bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognition and covariance in the producer–scrounger game
Authors: Reichert Michael S. , Morand‐Ferron Julie , Kulahci Ipek G. , Firth Josh A. , Davidson Gabrielle L. , Crofts Sam J. , Quinn John L.
Published: June 2021

The producer–scrounger game is a key element of foraging ecology in many systems. Producing and scrounging typically covary negatively, but partitioning this covariance into contributions of individual plasticity and consistent between individual differences is key to understanding population‐level consequences of foraging strategies. Furthermore, little is known about the role cognition plays in the producer–scrounger game.

We investigated the role of cognition in these alternative foraging tactics in wild mixed‐species flocks of great tits and blue tits, using a production learning task in which we measured individuals’ speed of learning to visit the single feeder in an array that would provide them with a food reward. We also quantified the proportion of individuals’ feeds that were scrounges (‘proportion scrounged’); scrounging was possible if individuals visited immediately after a previous rewarded visitor. Three learning experiments—initial and two reversal learning—enabled us to estimate the repeatability and covariance of each foraging behaviour.

First, we examined whether individuals learned to improve their scrounging success (i.e. whether they obtained food by scrounging when there was an opportunity to do so). Second, we quantified the repeatability of proportion scrounged, and asked whether proportion scrounged affected production learning speed among individuals. Third, we used multivariate analyses to partition within‐ and among‐individual components of covariance between proportion scrounged and production learning speed.

Individuals improved their scrounging success over time. Birds with a greater proportion scrounged took longer to learn their own rewarding feeder. Although multivariate analyses showed that covariance between proportion scrounged and learning speed was driven primarily by within‐individual variation, that is, by behavioural plasticity, among‐individual differences also played a role for blue tits.

This is the first demonstration of a cognitive trait influencing producing and scrounging in the same wild system, highlighting the importance of cognition in the use of alternative resource acquisition tactics. The results of our covariance analyses suggest the potential for genetic differences in allocation to alternative foraging tactics, which are likely species‐ and system‐dependent. They also point to the need to control for different foraging tactics when studying individual cognition in the wild.
Global patterns in bumble bee pollen collection show phylogenetic conservation of diet
Authors: Wood Thomas J. , Ghisbain Guillaume , Rasmont Pierre , Kleijn David , Raemakers Ivo , Praz Christophe , Killewald Michael , Gibbs Jason , Bobiwash Kyle , Boustani Mira , Martinet Baptiste , Michez Denis
Published: June 2021

Bumble bees (Bombus) are a group of eusocial bees with a strongly generalised feeding pattern, collecting pollen from many different botanical families. Though predominantly generalists, some bumble bee species seem to have restricted dietary choices. It is unclear whether restricted diets in bumble bees are inherent or a function of local conditions due to a lack of data for many species across different regions.

The objective of this study was to determine whether bumble bee species displayed specific patterns of pollen collection, and whether patterns were influenced by phylogenetic relatedness or tongue length, a trait known to be associated with structuring floral visitation.

Bumble bee pollen collection patterns were quantified from 4,132 pollen loads taken from 58 bumble bee species, representing 24% of the pollen‐collecting diversity of this genus.

Phylogenetic trait mapping showed a conserved pattern of dietary dissimilarity across species, but not for dietary breadth. Dietary dissimilarity was driven by collection of Fabaceae, with the most similar species collecting around 50%–60% of their diet from this botanical family. The proportion of the diet collected from Fabaceae also showed a conserved phylogenetic signal. Greater collection of Fabaceae was associated with longer tongue lengths, with shorter tongued species focusing on alternative botanical families. However, this result was largely driven by phylogenetic relatedness, not tongue length per se.

These results demonstrate that, though generalists, bumble bees are still subject to dietary restrictions that constrain their foraging choices. These dietary constraints have implications for their persistence should their core resources decline in abundance.
Reimagining the Protestant Missionary Family: The Malcolms of the China Inland Mission
Authors: Morrison Hugh
Published: June 2021

This article considers how to meaningfully discuss or understand the missionary family, focusing on the longer life and potential adjustments of family members beyond the mission‐field experience. It argues that the post‐missionary years were an important transitional space, that were just as formative as the original mission spaces occupied elsewhere. In that new liminality of place and time, there was the potential for other things to occur: re‐orientations of life direction, reconfigurations of modes of thought or belief, and reconstructions of identity and of purpose. It does so through a case study of the Malcolm family (Anna, William, and son Ronald) from Australia/New Zealand, who worked with the China Inland Mission between the 1890s and 1920s but then returned to New Zealand and eventually to a different set of outcomes for each family member. Their story moves from traditional, normative colonial evangelical Protestantism to a more complicated and differentiated story of juxtaposed divergent narratives either maintaining or discarding the religious status quo. As such, this article draws attention to the dynamic nature of the missionary family as a crucible for change and its essentially emotional role as a place of safety and security in the midst of profound intra‐ and extra‐familial disruptions.
Benign paroxysmal positional vertigo in the emergency department: An observational study of an Australian regional hospital's acute clinical practice
Authors: Neely Prue , Patel Hemal , Wellings Tom
Published: June 2021

Objective

To analyse adherence to evidence based practice in the diagnosis and treatment of benign paroxysmal positional vertigo (BPPV) in a regional ED.

