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Abstract All historical eruptions at Ruapehu have occurred from its Crater Lake, Te Wai ā-moe. This study aims to better understand Crater Lake dynamics by using visible light and long wavelength infrared images of the lake. Over 10,000 images from 1902 – 2021 were analysed to produce a time-series of lake observations. Our results show that visible light observations reveal colour changes on the entire Crater Lake surface from blue to grey, and localised grey, yellow, and black discolourations. Grey discolourations are interpreted as localised upwellings of lake-floor sediment, and yellow and black material to comprise vent-hosted sulphur/sulphides, both transported by volcanic fluids from subaqueous vents to the surface. The locations of upwellings were used to identify five vent locations beneath Crater Lake, three more vents than were previously recognised. Upwellings appeared and disappeared in 10 min. Steam above the lake surface was controlled by both lake temperature and cloud conditions. Blue lakes were most common in summer and autumn, implying a relationship with ice or snow melt entering the lake. Grey lakes were observed in the month before 97% of eruptions, suggesting a correlation between a grey lake and eruption precursors. Crater Lake processes are illustrated by three regimes. Regime 1, a vigorously convecting grey lake associated with steam, eruptions, and more frequently the high end of recorded lake temperatures (within the range of 7 – 69 °C). Regime 2, a blue lake to occasionally green that typically occurs in summer and autumn when ice or snow melt is significant and is associated with generally the low end of lake temperatures and reduced volcanic fluid input. Regime 3, a blue-grey lake, the most observed lake colour in this study and effectively a balance between volcanic and seasonal processes. We suggest that an array of cameras would be useful additions to the current volcano monitoring network at Ruapehu.

A virtual microscope resource was created when face-to-face labs were halted due to the COVID-19 pandemic in March 2020 to replicate the learning goals of an introductory petrology course on microscopy. This virtual microscope resource utilized images and videos of thin sections, as well as 3D rock models to allow students to complete labs online. It also incorporated directed questioning and feedback as would be provided by demonstrators (teaching assistants) in a face-to-face lab. Insights obtained from student reflective questionnaires (n = 75) were used to adapt the online resource so that it could be used in conjunction with the face-to-face lab, thus becoming a blended lab resource in the subsequent year. These reflective questionnaires were utilized again to provide feedback on the revised version of the resource for blended learning. Findings showed that students in the blended learning cohort rated the quality of the available online material higher than the previous students. The blended learning cohort appreciated the immediate feedback from the resource, as well as its ability to provide remote access to lab materials. They also gained confidence by being able to review the material multiple times online. We conclude that blended resources are a useful tool in introductory petrology which we hope to see become more commonplace in the future.

Accurate volcanic hazard assessments rely on a detailed understanding of the timing of past eruptions. While radiometric methods like 40Ar/39Ar or K/Ar are by far the most conventional lava flow dating tools, their low resolution for young ( ka) deposits interferes with the development of precise chronologies of recent effusive activity on most volcanoes. Mt Ruapehu (Aotearoa / New Zealand) has produced many lava flows throughout its history, but the precise timing of many recent eruptions remains largely unknown. In this study, we use cosmogenic 3He exposure dating to provide 23 eruption ages of young lava flows at Ruapehu. We then compare our results with existing 40Ar/39Ar and paleomagnetic constraints, highlighting the value of cosmogenic nuclide exposure dating in refining recent eruptive chronologies. Of the 23 sampled flows, 16 provided robust eruption ages (5 %–20 % internal 2σ; n≥3) between ca. 20 and 8 ka, except for one lava flow that erupted at around 43 ka, and their age distribution indicates that, during the last 20 kyr, effusive activity at Ruapehu peaked at 17–12 ka and at 9–7.5 ka. Nearly identical eruption ages of lavas located in different flanks of the volcanic edifice suggest concurrent activity from multiple vents during relatively short time intervals (0–2 kyr) at around 13, 10, and 8 ka. We analysed four individual lava flows previously dated by 40Ar/39Ar, two of which yield eruption ages older than the older limit of the 2σ interval of the radiometric dates, but the good clustering of individual samples from our sites suggests that our results better represent the real eruption age of these flows. Our 3He-based chronology shows excellent agreement with paleomagnetic constraints, suggesting that production rate uncertainties are unlikely to impact the accuracy of our eruption ages. This study demonstrates how cosmogenic nuclide dating can provide greater detail on the recent effusive chronology of stratovolcanoes, helping to resolve the low resolution of and difficulty in applying radiometric dating methods to young lava flows.

IntroductionIntrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) result in selective respiratory (e.g., phrenic) motor neuron death and mimics aspects of motor neuron disease [(e.g., amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)], such as breathing deficits. This rodent model allows us to study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited. Microglial density in the phrenic motor nucleus as well as cervical gene expression of markers associated with inflammation (e.g., tumor necrosis factor α; TNF-α) are increased following CTB-SAP-induced phrenic motor neuron death, and ketoprofen (nonsteroidal anti-inflammatory drug) delivery attenuated phrenic long-term facilitation (pLTF) in 7 day (d) CTB-SAP rats but enhanced pLTF in 28d CTB-SAP rats.MethodsHere, we worked to determine the impact of TNF-α in the phrenic motor nucleus by: 1) quantifying TNFR1 (a high affinity transmembrane receptor for TNF-α) expression; 2) investigating astrocytes (glial cells known to release TNF-α) by performing a morphological analysis in the phrenic motor nucleus; and 3) determining whether acute TNFR1 inhibition differentially affects phrenic plasticity over the course of CTB-SAP-induced motor neuron loss by delivering an inhibitor for TNF-α receptor 1 (sTNFR1i) in 7d and 28d male CTB-SAP and control rats.ResultsResults revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats (p < 0.05), and that astrocytes were increased and exhibited reactive morphology (consistent with an activated phenotype; p < 0.05) in the phrenic motor nucleus of CTB-SAP rats. Additionally, we found that pLTF was attenuated in 7d CTB-SAP rats but enhanced in 28d CTB-SAP rats (p < 0.05) following intrathecal sTNFR1i delivery.ConclusionThis work suggests that we could harness TNFR1 as a potential therapeutic agent in CTB-SAP rats and patients with respiratory motor neuron disease by increasing compensatory plasticity in surviving neurons to improve phrenic motor neuron function and breathing as well as quality of life. Future studies will focus on microglial and astrocytic cytokine release, the role they play in the differential mechanisms of pLTF utilized by 7d and 28d CTB-SAP rats, and potential therapies that target them.

Silicic caldera volcanoes present major volcanic and seismic hazards but also host dynamic hydrothermal and groundwater systems and a rich but largely unexplored subsurface biosphere. Many of these volcanoes are hosted in rift settings. The intricate connections and feedbacks among magmatism, rifting, hydrothermal processes, and the biosphere in these complex systems remain poorly understood, necessitating subsurface joint observations that are only enabled by scientific drilling. The CALDERA (Connections Among Life, geo-Dynamics and Eruptions in a Rifting Arc caldera) project workshop funded by the International Continental Scientific Drilling Program (ICDP) gathered multi-disciplinary international experts in January 2023 to advance planning of a scientific drilling project within one of these dynamic, rift-hosted calderas, the Okataina Volcanic Centre (OVC), Aotearoa New Zealand. The OVC's high eruption rate, frequent unrest events and earthquake swarms, location in a densely faulted rapidly extending rift, abundant groundwater–geothermal fluid circulations, and diverse surface hot spring microbiota make it an ideal location for exploring a connected geo-hydro-biosphere via scientific drilling and developing a test bed for novel volcano monitoring approaches. Drilling configurations with at least two boreholes (∼ 200 and ∼ 1000–1500 m deep) were favoured to achieve the multi-disciplinary objectives of the CALDERA project. Decadal monitoring including biosphere activity and composition has the potential to evaluate the response of the hydro-bio system to volcano-tectonic activity. In addition to the OVC caldera-scale datasets already available, site surveys will be conducted to select the best drilling locations. The CALDERA project at the OVC would provide, for the first time, an understanding of volcanic–tectonic–hydrological–biological connections in a caldera–rift system and a baseline for global comparisons with other volcanoes, rifts, and hydrothermal systems. CALDERA would serve as an unprecedented model system to understand how and how quickly the subsurface biosphere responds to geologic activities. Discoveries will improve assessment of volcanic and seismic hazards, guide the sustainable management and/or conservation of groundwater and geothermal resources and microbial ecosystems, and provide a forum for interweaving mātauranga Māori and Western knowledge systems.

