bluuebunny/crossref_metadata_2025 huggingface dataset:
Will harbor porpoises (Phocoena phocoena) be deterred by a pinger that cannot be used as a “dinner bell” by seals?
Authors: Königson Sara , Naddafi Rahmat , Hedgärde Maria , Pettersson Alice , Östman Örjan , Benavente Norrman Emilia , Amundin Mats
Published: October 2021

A measure proven successful in mitigating harbor porpoise bycatch, is the use of acoustic deterrents, i.e., pingers. However, most pingers are audible to seals. This may lead to seals associating pinger sounds with easily accessible food, leading to increased depredation, damage, and bycatch. In this study we tested if an experimental pinger, emitting sounds over 30 hr ON/OFF cycles, with low frequency components potentially audible to seals only at close distances, would effectively deter harbor porpoises. The porpoise response was measured by logging echolocation clicks, using C‐POD click detectors, moored at different distances from the pinger. In addition, we calculated the theoretical pinger detection range for seals. Results showed that the pinger had a significant negative effect on the porpoise click activity logged at 0 m and 100 m distance but not at 400 m from the pinger. During pinger ON periods, we found no significant increase in echolocation over consecutive days of the study, suggesting no habituation to pinger sounds. Our theoretical detection distances indicate that seals can only detect the pinger at close distances, preventing seals from using this pinger as a “dinner bell.”
A Meta‐Analysis of Hybrid Language Instruction and Call for Future Research
Authors: DIXON TÜLAY , CHRISTISON MARYANN , DIXON DANIEL H. , PALMER ADRIAN S.
Published: October 2021

In this meta‐analysis, we estimate the effectiveness of hybrid language instruction overall and across a number of moderator variables by aggregating effect sizes from 11 studies with 34 samples. Results suggest hybrid language instruction can be just as effective as traditional face‐to‐face (f2f) instruction, as indicated by the negligible differences between hybrid courses and traditional f2f courses (d = .14). Furthermore, studies employing within‐group designs indicate that students in hybrid language classes can improve their language skills considerably (d = 1.47). This is a positive finding given that many institutions have experienced a surge in hybrid teaching due to the COVID‐19 pandemic. We also report on a number of moderator variables that can impact the effectiveness of hybrid language courses, including (a) the amount of reduction in f2f time, (b) the use of online activities provided by textbook publishers, (c) the use of a learning management system, (d) advances in digital technologies, (e) the targeted language skills (e.g., speaking, writing), and (f) whether the data come from initial or subsequent iterations of a hybrid course. Additionally, we offer directions for future research regarding the substantive and methodological issues in the hybrid language instruction domain.
Severity of dysphagia is associated with hospitalizations and mortality in patients with Parkinson’s disease
Authors: Dilmaghani Saam , Atieh Jessica , Khanna Lehar , Hosfield Emily A. , Camilleri Michael , Katzka David A.
Published: October 2021

Background

Aspiration pneumonia is the commonest cause of hospitalizations and death in patients with Parkinson's disease (PD). Among these patients, the relationships between severity of dysphagia, hospitalizations for related complications, and death are not robustly defined. Our aim was to characterize the relationship between PD‐related oropharyngeal dysfunction and clinically relevant outcomes.

Methods

Retrospective cohort study of 312 patients with PD at a tertiary center who underwent videofluoroscopic swallow studies conducted by expert therapists between 2010 and 2015. Level of swallowing function was represented using the 7‐point Functional Oral Intake Scale (FOIS) (7 = normal function). Significance and relative risk calculations utilized Poisson regression. Time to composite outcome of first hospitalization or death was summarized using Kaplan‐Meier curve with log‐rank test.

Key Results

One hundred thirty eight patients had a recorded FOIS score. The prevalence of oropharyngeal dysfunction was 76.1%. The median duration of follow‐up was 26.8 months. In multivariate analyses, patients with FOIS 5 (RR = 2.01 [95% CI: 1.22, 3.32]), FOIS 3 (RR = 2.78 [95% CI: 1.75, 4.40]), and FOIS 1 (RR = 2.50 [95% CI: 1.49, 4.20]) were significantly associated with increased risk of hospitalization or death compared to FOIS 7 after co‐variate adjustments. GERD was also associated with a significant increased risk of hospitalization or death (RR = 1.28 [95% CI: 1.01, 1.64]). Time to first hospitalization or death was shorter in patients with lower FOIS scores (p < 0.00005).

Conclusions and Inferences

Severity of oropharyngeal dysphagia, as measured by the FOIS, is associated with poorer survival and shorter time to hospitalization for dysphagia‐related complications, pneumonia, or death in PD.
Arabidopsis ADR1 helper NLR immune receptors localize and function at the plasma membrane in a phospholipid dependent manner
Authors: Saile Svenja C. , Ackermann Frank M. , Sunil Sruthi , Keicher Jutta , Bayless Adam , Bonardi Vera , Wan Li , Doumane Mehdi , Stöbbe Eva , Jaillais Yvon , Caillaud Marie‐Cécile , Dangl Jeffery L. , Nishimura Marc T. , Oecking Claudia , El Kasmi Farid
Published: October 2021

Activation of nucleotide‐binding leucine‐rich repeat receptors (NLRs) results in immunity and a localized cell death. NLR cell death activity requires oligomerization and in some cases plasma membrane (PM) localization. The exact mechanisms underlying PM localization of NLRs lacking predicted transmembrane domains or recognizable lipidation motifs remain elusive.