Methods

Retrospective observational population study. Wyong Hospital's ED, Central Coast Local Health District, New South Wales, Australia. Medical records of patients with an ED diagnosis of BPPV (n = 101) between 2017 and 2018 were included for auditing. Adherence to clinical practice guidelines for BPPV4statements 1a, 3a, 4a and 6 were reviewed as primary outcomes using a de‐identified binary data excel tool. These outcomes were compared to available data from metropolitan tertiary EDs both in Australia and the USA.

Results

General compliance to best practice standards was low. Of patients diagnosed with BPPV in the ED only 45% (95% CI 35–54%) were diagnosed with the recommended Hallpike–Dix positional test. Of those patients who did receive diagnosis via the Hallpike–Dix test only 41% (95% CI 28–56%) went on to receive gold standard recommended treatment of a canalith repositioning manoeuvre/technique. In regards to the recommendations against practice, 36% (95% CI 28–46%) had neuroimaging performed in the ED and 58% (95% CI 48–68%) received vestibular suppressant medication as their only treatment prior to discharge.

Conclusion

Adherence to best practice diagnosis and management of BPPV was low in Wyong Hospital's ED. Although low, Wyong Hospital's ED appeared to perform better in compliance to the clinical guidelines to its metropolitan Australian peer. There is opportunity to improve the efficiency and effectiveness in the management of acute peripheral dizziness in EDs.
Inside the Commons Committee of Secrecy: George Treby's Shorthand and the Popish Plot
Authors: McKenzie Andrea
Published: June 2021

This article examines the hitherto undeciphered shorthand notes of George (later Sir George) Treby, an opposition MP and lawyer and the chairman of the house of commons committee of secrecy investigating the Popish Plot (1678–81). These shorthand memoranda, draft letters and marginalia not only open up a glimpse into the secret proceedings of this mysterious committee, composed of the leading opponents of Charles II and the duke of York in the lower house, but shed new light on how Whig MPs such as Treby viewed, and justified, the prosecution of a plot now widely accepted as a convenient political fiction. This new evidence allows us to re‐evaluate the allegations of Tory propagandists that Whig investigators deliberately suppressed and distorted evidence, suborning and coercing witnesses to further their oppositional agenda. Treby's shorthand annotations paint a more complicated picture of a lawyer selecting evidence but also painstakingly verifying facts and genuinely concerned about both a ‘popish plot’ (broadly defined) and obstruction and witness‐tampering on the part of the court.
The Man Who Enriched – and Robbed – the Tories
Authors: Lexden Alistair
Published: June 2021

Horace Farquhar, financier, courtier and politician, was a man without a moral compass. He combined ruthlessness and dishonesty with great charm. As a Liberal Unionist MP in the 1890s, his chief aim was to get a peerage, for which he paid handsomely. He exploited everyone who came his way to increase his wealth and boost his social position, gaining an earldom from Lloyd George, to whose notorious personal political fund he diverted substantial amounts from the Conservative Party, of which he was treasurer from 1911 to 1923, the first holder of that post. The Tories’ money went into his own pocket as well. During these years, he also held senior positions at court, retaining under George V the trust of the royal family which he had won under Edward VII. By the time of his death in 1923, however, his wealth had disappeared, and he was found to be bankrupt. He was a man of many secrets. They have been probed and explored, drawing on such material relating to his scandalous career as has so far come to light.
Does the Threat of a PCAOB Inspection Mitigate US Institutional Investors' Home Bias?*
Authors: He Yue , Li Bing , Liu Zhenbin , Pittman Jeffrey
Published: June 2021

We exploit the staggered introduction of the PCAOB's international inspection program to examine the role that the stringency of public audit oversight plays in shaping US institutional investors' home bias. Analyzing a sample of foreign firms listed in the United States, we evaluate whether US institutional investors hold larger equity stakes in these firms—a longstanding issue that reflects investor portfolio decisions—if their auditors are exposed to the threat of a PCAOB inspection. In a differences‐in‐differences framework, we find that US‐listed foreign firms enjoy an increase in US institutional investors' equity positions after their auditors become subject to PCAOB inspection access. Cross‐sectional analysis implies that the benefit of the PCAOB inspection threat in mitigating US institutional investors' home bias is concentrated in foreign countries without a strict local audit oversight system; active US institutional investors that are known to value accounting transparency; and firms from countries that grant PCAOB access later (after the onset of its international inspection program in 2005). Our evidence suggests that foreign firms become better known in the capital markets under the PCAOB inspection program, which induces US institutional investors to acquire larger equity stakes in US‐listed foreign firms given the lower information asymmetry that ensues under the PCAOB inspection threat.
Do PCAOB Inspections of Foreign Auditors Affect Global Financial Reporting Comparability?*
Authors: Ege Matthew , Kim Young Hoon , Wang Dechun
Published: June 2021