Abstract Dating young lava flows is essential for understanding volcano's eruption frequency, yet challenging due to methodological limitations of commonly used dating techniques. Ruapehu (Aotearoa New Zealand) produced many lava flows during the Holocene, but constraints on the timing of these eruptions are scarce. Here, we use paleomagnetic dating to deliver new eruption ages of 18 lava flows with uncertainties ranging between 500 and 2,700 years (at the 95% confidence level). Comparison between lava flows' paleomagnetic directions and a local paleosecular variation record indicates that the large lava flow field located on the Whakapapa area was emplaced during at least three distinct eruptive episodes between 10600 and 7400 BP. Two of these episodes closely followed a large collapse event that affected Ruapehu's northern area and generated large volumes of lava between 10600 and 8800 BP, with the third episode producing less voluminous lava flows between 8100 and 7400 BP. Following a smaller collapse of the southeastern sector of the edifice at ca. 5300 BP, several low‐volume lava flows were emplaced during at least two distinct eruptive episodes prior to ca. 1000 BP, which supplied the Whangaehu valley with lava. The youngest age inferred from our data represents the youngest eruption age provided for a lava flow outside Ruapehu's summit region. This research provides greater detail to the Holocene effusive chronology at Ruapehu, shedding light on partial cone reconstructions after edifice collapses during the Holocene, and the time relationships between trends observed in its effusive and explosive activity.

IntroductionTongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons.MethodsRats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles.ResultsResults showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise.ConclusionThese findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF.

IntroductionDysmenorrhea is associated with increased risk of chronic pain and hyperalgesia. Menstruating individuals with dysmenorrhea are more likely to have elevated pain reactivity when experiencing experimental pain, than those without. However, no study has examined intragroup differences in reactions to experimentally induced pain for individuals with dysmenorrhea. The main aim of this study was to examine the relative roles of dysmenorrhea severity and interference in the experience of experimentally-induced pain.MethodsParticipants were 120 menstruating individuals involved in a larger research study examining the influence of expectations on experimentally-induced pain. As part of the study, participants completed an online questionnaire regarding demographic and menstrual information and participated in a cold pressor task. Participants were randomized into four groups based on the manipulation of two independent variables: (1) high vs. low expectations about pain severity (pain-expectations); (2) and high vs. low expectations about one's pain tolerance (self-expectations). Participants verbally rated their pain severity throughout the cold pressor task using a 0–10 scale. Regression analyses were conducted examining the relationships between dysmenorrhea experience (i.e., average severity and interference) and cold pressor data [pain severity ratings and pain tolerance (i.e., total time in the cold pressor)], controlling for the manipulated expectations and age. Then, moderation analyses were conducted examining expectation group differences.ResultsWhen controlling for manipulated expectations and age, dysmenorrhea severity significantly predicted initial pain severity rating (p = 0.022) but did not predict final pain severity rating (p = 0.263) or pain tolerance (p = 0.120). Dysmenorrhea interference did not predict initial pain severity rating (p = 0.106), final pain severity rating (p = 0.134), or pain tolerance (p = 0.360). A moderation analysis indicated that the relationship between dysmenorrhea severity and initial pain severity rating was not moderated by pain-expectations, χ2(1) = 0.412, p = 0.521.DiscussionDuring an experimentally-induced pain task, dysmenorrhea severity but not interference predicted initial pain severity rating, such that higher levels of dysmenorrhea severity predicted greater initial pain severity rating. This suggests individuals with more severe dysmenorrhea pain may experience greater initial sensitivity to pain and be at risk for increased sensitivity to acute pain and potentially the development of chronic pain.

Rotaviruses (RVs) are 11-segmented, double-stranded (ds) RNA viruses and important causes of acute gastroenteritis in humans and other animal species. Early RV particle assembly is a multi-step process that includes the assortment, packaging and replication of the 11 genome segments in close connection with capsid morphogenesis. This process occurs inside virally induced, cytosolic, membrane-less organelles called viroplasms. While many viral and cellular proteins play roles during early RV assembly, the octameric nonstructural protein 2 (NSP2) has emerged as a master orchestrator of this key stage of the viral replication cycle. NSP2 is critical for viroplasm biogenesis as well as for the selective RNA–RNA interactions that underpin the assortment of 11 viral genome segments. Moreover, NSP2’s associated enzymatic activities might serve to maintain nucleotide pools for use during viral genome replication, a process that is concurrent with early particle assembly. The goal of this review article is to summarize the available data about the structures, functions and interactions of RV NSP2 while also drawing attention to important unanswered questions in the field.