We used confocal microscopy, genetically encoded molecular tools and protein‐lipid overlay assays to determine whether PM localization of members of the Arabidopsis HeLo‐/RPW8‐like domain ‘helper’ NLR (RNL) family is mediated by the interaction with negatively charged phospholipids of the PM.

Our results show that PM localization and stability of some RNLs and one CC‐type NLR (CNL) depend on the direct interaction with PM phospholipids. Depletion of phosphatidylinositol‐4‐phosphate from the PM led to a mis‐localization of the analysed NLRs and consequently inhibited their cell death activity. We further demonstrate homo‐ and hetero‐association of members of the RNL family. Our results provide new insights into the molecular mechanism of NLR localization and defines an important role of phospholipids for CNL and RNL PM localization and consequently, for their function.

We propose that RNLs interact with anionic PM phospholipids and that RNL‐mediated cell death and immune responses happen at the PM.
Interplay of above‐ and belowground resource limitations: a competition–facilitation shift maintains species coexistence
Authors: Douda Jan , Doudová Jana , Holeštová Anežka , Boublík Karel , Havrdová Alena , Slezák Michal
Published: October 2021

Forest ecosystems are commonly characterised by a hierarchy of resources. During a disturbance of a forest community, increased light availability in the understorey can support competitive interactions at the expense of facilitation. This may overwhelm the role of belowground resource heterogeneity in maintaining species coexistence and so result in biotic homogenisation of a site. We re‐surveyed species composition while estimating interspecific interactions along a microtopographic (moisture) gradient of a temperate swamp forest after increasing the availability of light into the undergrowth. We measured temporal changes in species diversity, compositional dissimilarity measures and functional traits, while belowground resource heterogeneity remained unchanged over time. To explain observed changes in terms of prevailing interspecific interactions, we evaluated temporal changes in the competition–facilitation balance. The productivity of understorey vegetation increased strongly over the five years of the study. This was accompanied by an increase in species diversity and the maintenance of compositional dissimilarity. The relative importance of competitive and facilitative interactions along the microtopographic gradient did not change over time. Rather than an overall biotic homogenisation of a site, we observed a spread of resource acquisitive species within the resource‐rich sites and of stress‐tolerant species within the resource‐limited sites. We have shown that the temporary increase in productivity did not mitigate the effects of belowground resource heterogeneity on plant species turnover, which is likely maintained by contrasting interspecific interactions prevalent in different parts of the resource gradient. This suggests contrasting community assembly processes maintain diversity and productivity even in a local community.
Declining Family Support, Changing Income Sources, and Older People Poverty: Lessons from South Korea
Authors: Ku Inhoe , Lee Wonjin , Lee Seoyun
Published: October 2021

This study decomposes the changes in income distribution among older adults between 1996 and 2016 in South Korea. We found that income distribution among older adults worsened between 1996 and 2010 and then improved between 2010 and 2016. From 1996 to 2010, the rapid change in living arrangements was the most powerful contributor to the worsening income distribution. The decrease in market income also contributed to reducing the median income and increasing poverty. Yet, expanded public transfers cancelled out most of the negative effects of the decrease in market income. From 2010 to 2016, the change in living arrangement still significantly decreased median income and increased inequality and poverty. The increase in market income considerably contributed to the increase in median income and the decrease in poverty. Above all, the rise in public transfer income became the most influential contributor to the increase in median income and the decrease in inequality and poverty.
Introgression of bruchid (Zabrotes subfasciatus) resistance into small red common bean (Phaseolus vulgaris) background and validation of the BRU_00261 (snpPV0007) resistance marker
Authors: Tigist Shiferaw Girsil , Raatz Bodo , Assefa Amelework , Melis Rob , Sibiya Julia , Keneni Gemechu , Mukankusi Clare , Fenta Berhanu , Ketema Selamawit , Tsegaye Dagmawit
Published: October 2021

Bruchids are a major storage pest of common bean. Genetic resistance is a suitable method to avoid grain losses during storage. The objective of the study was to introgress the arcelin‐based resistance locus into selected advanced breeding line and to validate the molecular marker BRU_00261. A total of 208 progeny F4 families were phenotyped using a randomized complete block design, with three replications. Highly significant differences (P <  .001) among the entries, parents and offspring were recorded for almost all traits. There was no significant difference between the two parents in the number of eggs laid. The progenies were grouped as highly resistant (34.3%), resistant (11.9%), moderately resistant (21.4%) and susceptible (32.4%). The levels of broad sense heritability ranged from 68.5%–93.9% for all the traits. Eighty‐three most resistant lines and the parental lines were genotyped with the marker BRU_00261 (snpPV0007). The marker segregation deviated significantly from the expected independent segregation towards a strong enrichment for the resistant marker in the selected families. This marker will be useful for selecting promising materials in early generations and phenotypic confirmation of positive lines in later generations.
Below‐ground plant–soil interactions affecting adaptations of rice to iron toxicity
Authors: Kirk Guy J. D. , Manwaring Hanna R. , Ueda Yoshiaki , Semwal Vimal K. , Wissuwa Matthias
Published: October 2021