This study investigates whether PCAOB inspections of foreign auditors affect global financial reporting comparability. Foreign auditors may adjust audit methodologies to address PCAOB inspection findings, which could affect financial reporting of local clients. Exploiting both within‐ and cross‐country variation in PCAOB inspections, we predict and find that non‐US‐listed foreign companies' financial reporting becomes more comparable to their US and non‐US industry peers after their auditors undergo an initial inspection. However, there is a decrease in comparability compared to local peers whose auditors have not been inspected. Subsample tests suggest that the improvement in comparability is driven by (i) auditors that satisfactorily address deficiencies and (ii) auditors that do not publicly push back against deficiencies. The effects are dampened after local audit regulators begin inspection programs. Overall, our evidence suggests that the PCAOB international inspection program affects audit methodologies of inspected auditors in a consistent way, improving comparability across jurisdictions. The improved comparability implies that the PCAOB international inspection program may unintentionally help meet accounting regulators' goals of cross‐country financial reporting convergence, which potentially promotes efficient cross‐country capital allocation.
Is There a Brain Drain in Auditing? The Determinants and Consequences of Auditors Leaving Public Accounting*
Authors: Knechel W. Robert , Mao Juan , Qi Baolei , Zhuang Zili
Published: June 2021

This study investigates why auditors leave public accounting and the consequences of auditor departures, both of which have been of great concern for audit firms and regulators worldwide. Using data from China and controlling for demographics, we find that audit partners and managers, auditors who generate more revenue, and auditors who provide higher audit quality have a lower likelihood of departure, while non–Big 4 auditors have a higher likelihood of departing public accounting. We also find that an audit firm is likely to lose clients when an auditor departs. Clients who stay with the same firm pay lower audit fees but with no drop‐off in audit quality after a signing auditor departs. In supplementary analyses, we also demonstrate that the determinants and consequences of auditor departures are different for auditors who leave the firm but not the profession (i.e., auditor turnover). Specifically, high audit quality is associated with a lower likelihood of auditor departure, but it increases auditor turnover. We also observe that audit quality is reduced for the clients who stay with an audit firm after highly skilled auditors depart for high‐visibility corporate positions. Our study provides insights that should be of interest to the audit profession, audit firms, and regulators.
Tax Haven Incorporation and the Cost of Capital*
Authors: Lewellen Christina M. , Mauler Landon , Watson Luke
Published: June 2021

Incorporating the firm's corporate parent in a tax haven is a major decision that receives significant attention from many stakeholders, yet certain implications of this corporate strategy remain unclear. While tax haven incorporation offers tax savings, it also imposes risks that are potentially costly and hence important to consider. We predict and find a higher cost of equity capital in firms with parent companies that are incorporated in tax havens but that are primarily based in nonhaven countries. We also predict and find that the observed cost of equity premium is more pronounced in firms with greater tax risk, firm‐level information risk, and country‐level legal risk. We also employ corporate inversions in a difference‐in‐differences test and again find a positive relation between tax haven parent incorporation and the cost of capital. Our findings imply that an increased cost of capital is a material cost of tax haven parent incorporation. We contribute to the literatures on valuation of tax haven use, tax and nontax costs of corporate tax strategies, corporate inversions, and the relation between taxes and the cost of capital. Our study provides evidence on the tax and nontax risks of a uniquely observable tax strategy (i.e., tax haven parent incorporation) that could factor into firms' decisions about whether to incorporate in a tax haven and policymakers' efforts to deter such activity.
Plasma secretory phospholipase A2 as an early marker for late‐onset sepsis in preterm infants—a pilot study
Authors: Hibbert Julie , Armstrong Nicola J. , Granland Caitlyn , Ng Sherrianne , Simmer Karen , Richmond Peter , Burgner David , Strunk Tobias , Currie Andrew
Published: June 2021

Preterm infants are particularly susceptible to bacterial late‐onset sepsis (LOS). Diagnosis by blood culture and inflammatory markers have sub‐optimal sensitivity and specificity and prolonged reporting times. There is an urgent need for more rapid, accurate adjunctive diagnostics in LOS to improve management and minimise antibiotic exposure. We measured the diagnostic performance of secretory phospholipase A2 type IIA (sPLA2‐IIA) in very preterm infants (<30 weeks gestational age) with suspected LOS. Plasma sPLA2‐IIA levels were elevated in infants with LOS (n = 28) compared to those without LOS (n = 21; median 30,970 vs. 2534 pg/ml, p < 0.0001). The mean area under the curve was 0.884 (95% CI: 0.771, 0.977) with a sensitivity of 0.907 (95% CI: 0.667, 1.00) and specificity of 0.804 (95% CI: 0.600, 1.00). The positive and negative predictive values were 0.833 (95% CI: 0.664, 0.927) and 0.842 (95% CI: 0.624, 0.945), respectively. This pilot study suggests that sPLA2‐IIA may have clinical utility for the early diagnosis of LOS in very preterm infants, potentially informing clinical management and antibiotic stewardship.
Amino acid transporters as emerging therapeutic targets in cancer
Authors: Saito Yasuhiro , Soga Tomoyoshi
Published: June 2021

