bluuebunny/crossref_metadata_2025 huggingface dataset:
Mind-Body Techniques in Pregnancy and Postpartum
Authors: Oyarzabal Esteban A. , Seuferling Barbara , Babbar Shaweta , Lawton-O’Boyle Shannon , Babbar Shilpa
Published: June 2021

Maternal stress can perturb physiology and psychiatric health leading to adverse outcomes. This review investigates the effectiveness of several mind-body therapies—namely biofeedback, progressive muscle relaxation, guided imagery, tai chi, and yoga—as interventions in reducing maternal stress and other pregnancy-related conditions. Through randomized trials, these techniques have shown promising benefits for reducing pain, high blood pressure, stress, anxiety, depressive symptoms, labor pain and outcomes, and postpartum mood disturbances. As these interventions are easy to implement, low cost, and safe to perform in pregnancy, they should be considered as alternative, nonpharmaceutical interventions to use during pregnancy and postpartum care.
Parents’ Perspective of Antibiotic Usage in Children: A Nationwide Survey in Italy
Authors: Pierantoni Luca , Lo Vecchio Andrea , Lenzi Jacopo , Corsi Vincenza , Campana Lara , Luca Trobia Gian , Amendolea Antonella , Di Felice Benedetta , Alighieri Giovanni , Fabrizio Giovanna Carmela , Bisceglia Massimo , Peia Francesco , Chiale Federica , Bartolomei Beatrice , Siciliano Chiara , Di Battista Caterina , Passone Eva , di Giovanni Chiara , Piergentili Edward , Donà Daniele , Buonsenso Danilo
Published: June 2021

Background:

Antibiotics represent the most widely prescribed drugs in children worldwide, both in hospital and community settings. A comprehensive approach to understanding the reasons and determinants of antibiotic prescription in the pediatric age is needed. This study aimed to assess parents’ attitudes and perspectives about antibiotic use.

Methods:

Prospective observational study was conducted in all Italian Regions between February 1 and April 30, 2020, using a standardized questionnaire.

Results:

Six thousand six hundred twenty-five parents from all Italian regions completed the survey. Seventy-six percent of parents were aware that only bacteria are the target of antibiotics, but 92.9% knew that the antibiotic has no direct effect on fever. Antibiotic self-prescription (10.4%) or by remote consultation by phone call (19.9%) or message (9.6%) were relatively common. Ninety-three percent of parents were aware that excessive use of antibiotics could select resistant bacteria and 84.7% of them knew that they could actively fight antibiotic resistance. About two thirds of participants (66.1%) received information on antibiotic resistance from their family pediatrician. Parents born of Italy or those with lower income had a higher probability of having less information from pediatricians or knowledge of proper antibiotic use.

Discussion:

Our study suggests that parents’ knowledge and attitudes toward antibiotic use and prescription are improving compared with previous studies, while there is still a gap regarding antibiotic resistance, particularly on practices that can reduce its burden. Our study’s negative finding is that families from low-income settings or those born abroad have significantly more misconceptions about important antibiotic practices.
Routine Use of Biomarkers to Rationalize Antibiotic Use During Febrile Episodes in Pediatric Bone Marrow Transplantation Units
Authors: Toro Jessica F. , Peña Eliana , Ramírez Oscar , López Pio , Portilla Carlos A. , López-Medina Eduardo
Published: June 2021

Background:

Children frequently develop fever after hematopoietic stem cell transplant (HSCT). Although the etiology of many febrile episodes (FEs) is not an infection, patients often receive broad-spectrum antibiotics in response.

Methods:

To improve the judicious use of antibiotics in pediatric HSCT patients, we performed a prospective cohort study of children receiving an HSCT in Clínica Imbanaco (Cali, Colombia) between September 2016 and December 2019. We assessed all FEs occurring during 3 periods (infusion, neutropenic and engraftment). We measured procalcitonin and C-reactive protein (CRP) sequentially during each FE and compared levels among patients with fever due to significant infection (FSI) versus fever not attributable to infection (FNI) in each transplant period.

Results:

There were 166 FEs in 95 patients. FSI accounted for 12%, 42% and 42% of FE during infusion, neutropenic and engraftment periods, respectively. CRP had better discriminatory capacity for FSI versus FNI in the infusion period [area under the curve (AUC) 0.80 (95% confidence interval [CI], 0.62–0.96) for a CRP level of 50 mg/L]. Neither biomarker performed well in the neutropenic period. During the engraftment period, a CRP of 65 mg/L had an AUC of 0.81 (95% CI, 0.65–0.96), while a procalcitonin level of 0.25 ng/mL had an AUC of 0.83 (95% CI, 0.63–1.0). In contrast to procalcitonin, the CRP’s pattern of change throughout the first 3 days of fever in each transplant period was different in FSI compared with FNI.