Iron toxicity is a major constraint to rice production, particularly in highly weathered soils of inland valleys in sub‐Saharan Africa where the rice growing area is rapidly expanding. There is a wide variation in tolerance of iron toxicity in the rice germplasm. However, the introgression of tolerance traits into high‐yielding germplasm has been slow owing to the complexity of the tolerance mechanisms and large genotype‐by‐environment effects. We review current understanding of tolerance mechanisms, particularly those involving below‐ground plant–soil interactions. Until now these have been less studied than above‐ground mechanisms. We cover processes in the rhizosphere linked to exclusion of toxic ferrous iron by oxidation, and resulting effects on the mobility of nutrient ions. We also cover the molecular physiology of below‐ground processes controlling iron retention in roots and root‐shoot transport, and also plant iron sensing. We conclude that future breeding programmes should be based on well‐characterized molecular markers for iron toxicity tolerance traits. To successfully identify such markers, the complex tolerance response should be broken down into its components based on understanding of tolerance mechanisms, and tailored screening methods should be developed for individual mechanisms.
ZRT‐IRT‐Like PROTEIN 6expression perturbs local ion homeostasis in flowers and leads to anther indehiscence and male sterility
Authors: Spielmann Julien , Detry Nathalie , Thiébaut Noémie , Jadoul Alice , Schloesser Marie , Motte Patrick , Périlleux Claire , Hanikenne Marc
Published: October 2021

Metallic micronutrients are essential throughout the plant life cycle. Maintaining metal homeostasis in plant tissues requires a highly complex and finely tuned network controlling metal uptake, transport, distribution and storage. Zinc and cadmium hyperaccumulation, such as observed in the model plantArabidopsis halleri, represents an extreme evolution of this network. Here, non‐ectopic overexpression of theA. halleri ZIP6(AhZIP6) gene, encoding a zinc and cadmium influx transporter, inArabidopsis thalianaenabled examining the importance of zinc for flower development and reproduction. We show thatAhZIP6expression in flowers leads to male sterility resulting from anther indehiscence in a dose‐dependent manner. The sterility phenotype is associated to delayed tapetum degradation and endothecium collapse, as well as increased magnesium and potassium accumulation and higher expression of theMHXgene in stamens. It is rescued by the co‐expression of the zinc efflux transporter AhHMA4, linking the sterility phenotype to zinc homeostasis. Altogether, our results confirm thatAhZIP6is able to transport zincin plantaand highlight the importance of fine‐tuning zinc homeostasis in reproductive organs. The study illustrates how the characterization of metal hyperaccumulation mechanisms can reveal key nodes and processes in the metal homeostasis network.
Evaluation of the core 5 social determinants of health screening tool
Authors: Bechtel Nancie , Jones Alexandria , Kue Jennifer , Ford Jodi L.
Published: October 2021

Objective

This study evaluated the effects of a social determinants of health (SDH) screening tool and service referral on emergency department (ED) use among patients at a Federally Qualified Health Center primary care clinic.

Study design

Quasi‐experimental.

Sample

Three‐hundred and eleven English‐speaking patients 18 years and older.

Measures

The Core 5 SDH screening tool consists of five yes/no items assessing food, housing, utilities, transportation, and safety needs. The number of ED visits 3 months before and after the intervention were collected from electronic health records.

Intervention

The research team administered the Core 5 SDH screening tool and if desired, referred patients with an identified need for SDH services.

Results

Approximately 43% of patients reported a SDH need with food insecurity most prevalent (62.2%). The number of ED visits was significantly lower 3 months post‐intervention compared to 3 months before for the 125 participants who wanted and received the SDH service referral (IRR = 0.64, 95% CI = 0.41, 0.99) and for the 35 participants who reported receiving some/all of the needed services at the 2‐week follow‐up (IRR = 0.36, 95% CI = 0.17, 0.76).

Conclusions

Addressing patients’ SDH needs may reduce ED visits, lower healthcare costs, and ultimately, improve health.
Protecting persons experiencing homelessness through a global pandemic
Authors: Lashley Mary , Stoltzfus K. Daniel
Published: October 2021

In response to the challenges imposed by the COVID‐19 global pandemic, the leadership of a large homeless service and residential recovery organization transformed its organizational practices in accordance with best available evidence for prevention and containment of the SARS‐CoV‐2 virus. The coordinated organizational response was based on the CDC's “whole community” framework for addressing the threat of COVID‐19 among persons experiencing homelessness and included strategies for preparation and containment of the virus and identification of exposures and disease outbreaks. Organizational practice changes were also instituted to mitigate spread. New protocols and procedures addressed admission intake processes, testing and monitoring, and guidelines for managing staff, vendors, and volunteers. Finally, an on‐site vaccination clinic was organized through the establishment of a four‐pronged coalition. The program outreached to staff, residents, and essential volunteers. Following implementation of this coordinated organizational response, confirmed SARS CoV‐2 cases in the facility declined to zero. Through this experience, the leadership became more adept at improving its digital fitness and pivoting when circumstances dictated a shift in policy and practice. In every major initiative or policy change aimed at addressing the spread of the virus, community partnerships were key to effective implementation of COVID‐19 prevention and containment strategies.
Moral Polarization Predicts Support for Authoritarian and Progressive Strong Leaders via the Perceived Breakdown of Society
Authors: Crimston Charlie R. , Selvanathan Hema Preya , Jetten Jolanda
Published: October 2021