Amino acids are indispensable nutrients for both normal and cancer cells. Cancer cells are unable to synthesize essential amino acids as well as some non‐essential amino acids adequately to support rapid proliferation, and must take up amino acids from the surroundings. To meet the increased demand for the amino acid needed for proliferation, high levels of amino acid transporters are expressed on the surface of cancer cells. Cancer cells utilize amino acids to synthesize proteins and nucleotides, as well as to obtain energy. In addition, amino acids are known to play pathological roles in cancer cells. Interestingly, breast cancer cells limit the use of amino acids for cell proliferation based on amino acid availability, which depends on estrogen receptor status. Here, we present a summarized literature review of novel amino acid functions in cancer cells. This review organizes the available knowledge on 2 amino acid transporters, SLC7A5 and SLC7A11, which are considered essential for breast cancer cell growth in a cell‐dependent manner. In particular, we propose the glutamine recycling model to clarify the mechanism underlying aberrant SLC7A5 activation. Finally, we overview the pathological significances of SLC7A5 and SLC7A11 in cancer tissues.
AQP3‐mediated H2O2 uptake inhibits LUAD autophagy by inactivating PTEN
Authors: Wang Yawei , Chen Di , Liu Yu , Zhang Yong , Duan Chao , Otkur Wuxiyar , Chen Huan , Liu Xiaolong , Xia Tian , Qi Huan , Piao Hai‐long , Liu Hong‐Xu
Published: June 2021

It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In the current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H2O2) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H2O2 in LUAD cells and that the AQP3‐dependent transport of H2O2 accelerated cell growth and inhibited rapamycin‐induced autophagy. Mechanistically, AQP3‐mediated H2O2 uptake increased intracellular ROS levels to inactivate PTEN and activate the AKT/mTOR pathway to subsequently inhibit autophagy and promote proliferation in LUAD cells. Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3‐induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.
Indications and long‐term outcomes of preoperative inferior vena caval filters in 111 patients at high risk of pulmonary embolism undergoing major abdominal surgery
Authors: Kostadinov Danko , Tzivanakis Alexios , Ubhayakar Gaurang , Dixon Shaheen , Helyar Vincent , Dayal Sanjeev Paul , Mohamed Faheez , Cecil Thomas Desmond , Moran Brendan John
Published: June 2021

Aims

Patients with abdominal cancer requiring major surgical intervention are at high risk of venous thromboembolic events (VTE), particularly pulmonary emboli (PE). A proportion of patients with cancer can present with, or have had, major VTEs prior to definitive surgical treatment. Preoperative percutaneous inferior venal caval filters (IVCF) may reduce the risk of PE. The aim of this study was to assess the indications, complications, retrieval rates, and long‐term outcome of IVCFs in patients undergoing major abdominal surgery.

Methods

This was a retrospective analysis of a prospective IVCF database between 2007 and 2018 of all patients with IVCF insertion prior to major abdominal surgery. The indications for an IVCF, procedural complications and surgical interventions were recorded.

Results

Overall, 111 patients had IVCF insertion. IVCF placement failed in one patient with gross abdominal disease. Indications for an IVCF were: prior PE in 65/111 (59%) and major vein thrombus in 42 (38%). Overall, 26/111 (23%) had the IVCF removed at a median of 91 days. In two patients IVCF removal failed. At follow‐up of the 85 patients who had the IVCF left in situ, six developed filter‐related thrombus and 13 a deep vein thrombosis (DVT). Four patients had a PE with an indwelling IVCF.

Conclusion

Preoperative IVCF may reduce perioperative PE in patients at high risk of thrombosis undergoing major abdominal surgery where early anticoagulation is contraindicated. Long‐term follow‐up of retained IVCF suggests that major problems are infrequent, though further thrombosis may occur and long‐term anticoagulation may be needed.
Acute increase in arterial stiffness after swimming in cooler water
Authors: Hayashi Suguru , Otsuki Takeshi
Published: June 2021

Cold stimuli increase arterial stiffness, but it has not been explored whether arterial stiffness increases after swimming in cooler water. To investigate the effects of water temperature on changes in arterial stiffness after swimming, 13 men participated in three trials of 20‐min swimming in 25 and 30°C water (S25 and S30, respectively) and sitting at poolside (CON) in random order. There were no significant differences between the S25 and S30 trials in mean swimming distance (719 vs. 722 m) and heart rate reserve during swimming (63% vs. 63%). Sublingual temperature was lower after swimming in 25°C water versus before swimming. Aortic pulse wave velocity (aortic PWV, an index of central arterial stiffness based on applanation tonometry) and brachial‐ankle pulse wave velocity (baPWV, an index of systemic arterial stiffness based on air plethysmography) were higher 30 min after versus before swimming in 25°C water. Aortic PWV recovered to pre‐swimming levels by 60 min after swimming in 25°C water, but baPWV was higher even at 60 min after swimming. PWVs did not change in the CON and S30 trials. Systemic vascular resistance based on Doppler ultrasonography did not change, but forearm vascular resistance based on strain‐gauge plethysmography was higher 30 and 60 min after swimming in 25°C water. Heart rate was higher, but stroke volume was lower 30 min after swimming in 25°C water, resulting in no detectable change in cardiac output. In conclusion, arterial stiffness increases acutely after moderate‐intensity swimming in cooler water.
Measuring resilience in adults with spina bifida
Authors: Bruegel Karlin
Published: June 2021