Conclusion:

Sequential measurement of biomarkers, especially CRP, may allow clinicians to more appropriately manage antibiotic use in pediatric HSCT units.
Bannwarth Syndrome
Authors: Dutta Ankhi , Hunter Jill V. , Vallejo Jesus G.
Published: June 2021

Lymphocytic meningoradiculitis (Bannwarth syndrome) is a rare manifestation of Lyme neuroborreliosis in children. It is the most common clinical manifestation of early Lyme neuroborreliosis in adults in European countries where the disease is endemic but is rare in children. We report an imported case of Bannwarth syndrome in a pediatric patient and review the literature for other pediatric cases reported.
Lysophosphatidic acid activates nociceptors and causes pain or itch depending on the application mode in human skin
Authors: Düll Miriam M. , Stengel Martina , Ries Vivien , Strupf Marion , Reeh Peter W. , Kremer Andreas E. , Namer Barbara
Published: June 2021

Lysophosphatidic acid (LPA) is involved in the pathophysiology of cholestatic pruritus and neuropathic pain. Slowly conducting peripheral afferent C-nerve fibers are crucial in the sensations of itch and pain. In animal studies, specialized neurons (“pruriceptors”) have been described, expressing specific receptors, eg, from the Mas-related G-protein-coupled receptor family. Human nerve fibers involved in pain signaling (“nociceptors“) can elicit itch if activated by focalized stimuli such as cowhage spicules. In this study, we scrutinized the effects of LPA in humans by 2 different application modes on the level of psychophysics and single nerve fiber recordings (microneurography). In healthy human subjects, intracutaneous LPA microinjections elicited burning pain, whereas LPA application through inactivated cowhage spicules evoked a moderate itch sensation. Lysophosphatidic acid microinjections induced heat hyperalgesia and hypersensitivity to higher electrical stimulus frequencies. Pharmacological blockade of transient receptor potential channel A1 or transient receptor potential channel vanilloid 1 reduced heat hyperalgesia, but not acute chemical pain. Microneurography revealed an application mode–dependent differential activation of mechanosensitive (CM) and mechanoinsensitive C (CMi) fibers. Lysophosphatidic acid microinjections activated a greater proportion of CMi fibers and more strongly than CM fibers; spicule application of LPA activated CM and CMi fibers to a similar extent but excited CM fibers more and CMi fibers less intensely than microinjections. In conclusion, we show for the first time in humans that LPA can cause pain as well as itch dependent on the mode of application and activates afferent human C fibers. Itch may arise from focal activation of few nerve fibers with distinct spatial contrast to unexcited surrounding afferents and a specific combination of activated fiber subclasses might contribute.
Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder
Authors: dos Santos Rafael G. , Osório Flávia de Lima , Rocha Juliana Mendes , Rossi Giordano Novak , Bouso José Carlos , Rodrigues Lucas S. , de Oliveira Silveira Gabriela , Yonamine Mauricio , Hallak Jaime E. Cecílio
Published: June 2021

Background

Ayahuasca is a classic hallucinogen with anxiolytic and antidepressive properties. Anecdotal evidence also suggests that it improves performance (eg, singing, speech). This controlled trial assessed the effects of ayahuasca on speech performance and anxiety in individuals with social anxiety disorder.

Methods

Seventeen volunteers with social anxiety disorder participated in a pilot, proof-of-concept, randomized, parallel-group trial. Self-perception of performance during a public-speaking test was assessed with the Self-statements During Public Speaking Scale primary outcome). Secondary outcomes included anxiety/subjective effects (Visual Analog Mood Scale; Bodily Symptoms Scale), recognition of emotions in facial expressions (REFE), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. Effects on anxiety and REFE were assessed again 7, 14, and 21 days postdrug.

Findings

Compared with placebo, ayahuasca significantly improved self-perception of speech performance (Self-statements During Public Speaking Scale) and increased somatic symptoms (Bodily Symptoms Scale). There was also a significant time × group interaction in the cognitive deterioration Visual Analog Mood Scale factor and a significant effect of time in the REFE task, especially in reaction time. Other measures were not significantly modified. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting.

Conclusions

Ayahuasca improved self-perception of speech performance in socially anxious individuals. These effects occurred independent of task-related anxiety and REFE, suggesting that ayahuasca could specifically improve the cognitive aspect of speech performance. Further studies should try to unveil the mechanisms involved in the effects of ayahuasca and to better understand its effects on anxiety.
Forensic Nursing Research: The Basics Explained
Authors: Wickwire Karin A. , Valentine Julie L. , Downing Nancy , Cochran Courtney Bagents , Drake Stacy , Sekula L. Kathleen , Jennings Sara
Published: June 2021

As a growing profession, forensic nursing requires research to establish best practice guidelines leading to evidence-based practice. In addition, forensic nursing quality improvement projects are necessary to evaluate and improve practices and policies. The purpose of this article is to provide step-by-step guidelines on research and quality improvement projects to encourage all forensic nurses to actively contribute to and utilize research in practice. Research will expand our forensic nursing science and knowledge base. Ultimately, forensic nursing research will benefit our patients and communities by establishing enhanced, evidence-based care.
Is Interview Length Associated With Blood Test Participation? Evidence From Three Population-Based HIV Impact Assessment Surveys Conducted From 2016 to 2017
Authors: Bray Rachel , Palma Anton M. , Philip Neena M. , Brown Kristin , Levin Bruce , Thompson John L. P. (Seamus) , Ginindza Choice , Mulenga Lloyd B.
Published: June 2021

Background:

High response rates in surveys are critical to ensuring that findings are unbiased and representative of the target population. Questionnaire length affects response rates, with long interviews associated with partially complete surveys, higher item nonresponse (“don't know” and “refuse” responses), and willingness to participate in future surveys. Our aim is to determine the impact of questionnaire length on blood test participation in population-based HIV surveys.