Polarization in society may hold consequences beyond the undermining of social cohesion. Here we provide the first evidence highlighting the power of perceived moral polarization in society to drive support for strong leaders. Across two studies and four samples drawn from the United Kingdom, Australia, and the United States (N = 1,664), we found evidence linking perceived moral polarization with perceived anomie in society (defined as the perceived breakdown of social fabric and leadership) and with the rise in support for leaders with both a conservative/authoritarian and progressive/democratic style. Specifically, via the perceived breakdown in social fabric, heightened moral polarization predicted increased support for conservative/authoritarian style strong leaders, and via the perceived breakdown of leadership, increased support for progressive/democratic style strong leaders. Experimentally, using a fictionalized society paradigm, we then established causal links between moral polarization and the desire to elect conservative/authoritarian and progressive/democratic strong leaders. The current research is the first to identify the potential political consequences of heightened perceived moral polarization in two‐party liberal democracies and contributes to the growing body of research highlighting the role of societal factors in driving support for strong leaders.
Identification of parking spaces from multi‐modal trajectory data
Authors: Dey Subhrasankha , Winter Stephan , Goel Salil , Tomko Martin
Published: October 2021

Mapping the parking spaces in cities is desirable for reducing cruising time and congestion in the city. But map information regarding parking spaces is often missing or incomplete, due to the variety of their nature: marked or unmarked, on‐street or off‐street, or public, domestic or commercial. Hence, we develop a new method for mapping parking spaces, and deliberately focus on a crowd‐sourcing solution because of its global applicability. We will use smartphone trajectory data, as collected by person‐bound navigation apps. A person‐bound navigation app collects multi‐modal trajectory data where the transitions from drive to walk or from walk to drive contain valuable information about parking spaces. Hence, mode detection is required with sufficient accuracy to be able to map parking spaces. We develop a novel mode detection focusing just on this problem and outperforming existing, generic mode detection algorithms. Further, we provide a methodology to identify the geographic locations of parking spaces from these collected trajectory data. The article presents the methodologies, their implementations, and a critical evaluation to achieve mapping of parking spaces.
Urban spatial epidemic simulation model: A case study of the second COVID‐19 outbreak in Beijing, China
Authors: Huang Qiang , Liu Qiyong , Song Ci , Liu Xiaobo , Shu Hua , Wang Xi , Liu Yaxi , Chen Xiao , Chen Jie , Pei Tao
Published: October 2021

The second COVID‐19 outbreak in Beijing was controlled by non‐pharmaceutical interventions, which avoided a second pandemic. Until mass vaccination achieves herd immunity, cities are at risk of similar outbreaks. It is vital to quantify and simulate Beijing's non‐pharmaceutical interventions to find effective intervention policies for the second outbreak. Few models have achieved accurate intra‐city spatio‐temporal epidemic spread simulation, and most modeling studies focused on the initial pandemic. We built a dynamic module of infected case movement within the city, and established an urban spatially epidemic simulation model (USESM), using mobile phone signaling data to create scenarios to assess the impact of interventions. We found that: (1) USESM simulated the transmission process of the epidemic within Beijing; (2) USESM showed the epidemic curve and presented the spatial distribution of epidemic spread on a map; and (3) to balance resources, interventions, and economic development, nucleic acid testing intensity could be increased and restrictions on human mobility in non‐epidemic areas eased.
Structural property, molecular regulation, and functional diversity of glutamine synthetase in higher plants: a data‐mining bioinformatics approach
Authors: Mondal Raju , Kumar Amit , Chattopadhyay Sanjib Kumar
Published: October 2021

Glutamine synthetase (GS; E.C.6.3.1.2) is a key enzyme in higher plants with two isozymes, cytosolic GS1 and plastidic GS2, and involves in the assimilation and recycling of NH4+ ions and maintenance of complex traits such as crop nitrogen‐use efficiency and yield. Our present understanding of crop nitrogen‐use efficiency and its correlation with the functional role of the GS family genes is inadequate, which delays harnessing the benefit of this key enzyme in crop improvement. In this report, we performed a comprehensive investigation on the phylogenetic relationship, structural properties, complex multilevel gene regulation, and expression patterns of the GS genes to enrich present understanding about the enzyme. Our Gene Ontology and protein–protein interactions analysis revealed the functional aspects of GS isozymes in stress mitigation, aging, nucleotide biosynthesis/transport, DNA repair and response to metals. The insight gained here contributes to the future research strategies in developing climate‐smart crops for global sustainability.
WHITE AND LESION‐MIMIC LEAF1, encoding a lumazine synthase, affects reactive oxygen species balance and chloroplast development in rice
Authors: Hu Haitao , Ren Deyong , Hu Jiang , Jiang Hongzhen , Chen Ping , Zeng Dali , Qian Qian , Guo Longbiao
Published: October 2021