Abstract Background The survival of coronaviruses are influenced by weather conditions and seasonal coronaviruses are more common in winter months. We examine the seasonality of respiratory infections in England and Wales and the associations between weather parameters and seasonal coronavirus cases. Methods Respiratory virus disease data for England and Wales between 1989 and 2019 was extracted from the Second-Generation Surveillance System (SGSS) database used for routine surveillance. Seasonal coronaviruses from 2012 to 2019 were compared to daily average weather parameters for the period before the patient’s specimen date with a range of lag periods. Results The seasonal distribution of 985,524 viral infections in England and Wales (1989–2019) showed coronavirus infections had a similar seasonal distribution to influenza A and bocavirus, with a winter peak between weeks 2 to 8. Ninety percent of infections occurred where the daily mean ambient temperatures were below 10 °C; where daily average global radiation exceeded 500 kJ/m2/h; where sunshine was less than 5 h per day; or where relative humidity was above 80%. Coronavirus infections were significantly more common where daily average global radiation was under 300 kJ/m2/h (OR 4.3; CI 3.9–4.6; p

Abstract Background Rates of recommending percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) vary across clinicians. Whether clinicians agree on preferred treatment options for multivessel coronary artery disease patients has not been well studied. Methods and results We distributed a survey to 104 clinicians from the Northern New England Cardiovascular Study Group through email and at a regional meeting with 88 (84.6%) responses. The survey described three clinical vignettes of multivessel coronary artery disease patients. For each patient vignette participants selected appropriate treatment options and whether they would use a patient decision aid. The likelihood of choosing PCI only or PCI/CABG over CABG only was modeled using a multinomial regression. Across all vignettes, participants selected CABG only as an appropriate treatment option 24.2% of the time, PCI only 25.4% of the time, and both CABG or PCI as appropriate treatment options 50.4% of the time. Surgeons were less likely to choose PCI over CABG (RR 0.14, 95% CI 0.03, 0.59) or both treatments over CABG only (RR 0.10, 95% CI 0.03, 0.34) relative to cardiologists. Overall, 65% of participants responded they would use a patient decision aid with each vignette. Conclusions There is a lack of consensus on the appropriate treatment options across cardiologists and surgeons for patients with multivessel coronary artery disease. Treatment choice is influenced by both patient characteristics and clinician specialty.

Abstract Evolutionary arms races are broadly prevalent among organisms including bacteria, which have evolved defensive strategies against various attackers. A common microbial aggression mechanism is the type VI secretion system (T6SS), a contact-dependent bacterial weapon used to deliver toxic effector proteins into adjacent target cells. Sibling cells constitutively express immunity proteins that neutralize effectors. However, less is known about factors that protect non-sibling bacteria from T6SS attacks independently of cognate immunity proteins. In this study, we observe that human Escherichia coli commensal strains sensitive to T6SS attacks from Vibrio cholerae are protected when co-cultured with glucose. We confirm that glucose does not impair V. cholerae T6SS activity. Instead, we find that cells lacking the cAMP receptor protein (CRP), which regulates expression of hundreds of genes in response to glucose, survive significantly better against V. cholerae T6SS attacks even in the absence of glucose. Finally, we show that the glucose-mediated T6SS protection varies with different targets and killers. Our findings highlight the first example of an extracellular small molecule modulating a genetically controlled response for protection against T6SS attacks. This discovery may have major implications for microbial interactions during pathogen-host colonization and survival of bacteria in environmental communities.

Oligodendrocytes are the myelinating cell of the CNS and are critical for the functionality of the nervous system. In the packed CNS, we know distinct profiles of oligodendrocytes are present. Here, we used intravital imaging in zebrafish to identify a distinct oligodendrocyte lineage cell (OLC) that resides on the dorsal root ganglia sensory neurons in the spinal cord. Our profiling of OLC cellular dynamics revealed a distinct cell cluster that interacts with peripheral sensory neurons at the dorsal root entry zone (DREZ). With pharmacological, physical and genetic manipulations, we show that the entry of dorsal root ganglia pioneer axons across the DREZ is important to produce sensory located oligodendrocyte lineage cells. These oligodendrocyte lineage cells on peripherally derived sensory neurons display distinct processes that are stable and do not express mbpa. Upon their removal, sensory behavior related to the DRG neurons is abolished. Together, these data support the hypothesis that peripheral neurons at the DREZ can also impact oligodendrocyte development.