Methods:

Data are from population-based HIV impact assessments conducted in Zambia, Eswatini, and Lesotho in 2016–2017. The population-based HIV impact assessments consist of an interview followed by a blood draw. Consent for blood draw was obtained before the interview in Eswatini and after the interview in Zambia and Lesotho. Interview length was measured by the survey tablet as the time to complete the survey (interview duration) and the number of questions answered by the participant (questionnaire length). We assessed the effects of questionnaire length and interview duration on blood test participation using logistic regression.

Results:

Across all 3 surveys, the median interview duration was 16 minutes and the median number of questions was 77. In adjusted analyses, there was a negative impact of interview duration on blood draw consent for individuals with unknown status in Lesotho and a positive relationship between questionnaire length and blood draw consent in Zambia for those with HIV-negative and unknown status.

Conclusion:

Although interview length is an important consideration to reduce respondent burden, a longer questionnaire does not necessarily result in lower consent rates for blood testing.
Lessons From Rapid Field Implementation of an HIV Population-Based Survey in Nigeria, 2018
Authors: Jahun Ibrahim , Greby Stacie M. , Adesina Tina , Agbakwuru Chinedu , Dalhatu Ibrahim , Yakubu Aminu , Jelpe Tapdiyel , Okoye McPaul , Ikpe Sunday , Ehoche Akipu , Abimiku Alash'le , Aliyu Gambo , Charurat Manhattan , Greenwell Geoffrey , Bronson Megan , Patel Hetal , McCracken Stephen , Voetsch Andrew C. , Parekh Bharat , Swaminathan Mahesh , Adewole Isaac , Aliyu Sani
Published: June 2021

Background:

The need for accurate HIV annual program planning data motivated the compressed timeline for the 2018 Nigerian HIV/AIDS Indicator and Impact Survey (NAIIS). The survey team used stakeholder cooperation and responsive design, using survey process and paradata to refine survey implementation, to quickly collect high-quality data. We describe processes that led to generation of data for program and funding decisions, ensuring HIV services were funded in 2019.

Setting:

Nigeria is the most populous country in Africa, with approximately 195 million people in 36 states and the Federal Capital Territory. Challenges include multiple security threats, poor infrastructure, seasonal rains, and varied health system capacity.

Methods:

Stakeholders worked together to plan and implement NAIIS. Methods from other population-based HIV impact assessments were modified to meet challenges and the compressed timeline. Data collection was conducted in 6 webs. Responsive design included reviewing survey monitoring paradata and laboratory performance. Costs required to correct data errors, for example, staff time and transportation, were tracked.

Results:

NAIIS data collection was completed in 23 weeks, ahead of the originally scheduled 24 weeks. Responsive design identified and resolved approximately 68,000 interview errors, affecting approximately 62,000 households, saving about US$4.4 million in costs. Biweekly field laboratory test quality control improved from 50% to 100% throughout NAIIS.

Conclusions:

Cooperation across stakeholders and responsive design ensured timely release of NAIIS results and informed planning for HIV epidemic control in Nigeria. Based on NAIIS results, funds were provided to place an additional 500,000 HIV-positive Nigerians on antiretroviral therapy by the end of 2020, pushing Nigeria toward epidemic control.
Evolutionary responses to codon usage of horizontally transferred genes in Pseudomonas aeruginosa: gene retention, amelioration and compensatory evolution
Authors: Callens Martijn , Scornavacca Celine , Bedhomme Stéphanie
Published: June 2021

Prokaryote genome evolution is characterized by the frequent gain of genes through horizontal gene transfer (HGT). For a gene, being horizontally transferred can represent a strong change in its genomic and physiological context. If the codon usage of a transferred gene deviates from that of the receiving organism, the fitness benefits it provides can be reduced due to a mismatch with the expression machinery. Consequently, transferred genes with a deviating codon usage can be selected against or elicit evolutionary responses that enhance their integration, such as gene amelioration and compensatory evolution. Within bacterial species, the extent and relative importance of these different mechanisms has never been considered altogether. In this study, a phylogeny-based method was used to investigate the occurrence of these different evolutionary responses in

