bluuebunny/crossref_metadata_2025 huggingface dataset:
The Psychopathology, Depression, and Anxiety Levels of Children and Adolescents With Vasovagal Syncope
Authors: Kara Aziz , Doğan Melih Timuçin
Published: April 2021

Vasovagal syncope constitutes 61% to 80% of syncope cases in the pediatric age group. Syncope is frequently associated with psychopathologies such as depressive disorders, anxiety disorders, somatization disorders, etc. Our study aims to evaluate vasovagal syncope cases in terms of additional psychopathologies, depression, and anxiety levels with a control group. A total of 97 people were included in the study (47 cases and 50 controls). After conducting a cardiological examination, the participants were evaluated for psychopathologies using Kiddie-Sads-Present and Lifetime Version, Child Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. The case group had a higher rate of psychopathology compared with the control group. Depression, social anxiety disorder, generalized anxiety disorder, separation anxiety, and conversion disorder were significantly higher in the case group than in the control group. Syncope in children can be an underlying psychopathology or the clinical manifestation of a psychosomatic condition. Psychological assessment, which could offer beneficial contributions to the diagnosis and treatment of syncope, was considered necessary for a holistic evaluation of patients.
Specific Phobia
Authors: Wetzer Guido , ten Have Margreet , de Graaf Ron , Batelaan Neeltje M. , van Balkom Anton J.L.M.
Published: April 2021

Predicting the onset and persistence of psychopathology and limited functioning might enable personalized care. Specific phobia (SP) might serve as a predictor, but this needs further evaluation. Participants of the Netherlands Mental Health Survey and Incidence Study-2 were divided into three groups: no-SP (n = 6094), history of SP (n = 204), and current SP (n = 348). Results showed that current SP was associated with a higher prevalence of other anxiety disorders, mood and substance use disorders, and lower levels of functioning. The 6-year onset of other anxiety disorders was associated with history and current SP. Current-SP was also associated with the onset of mood disorders. Neuroticism and childhood trauma only partly accounted for these associations. To conclude, SP was independently associated with presence and onset of other disorders and with limited functioning over time. The presence of SP may serve as an identifier of persons vulnerable to the development of other psychopathologies.
Effectivity of a Program for the Control and Prevention of COVID-19 Healthcare-Associated Infections in a Spanish Academic Hospital
Authors: Gras-Valentí Paula , Mora-Muriel Juan G. , Chico-Sánchez Pablo , Algado-Sellés Natividad , Soler-Molina Victor M. , Hernández-Maldonado María , Lameiras-Azevedo Ana S. , Jiménez Sepúlveda Natali J. , Gómez Sotero Isel L. , Villanueva-Ruiz César O. , Barrenengoa-Sañudo Julio , Fuster-Pérez Marina , Cánovas-Jávega Sandra , Cerezo-Milan Patricia , Monerris-Palmer Miranda , Llorens-Soriano Pere , Merino-Lucas Esperanza , Rodríguez-Diaz Juan C. , Gil-Carbonell Joan , Sánchez-Martínez Rosario , Pastor-Cesteros Rogelio , Mena-Esquivias Luis , Galiana-Ivars Maria , Jaime-Sánchez Francisco A. , Margarit-Ferri Cesar , Gonzalez-deDios Javier , Lloret German , García-Alonso Miguel A. , Sánchez-Vela Pablo , Sánchez-Payá José
Published: April 2021

Background

Although recommendations to prevent COVID-19 healthcare-associated infections (HAIs) have been proposed, data on their effectivity are currently limited.

Objective

The aim was to evaluate the effectivity of a program of control and prevention of COVID-19 in an academic general hospital in Spain.

Methods

We captured the number of COVID-19 cases and the type of contact that occurred in hospitalized patients and healthcare personnel (HCP). To evaluate the impact of the continuous use of a surgical mask among HCP, the number of patients with COVID-19 HAIs and accumulated incidence of HCP with COVID-19 was compared between the preintervention and intervention periods.

