Aristotelian first cause (3) for novelistic narrative in the Richardsonian tradition. Indeed the novel form, Lee concludes, "is the ultimate insensible" (171). Insensibility is a kind of literalization of Adam Smith's sympathetic paradox: "our senses will never inform us of what [a tortured person] suffers…and it is by imagination alone that we form any conception of what are his sensations" (Theory of Moral Sentiments 9 [Clarendon, 1982]). Smith's law seems pivotal to Lee's formulation of insensibility as a vexing confluence of blockages—of affect, sensation, and perception. She does not quote that passage, though it is a premise for the citations from Smith that she does incorporate, and key interlocutors, particularly Rae Greiner, have discussed it in detail. Failures of Feeling is threaded throughout with ellipsis and implication, more than critical monographs usually are, and its gestures can feel elusive. At times Lee's quicksilver stylistics verge on mixed metaphor: for instance, an F. R. Leavis aphorism "signals [George] Eliot's best effort to entomb, or at least quarantine, the novel's blighted formula of gendered insensibility, sending it back to its crib with the half-hearted hope that it might try again" (169). These proliferating figures of speech do seem congruent with the figural logics of insensibility: it appears at loci of intense overdetermination. It is "the unmoving center or 'millstone' in a field of causes and effects, agents and patients" (26). The most conspicuous example is Clarissa's fixation on the young unmarried woman's consent, one of the century's favorite symptomatic preoccupations. Lee draws on Frances Ferguson to argue that fetishized consent-under-duress is central to the construction of interiority as "a back projection of a relational structure like marriage or intercourse" (65). In a longer version of this study, Lee might also have cited Ann Radcliffe's heroines, who discover that their consent is the arena in which property relations are renegotiated, as well as Edmund Burke's Reflections of...

Bistable, Biphasic Regulation of PP2A-B55 Accounts for the Dynamics of Mitotic Substrate Phosphorylation

SUMMARYThe phosphorylation of mitotic proteins is bistable, which contributes to the decisiveness of the transitions into and out of M phase. The bistability in substrate phosphorylation has been attributed to bistability in the activation of the cyclin-dependent kinase Cdk1. However, more recently it has been suggested that bistability also arises from positive feedback in the regulation of the Cdk1-counteracting phosphatase PP2A-B55. Here, we demonstrate biochemically using Xenopus laevis egg extracts that the Cdk1-counter-acting phosphatase PP2A-B55 functions as a bistable switch, even when the bistability of Cdk1 activation is suppressed. In addition, Cdk1 regulates PP2A-B55 in a biphasic manner; low concentrations of Cdk1 activate PP2A-B55 and high concentrations inactivate it. As a consequence of this incoherent feedforward regulation, PP2A-B55 activity rises concurrently with Cdk1 activity during interphase and suppresses substrate phosphorylation. PP2A-B55 activity is then sharply downregulated at the onset of mitosis. During mitotic exit, Cdk1 activity initially falls with no obvious change in substrate phosphorylation; dephosphorylation then commences once PP2A-B55 spikes in activity. These findings suggest that changes in Cdk1 activity are permissive for mitotic entry and exit but that the changes in PP2A-B55 activity are the ultimate trigger.

Exposure to inorganic arsenic and its methylated metabolites alters metabolomics profiles in INS-1 832/13 insulinoma cells and isolated pancreatic islets.