The tongue plays a crucial role in the swallowing process, and impairment can lead to dysphagia, particularly in motor neuron diseases (MNDs) resulting in hypoglossal-tongue axis degeneration (e.g., amyotrophic lateral sclerosis and progressive bulbar palsy). This study utilized our previously established inducible rodent model of dysphagia due to targeted degeneration of the hypoglossal-tongue axis. This model was created by injecting cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue base for retrograde transport to the hypoglossal (XII) nucleus via the hypoglossal nerve, which provides the sole motor control of the tongue. Our goal was to investigate the effect of high-repetition/low-resistance tongue exercise on tongue function, strength, and structure in four groups of male rats: (1) control + sham exercise (n = 13); (2) control + exercise (n = 10); (3) CTB-SAP + sham exercise (n = 13); and (4) CTB-SAP + exercise (n = 12). For each group, a custom spout with adjustable lick force requirement for fluid access was placed in the home cage overnight on days 4 and 6 post-tongue injection. For the two sham exercise groups, the lick force requirement was negligible. For the two exercise groups, the lick force requirement was set to ∼40% greater than the maximum voluntary lick force for individual rats. Following exercise exposure, we evaluated the effect on hypoglossal-tongue axis function (via videofluoroscopy), strength (via force-lickometer), and structure [via Magnetic Resonance Imaging (MRI) of the brainstem and tongue in a subset of rats]. Results showed that sham-exercised CTB-SAP rats had significant deficits in lick rate, swallow timing, and lick force. In exercised CTB-SAP rats, lick rate and lick force were preserved; however, swallow timing deficits persisted. MRI revealed corresponding degenerative changes in the hypoglossal-tongue axis that were mitigated by tongue exercise. These collective findings suggest that high-repetition/low-resistance tongue exercise in our model is a safe and effective treatment to prevent/diminish signs of hypoglossal-tongue axis degeneration. The next step is to leverage our rat model to optimize exercise dosing parameters and investigate corresponding treatment mechanisms of action for future translation to MND clinical trials.

Abstract Background Disaccharides such as lactose and sucrose are sugars commonly found in human diet. They are broken down by mucosal disaccharidases in the duodenum. Previous small studies found no associations between gastrointestinal (GI) symptoms and combined low disaccharidase activity. We aim to explore the associations of low activity of disaccharidase and combinations of low activity of different disaccharidases with general GI symptom presentations in a large cohort of pediatric patients. Methods We examined a cohort (0–21 yrs.) who have undergone esophagogastroduodenoscopy and received disaccharidase activity assay from duodenal biopsy in the time period 2010 to 2012. Disaccharidase assays tested for activity of lactase, sucrase, maltase, and palatinase. GI symptoms were grouped into four categories, abdominal pain, diarrhea, weight loss, and gastroesophageal reflux. Results Of the 347 subjects, we found an association between low lactase activity and abdominal pain (OR = 1.78; 95% CI = 1.07–2.97; p

Despite recent advances in reaction methodologies, organic synthesis remains complex and challenging. Many of the fundamental processes in use have not changed in over 100 years, with a large proportion of the work being carried out manually, using lengthy procedures and difficult or hazardous reaction conditions. As such, organic synthesis still presents a bottle-neck in discovery research. Endeavours to automate synthesis in discovery, through robotic platforms, have so far not been widely successful because the highly complex nature of such machines, and the level of skill required for their operation, presents a barrier too great for most discov- ery chemists. Synple Chem has developed a safe, easy to use, efficiency-enhancing automated technology for the acceleration of discovery research. The automated flow-batch hybrid system utilises a range of innovative pre-packed reagent cartridges for different reaction classes, along with pre-programmed, highly optimised but editable reaction protocols. The combination of these three key elements, provides users with a convenient, easy to use, time-saving technology that makes the synthesis of molecules far simpler, faster and more efficient. The described technology offers all discovery chemists access to real synthesis automation without any of the barriers that have previously restricted its utility.