This commentary is on the original article by Showen et al. on pages 1229–1235 of this issue.
Resurrection and characterization of ancestral CYP11A1 enzymes
Authors: Hartz Philip , Strohmaier Silja J. , EL‐Gayar Basma M. , Abdulmughni Ammar , Hutter Michael C. , Hannemann Frank , Gillam Elizabeth M. J. , Bernhardt Rita
Published: June 2021

Mitochondrial cytochromes P450 presumably originated from a common microsomal P450 ancestor. However, it is still unknown how ancient mitochondrial P450s were able to retain their oxygenase function following relocation to the mitochondrial matrix and later emerged as enzymes specialized for steroid hormone biosynthesis in vertebrates. Here, we used the approach of ancestral sequence reconstruction (ASR) to resurrect ancient CYP11A1 enzymes and characterize their unique biochemical properties. Two ancestral CYP11A1 variants, CYP11A_Mammal_N101 and CYP11A_N1, as well as an extant bovine form were recombinantly expressed and purified to homogeneity. All enzymes showed characteristic P450 spectral properties and were able to convert cholesterol as well as other sterol substrates to pregnenolone, yet with different specificities. The vertebrate CYP11A_N1 ancestor preferred the cholesterol precursor, desmosterol, as substrate suggesting a convergent evolution of early cholesterol metabolism and CYP11A1 enzymes. Both ancestors were able to withstand increased levels of hydrogen peroxide but only the ancestor CYP11A_N1 showed increased thermostability (˜ 25 °C increase in T50) compared with the extant CYP11A1. The extraordinary robustness of ancient mitochondrial P450s, as demonstrated for CYP11A_N1, may have allowed them to stay active when presented with poorly compatible electron transfer proteins and resulting harmful ROS in the new environment of the mitochondrial matrix. To the best of our knowledge, this work represents the first study that describes the resurrection of ancient mitochondrial P450 enzymes. The results will help to understand and gain fundamental functional insights into the evolutionary origins of steroid hormone biosynthesis in animals.
Exosomal and vesicle‐free tau seeds—propagation and convergence in endolysosomal permeabilization
Authors: Polanco Juan Carlos , Götz Jürgen
Published: June 2021

In Alzheimer's disease (AD), β‐amyloid peptides aggregate to form amyloid plaques, and the microtubule‐associated protein tau forms neurofibrillary tangles. However, severity and duration of AD correlate with the stereotypical emergence of tau tangles throughout the brain, suggestive of a gradual region‐to‐region spreading of pathological tau. The current notion in the field is that misfolded tau seeds propagate transsynaptically and corrupt the proper folding of soluble tau in recipient neurons. This is supported by accumulating evidence showing that in AD, functional connectivity and not proximity predicts the spreading of tau pathology. Tau seeds can be found in two flavors, vesicle‐free, that is, naked as in oligomers and fibrils, or encapsulated by membranes of secreted vesicles known as exosomes. Both types of seeds have been shown to propagate between interconnected neurons. Here, we describe potential ways of how their propagation can be controlled in several subcellular compartments by manipulating mechanisms affecting production, neuron‐to‐neuron transmission, internalization, endosomal escape, and autophagy. We emphasize that although vesicle‐free tau seeds and exosomes differ, they share the ability to trigger endolysosomal permeabilization. Such a mechanistic convergence in endolysosomal permeabilization presents itself as a unique opportunity to target both types of tau seeding. We discuss the cellular response to endolysosomal damage that might be key to control permeabilization, and the significant overlap in the seeding mechanism of proteopathic agents other than tau, which suggests that targeting the endolysosomal pathway could pave the way toward developing broad‐spectrum treatments for neurodegenerative diseases.
Essential functions of chaperones and adaptors of protein secretion systems in Gram‐negative bacteria
Authors: Manera Kevin , Kamal Fatima , Burkinshaw Brianne , Dong Tao G.
Published: June 2021

Equipped with a plethora of secreted toxic effectors, protein secretion systems are essential for bacteria to interact with and manipulate their neighboring environment to survive in host microbiota and other highly competitive communities. While effectors have received spotlight attention in secretion system studies, many require accessory chaperone and adaptor proteins for proper folding/unfolding and stability throughout the secretion process. Here, we review the functions of chaperones and adaptors of three protein secretions systems, type 3 secretion system (T3SS), type 4 secretion system (T4SS), and type 6 secretion system (T6SS), which are employed by many Gram‐negative bacterial pathogens to deliver toxins to bacterial, plant, and mammalian host cells through direct contact. Since chaperone and adaptor functions of the T3SS and the T4SS are relatively well studied, we discuss in detail the methods of chaperone‐facilitated effector secretion by the T6SS and highlight commonalities between the effector chaperone/adaptor proteins of these diverse secretion systems. While the chaperones and adaptors are generally referred to as accessory proteins as they are not directly involved in toxicities to target cells, they are nonetheless vital for the biological functions of the secretion systems. Future research on biochemical and structural properties of these chaperones will not only elucidate the mechanisms of chaperone‐effector binding and release process but also facilitate custom design of cargo effectors to be translocated by these widespread secretion systems for biotechnological applications.
PRL‐3 induces a positive signaling circuit between glycolysis and activation of STAT1/2
Authors: Vandsemb Esten Nymoen , Rye Morten Beck , Steiro Ida Johnsen , Elsaadi Samah , Rø Torstein Bade , Slørdahl Tobias Schmidt , Sponaas Anne‐Marit , Børset Magne , Abdollahi Pegah
Published: June 2021