Pseudomonas aeruginosa

. Selection on codon usage of genes acquired through HGT was observed over evolutionary time, with the overall codon usage converging towards that of the core genome. Gene amelioration, through the accumulation of synonymous mutations after HGT, did not seem to systematically affect transferred genes. This pattern therefore seemed to be mainly driven by selective retention of transferred genes with an initial codon usage similar to that of the core genes. Additionally, variation in the copy number of tRNA genes was often associated with the acquisition of genes for which the observed variation could enhance their expression. This provides evidence that compensatory evolution might be an important mechanism for the integration of horizontally transferred genes.
Optimal Selection of COVID-19 Vaccination Sites at the Municipal Level
Authors: Cabanilla Kurt Izak M. , Enriquez Erika Antonette T. , Mendoza Renier , Mendoza Victoria May P.
Published: June 2021

In this work, we present an approach to determine the optimal location of coronavirus disease (COVID-19) vaccination sites at the municipal level. We assume that each municipality or town is subdivided into smaller administrative units, which we refer to as villages or barangays. The proposed method solves a minimization problem arising from a facility location problem, which is formulated based on the proximity of the vaccination sites to the villages, number of COVID-19 cases, and population densities of the villages. We present a numerical scheme to solve the optimization problem and give a detailed description of the algorithm, which is coded in Python. To make the results reproducible, the codes used in this study are uploaded to a public repository, which also contains complete instructions on how to use them. As an illustration, we apply our method in determining the optimal location of vaccination sites in San Juan, a town in the province of Batangas, in the Philippines. We hope that this study may guide the local government units in coming up with strategic plans for the COVID-19 vaccine rollout.
High Bandwidth Power Electronics and Magnetic Nanoparticles for Multichannel Magnetogenetic Neurostimulation
Authors: Wang Boshuo , Li Zhongxi , Sebesta Charles E. , Hinojosa Daniel Torres , Zhang Qingbo , Robinson Jacob T. , Bao Gang , Peterchev Angel V. , Goetz Stefan M.
Published: June 2021

Objective

We present a power electronic system and magnetic nanoparticles for multiplexed magnetogenetic neurostimulation with three channels spanning a wide frequency range and rapid channel switching capability. This enables selective heating of magnetic nanoparticles with different coercivity using various frequency–amplitude combinations of the magnetic field. Such multiplexed operation could provide the technical means for selective magnetogenetic neurostimulation beyond its spatial focality limits.

Approach

The electronic system uses a hybrid of silicon metal–oxide–semiconductor and gallium-nitride field-effect transistors, which generate the required high-amplitude current up to 500 A in the sub-MHz range and the high-frequency current in the MHz range, respectively. Via three discrete resonance capacitor banks, the system generates an alternating magnetic field in the same liquid-cooled field coil at three distinct frequency channels spanning 50 kHz to 4 MHz. Fast switching between channels is achieved with high-voltage contactors connecting the coil to different capacitor banks. We characterized the system by the output channels’ frequencies, field strength, and switching time, as well as the system’s overall operation stability. Three types of iron oxide nanoparticles with different coercivity are developed to form three magnetothermal channels. Specific absorption rate and infrared thermal imaging measurements are performed with the nanoparticles to characterize their heating and demonstrate selective actuation for all three channels.

Main results

The system achieved the desired target field strengths for three frequency channels (70 kA/m at 50 kHz, 10 kA/m at 500 kHz, and 1 kA/m at ≥2 MHz), with rapid switching speed between channels on the order of milliseconds. The system can operate continuously for at least two hours at 30% duty cycle with 125 Arms load in the coil, corresponding to a stimulation protocol of cycling the three channels at target strength with 3 s pulses and 7 s interpulse intervals. The nanoparticles were heated with selectivity between 2.3× and 9× for their respective frequency channel. The system’s intended use was thus validated with three distinct channels available for magnetothermal heating.

Significance

We describe the first combination of a power electronic system and magnetic nanoparticles that achieves three stimulation channels. Selective actuation of nanoparticles is demonstrated for each channel using the same field coil, including a novel composition responding to magnetic fields in the MHz range. This approach could improve the speed and flexibility of frequency-multiplexed magnetogenetic neural stimulation.
LAP1 supports nuclear plasticity during constrained migration
Authors: Jung-Garcia Yaiza , Maiques Oscar , Rodriguez-Hernandez Irene , Fanshawe Bruce , Domart Marie-Charlotte , Renshaw Matt , Marti Rosa M , Matias-Guiu Xavier , Collinson Lucy M , Sanz-Moreno Victoria , Carlton Jeremy G
Published: June 2021

Metastasis involves dissemination of cancer cells away from a primary tumour and colonisation at distal sites. During this process, cancer cells must negotiate multiple physical constraints imposed by the microenvironment and tissue structure. The biophysical properties of the nucleus must be tuned since they pose a challenge to constrained migration. By analysing nuclear genes upregulated during the acquisition of metastatic potential, we discovered increased expression of the inner nuclear membrane protein LAP1 in metastatic melanoma cells and at the invasive fronts of human primary tumours and in metastases. Human cells express two LAP1 isoforms (LAP1B and LAP1C), which differ in their amino terminus. We found that whereas the longer isoform, LAP1B, binds more strongly to nuclear lamins and has restricted motility within the nuclear envelope, the shorter isoform, LAP1C, favours nuclear envelope blebbing and allows migration through constraints. We propose that LAP1 renders the nucleus plastic and enhances melanoma aggressiveness.
Neuronal hyperactivity in a LRRK2-G2019S cellular model of Parkinson’s Disease
Authors: Lucumi Moreno Edinson , Hachi Siham , Nickels Sarah L. , Kane Khalid I.W. , Moein Masha , Schwamborn Jens C. , Skupin Alexander , Vanden Berghe Pieter , Fleming Ronan M.T.
Published: June 2021