Inorganic arsenic (iAs) is an environmental diabetogen, but mechanisms underlying its diabetogenic effects are poorly understood. Exposures to arsenite (iAsIII) and its methylated metabolites, methylarsonite (MAsIII) and dimethylarsinite (DMAsIII), have been shown to inhibit glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells and isolated pancreatic islets. GSIS is regulated by complex mechanisms. Increase in ATP production through metabolism of glucose and other substrates is the ultimate trigger for GSIS in β-cells. In the present study, we used metabolomics to identify metabolites and pathways perturbed in cultured INS-1 832/13 rat insulinoma cells and isolated murine pancreatic islets by exposures to iAsIII, MAsIII and DMAsIII. We found that the exposures perturbed multiple metabolites, which were enriched primarily in the pathways of amino acid, carbohydrate, phospholipid and carnitine metabolism. However, the effects of arsenicals in INS-1 832/13 cells differed from those in the islets and were exposure specific with very few overlaps between the three arsenicals. In INS-1 832/13 cells, all three arsenicals decreased succinate, a metabolite of Krebs cycle, which provides substrates for ATP synthesis in mitochondria. Acetylcarnitine was decreased consistently by exposures to arsenicals in both the cells and the islets. Acetylcarnitine is usually found in equilibrium with acetyl-CoA, which is the central metabolite in the catabolism of macronutrients and the key substrate for Krebs cycle. It is also thought to play an antioxidant function in mitochondria. Thus, while each of the three trivalent arsenicals perturbed specific metabolic pathways, which may or may not be associated with GSIS, all three arsenicals appeared to impair mechanisms that support ATP production or antioxidant defense in mitochondria. These results suggest that impaired ATP production and/or mitochondrial dysfunction caused by oxidative stress may be the mechanisms underlying the inhibition of GSIS in β-cells exposed to trivalent arsenicals.

Contemporary portable oxygen concentrators and diverse breathing behaviours -- a bench comparison

BackgroundDecades of clinical research into pulsed oxygen delivery has shown variable efficacy between users, and across a user’s behaviours (sleep, rest, activity). Modern portable oxygen concentrators (POCs) have been shown as effective as other oxygen delivery devices in many circumstances. However, there are concerns that they are not effective during sleep when the breathing is shallow, and at very high respiratory rates as during physical exertion. It can be challenging to examine the determinants of POC efficacy clinically due to the heterogeneity of lung function within oxygen users, the diversity of user behaviour, and measurement issues. Representative bench testing may help identify key determinants of pulsed-oxygen device efficacy.MethodsThree contemporary devices were bench-evaluated across three simulated breathing behaviours: activity, rest, & oronasal breathing during sleep. Emphasis was placed on breathing patterns representative of oxygen users.ResultsAll three POCs performed well during simulated breathing during exertion and at rest. Differences in triggering ability were noted for the scenario of oronasal breathing during sleep.ConclusionsThe results are supportive of contemporary POC triggering abilities. The differences shown in ultimate trigger sensitivity may have relevance to oronasal breathing during sleep or other challenging scenarios for pulsed oxygen delivery, such as dominant mouth breathing during exertion or unfavourable nasal geometry.

Decadal-scale progression of the onset of Dansgaard–Oeschger warming events

Abstract. During the last glacial period, proxy records throughout the Northern Hemisphere document a succession of rapid millennial-scale warming events, called Dansgaard–Oeschger (DO) events. A range of different mechanisms has been proposed that can produce similar warming in model experiments; however, the progression and ultimate trigger of the events are still unknown. Because of their fast nature, the progression is challenging to reconstruct from paleoclimate data due to the limited temporal resolution achievable in many archives and cross-dating uncertainties between records. Here, we use new high-resolution multi-proxy records of sea-salt (derived from sea spray and sea ice over the North Atlantic) and terrestrial (derived from the central Asian deserts) aerosol concentrations over the period 10–60 ka from the North Greenland Ice Core Project (NGRIP) and North Greenland Eemian Ice Drilling (NEEM) ice cores in conjunction with local precipitation and temperature proxies from the NGRIP ice core to investigate the progression of environmental changes at the onset of the warming events at annual to multi-annual resolution. Our results show on average a small lead of the changes in both local precipitation and terrestrial dust aerosol concentrations over the change in sea-salt aerosol concentrations and local temperature of approximately one decade. This suggests that, connected to the reinvigoration of the Atlantic meridional overturning circulation and the warming in the North Atlantic, both synoptic and hemispheric atmospheric circulation changes at the onset of the DO warming, affecting both the moisture transport to Greenland and the Asian monsoon systems. Taken at face value, this suggests that a collapse of the sea-ice cover may not have been the initial trigger for the DO warming.