The riboflavin derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential cofactors for enzymes in multiple cellular processes. Characterizing mutants with impaired riboflavin metabolism can help clarify the role of riboflavin in plant development. Here, we characterized a rice (Oryza sativa) white and lesion‐mimic (wll1) mutant, which displays a lesion‐mimic phenotype with white leaves, chlorophyll loss, chloroplast defects, excess reactive oxygen species (ROS) accumulation, decreased photosystem protein levels, changes in expression of chloroplast development and photosynthesis genes, and cell death. Map‐based cloning and complementation test revealed that WLL1 encodes lumazine synthase, which participates in riboflavin biosynthesis. Indeed, the wll1 mutant showed riboflavin deficiency, and application of FAD rescued the wll1 phenotype. In addition, transcriptome analysis showed that cytokinin metabolism was significantly affected in wll1 mutant, which had increased cytokinin and δ‐aminolevulinic acid contents. Furthermore, WLL1 and riboflavin synthase (RS) formed a complex, and the rs mutant had a similar phenotype to the wll1 mutant. Taken together, our findings revealed that WLL1 and RS play pivotal roles in riboflavin biosynthesis, which is necessary for ROS balance and chloroplast development in rice.
A comparison of platelet function in cold‐stored whole blood and platelet concentrates
Authors: Huish Sian , Green Laura , Kempster Carly , Smethurst Peter , Wiltshire Michael , Prajapati Chetankumar , Allen Elisa , Cardigan Rebecca
Published: October 2021

Background

There is renewed interest in the use of whole blood (WB) for the resuscitation of trauma patients. Platelet function in stored WB compared to platelet concentrates is not well established and was assessed in vitro in this study.

Methods

Leucocyte‐depleted cold‐stored WB (CS‐WB) was prepared using a Terumo WB‐SP Imuflex kit and held at 2–6°C alongside: (A) UK standard pooled platelets stored at 20–24°C (RT‐PLTS), (B) pooled platelets stored at 2–6°C (CS‐PLTS), and (C) platelet‐rich plasma produced using the Terumo kit (CS‐PRP), for 21 days. A series of in vitro assays were assessed platelet function.

Results

Platelet count was retained to 57 ± 14% of starting number at day 21 in CS‐WB. Over time, CS‐WB platelets become more activated, with increased CD62P expression (day 1: 7 ± 3.7% vs. day 21: 59 ± 17.1%) and annexin V binding (day 1: 2 ± 0.2% vs. day 21: 21 ± 15.1%). For comparison, 18.6 ± 6% of platelets in RT‐PLTS demonstrated CD62P expression at day 7, whereas annexin V binding in RT‐PLTS at day 7 was 2.6 ± 0.5%. Over storage, aggregatory response to agonists decreased in all arms. Functional platelet microparticles increased steadily in CS‐WB throughout storage.

Conclusion

During storage, platelet count reduced in CS‐WB, whereas CD62P expression and annexin V binding increased. This was accompanied by a reduced aggregatory response, although compared to 7‐day‐old RT‐PLTS, CS‐WB maintained a maximal response to agonists for longer, suggesting that the shelf life for CS‐WB can be considered for up to 21 days.
Charge dynamics in quantum-circuit refrigeration: Thermalization and microwave gain
Authors: Hsu Hao , Silveri Matti , Sevriuk Vasilii , Möttönen Mikko , Catelani Gianluigi
Published: October 2021

Previous studies of photon-assisted tunneling through normal-metal–insulator–superconductor junctions have exhibited potential for providing a convenient tool to control the dissipation of quantum-electric circuits in situ. However, the current literature on such a quantum-circuit refrigerator (QCR) does not present a detailed description for the charge dynamics of the tunneling processes or the phase coherence of the open quantum system. Here, we derive a master equation describing both quantum-electric and charge degrees of freedom, and discover that typical experimental parameters of low temperature and yet lower charging energy yield a separation of time scales for the charge and quantum dynamics. Consequently, the minor effect of the different charge states can be taken into account by averaging over the charge distribution. We also consider applying an ac voltage to the tunnel junction, which enables control of the decay rate of a superconducting qubit over four orders of magnitude by changing the drive amplitude; we find an order-of-magnitude drop in the qubit excitation in 40 ns and a residual reset infidelity below 10−4. Furthermore, for the normal island, we consider the case of charging energy and single-particle level spacing large compared to the superconducting gap, i.e., a quantum dot. Although the decay rates arising from such a dot QCR appear low for use in qubit reset, the device can provide effective negative damping (gain) to the coupled microwave resonator. The Fano factor of such a millikelvin microwave source may be smaller than unity, with the latter value being reached close to the maximum attainable power.
Cystic ibrosis: Molecular Biology and Therapeutic Implications
Authors: Collins Francis S.
Published: October 2021

Cystic fibrosis is the most common potentially lethal autosomal recessive disease of Caucasians, affecting 1 in 2500 newborns. Since the recent identification of the gene that is defective in patients with cystic fibrosis, a wealth of information about gene structure, the mutational basis of disease, and the function of the protein product has been derived. The product of the gene is a chloride channel that is regulated by adenosine 3′,5′-monophosphate (cyclic AMP)-dependent protein kinase phosphorylation and that requires binding of adenosine triphosphate (ATP) for channel opening. Several new approaches to drug therapy for cystic fibrosis are now emerging, and the possibility of successful gene therapy by transfer of the normal gene to airway epithelial cells is being vigorously pursued.
Alzheimer's Disease: a Cell Biological Perspective
Authors: Kosik Kenneth S.
Published: October 2021