Results

Two hundred fifty-two patients with COVID-19 have been admitted to the hospital. Seven of them had an HAI origin (6 in the preintervention period and 1 in the intervention period). One hundred forty-two HCP were infected with SARS-CoV-2. Of them, 22 (15.5%) were attributed to healthcare (2 in the emergency department and none in the critical care departments), and 120 (84.5%) were attributed to social relations in the workplace or during their non–work-related personal interactions. The accumulated incidence during the preintervention period was 22.3 for every 1000 HCP and 8.2 for every 1000 HCP during the intervention period. The relative risk was 0.37 (95% confidence interval, 0.25 to 0.55) and the attributable risk was −0.014 (95% confidence interval, −0.020 to −0.009).

Conclusions

A program of control and prevention of HAIs complemented with the recommendation for the continuous use of a surgical mask in the workplace and social environments of HCP effectively decreased the risk of COVID-19 HAIs in admitted patients and HCP.
Estrogen as a Safe Therapeutic Adjunct in Reducing the Inflammatory Storm in Trauma Hemorrhagic Shock Patients
Authors: Gupta Dablu Lal , Tiwari Shrestha , Sinha Tej Prakash , Soni Kapil Dev , Galwankar Sagar , Kumar Subodh , Rao D.N , Bhoi Sanjeev
Published: April 2021

Trauma is a major cause of death and disability throughout the world. It is a leading cause of death with or without sepsis in about 50% of patients. Limited therapeutic options are available besides definitive care with a mortality benefit. Preclinical studies have demonstrated the mortality benefit of estrogen in trauma hemorrhagic shock (THS). Based on encouraging results from preclinical studies, we hypothesized that early administration of estrogen in male THS patients may reduce the inflammatory storm, prevent sepsis-associated problems, and subsequently reduce mortality. The authors studied the safety of early administration of estrogen as a therapeutic adjunct in the emergency department (ED) and its effects on the inflammatory storm, prevention of sepsis, and mortality during the intensive care unit stay. Forty THS patients were recruited. THS patients were divided into experimental and placebo control groups based on the estrogen administration in the ED. Serum levels of cytokines and immune cells were measured at different time points on days 0, 3, 7, and 14 in both groups of THS patients. The experimental group received intravenous estrogen (25 mg) at a single time point in the ED beside standard of care as per advanced trauma life support guidelines. Patients did not develop any major or minor adverse events and showed favorable clinical outcomes in the experimental group. The levels of T regulatory cells, monocytes, and systemic cytokines significantly reduced and showed a balanced inflammatory response in THS patients who received estrogen.

In conclusion, this preliminary study showed that intravenous estrogen therapy is safe and reduced the inflammatory insult due to trauma hemorrhagic shock. It may protect THS patients from sepsis-associated complications. Future clinical trials are required to study the efficacy and mechanistic pathway.
Electroconvulsive Therapy for Patients With Depression Who Lack Capacity for Consent
Authors: Takamiya Akihiro , Bouckaert Filip , Sienaert Pascal , Uchida Takahito , Kudo Shun , Yamagata Bun , Kishimoto Taishiro , Mimura Masaru , Hirano Jinichi
Published: April 2021

Objective

Electroconvulsive therapy (ECT) is provided in real-world clinical settings for patients lacking capacity for consent. The aim of this study was to investigate the clinical characteristics and clinical effectiveness of ECT in this population.

Methods

A retrospective chart review was conducted to collect data from patients who received ECT to treat their depressive episodes between April 2012 and March 2019. Differences in clinical characteristics and short-/long-term clinical outcomes between patients who received ECT with their relatives' consent and patients who received ECT by their own consent were examined. The short-/long-term clinical outcomes were determined by clinical global impression scores and readmission rate, respectively.

Results

Of 168 patients with depressive episodes, 34 (20.2%) received ECT with their relatives' consent. Those patients were older, had lower body mass index, and had shorter episode duration. They also exhibited more frequent psychotic, melancholic, and catatonic features. The main indication for ECT in this population was the need for rapid recovery. Patients lacking capacity for consent showed similar remission (61.8%) and response (82.4%) rates to those with capacity for consent. Readmission rate was not significantly different between groups.