The effects of ultrasound pressure and temperature fields in millisecond bubble nucleation

A phenomenological implementation of Classical Nucleation Theory (CNT) is employed to investigate the connection between high intensity focused ultrasound (HIFU) pressure and temperature fields with the energetic requirements of bubble nucleation. As a case study, boiling histotripsy in tissue-mimicking phantoms is modelled. The physics of key components in the implementation of CNT in HIFU conditions such as the derivation of nucleation pressure thresholds and approximations regarding the surface tension of the liquid are reviewed and discussed. Simulations show that the acoustic pressure is the ultimate trigger for millisecond bubble nucleation in boiling histotripsy, however, HIFU heat deposition facilitates nucleation by lowering nucleation pressure thresholds. Nucleation thus occurs preferentially at the regions of highest heat deposition within the HIFU field. This implies that bubble nucleation subsequent to millisecond HIFU heat deposition can take place at temperatures below 100 °C as long as the focal HIFU peak negative pressure exceeds the temperature-dependent nucleation threshold. It is also found that the magnitude of nucleation pressure thresholds decreases with decreasing frequencies. Overall, results indicate that it is not possible to separate thermal and mechanical effects of HIFU in the nucleation of bubbles for timescales of a few milliseconds. This methodology provides a promising framework for studying time and space dependencies of the energetics of bubble nucleation within a HIFU field.

Preconditioning and Formation of Maud Rise Polynyas in a High-Resolution Earth System Model

AbstractOpen-ocean polynyas (OOPs) in the Southern Ocean are ice-free areas within the winter ice pack that are associated with deep convection, potentially contributing to the formation of Antarctic Bottom Water. To enhance the credibility of Earth system models (ESMs), their ability to simulate OOPs realistically is thus crucial. Here we investigate OOPs that emerge intermittently in a high-resolution (HR) preindustrial simulation with the Energy Exascale Earth System Model, version 0.1 (E3SMv0), an offspring of the Community Earth System Model (CESM). While low-resolution (LR) simulations with E3SMv0 show no signs of OOP formation, the preindustrial E3SMv0-HR simulation produces both large Weddell Sea polynyas (WSPs) as well as small Maud Rise polynyas (MRPs). The latter are associated with a prominent seamount in the eastern Weddell Sea, and their preconditioning and formation is the focus of this study. The steep flanks of the rugged topography in this region are in E3SMv0-HR sufficiently well resolved for the impinging flow to produce pronounced Taylor caps that precondition the region for convection. Aided by an accumulation of heat in the Weddell Deep Water layer, the ultimate trigger of convection that leads to MRPs is the advection of anomalously high upper-ocean-layer salinity. The crucial difference to WSP-producing LR ESM simulations is that in E3SMv0-HR, WSPs are realistically preceded by MRPs, which in turn are a result of the flow around bathymetry being represented with unprecedented detail.

Geochronology, classification and mantle source characteristics of kimberlites and related rocks from the Rae Craton, Melville Peninsula, Nunavut, Canada

Detailed geochronology along with petrographic, mineralogical and geochemical studies have been conducted on recently found diamond-bearing kimberlitic and related rocks in the Rae Craton at Aviat and Qilalugaq, Melville Peninsula, north-east Canada. Magmatic rocks from the Aviat pipes have geochemical (both bulk rock and isotopic) and mineralogical signatures (e.g., core to rim Al and Ba enrichment in phlogopite) similar to Group I kimberlite. In contrast, Aviat intrusive sheets are similar to ‘micaceous’ Group II kimberlite (orangeite) in their geochemical and mineralogical characteristics (e.g., phlogopite and spinel compositions, highly enriched Sr isotopic signature). Qilalugaq rocks with the least crustal contamination have geochemical and mineralogical signatures [e.g., high SiO2, Al2O3 and H2O; low TiO2 and CO2; less fractionated REE (rare earth elements), presence of primary clinopyroxene, phlogopite and spinel compositions] that are similar to features displayed by olivine lamproites from Argyle, Ellendale and West Greenland. The Naujaat dykes, in the vicinity of Qilalugaq, are highly altered due to extensive silicification and carbonation. However, their bulk rock geochemical signature and phlogopite chemistry are similar to Group I kimberlite. U–Pb perovskite geochronology reveals that Aviat pipes and all rocks from Qilalugaq have an early Cambrian emplacement age (540–530 Ma), with the Aviat sheets being ~30 Ma younger. This volatile-rich potassic ultramafic magmatism probably formed by varying degrees of involvement of asthenospheric and lithospherically derived melts. The spectrum of ages and compositions are similar to equivalent magmatic rocks observed from the nearby north–eastern North America and Western Greenland. The ultimate trigger for this magmatism could be linked to Neoproterozoic continental rifting during the opening of the Iapetus Ocean and breakup of the Rodinia supercontinent.