An almost bewildering number of findings concerning Alzheimer's disease mask the significant recent progress in understanding the molecular basis of some inherited forms of this disease and the proteolytic processing of proteins related to the disease. Alzheimer's disease is an amyloidosis, a condition in which certain proteins or protein fragments precipitate in various tissues as amyloid, fibrillar aggregates with a β-pleated sheet conformation. Alzheimer's is also characterized by neuritic lesions and cell death. Some rare forms of the disease are now known to arise from a mutation in an amyloidogenic protein. Another recent insight is the discovery of an endosomal-lysosomal processing pathway capable of generating protein fragments that can deposit extracellularly as amyloid fibrils. Key future directions for cellular-based research in Alzheimer's disease include the study of membrane trafficking and the passage of intracellular material to the extracellular milieu, molecular signaling among intracellular compartments, the interaction between organelles and the neuronal cytoskeleton, and the nature of cytoskeletal reorganization after neuronal injury.
The Role of Crystal Polarity in α-Amino Acid Crystals for Induced Nucleation of Ice
Authors: Gavish M. , Wang J.-L. , Eisenstein M. , Lahav M. , Leiserowitz L.
Published: October 2021

The hydrophobic faces of single crystals of a series of pairs of racemic and chiral-resolved hydrophobic α-amino acids were used as a substrate, onto which water vapor has been cooled to freezing. The morphologies and molecular packing arrangements within each crystal pair are similar but only one of each pair exhibits a polar axis, parallel to the hydrophobic face exposed to water. Those crystals that have a polar axis induce a freezing point higher by 4° to 5°C than the corresponding crystals that do not have a polar axis. The results are interpreted in terms of an electric field mechanism that helps align the water molecules into ice-like clusters en route to crystallization.
Recovery from Experimental Parkinsonism in Primates with GM
1
Ganglioside Treatment
Authors: Schneider J. S. , Pope A. , Simpson K. , Taggart J. , Smith M. G. , DiStefano L.
Published: October 2021

A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with G
M1
ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with G
M1
ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that G
M1
ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.
Lateralization of Phonetic and Pitch Discrimination in Speech Processing
Authors: Zatorre Robert J. , Evans Alan C. , Meyer Ernst , Gjedde Albert
Published: October 2021

Cerebral activation was measured with positron emission tomography in ten human volunteers. The primary auditory cortex showed increased activity in response to noise bursts, whereas acoustically matched speech syllables activated secondary auditory cortices bilaterally. Instructions to make judgments about different attributes of the same speech signal resulted in activation of specific lateralized neural systems. Discrimination of phonetic structure led to increased activity in part of Broca's area of the left hemisphere, suggesting a role for articulatory recoding in phonetic perception. Processing changes in pitch produced activation of the right prefrontal cortex, consistent with the importance of right-hemisphere mechanisms in pitch perception.
Fellowship highlights need for science communicators
Authors: Ham Becky
Published: October 2021

Mass Media internships provide new careers and skills
Neonatal-onset mitochondrial disease: clinical features, molecular diagnosis and prognosis
Authors: Ebihara Tomohiro , Nagatomo Taro , Sugiyama Yohei , Tsuruoka Tomoko , Osone Yoshiteru , Shimura Masaru , Tajika Makiko , Matsuhashi Tetsuro , Ichimoto Keiko , Matsunaga Ayako , Akiyama Nana , Ogawa-Tominaga Minako , Yatsuka Yukiko , Nitta Kazuhiro R , Kishita Yoshihito , Fushimi Takuya , Imai-Okazaki Atsuko , Ohtake Akira , Okazaki Yasushi , Murayama Kei
Published: October 2021

Objective

Neonatal-onset mitochondrial disease has not been fully characterised owing to its heterogeneity. We analysed neonatal-onset mitochondrial disease in Japan to clarify its clinical features, molecular diagnosis and prognosis.

Design

Retrospective observational study from January 2004 to March 2020.

Setting

Population based.

Patients

Patients (281) with neonatal-onset mitochondrial disease diagnosed by biochemical and genetic approaches.

Interventions

None.

Main outcome measures

Disease types, initial symptoms, biochemical findings, molecular diagnosis and prognosis.

Results

Of the 281 patients, multisystem mitochondrial disease was found in 194, Leigh syndrome in 26, cardiomyopathy in 38 and hepatopathy in 23 patients. Of the 321 initial symptoms, 236 occurred within 2 days of birth. Using biochemical approaches, 182 patients were diagnosed by mitochondrial respiratory chain enzyme activity rate and 89 by oxygen consumption rate. The remaining 10 patients were diagnosed using a genetic approach. Genetic analysis revealed 69 patients had nuclear DNA variants in 36 genes, 11 of 15 patients had mitochondrial DNA variants in five genes and four patients had single large deletion. The Cox proportional hazards regression analysis showed the effects of Leigh syndrome (HR=0.15, 95% CI 0.04 to 0.63, p=0.010) and molecular diagnosis (HR=1.87, 95% CI 1.18 to 2.96, p=0.008) on survival.

Conclusions

Neonatal-onset mitochondrial disease has a heterogenous aetiology. The number of diagnoses can be increased, and clarity regarding prognosis can be achieved by comprehensive biochemical and molecular analyses using appropriate tissue samples.
Changes in exposure to ambient fine particulate matter after relocating and long term survival in Canada: quasi-experimental study
Authors: Chen Hong , Kaufman Jay S , Olaniyan Toyib , Pinault Lauren , Tjepkema Michael , Chen Li , van Donkelaar Aaron , Martin Randall V , Hystad Perry , Chen Chen , Kirby-McGregor Megan , Bai Li , Burnett Richard T , Benmarhnia Tarik
Published: October 2021

Objective

To investigate the association between changes in long term residential exposure to ambient fine particulate matter (PM2.5) and premature mortality in Canada.