Conclusions

There were no significant differences in short-/long-term ECT effectiveness between patients with/without capacity for consent. Electroconvulsive therapy is the only established and effective treatment in clinical settings for the most severe cases, wherein patients are incapable of giving consent but need rapid recovery. A general rejection of this practice due to concerns surrounding consent may be unethical under the ethical principles of medical care.
Entropic stochastic resonance induced by a transverse driving force
Authors: Du L. C. , Yue W. H. , Jiang J. H. , Yang L. L. , Ge M. M.
Published: April 2021

The phenomenon of entropic stochastic resonance (ESR) is investigated with the presence of a time-periodic force in the transverse direction. Simulation results manifest that the ESR can survive even if there is no static bias force in any direction, just if a transverse driving field is applied. In the weak noise region, the transverse driving force leads to a giant-suppression of the escape rate from one well to another, i.e. the entropic trapping. The increase in noise intensity will eliminate this suppression and induce the ESR phenomenon. An alternative quantity, called the mean free flying time, is also proposed to characterize the ESR as well as the conventional spectral power amplification. The ESR can be modulated conveniently by the transverse periodic force, which implies an alternative method for controlling the dynamics of small-scale systems.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
Characterizing stochastic resonance in a triple cavity
Authors: Mei Ruoxing , Xu Yong , Li Yongge , Kurths Jürgen
Published: April 2021

Many biological systems possess confined structures, which produce novel influences on the dynamics. Here, stochastic resonance (SR) in a triple cavity that consists of three units and is subjected to noise, periodic force and vertical constance force is studied, by calculating the spectral amplificationηnumerically. Meanwhile, SR in the given triple cavity and differences from other structures are explored. First, it is found that the cavity parameters can eliminate or regulate the maximum ofηand the noise intensity that induces this maximum. Second, compared to a double cavity with similar maximum/minimum widths and distances between two maximum widths as the triple cavity,ηin the triple one shows a larger maximum. Next, the conversion of the natural boundary in the pure potential to the reflection boundary in the triple cavity will create the necessity of a vertical force to induce SR and lead to a decrease in the maximum ofη. In addition,ηmonotonically decreases with the increase of the vertical force and frequency of the periodic force, while it presents several trends when increasing the periodic force’s amplitude for different noise intensities. Finally, our studies are extended to the impact of fractional Gaussian noise excitations.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
Stochastic and vibrational resonance in complex networks of neurons
Authors: Calim Ali , Palabas Tugba , Uzuntarla Muhammet
Published: April 2021

The concept of resonance in nonlinear systems is crucial and traditionally refers to a specific realization of maximum response provoked by a particular external perturbation. Depending on the system and the nature of perturbation, many different resonance types have been identified in various fields of science. A prominent example is in neuroscience where it has been widely accepted that a neural system may exhibit resonances at microscopic, mesoscopic and macroscopic scales and benefit from such resonances in various tasks. In this context, the two well-known forms are stochastic and vibrational resonance phenomena which manifest that detection and propagation of a feeble information signal in neural structures can be enhanced by additional perturbations via these two resonance mechanisms. Given the importance of network architecture in proper functioning of the nervous system, we here present a review of recent studies on stochastic and vibrational resonance phenomena in neuronal media, focusing mainly on their emergence in complex networks of neurons as well as in simple network structures that represent local behaviours of neuron communities. From this perspective, we aim to provide a secure guide by including theoretical and experimental approaches that analyse in detail possible reasons and necessary conditions for the appearance of stochastic resonance and vibrational resonance in neural systems.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
Suppression of galloping oscillations by injecting a high-frequency excitation
Authors: Alhadidi Ali H. , Khazaaleh Shadi , Daqaq Mohammed F.
Published: April 2021