Phase-shift evolution of the thermally-induced refractive index grating in high-power fiber laser systems induced by pump-power variations.

A phase shift between the modal interference pattern and the thermally-induced refractive index grating is most likely the ultimate trigger for the damaging effect of transverse mode instabilities (TMI) in high-power fiber laser systems. By using comprehensive simulations, the creation and evolution of a thermally-induced phase shift is explained and illustrated in detail. It is shown that such a phase shift can be induced by a variation of the pump power. The gained knowledge about the generation and evolution of the phase shift will allow for the development of new mitigation strategies for TMI.

The Embodied Subjectivity of a Half-Formed Narrator: Sexual Abuse, Language (Un)formation and Melancholic Girlhood in Eimear McBride’s A Girl is a Half-Formed Thing

Set in Ireland, in some undetermined time and place, Eimear McBride’s A Girl is a Half-formed Thing (2014) is a story about the crisis of identity of a nameless girl who has been sexually abused by her uncle in her teens. The aberrant sexualisation resulting from rape and the socially pre-established discourses of girlhood and womanhood provoke the fragmentation of the protagonist’s identity as a female subject and her transformation into a “half-formed thing”. McBride tries to capture this process of half-formation by means of language and other experimental narrative strategies, which are a clear legacy of modernism and the works by female writers from the Celtic Tiger period. The violent world, in which the main character is under the rule of her authoritative mother and predatory uncle, contrasts with the loving relationship with her terminally ill brother. The melancholic experiences of shame and guilt invade the Girl’s sense of embodied identity and interfere with the process of becoming an individual. The death of her brother is the ultimate trigger for the half-formed girl to disengage permanently from her “sinful” body, opening the possibility of an alternative mode of being in the world. The analysis of this novel-long stream-of-consciousness focuses on the narration of the conflicts with corporeality, abnormal sexualisation, the dissolution of subjectivity and failure to regain agency over a powerless body.

Local and regional control of calcium dynamics in the pancreatic islet.

Ca2+ is the key intracellular regulator of insulin secretion, acting in the β-cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K+ channel closure and plasma membrane depolarization engage a sophisticated machinery to drive pulsatile cytosolic Ca2+ changes. Voltage-gated Ca2+ channels, Ca2+ -activated K+ channels and Na+ /Ca2+ exchange all play important roles. The use of targeted Ca2+ probes has revealed that during each cytosolic Ca2+ pulse, uptake of Ca2+ by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca2+ dynamics and control organellar function. For example, changes in the expression of the Ca2+ -binding protein Sorcin appear to provide a link between ER Ca2+ levels and ER stress, affecting β-cell function and survival. Across the islet, intercellular communication between highly interconnected "hubs," which act as pacemaker β-cells, and subservient "followers," ensures efficient insulin secretion. Loss of connectivity is seen after the deletion of genes associated with type 2 diabetes (T2D) and follows metabolic and inflammatory insults that characterize this disease. Hubs, which typically comprise ~1%-10% of total β-cells, are repurposed for their specialized role by expression of high glucokinase (Gck) but lower Pdx1 and Nkx6.1 levels. Single cell-omics are poised to provide a deeper understanding of the nature of these cells and of the networks through which they communicate. New insights into the control of both the intra- and intercellular Ca2+ dynamics may thus shed light on T2D pathology and provide novel opportunities for therapy.