Monogenic Parkinson’s Disease can be caused by a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene, causing a late-onset autosomal dominant inherited form of Parkinson’s Disease. The function of the LRRK2 gene is incompletely understood, but several in vitro studies have reported that LRRK2-G2019S mutations affect neurite branching, calcium homeostasis and mitochondrial function, but thus far, there have been no reports of effects on electrophysiological activity. We assessed the neuronal activity of induced pluripotent stem cell derived neurons from Parkinson’s Disease patients with LRRK2-G2019S mutations and isogenic controls. Neuronal activity of spontaneously firing neuronal populations was recorded with a fluorescent calcium-sensitive dye (Fluo-4) and analysed with a novel image analysis pipeline that combined semi-automated neuronal segmentation and quantification of calcium transient properties. Compared with controls, LRRK2-G2019S mutants have shortened inter-spike intervals and an increased rate of spontaneous calcium transient induction.
Post-Insemination Selection Dominates Pre-Insemination Selection in Driving Rapid Evolution of Male Competitive Ability
Authors: Kasimatis Katja R. , Moerdyk-Schauwecker Megan J. , Lancaster Ruben , Smith Alexander , Willis John H. , Phillips Patrick C.
Published: June 2021

Sexual reproduction is a complex process that contributes to differences between the sexes and divergence between species. From a male’s perspective, sexual selection can optimize reproductive success by acting on the variance in mating success (pre-insemination selection) as well as the variance in fertilization success (post-insemination selection). The balance between pre- and post-insemination selection has not yet been investigated using a strong hypothesis-testing framework that directly quantifies the effects of post-insemination selection on the evolution of reproductive success. Here we use experimental evolution of a uniquely engineered genetic system that allows sperm production to be turned off and on in obligate male-female populations of Caenorhabditis elegans. We show that enhanced post-insemination competition increases the efficacy of selection and surpasses pre-insemination sexual selection in driving a polygenic response in male reproductive success. We find that after 30 generations post-insemination selection increased male reproductive success by an average of 5- to 7-fold. Contrary to expectation, enhanced pre-insemination competition hindered selection and slowed the rate of evolution. Furthermore, we found that post-insemination selection resulted in a strong polygenic response at the whole-genome level. Our results demonstrate that post-insemination sexual selection plays a critical role in the rapid optimization of male reproductive fitness. Therefore, explicit consideration should be given to post-insemination dynamics when considering the population effects of sexual selection.
Alcohol and Vapourized Nicotine Co-Exposure During Adolescence Contribute Differentially to Sex-Specific Behavioural Effects in Adulthood
Authors: Ruffolo Jessica , Frie Jude A. , Thorpe Hayley H.A. , Talhat M. Asfandyaar , Khokhar Jibran Y.
Published: June 2021

Introduction

Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. However, little is known about their long-lasting effects when combined. Here, we examined whether adolescent co-exposure to alcohol drinking and vapourized nicotine would impact reward- and cognition-related behaviours in adult male and female rats during adulthood.

Methods

Four groups of male and female Sprague Dawley rats (n=8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapour daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, rats underwent behavioural testing utilizing Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference test.

Results

A sex-dependent effect was found in the two-bottle preference test in adulthood such that females had a higher intake and preference for alcohol compared to males regardless of adolescent exposure; both male and female adult rats had greater alcohol preference compared to adolescents. Male rats exposed to vapourized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behaviour. Male rats that drank alcohol with or without nicotine vapour in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapour during adolescence.

Conclusions

The present study provides evidence that co-exposure to alcohol and vapourized nicotine during adolescence in male, but not female, rats produces longterm changes in reward- and cognition-related behaviours.

Implications

These findings enhance our understanding of the effects of alcohol drinking and nicotine vapour exposure in adolescence. Moreover, they highlight potential sex differences that exist in the response to alcohol and nicotine vapour, underscoring the need for follow-up studies elucidating the neurobiological mechanisms that drive these sex differences, as well as the long-term effects of alcohol and nicotine vapour use.
Comparative Structural Analyses of Selected Spike Protein-RBD Mutations in SARS-CoV-2 Lineages
Authors: Roy Urmi
Published: June 2021