Galloping is an aeroelastic instability which incites oscillatory motion of elastic structures when subjected to an incident flow. Because galloping is often detrimental to the integrity of the structure, many research studies have focused on investigating methodologies to suppress these oscillations. These include using passive energy sinks, altering the surface characteristics of the structure, actively changing the shape of the boundary layer through momentum injection and using feedback control algorithms. In this paper, we demonstrate that the critical flow speed at which galloping is activated can be substantially increased by subjecting the galloping structure to a high-frequency non-resonant base excitation. The average effect of the high-frequency excitation is to produce additional linear damping in the slow response which serves to suppress the galloping instability. We study this approach theoretically and demonstrate its effectiveness using experimental tests performed on a galloping cantilevered structure. It is demonstrated that the galloping speed can be tripled in some experimental cases.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
The response of a bistable energy harvester to different excitations: the harvesting efficiency and links with stochastic and vibrational resonances
Authors: Khovanov I. A.
Published: April 2021

Energy harvesting of ambient vibrations using a combination of a mechanical structure (oscillator) and an electrical transducer has become a valuable technique for powering small wireless sensors. Bistable mechanical oscillators have recently attracted the attention of researchers as they can be used to harvest energy within a wider band of frequencies. In this study, the response of a bistable harvester to different forms of ambient vibration is analysed. In particular, harmonic noise, which has a narrow spectrum, similarly to harmonic signals, yet is stochastic, like broad-spectrum white noise, is considered. Links between bistable harvester responses and stochastic and vibrational resonance are explored.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
Vibrational resonance in a neuron–astrocyte coupled model
Authors: Calim Ali , Longtin Andre , Uzuntarla Muhammet
Published: April 2021

Recent findings have revealed that not only neurons but also astrocytes, a special type of glial cells, are major players of neuronal information processing. It is now widely accepted that they contribute to the regulation of their microenvironment by cross-talking with neurons via gliotransmitters. In this context, we here study the phenomenon of vibrational resonance in neurons by considering their interaction with astrocytes. Our analysis of a neuron–astrocyte pair reveals that intracellular dynamics of astrocytes can induce a double vibrational resonance effect in the weak signal detection performance of a neuron, exhibiting two distinct wells centred at different high-frequency driving amplitudes. We also identify the underlying mechanism of this behaviour, showing that the interaction of widely separated time scales of neurons, astrocytes and driving signals is the key factor for the emergence and control of double vibrational resonance.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
Vibrational and stochastic resonances in driven nonlinear systems: part 2
Authors: Vincent U. E. , McClintock P. V. E. , Khovanov I. A. , Rajasekar S.
Published: April 2021

Nonlinearity is ubiquitous in both natural and engineering systems. The resultant dynamics has emerged as a multidisciplinary field that has been very extensively investigated, due partly to the potential occurrence of nonlinear phenomena in all branches of sciences, engineering and medicine. Driving nonlinear systems with external excitations can yield a plethora of intriguing and important phenomena—one of the most prominent being that of resonance. In the presence of additional harmonic or stochastic excitation, two exotic forms of resonance can arise: vibrational resonance or stochastic resonance, respectively. Several promising state-of-the-art technologies that were not covered in part 2 of this theme issue are discussed here. They include
inter alia
the improvement of image quality, the design of machines and devices that exert vibrations on materials, the harvesting of energy from various forms of ambient vibration and control of aerodynamic instabilities. They form an important part of the theme issue as a whole, which is dedicated to an overview of vibrational and stochastic resonances in driven nonlinear systems.

This article is part of the theme issue ‘Vibrational and stochastic resonance in driven nonlinear systems (part 2)’.
Genome-wide analysis in Escherichia coli unravels a high level of genetic homoplasy associated with cefotaxime resistance
Authors: Coolen Jordy P. M. , den Drijver Evert P. M. , Verweij Jaco J. , Schildkraut Jodie A. , Neveling Kornelia , Melchers Willem J. G. , Kolwijck Eva , Wertheim Heiman F. L. , Kluytmans Jan A. J. W. , Huynen Martijn A.
Published: April 2021

Cefotaxime (CTX) is a third-generation cephalosporin (3GC) commonly used to treat infections caused by