Design

Population based quasi-experimental study.

Setting

Canada.

Participants

663 100 respondents to the 1996, 2001, and 2006 Canadian censuses aged 25-89 years who had consistently lived in areas with either high or low PM2.5levels over five years preceding census day and moved during the ensuing five years.

Interventions

Changes in long term exposure to PM2.5arising from residential mobility.

Main outcome measures

The primary outcome was deaths from natural causes. Secondary outcomes were deaths from any cardiometabolic cause, any respiratory cause, and any cancer cause. All outcomes were obtained from the national vital statistics database.

Results

Using a propensity score matching technique with numerous personal, socioeconomic, health, and environment related covariates, each participant who moved to a different PM2.5area was matched with up to three participants who moved within the same PM2.5area. In the matched groups that moved from high to intermediate or low PM2.5areas, residential mobility was associated with a decline in annual PM2.5exposure from 10.6 μg/m3to 7.4 and 5.0 μg/m3, respectively. Conversely, in the matched groups that moved from low to intermediate or high PM2.5areas, annual PM2.5increased from 4.6 μg/m3to 6.7 and 9.2 μg/m3. Five years after moving, individuals who experienced a reduction in exposure to PM2.5from high to intermediate levels showed a 6.8% (95% confidence interval 1.7% to 11.7%) reduction in mortality (2510 deaths in 56 025v4925 deaths in 101 960). A greater decline in mortality occurred among those exposed to a larger reduction in PM2.5. Increased mortality was found with exposure to PM2.5from low to high levels, and to a lesser degree from low to intermediate levels. Furthermore, the decreases in PM2.5exposure were most strongly associated with reductions in cardiometabolic deaths, whereas the increases in PM2.5exposure were mostly related to respiratory deaths. No strong evidence was found for the changes in PM2.5exposure with cancer related deaths.

Conclusions

In Canada, decreases in PM2.5were associated with lower mortality, whereas increases in PM2.5were associated with higher mortality. These results were observed at PM2.5levels considerably lower than many other countries, providing support for continuously improving air quality.
Changes in granule mobility and age contribute to changes in insulin secretion after desensitization or rest
Authors: Gaus Bastian , Brüning Dennis , Hatlapatka Kathrin , Rustenbeck Ingo
Published: October 2021

Introduction

Functional impairment of the stimulus secretion coupling in pancreatic beta cells is an essential component of type 2 diabetes. It is known that prolonged stimulation desensitizes the secretion of insulin and thus contributes to beta cell dysfunction. Beta cell rest, in contrast, was shown to enhance the secretory response. Here, the underlying mechanisms were investigated.

Research design and methods

To characterize the consequences of desensitization or rest for the number and mobility of submembrane granules, insulin-secreting MIN6 cells were desensitized by 18-hour culture with 500 µM tolbutamide or rested by 18-hour culture with 1 µM clonidine. The granules were labeled by hIns-EGFP or hIns-DsRed E5, imaged by TIRF microscopy of the cell footprint area and analyzed with an observer-independent program. Additionally, the insulin content and secretion were measured.

Results

Concurrent with the insulin content, submembrane granules were only slightly reduced after desensitization but markedly increased after rest. Both types of pretreatment diminished arrivals and departures of granules in the submembrane space and increased the proportion of immobile long-term resident granules, but desensitization lowered and rest increased the number of exocytoses, in parallel with the effect on insulin secretion. Labeling with hIns-DsRed E5 (‘timer’) showed that desensitization did not affect the proportion of aged granules, whereas rest increased it. Aged granules showed a high mobility and made up only a minority of long-term residents. Long-term resident granules were more numerous after rest and had a lower lateral mobility, suggesting a firmer attachment to the membrane.

Conclusion

The number, mobility and age of submembrane granules reflect the preceding functional states of insulin-secreting cells. Representing the pool of releasable granules, their quantity and quality may thus form part of the beta cell memory on renewed stimulation.
Glycemic efficacy and safety of the SGLT2 inhibitor ertugliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease: an analysis from the VERTIS CV randomized trial
Authors: Dagogo-Jack Samuel , Pratley Richard E , Cherney David Z I , McGuire Darren K , Cosentino Francesco , Shih Weichung J , Liu Jie , Frederich Robert , Mancuso James P , Raji Annaswamy , Gantz Ira
Published: October 2021

Introduction

Here we report the glycemic efficacy and safety of ertugliflozin in patients in the VERTIS CV cardiovascular outcome trial with chronic kidney disease (CKD) stage 3.

Research design and methods

Prespecified and post-hoc analyses were performed in patients with an estimated glomerular filtration rate (eGFR) 30–<60 mL/min/1.73 m2at screening. The primary endpoint was glycemic efficacy at week 18. Longer term glycemic efficacy and changes in body weight, systolic blood pressure (SBP), and eGFR were also evaluated.