Multiple myeloma (MM) is an incurable hematologic malignancy resulting from the clonal expansion of plasma cells. MM cells are interacting with components of the bone marrow microenvironment such as cytokines to survive and proliferate. Phosphatase of regenerating liver (PRL)‐3, a cytokine‐induced oncogenic phosphatase, is highly expressed in myeloma patients and is a mediator of metabolic reprogramming of cancer cells. To find novel pathways and genes regulated by PRL‐3, we characterized the global transcriptional response to PRL‐3 overexpression in two MM cell lines. We used pathway enrichment analysis to identify pathways regulated by PRL‐3. We further confirmed the hits from the enrichment analysis with in vitro experiments and investigated their function. We found that PRL‐3 induced expression of genes belonging to the type 1 interferon (IFN‐I) signaling pathway due to activation of signal transducer and activator of transcription (STAT) 1 and STAT2. This activation was independent of autocrine IFN‐I secretion. The increase in STAT1 and STAT2 did not result in any of the common consequences of increased IFN‐I or STAT1 signaling in cancer. Knockdown of STAT1/2 did not affect the viability of the cells, but decreased PRL‐3‐induced glycolysis. Interestingly, glucose metabolism contributed to the activation of STAT1 and STAT2 and expression of IFN‐I‐stimulated genes in PRL‐3‐overexpressing cells. In summary, we describe a novel signaling circuit where the key IFN‐I‐activated transcription factors STAT1 and STAT2 are important drivers of the increase in glycolysis induced by PRL‐3. Subsequently, increased glycolysis regulates the IFN‐I‐stimulated genes by augmenting the activation of STAT1/2.
Signaling pathways and defense mechanisms of ferroptosis
Authors: Liu Jiao , Kang Rui , Tang Daolin
Published: June 2021

As a type of lytic cell death driven by unrestricted lipid peroxidation and subsequent plasma membrane damage, ferroptosis occurs and develops because of sophisticated signals and regulatory mechanisms. The reactive oxygen species (ROS) used to initiate ferroptosis come from a variety of sources, including iron‐mediated Fenton reactions, mitochondrial ROS, and membrane‐associated ROS driven by the NOX protein family. Polyunsaturated fatty acid‐containing phospholipids are the main substrates of lipid peroxidation in ferroptosis, which is positively regulated by enzymes, such as ACSL4, LPCAT3, ALOXs, or POR. Selective activation of autophagic degradation pathways promotes ferroptosis by increasing iron accumulation to cause lipid peroxidation. In contrast, system xc–‐glutathione–GPX4 axis plays a central role in limiting lipid peroxidation, although other antioxidants (such as coenzyme Q10 and tetrahydrobiopterin) can also inhibit ferroptosis. A main nuclear mechanism of cell defense against ferroptosis is the activation of the NFE2L2‐dependent antioxidant response by transcriptionally upregulating the expression of antioxidants or cytoprotective genes. Additionally, the membrane damage caused by ferroptotic stimulus can be repaired by ESCRT‐III‐dependent membrane scission machinery. In this review, we summarize recent progress in understanding the signaling pathways and defense mechanisms of ferroptosis.
Trait‐based vulnerability reveals hotspots of potential impact for a global marine invader
Authors: Linardich Christi , Brookson Cole B. , Green Stephanie J.
Published: June 2021

Predation from the invasive Indo‐Pacific lionfish is likely to amplify declines in marine fishes observed in multiple ocean basins. As the invasion intensifies and expands, there is an urgent need to identify species that are most at risk for extirpation—and possible extinction—from this added threat. To address this gap and inform conservation plans, we develop and apply a quantitative framework for classifying the relative vulnerability of fishes based on morphological and behavioural traits known to influence susceptibility to lionfish predation (e.g. body shape, water column position and aggregation behaviour), habitat overlap with lionfish, and degree of geographic range restriction. Applying the framework to fishes across the invaded Caribbean Sea and ahead of the invasion front in the southwestern Atlantic revealed the identity of at least 77 fishes with relatively small ranges that are likely to be most affected by lionfish predation. Trait‐based vulnerability scores significantly predict the probability of fishes appearing within the diets of lionfish across the invaded region. Spatial richness analyses reveal hotspots of vulnerable species in the Bahamas, Belize and Curaçao. Crucially, our framework identifies 29 vulnerable fishes endemic to Brazil, which has not yet been colonized by lionfish. Of these, we suggest reefs around offshore island groups occupied by a dozen highly vulnerable and range‐restricted species as priorities for intervention should lionfish spread to the region. Observations of the rate of lionfish spread across the invaded range suggest that an average of 5 years (with a median of nearly 2 years) elapses from first sighting to maximum observed densities. This lag may allow managers to mobilize plans to suppress lionfish ahead of an invasion front in priority locations. Our framework also provides a method for assessing the relative vulnerability of cryptobenthic and/or deep‐reef fishes, for which population‐monitoring data are limited.
An integrative synthesis to global amphibian conservation priorities
Authors: Button Sky , Borzée Amaël
Published: June 2021