Escherichia coli

. Two genetic mechanisms have been associated with 3GC resistance in

E. coli

. The first is the conjugative transfer of a plasmid harbouring antibiotic-resistance genes. The second is the introduction of mutations in the promoter region of the ampC β-lactamase gene that cause chromosome-encoded β-lactamase hyperproduction. A wide variety of promoter mutations related to AmpC hyperproduction have been described. However, their link to CTX resistance has not been reported. We recultured 172 cefoxitin-resistant

E. coli

isolates with known CTX minimum inhibitory concentrations and performed genome-wide analysis of homoplastic mutations associated with CTX resistance by comparing Illumina whole-genome sequencing data of all isolates to a PacBio sequenced reference chromosome. We mapped the mutations on the reference chromosome and determined their occurrence in the phylogeny, revealing extreme homoplasy at the −42 position of the ampC promoter. The 24 occurrences of a T at the −42 position rather than the wild-type C, resulted from 18 independent C>T mutations in five phylogroups. The −42 C>T mutation was only observed in

E. coli

lacking a plasmid-encoded ampC gene. The association of the −42 C>T mutation with CTX resistance was confirmed to be significant (false discovery rate <0.05). To conclude, genome-wide analysis of homoplasy in combination with CTX resistance identifies the −42 C>T mutation of the ampC promotor as significantly associated with CTX resistance and underlines the role of recurrent mutations in the spread of antibiotic resistance.
Combinatorial approach with mass spectrometry and lectin microarray dissected glycoproteomic features of virion-derived spike protein of SARS-CoV-2
Authors: Hiono Takahiro , Tomioka Azusa , Kaji Hiroyuki , Sasaki Michihito , Orba Yasuko , Sawa Hirofumi , Kuno Atsushi
Published: April 2021

The COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has a global impact on public health. Since glycosylation of the viral envelope glycoproteins is known to be deeply associated with their immunogenicity, intensive studies on the glycans of its major glycoprotein, S protein, have been conducted. Nevertheless, the detailed site-specific glycan compositions of virion-associated S protein have not yet been clarified. Here, we conducted intensive glycoproteomic analyses of SARS-CoV-2 S protein using a combinatorial approach with two different technologies: mass spectrometry (MS) and lectin microarray. Using our unique MS1-based glycoproteomic technique, Glyco-RIDGE, in addition to MS2-based Byonic search, we identified 1,759 site-specific glycan compositions. The most frequent was HexNAc:Hex:Fuc:NeuAc:NeuGc = 6:6:1:0:0, suggesting a tri-antennaryN-glycan terminating with LacNAc and having bisecting GlcNAc and a core fucose, which was found in 20 of 22 glycosylated sites. The subsequent lectin microarray analysis emphasized intensive outer arm fucosylation of glycans, which efficiently complemented the glycoproteomic features. The present results illustrate the high-resolution glycoproteomic features of SARS-CoV-2 S protein and significantly contribute to vaccine design, as well as the understanding of viral protein synthesis.
Aging affects KV7 channels and perivascular-adipose tissue-mediated vascular tone
Authors: Wang Yibin , Yildiz Fatima , Struve Andrey , Kassmann Mario , Luft Friedrich C. , Gollasch Maik , Tsvetkov Dmitry
Published: April 2021

Aging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and downstream vasoconstriction targets, voltage-dependent KV7 channels, and their pharmacological modulators (flupirtine, retigabine, QO58, QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteriesin vitrousing wire myography. We also performed bulk RNA sequencing and quantitative reverse transcription polymerase chain reaction tests in mesenteric arteries and perivascular adipose tissue to elucidate molecular underpinnings of age-related phenotypes. Results revealed impaired perivascular adipose tissue-mediated control of vascular tone particularly via KV7.3-5 channels with increased age through metabolic and inflammatory processes and release of perivascular adipose tissue-derived relaxation factors. Moreover, QO58 was identified as novel pharmacological vasodilator to activate XE991-sensitive KCNQ channels in old mesenteric arteries. Our data suggest that targeting inflammation and metabolism in perivascular adipose tissue could represent novel approaches to restore vascular function during aging. Furthermore, QO58 represents a novel tool for cardiovascular and hypertension research in aging.
A complex feature-based representation of vocalizations emerges in the superficial layers of primary auditory cortex
Authors: Montes-Lourido Pilar , Kar Manaswini , David Stephen V. , Sadagopan Srivatsun
Published: April 2021