Results

Among 8246 patients in VERTIS CV, 1776 patients had CKD stage 3; 1319 patients had CKD stage 3A (eGFR 45–<60 mL/min/1.73 m2); 457 patients had CKD stage 3B (eGFR 30–<45 mL/min/1.73 m2). Week 18 least squares (LS)-mean (95% CI) placebo-adjusted changes from baseline in glycated hemoglobin (HbA1c) for 5 mg and 15 mg ertugliflozin were −0.27% (−0.37% to –0.17%) and −0.28% (−0.38% to –0.17%), respectively, for CKD stage 3 overall and −0.27% (−0.38% to –0.15%) and −0.31% (−0.43% to –0.19%), respectively, for CKD stage 3A (all p<0.001). For CKD stage 3B, the reduction in HbA1c for 5 mg ertugliflozin was −0.28% (−0.47% to –0.08%) (p=0.006) and for 15 mg ertugliflozin was −0.19% (−0.39% to 0.01%) (p=0.064). LS-mean placebo-adjusted reductions in body weight (range: −1.32 to −1.95 kg) and SBP (range: −2.42 to −3.41 mm Hg) were observed across CKD stage 3 categories with ertugliflozin. After an initial dip, eGFR remained above or near baseline with ertugliflozin treatment. The incidence of overall adverse events (AEs), symptomatic hypoglycemia, hypovolemia, and kidney-related AEs did not differ between ertugliflozin and placebo across CKD stage 3 subgroups.

Conclusions

In VERTIS CV patients with CKD stage 3A, ertugliflozin resulted in reductions in HbA1c, body weight and SBP, maintenance of eGFR, and was generally well tolerated. Results in the CKD stage 3B subgroup were generally similar except for an attenuated HbA1c response with the 15 mg dose.

Trial registration number

NCT01986881.
Association between self-monitoring of blood glucose and hepatitis B virus infection among people with diabetes mellitus: a cross-sectional study in Gansu Province, China
Authors: Han Bingfeng , Liu Wu , Yang Shubo , Wang Shuai , Du Juan , Liu Yaqiong , Cui Fuqiang
Published: October 2021

Objective

The purpose was to explore the association between self-monitoring of blood glucose (SMBG) and hepatitis B virus (HBV) infection among people with diabetes.

Design

A cross-sectional comparative study.

Setting

Six township hospitals in Gansu Province, China in October 2018.

Participants

408 patients with diabetes were systematically recruited, and based on their characteristics 408 people without diabetes were randomly matched 1:1.

Interventions

Venous blood was collected for HBV serological testing and blood glucose testing.

Primary and secondary outcome measures

The primary outcome was comparison of hepatitis B surface antigen (HBsAg) positive rates between the two groups. The secondary outcome was the relationship between frequency of SMBG and HBsAg positivity.

Results

HBsAg positive rate in people without diabetes was 2.0% and in those with diabetes was 4.2%. Whether in people without diabetes or patients with diabetes, higher frequency of SMBG was associated with higher HBsAg positive rate. Increases in the duration of diabetes were correlated with increasing rates of HBsAg. Compared with people without diabetes, logistic regression identified an association between diabetes and HBV infection (OR=2.8; 95% CI 1.0 to 7.6), but impaired fasting glucose was not (OR=2.3; 95% CI 0.5 to 9.9).

Conclusion

Routine blood glucose monitoring at home was associated with HBV infection, which meant people with diabetes may be at high risk of HBV infection. China is a country with high prevalence of both HBsAg and diabetes, and the increased risk of HBV infection in populations with diabetes needs more attention.
Impact of school closures on the health and well-being of primary school children in Wales UK: a routine data linkage study using the HAPPEN Survey (2018–2020)
Authors: James Michaela , Marchant Emily , Defeyter Margaret Anne , Woodside Jayne , Brophy Sinead
Published: October 2021

Objectives

This study aimed to explore the relationship between initial school closures and children’s health by comparing health and well-being outcomes collected during school closures (April–June 2020) via HAPPEN (the Health and Attainment of Pupils in a Primary Education Network) with data from the same period in 2019 and 2018 via the HAPPEN Survey.

Setting

The study was conducted online with 161 primary schools across Wales involved in the ‘HAPPEN At Home’ Survey.

Participants

Data were collected via the ‘HAPPEN At Home’ Survey capturing the typical health behaviours of children aged 8–11 years from 1333 participants across Wales. These data were compared with data in 2018 and 2019 also collected between April and June, from HAPPEN (2019 (n=1150) and 2018 (n=475)).

Primary and secondary outcome measures

Primary outcomes included validated measures of physical activity, screen time, diet and dental health, as well as well-being, competency and autonomy. Free school meal (FSM) status was used as a proxy for socioeconomic deprivation. Analyses were repeated stratifying by FSM.

Results

Comparing responses between April–June in 2020 (n=1068), 2019 (n=1150) and 2018 (n=475), there were improvements in physical activity levels, sleep time, happiness and general well-being for children during school closures compared with previous years. However, children on FSM ate fewer fruits and vegetables (21% less at five or more portions of fruits and vegetables (95% CI: 5.7% to 37%)) and had lower self-assessed school competence compared with 2019. Compared with those not on FSM, they also spent less time doing physical activity (13.03%, 95% CI: 3.3% to 21.7%) and consumed more takeaways (16.3%, 95% CI: 2% to 30%) during school closures.

Conclusions

This study suggests that schools are important in reducing inequalities in physical health. The physical health (eg, physical activity and diet) of children eligible for FSM may be affected by prolonged school closures.