The severity of the covid 19 has been observed throughout the world as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had spread globally claiming more than 2 million lives and left a devastating impact on peoples’ life. Recently several virulent mutant strains of this virus, such as the B.1.1.7, B.1.351, and P1 lineages have emerged. These strains are predominantly observed in UK, South Africa and Brazil. Another extremely pathogenic B.1.617 lineage and its sub-lineages, first detected in India, are now affecting some countries at notably stronger spread-rates. This paper computationally examines the time-based structures of B.1.1.7, B.1.351, P1 lineages with selected spike protein mutations. Additionally, the mutations in the more recently found B.1.617 lineage and some of its sub-lineages are explored, and the implications for multiple point mutations of the spike protein’s receptor-binding domain (RBD) are described.
An F-actin mega-cable supports the migration of the sperm nucleus during the fertilization of the polarity-inverted central cell of Agave inaequidens
Authors: González-Gutiérrez Alejandra G. , Gutiérrez-Mora Antonia , Verdín Jorge , Rodríguez-Garay Benjamín
Published: June 2021

Asparagaceae’s large embryo sacs display a central cell nucleus polarized toward the chalaza, which means the sperm nucleus that fuses it during double fertilization migrates a long distance before karyogamy. Because of the size and inverted polarity of the central cell in Asparagaceae, we hypothesize that the second fertilization process is supported by F-actin structures different from the short-range aster-like ones observed in Arabidopsis. Here, we analyzed the F-actin dynamics of Agave inaequidens, a typical Asparagaceae, before, during, and after central cell fertilization. Several parallel F-actin cables emerging from the nucleus within the central cell, enclosing the vacuole, and reaching the micropylar pole were observed. As fertilization progressed, a thick F-actin mega-cable traversing the vacuole appeared, connecting the central cell nucleus with the micropylar pole near the egg cell. This mega-cable wrapped the sperm nucleus in transit to fuse the central cell one. Once karyogamy finished, the mega-cable disassembled, but new F-actin structures formed during the endosperm development. These observations suggest that Asparagaceae, and probably other plant species with similar embryo sacs, evolved an F-actin machinery specifically adapted to support the migration of the fertilizing sperm nucleus within a large-sized and polarity-inverted central cell.
Dendrimer-like supramolecular assembly of proteins with a tunable size and valency through stepwise iterative growth
Authors: Bae Jin-Ho , Kim Hong-Sik , Kim Gijeong , Song Ji-Joon , Kim Hak-Sung
Published: June 2021

The assembly of proteins in a programmable manner provides insight into the underlying mechanisms of protein self-assembly in nature as well as the creation of novel functional nanomaterials for practical applications. Despite many advances, however, a rational protein assembly with an easy scalability in terms of size and valency remains a challenging task. Here, we present a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner. The dendrimer-like protein assembly, called a “prodrimer,” was constructed using a total of three monomeric proteins: a core and two building-block proteins. The prodrimer generations were grown by a stepwise and alternate addition of a building block using two pairs of orthogonal protein-peptide interactions, leading to a higher-generation prodrimer with a mega-dalton size and multi-valency. The valency of the prodrimers at the periphery was tunable with the generation, enabling a single-step functionalization. A second-generation prodrimer functionalized with a target-specific protein binder showed a three-order of magnitude increase in binding affinity compared to a monomeric counterpart due to the avidity. The prodrimers functionalized with a targeting moiety and a cytotoxic protein cargo exhibited a highly enhanced cellular cytotoxicity, exemplifying their utility as a protein delivery platform. The present approach can be effectively used in the creation of protein architectures with new functions for biotechnological and medical applications.
How does the brain represent the semantic content of an image?
Authors: Xu Huawei , Liu Ming , Zhang Delong
Published: June 2021

Using deep neural networks (DNNs) as models to explore the biological brain is controversial, which is mainly due to the impenetrability of DNNs. Inspired by neural style transfer, we circumvented this problem by using deep features that were given a clear meaning—the representation of the semantic content of an image. Using encoding models and the representational similarity analysis, we quantitatively showed that the deep features which represented the semantic content of an image mainly predicted the activity of voxels in the early visual areas (V1, V2, and V3) and these features were essentially depictive but also propositional. This result is in line with the core viewpoint of the grounded cognition to some extent, which suggested that the representation of information in our brain is essentially depictive and can implement symbolic functions naturally.
SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury
Authors: Wu Meng-Li , Liu Feng-Liang , Sun Jing , Li Xin , He Xiao-Yan , Zheng Hong-Yi , Pei Rong-Juan , Sun Hao , Zhou Yan-Heng , Yan Qi-Hong , Wu Cai-Xia , Chen Ling , Yu Guo-Ying , Chang Junbiao , Jin Xia , Zhao Jincun , Chen Xin-Wen , Zheng Yong-Tang , Wang Jian-Hua
Published: June 2021

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.

Graphical abstract

In Brief

SARS-CoV-2 triggers an immediate mast cell (MC) degranulation, which initiates the alveolar epithelial inflammation and disrupts the tight junction. MC stabilizers that block degranulation reduce virus-induced lung inflammation and injury.