Early in auditory processing, neural responses faithfully reflect acoustic input. At higher stages of auditory processing, however, neurons become selective for particular call types, eventually leading to specialized regions of cortex that preferentially process calls at the highest auditory processing stages. We previously proposed that an intermediate step in how non-selective responses are transformed into call-selective responses is the detection of informative call features. But how neural selectivity for informative call features emerges from non-selective inputs, whether feature selectivity gradually emerges over the processing hierarchy, and how stimulus information is represented in non-selective and feature-selective populations remain open questions. In this study, using unanesthetized guinea pigs, a highly vocal and social rodent, as an animal model, we characterized the neural representation of calls in three auditory processing stages – the thalamus (vMGB), and thalamorecipient (L4) and superficial layers (L2/3) of primary auditory cortex (A1). We found that neurons in vMGB and A1 L4 did not exhibit call-selective responses and responded throughout the call durations. However, A1 L2/3 neurons showed high call-selectivity with about a third of neurons responding to only one or two call types. These A1 L2/3 neurons only responded to restricted portions of calls suggesting that they were highly selective for call features. Receptive fields of these A1 L2/3 neurons showed complex spectrotemporal structures that could underlie their high call feature selectivity. Information theoretic analysis revealed that in A1 L4 stimulus information was distributed over the population and was spread out over the call durations. In contrast, in A1 L2/3, individual neurons showed brief bursts of high stimulus-specific information, and conveyed high levels of information per spike. These data demonstrate that a transformation in the neural representation of calls occurs between A1 L4 and A1 L2/3, leading to the emergence of a feature-based representation of calls in A1 L2/3. Our data thus suggest that observed cortical specializations for call processing emerge in A1, and set the stage for further mechanistic studies.
Brevibacillin 2V, a novel antimicrobial lipopeptide with an exceptional low hemolytic activity
Authors: Zhao Xinghong , Wang Xiaoqi , Shukla Rhythm , Kumar Raj , Weingarth Markus , Breukink Eefjan , Kuipers Oscar P.
Published: April 2021

Bacterial non-ribosomally produced peptides (NRPs) form a rich source of antibiotics, including more than twenty of these antibiotics that are used in the clinic, such as penicillin G, colistin, vancomycin, and chloramphenicol. Here we report the identification, purification, and characterization of a novel NRP, i.e., brevibacillin 2V, fromBrevibacillus laterosporusDSM 25. Brevibacillin 2V has strong antimicrobial activity against Gram-positive bacterial pathogens, including difficult-to-treat antibiotic-resistantEnterococcus faecium, Enterococcus faecalis, andStaphylococcus aureus. Notably, brevibacillin 2V has a much lower hemolytic activity to eukaryotic cells than previously reported NRPs of the lipo-tridecapeptide family, including other brevibacillins, which makes it a promising candidate for antibiotic development. In addition, our results demonstrate that brevibacillins display synergistic action with established antibiotics against Gram-negative bacterial pathogens. Thus, we identified and characterized a novel and promising antibiotic candidate (brevibacillin 2V) with a low hemolytic activity, which can be used either on its own or as a template for further total synthesis and modification.
Texture is encoded in precise temporal spiking patterns in primate somatosensory cortex
Authors: Long Katie H. , Lieber Justin D. , Bensmaia Sliman J.
Published: April 2021