Human activities are driving many species to the brink of extinction, and the current distribution of protected areas only weakly alleviates pressure on threatened species. This discrepancy reflects the presence of protected areas on lands available instead of the ecological, evolutionary, or conservation values of species present. Habitat loss consequently continues to impact threatened species, as illustrated by geographic patterns of biodiversity loss for amphibians. Given the need to better align the boundaries of protected areas with at‐risk biodiversity, we assessed the importance of various factors for identifying global and biome‐level conservation priority areas, specifically for amphibians. We identified, mapped, and ranked areas of critical conservation importance for all amphibian species on earth using a new integrative tool that scores the urgency of conserving each species and location based on a combination of species characteristics and ecoregion‐level human impacts. Our integrative approach is novel in that it accounts for likely threats to Data Deficient species, considers the irreplaceability of unique species that are phylogenetically isolated, and addresses the localized conservation implications of species endemicity and projected future human impacts to an ecoregion. For comparison, we also mapped and ranked amphibian biodiversity using species richness and an Evolutionarily Distinct and Globally Endangered (EDGE) score proxy. Our integrative approach predicted key regions for amphibian conservation that were not apparent when using a simple species richness or EDGE score proxy‐based approach. Furthermore, by scaling conservation priority scores relative to biome, we identified several temperate and xeric regions of crucial yet overlooked conservation importance for amphibians. Until global amphibian diversity is thoroughly catalogued, we recommend using our integrative scoring approach to set geographic priorities for amphibian habitat protection, while acknowledging that this approach may be complemented by others (e.g., EDGE scores). Our study provides an avenue for avoiding common pitfalls of more simplistic species richness‐based approaches for conservation planning, and can be used to improve the future design of protected areas.
Solidification depth and crystallization age of the Shiaidani Granodiorite: Constraints to the average denudation rate of the Hida Range, central Japan
Authors: Kawakami Tetsuo , Sueoka Shigeru , Yokoyama Tatsunori , Kagami Saya , King Georgina E. , Herman Frédéric , Tsukamoto Sumiko , Tagami Takahiro
Published: June 2021

Solidification pressure and crystallization age of the ~5 Ma Shiaidani Granodiorite (Hida Mountain Range, central Japan) are determined based on Al‐in‐hornblende geobarometry and U–Pb zircon dating. Al‐poor patchy replacements developed in amphiboles are common in this granite and petrographic study revealed that the replacements include chloritized biotite and albitic plagioclase. These are probably the hydrothermally recrystallized domains, and should not be used for solidification pressure estimates. Magmatic rim of amphibole is characterized by Si < 7.3 a.p.f.u. (AlIV > 0.7 a.p.f.u.), and utilized in solidification pressure estimate that yielded 0.17–0.29 GPa. The solidification age of the granite is estimated as ~5.6–5.2 Ma using U–Pb zircon dating. From these data, the lower limit of an average denudation rate after ~5.6–5.2 Ma for the area where Shiaidani Granodiorite is exposed is estimated as 0.93–2.5 mm/year.
Measuring workplace violence for clinical dental hygienists
Authors: Won Seung‐Eun , Choi Ma‐I , Noh Hiejin , Han Sun‐Young , Mun So‐Jung
Published: June 2021

Objective

This study aimed to develop and assess a tool for measuring violence experienced by clinical dental hygienists in the workplace.

Methods

The basic questionnaire used in this study was created by referring to previous studies, the Negative Acts Questionnaire‐Revised (NAQ‐R) and the Workplace Bullying in Nursing–Type Inventory (WPBN‐TI). The content feasibility was verified by ten experts in the field, and irrelevant questions were deleted, based on a content validity index value of 0.8. This study surveyed 205 clinical dental hygienists to test the tool's validity and reliability. Frequency analysis was conducted on items related to general characteristics and workplace violence.

Results

The questionnaire set was 31 questions, which, comprised five domains, were finalized through reliability verification. These domains were verbal attacks and alienation (9 questions), inappropriate work experiences (6 questions), physical threats (4 questions), workplace sexual harassment (6 questions) and verbal violence (6 questions) from patients and their family members. Among the study participants, 47.3% said they received rude signals from others, 17.9% said they were subjected to sexual evaluations regarding their appearance, and 29.4% said their abilities were ignored by patients and family members of patients.