Highlights

The binding of RBD of Spike protein of SARS-CoV-2-to ACE2 receptor protein triggers an immediate MC degranulation

MC degranulation induces transcriptomic changes include an upregulated inflammatory signaling and a downregulated cell-junction signaling

MC degranulation leads to alveolar epithelial inflammation and disruption of tight junctions

MC stabilizer that inhibits degranulation reduces SARS-CoV-2-induced lung inflammation and injury in vivo
Context coding in the mouse nucleus accumbens modulates motivationally-relevant information
Authors: Gmaz Jimmie M. , van der Meer Matthijs A. A.
Published: June 2021

Neural activity in the nucleus accumbens (NAc) is thought to track fundamentally value-centric quantities such as current or future expected reward, reward prediction errors, the value of work, opportunity cost, and approach vigor. However, the NAc also contributes to flexible behavior in ways that are difficult to explain based on value signals alone, raising the question of if and how non-value signals are encoded in NAc. We recorded NAc neural ensembles while head-fixed mice performed a biconditional discrimination task where context-setting cues modulated the stimulus-outcome association of subsequently presented reward-predictive cues. We extracted single-unit and population-level correlates of task features, and found value-independent coding for the context cues. This context signal occupied a subspace orthogonal to outcome-predictive representations, and was predictive of subsequent behaviorally-relevant coding. Together, these findings support a circuit-level gating model for how the NAc contributes to behavioral flexibility and provide a novel population-level perspective from which to view NAc computations.
Machine Learning based Genome-Wide Association Studies for Uncovering QTL Underlying Soybean Yield and its Components
Authors: Yoosefzadeh-Najafabadi Mohsen , Torabi Sepideh , Torkamaneh Davoud , Tulpan Dan , Rajcan Istvan , Eskandari Milad
Published: June 2021

Genome-wide association study (GWAS) is currently one of the important approaches for discovering quantitative trait loci (QTL) associated with traits of interest. However, insufficient statistical power is the limiting factor in current conventional GWAS methods for characterizing quantitative traits, especially in narrow genetic bases plants such as soybean. In this study, we evaluated the potential use of machine learning (ML) algorithms such as support vector machine (SVR) and random forest (RF) in GWAS, compared with two conventional methods of mixed linear models (MLM) and fixed and random model circulating probability unification (FarmCPU), for identifying QTL associated with soybean yield components. In this study, important soybean yield component traits, including the number of reproductive nodes (RNP), non-reproductive nodes (NRNP), total nodes (NP), and total pods (PP) per plant along with yield and maturity were assessed using 227 soybean genotypes evaluated across four environments. Our results indicated SVR-mediated GWAS outperformed RF, MLM and FarmCPU in discovering the most relevant QTL associated with the traits, supported by the functional annotation of candidate gene analyses. This study for the first time demonstrated the potential benefit of using sophisticated mathematical approaches such as ML algorithms in GWAS for identifying QTL suitable for genomic-based breeding programs.
Familial Danish dementia young Knock-in rats expressing humanized APP and human Aβ show impaired pre and postsynaptic glutamatergic transmission
Authors: Yin Tao , Yao Wen , Norris Kelly A. , D’Adamio Luciano
Published: June 2021

Familial British and Danish dementia (FBD and FDD) are two neurodegenerative disorders caused by mutations in the Integral membrane protein 2B (ITM2b). BRI2, the protein encoded by ITM2b, tunes excitatory synaptic transmission at both pre- and post-synaptic terminus. Too, BRI2 interacts with and modulates proteolytic processing of Amyloid-β precursor Protein (APP), whose mutations cause familial forms of Alzheimer disease (FAD). To study pathogenic mechanism triggered by the Danish mutation we generated rats carrying the Danish mutation into the rat Itm2b gene (Itm2bD rats). Given the BRI2/APP interaction and the widely accepted relevance of human Aβ, a proteolytic product of APP, to AD, Itm2bD rats were engineered to express two humanized App alleles, to produce human Aβ. Here, we studied young Itm2bD rats to investigate early pathogenic changes. We found that peri-adolescent Itm2bD rats present subtle changes in human Aβ levels along with decreased spontaneous glutamate release and AMPAR-mediated responses but increased short-term synaptic facilitation in the hippocampal Schaeffer-collateral pathway. These changes are like those observed in adult mice producing rodent Aβ and carrying either the Danish or British mutations into the mouse Itm2b gene. Collectively, the data show that the pathogenic Danish mutation alters the physiological function of BRI2 at glutamatergic synapses; these functional alterations are detected across species and occur early in life. Future studies will be needed to determine whether this phenomenon represents an early pathogenic event in human dementia.
Autophagy in stromal fibroblasts promotes tumor desmoplasia and mammary tumorigenesis
Authors: Rudnick Jenny A. , Monkkonen Teresa , Mar Florie A. , Barnes James M. , Starobinets Hanna , Goldsmith Juliet , Roy Srirupa , Bustamante Eguiguren Sofía , Weaver Valerie M. , Debnath Jayanta
Published: June 2021