Abstract

We are exquisitely sensitive to the microstructure and material properties of surfaces. In the peripheral nerves, two separate mechanisms convey texture information: coarse textural features are encoded in spatial patterns of activation that reflect their spatial layout and fine features are encoded in highly repeatable, texture specific temporal spiking patterns evoked as the skin moves across the surface. In the present study, we examined whether this temporal code is preserved in the responses of neurons in somatosensory cortex. To this end, we scanned a diverse set of everyday textures across the fingertip of awake macaques while recording the responses evoked in individual cortical neurons. We found that temporal spiking patterns are highly repeatable across multiple presentations of the same texture, with millisecond precision. As a result, texture identity can be reliably decoded from the temporal patterns themselves, even after information carried in the spike rates is eliminated. However, the combination of rate and timing does is more informative than either code in isolation. The temporal precision of the texture response is heterogenous across cortical neurons and depends on the submodality composition of their input and on their location along the somatosensory neuraxis. Furthermore, temporal spiking patterns in cortex dilate and contract with decreases and increases in scanning speed and this systematic relationship between speed and patterning may contribute to the observed perceptual invariance to speed. Finally, we find that the quality of a texture percept can be better predicted when these temporal patterns are taken into consideration. We conclude that high-precision spike timing complements rate-based signals to encode texture in somatosensory cortex.
In vivo Monitoring of Glucose using Ultrasound-induced Resonance in Implantable Smart Hydrogel Microstructures
Authors: Farhoudi Navid , Laurentius Lars B. , Magda Jules J. , Reiche Christopher F. , Solzbacher Florian
Published: April 2021

A novel glucose sensor is presented that uses smart hydrogels as a biocompatible implantable sensing element, which completely eliminates the need for any implanted electronics and uses an external conventional medical-grade ultrasound transducer for readout. The readout mechanism makes use of resonance absorption of ultrasound waves in glucose-sensitive hydrogels. Changes in in vivo glucose concentration in the interstitial tissue lead to swelling and de-swelling of the gels which in turn lead to changes in resonance behavior. The hydrogels are designed and shaped such as to exhibit specific mechanical resonance frequencies while remaining sonolucent to other frequencies. Thus, they allow conventional and continued ultrasound imaging, while yielding a sensing signal at specific frequencies that is correlated with glucose concentration. The resonance frequencies can be tuned by changing the shape and mechanical properties of the gel structures, such as to allow for multiple, co-located implanted hydrogels with different sensing characteristics or targets to be employed and read out, without interference, using the same ultrasound transducer, by simply toggling frequencies. The fact that there is no need for any implantable electronics, also opens the path towards future use of biodegradable hydrogels, thus creating a platform that allows injection of sensors that do not need to be retrieved when they reach the end of their useful lifespan.
Cypripedium wardii(Orchidaceae) employs pseudopollen with both reward and deception to attract both flis and bees as pollinators
Authors: Zheng Chen-Chen , Luo Yi-Bo , Gao Yun-Dong , Bernhardt Peter , Li Shi-Qi , Xu Bo , Gao Xin-Fen
Published: April 2021

Flowering plants always attract animals providing rewards or deceptive signals to gain reproductive success. However, there is no well-documented reporting about a pollination mechanism with both rewards and deceptive signals by a same object. We foundCypripedium wardiiflowers seem to attract visitors by the white pseudopollenlike trichomes on labella in our preliminary field observation.

To explore the pollination mechanism ofCypripedium wardii, especially, the ecological function of the pseudopollen-like trichomes, we conducted field observations, analyses of the traits of visitors and flowers, and breeding system experiments.

The white trichomes composed by multicellular moniliform hairs on the floral labella played a crucial role to attract pollinators, causing a high natural fruit set ratio inC. wardii. We established the direct connection of the white trichomes and real pollen.

We propose that flowers ofC. wardiiprovide pseudopollen to attract suitable bees and hoverflies as pollinators. And our evidence indicate that the pseudopollen owns both deceptive and rewarding ecological functions. Our study provide a clear pollination mechanism with both rewards and deceptive signals by a same object in angiosperm for the first time. However, an inbreeding depression seem to be caused by this strategy. And we speculated that the pollen mimicry strategy with both rewarding and deceptive functions inC. wardiimay be an adaptation to the habitat fragmentation of this species to gain a reproductive assurance.
The PD-L1 and TLR7 dual-targeting nanobody-drug conjugate exerts potent antitumor efficacy by orchestrating innate and adaptive immune responses
Authors: Yu Xiaolu , Long Yiru , Chen Binfan , Tong Yongliang , Jia Xiaomin , Zhou Ji , Tang Feng , Xu Pan , Cao Yuhan , Huang Wei , Ren Jin , Wan Yakun , Sun Jianhua , Jin Guangyi , Gong Likun
Published: April 2021