Magma ascending in the Earth’s crust can undergo oscillations in pressure, from ultra-low frequency changes associated with tectonics, to relatively higher frequency oscillations associated with seismicity. Seismic waves travelling through shallow magma bodies can lead to a range of unrest phenomena and potentially trigger volcanic eruptions. The mechanisms by which pressure oscillations can induce unrest or eruption remain debated. Here, we experimentally impose pressure oscillations on magma and study how they affect vesiculation processes. We use cylindrical samples (4.00 mm long, 4.85 mm diameter) of hydrous rhyolitic obsidian (0.11 ± 0.01 wt% H2O) placed in alumina (AL23) crucibles and vary pressure by the uniaxial loading of an alumina plunger in a thermo-mechanical analyzer. We monitor vesiculation at temperatures of 950–990°C and confining pressure of 177 kPa. We perform two types of experiment: 1) “static” experiments (at constant pressure) and 2) “oscillating” experiments in which we impose sinusoidal pressure oscillations of up to 71 kPa upon the static pressure (i.e., between 106 and 250 kPa). In both cases, we dilatometrically observe sample expansion driven by vesiculation. Post-experimental bubble textures reveal that bubbles formed preferentially at the sample margins. For the oscillating experiments, the sample expansion rate is lower than in the static experiments, and there are fewer vesicles at the sample margins. We examine the constituent processes of bubble formation (nucleation, growth, coalescence) and gas loss (diffusion, permeable flow) occurring during static experiments and with the added element of pressure oscillations. The most likely mechanism responsible for reduced sample expansion is that pressure oscillations drive the sample in and out of water saturation conditions and thus reduce the fraction of residence time over which bubble nucleation and/or growth are driven. Future work will be needed to confirm this hypothesis. These results are relevant to the study of earthquake-volcano interactions, where a magma body that sits close to volatile saturation is subject to pressure fluctuations.

Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives – 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by >30-fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.

Abstract Basaltic lavas sample recycled crustal materials from their mantle source. Constraining the location and residence time of these recycled materials in the mantle is critical to understand global mantle dynamics. In this study, we present new whole‐rock major and trace element abundances, Sr‐Nd‐Mo‐Os isotopes, water contents and He isotopes of volcanic glasses, U‐Pb ages of zircons, and compositions of melt inclusions, spinels and olivines from the South China Sea (SCS) seamounts lavas. These new data are compared with literature data from intraplate volcanism of similar age from Southeast (SE) Asia. The isotope data of late Cenozoic lavas from the SCS seamounts and SE Asia can be explained by mixing between enriched mantle 2 (EM2) and depleted mid‐ocean ridge basalt mantle components. Our data are consistent with the EM2 signature of late Cenozoic lavas derived from recycled young oceanic crust and sediments. The compositions of olivine phenocrysts indicate an olivine‐dominated (peridotitic) mantle source. There is currently no evidence for a high‐3He/4He mantle plume component beneath the SCS. Our results combined with geophysical data and plate reconstructions suggest that the late Cenozoic magmatism is related to the upwelling of instabilities from the mantle transition zone (MTZ) triggered by a stagnant slab. The SCS seamount lavas sample an enriched MTZ containing young recycled materials, consistent with regional past subduction. Our study provides additional evidence that storage and recycling of crustal materials in or near the MTZ is an important mechanism to develop global mantle heterogeneities sampled by intraplate volcanoes.

Abstract Background Campylobacteriosis is a major public health concern. The weather factors that influence spatial and seasonal distributions are not fully understood. Methods To investigate the impacts of temperature and rainfall on Campylobacter infections in England and Wales, cases of Campylobacter were linked to local temperature and rainfall at laboratory postcodes in the 30 days before the specimen date. Methods for investigation included a comparative conditional incidence, wavelet, clustering, and time series analyses. Results The increase of Campylobacter infections in the late spring was significantly linked to temperature two weeks before, with an increase in conditional incidence of 0.175 cases per 100,000 per week for weeks 17 to 24; the relationship to temperature was not linear. Generalized structural time series model revealed that changes in temperature accounted for 33.3% of the expected cases of Campylobacteriosis, with an indication of the direction and relevant temperature range. Wavelet analysis showed a strong annual cycle with additional harmonics at four and six months. Cluster analysis showed three clusters of seasonality with geographic similarities representing metropolitan, rural, and other areas. Conclusions The association of Campylobacteriosis with temperature is likely to be indirect. High-resolution spatial temporal linkage of weather parameters and cases is important in improving weather associations with infectious diseases. The primary driver of Campylobacter incidence remains to be determined; other avenues, such as insect contamination of chicken flocks through poor biosecurity should be explored.

The fundamental mechanism of how sensory axons traverse a spinal cord glia limitans remains debatable, with some suggesting a role for boundary cap cells at the dorsal root entry zone (DREZ). Here, authors use time-lapse imaging of DRG axons at the DREZ to show that pioneer axons enter the DREZ before the presence of boundary cap cells, and that this entry is critically dependent on the development of actin-rich invasion structures reminiscent of invadopodia.