Autophagy inhibitors are currently being evaluated in clinical trials for the treatment of diverse cancers, largely due to their ability to impede tumor cell survival and metabolic adaptation. More recently, there is growing interest in whether and how modulating autophagy in the host stroma influences tumorigenesis. Fibroblasts play prominent roles in cancer initiation and progression, including depositing type 1 collagen and other extracellular matrix (ECM) components, thereby stiffening the surrounding tissue to enhance tumor cell proliferation and survival, as well as secreting cytokines that modulate angiogenesis and the immune microenvironment. This constellation of phenotypes, pathologically termed desmoplasia, heralds poor prognosis and reduces patient survival. Using mouse mammary cancer models and syngeneic transplantation assays, we demonstrate that genetic ablation of stromal fibroblast autophagy significantly impedes fundamental elements of the stromal desmoplastic response, including collagen and proinflammatory cytokine secretion, extracellular matrix stiffening, and neoangiogenesis. As a result, autophagy in stromal fibroblasts is required for mammary tumor growth in vivo, even when the cancer cells themselves remain autophagy-competent . We propose the efficacy of autophagy inhibition is shaped by this ability of host stromal fibroblast autophagy to support tumor desmoplasia.
The impact of hybridity on PPP governance and related accountability mechanisms: the case of UK education PPPs
Authors: Stafford Anne , Stapleton Pamela
Published: June 2021

Purpose

Contemporary organisational landscapes offer opportunities for hybrids to thrive. Public–private partnerships (PPPs) are one thriving hybrid form incorporating the use of resources and/or structures from both public and private sectors. The study examines the impact of such a hybrid structure on governance and accountability mechanisms in a context of institutional complexity.

Design/methodology/approach

This study uses an approach that draws on institutional logics and hybridity to examine governance arrangements in the PPP policy created for the delivery of UK schools. Unusually, it employs a comparative case study of how four local governments implemented the policy. It draws on a framework developed by Polzeret al.(2017) to examine the level of engagement between multiple logics and hybrid structures and applies this to the delivery of governance and accountability for public money.

Findings

The Polzeret al.framework enables a study of how the nature of hybrids can vary in terms of their governance, ownership and control relations. The findings show how the relationships between levels of engagement of multiple logics and hybrid structures can impact on governance and accountability for public money. Layering and blending combinations led to increased adoption of private sector accountability structures, whilst a hybrid with parallel co-existence of community and market logics delivered a long-term governance structure.

Research limitations/implications

The paper examines the operation of hybrids in a complex education PPP environment in only four local governments and therefore cannot provide representative answers across the population as a whole. However, given the considerable variation found across the four examples, the paper shows there can be significant differentiation in how multiple logics engage at different levels and in varying combinations even in the same hybrid setting. The paper focuses on capital investment implementation and its evaluation, so it is a limitation that the operational stage of PPP projects is not studied.

Practical implications

The findings have political relevance because the two local government bodies with more robust combinations of multiple logics were more successful in getting funds and delivering schools in their geographical areas.

Originality/value

The study extends Polzeret al.'s (2017) research on hybridity by showing that there can be significant differentiation in how multiple logics engage at different levels and in varying combinations even in what was planned to be the same hybrid setting. It shows how in situations of institutional complexity certain combinations of logics lead to differentiation in governance and accountability, creating fragmented focus on the related public accountability structures. This matters because it becomes harder to hold government to account for public spending.
The development, implementation and challenges to water-saving practices in a water-stressed destination: a case study of the Songkran Festival, Thailand
Authors: Intason Montira , Coetzee Willem , Lee Craig
Published: June 2021

Purpose

The contradiction between the purpose of the water-splashing tradition, the use of water in a water-stressed destination and overconsumption during a time of water shortage led the researchers to question the spirit of the Songkran Festival. It is important to keep the spirit of the festival alive without interrupting the livelihoods of the community and to critically engage with opportunities and challenges related to water-saving practices during the festival. Thus, this study aims to investigate the opportunities and challenges to responsible practices of water-saving at a cultural festival, using a case study of the water-splashing practice at the Songkran Festival in Thailand.

Design/methodology/approach

This study used the cultural practice, namely, the water-splashing tradition at the Songkran Festival in Thailand, as a case study. The researchers conducted document analysis on local newspapers, the Bangkok Post specifically and participant observation at the Songkran Festival in the Khao San Road area in Bangkok, to gain first-hand insights to develop comprehensive results which answers the study’s objectives.

Findings

The key findings show three significant themes representing the opportunities for implementing sustainable water-saving practices; a call for a water-saving campaign, education on water saving and water-splashing restrictions. In terms of challenges to implementing water-saving practices, two key themes emerged; a lack of water stress and drought awareness and the hedonistic characteristic of water splashing. The study findings provide important implications to theory and practice for sustainable event management and provide considerations for event stakeholders to minimise water overuse in festivals.

Originality/value

Environmental degradation is a key global issue that the United Nations addresses in the Sustainable Development Goals (SDGs) scheme (United Nations Development Program, 2016). According to Pereira et al. (2009), water scarcity can be caused by both human activities and natural causes. Factors such as unlimited water consumption, population growth and climate change are some of the contributing factors that not only affects resident's access to water but also on events hosted within communities. It is crucial that event managers critically re-think the way festivals are designed in water-stressed destinations.