Conclusions

Clinical dental hygienists have been exposed to various types of violence in their workplaces, such as sexual and verbal harassment, by patients and their family members. This tool can be used in the dental setting to conduct surveys on workplace violence and establish a monitoring and support system.
Oral health‐related quality of life and associated factors in patients with xerostomia
Authors: Choi Jee‐Hye , Kim Moon‐Jong , Kho Hong‐Seop
Published: June 2021

Objective

This study aimed to investigate clinical and demographic factors associated with oral health‐related quality of life (OHRQoL) in patients with xerostomia.

Methods

Forty‐one patients (55.2 ± 13.8 years) with xerostomia as a chief complaint participated in the study. Comprehensive information about clinical and demographic characteristics of the patients with xerostomia, xerostomia‐related symptoms and behaviours, and xerostomia‐associated complaints was investigated using a xerostomia questionnaire. Flow rates of unstimulated and stimulated whole saliva were measured. The Oral Health Impact Profile‐14 (OHIP‐14) score was used to assess the OHRQoL of patients. The relationships between various factors and the OHIP‐14 score were assessed by simple and multiple linear regression analyses.

Results

The OHIP‐14 score of patients with xerostomia was high (44.3 ± 13.2). Characteristics of the patients with xerostomia associated with high OHIP‐14 score were the intensity of xerostomia‐related symptoms, frequency of xerostomia‐related behaviours and the presence of speaking difficulty. Results from multiple linear regressions found that self‐reported amount of saliva in usual, everyday life (β = 0.622, p = 0.012) and the presence of a speaking difficulty (β = 0.348, p = 0.014) had significant adversely affected the OHRQoL in patients with xerostomia.

Conclusions

Subjective perceptions of the amount of saliva in the mouth and the experience of speaking difficulty affected the OHRQoL in patients with xerostomia.
Interpreting sulfhemoglobin and methemoglobin in patients with cyanosis: An overview of patients with M‐hemoglobin variants
Authors: Rangan Aruna , Savedra Michelle E. , Dergam‐Larson Camila , Swanson Kenneth C. , Szuberski Jessica , Go Ronald S. , Porter Tavanna R. , Brunker Sarah E. , Shi Min , Nguyen Phuong L. , Hoyer James D. , Oliveira Jennifer L.
Published: June 2021

Introduction

Methemoglobin (MetHb) and sulfhemoglobin (SHb) measurements are useful in the evaluation of cyanosis. When one or both values are elevated, additional analysis is important to establish the etiology of the disorder. Methemoglobinemia occurs from acquired or hereditary causes with diverse treatment considerations, while true sulfhemoglobinemia is only acquired and treatment is restricted to toxin removal. Some toxic exposures can result in a dual increase in MetHb and SHb. Hereditary conditions, such as M‐Hemoglobin variants (M‐Hbs), can result in increased MetHb and/or SHb values but are clinically compensated and do not require treatment if they are cyanotic but otherwise clinically well.

Methods

Herein, we report 53 hemoglobin variant cases that have associated MetHb and SHb levels measured by an adapted Evelyn‐Malloy laboratory assay method.

Results

Our data indicate M‐Hbs cause variable patterns of MetHb and SHb elevation in a fairly reproducible pattern for the particular variant. In particular, α globin chain M‐Hbs can mimic acquired sulfhemoglobinemia due to an isolated increased SHb value.

Conclusion

If the patient appears clinically well other than cyanosis, M‐Hbs should be considered early in the evaluation process to differentiate from acquired conditions to avoid unnecessary testing and treatment regimens and prompt genetic counseling.
Safety and efficacy of high‐flow nasal cannula therapy in acute hypercapnic respiratory failure: a retrospective audit
Authors: Golmohamad Amin , Johnston Rachel , Hay Karen , Tay George
Published: June 2021

Background

While the role of high‐flow nasal cannulae (HFNC) in the management of respiratory failure continues to expand, few studies describe its use in acute hypercapnic respiratory failure.

Aims

In this retrospective study, we assessed the safety and efficacy of HFNC for the treatment of acute hypercapnic respiratory failure.

Methods

Admissions with acute hypercapnic respiratory failure to a thoracic medicine unit at a tertiary centre between January and August 2018 were included if treated with either HFNC or non‐invasive ventilation (NIV). The primary outcome was post‐treatment change in arterial pCO2. Demographics, comorbidities, length of stay, readmission rate and mortality were also collected.

Results

Sixty‐four patients were identified, comprising 69 presentations grouped according to initial treatment: HFNC (n = 24) or NIV (n = 45). Patients in the NIV group had more severe blood gas derangement. In both groups, mean arterial pCO2 improved significantly (−10 (95% confidence interval: −14 to −6) mmHg) from baseline with no evidence of a differential effect between groups. Six (25%) patients, of whom three had comorbid obesity and two had sleep‐disordered breathing, were transitioned from HFNC to NIV. No significant differences in hospital length of stay, 30‐day readmission rate or 90‐day mortality were observed.

Conclusions

HFNC might be a reasonable initial treatment for patients with mild acute hypercapnic respiratory failure who do not have comorbid obesity or sleep‐disordered breathing. A prospective study might help identify clinical factors or phenotypes predictive of success with this treatment modality.