A variety of tumors are insensitive to immune checkpoint blockade (ICB) therapy. We propose that ICB therapy alone is insufficient to fully reactivate antitumor T cells, while effective mobilization of antigen-presenting cells (APCs) to assist adaptive immune cell activation can lead to potent antitumor effects with broad responsiveness. The Toll-like receptor 7 (TLR7) agonist SZU-101 we developed can induce the innate immune response against tumors and increase the immunogenicity of tumors. Interestingly, SZU-101-induced upregulation of programmed death ligand 1 (PD-L1) expression in tumor tissues can further enhance the response rate of the PD-L1 antibody. In addition, PD-L1 nanobodies have better solid tumor penetration ability, and because of this ability, they can be used to precisely deliver SZU-101 to tumor tissues. Therefore, a PD-L1 and TLR7 dual-targeting nanobody-drug conjugate (NDC), a novel drug molecule, was developed. We found that TLR7 agonists and PD-L1 nanobodies act synergistically and that NDC treatment reshapes the tumor immune microenvironment, activates both innate and adaptive immune cells, and exerts antitumor effects in both “hot” and “cold” tumors primarily through CD8+T cells and natural killer (NK) cells. Our data show that a PD-L1 and TLR7 dual-targeting NDC can exhibit potent antitumor efficacy by orchestrating innate and adaptive immune responses and shows good prospects for clinical development.

One Sentence Summary

Based on results showing that TLR7 agonists and PD-L1 nanobodies exert synergistic antitumor effects, a PD-L1 and TLR7 dual-targeting nanobody-drug conjugate that we developed shows good prospects for clinical development because it can orchestrate innate and adaptive immune responses, reshape the tumor immune microenvironment, and exert potent antitumor effects against both “hot” and “cold” tumors.
Expression of the ACE2 virus entry protein in the nervus terminalis reveals the potential for an alternative route to brain infection in COVID-19
Authors: Bilinska Katarzyna , von Bartheld Christopher S. , Butowt Rafal
Published: April 2021

Previous studies suggested that the SARS-CoV-2 virus may gain access to the brain by using a route along the olfactory nerve. However, there is a general consensus that the obligatory virus entry receptor, angiotensin converting enzyme 2 (ACE2), is not expressed in olfactory receptor neurons, and the timing of arrival of the virus in brain targets is inconsistent with a neuronal transfer along olfactory projections. We determined whether nervus terminalis neurons and their peripheral and central projections should be considered as a potential alternative route from the nose to the brain. Nervus terminalis neurons in postnatal mice were double-labeled with antibodies against ACE2 and two nervus terminalis markers, gonadotropin-releasing hormone (GnRH) and choline acetyltransferase (CHAT). We show that a small fraction of CHAT-labeled nervus terminalis neurons, and the large majority of GnRH-labeled nervus terminalis neurons with cell bodies in the region between the olfactory epithelium and the olfactory bulb express ACE2 and cathepsins B and L. Nervus terminalis neurons therefore may provide a direct route for the virus from the nasal epithelium, possibly via innervation of Bowman’s glands, to brain targets, including the telencephalon and diencephalon. This possibility needs to be examined in suitable animal models and in human tissues.
Intracellular transport of electrotransferred DNA cargo is governed by coexisting ergodic and non ergodic anomalous diffusion
Authors: Muralidharan Aswin , Uitenbroek Hans , Boukany Pouyan E.
Published: April 2021

The ability of exogenous DNA cargo to overcome the active and viscoelastic eukaryotic cytoplasm is a principal determinant for the gene delivery efficacy. During DNA electrotransfer, DNA forms complexes with the membrane (DNA cargo) which is transported through the cytoplasm through a combination of passive diffusion and active transport. However, this process is poorly understood limiting rational optimization of DNA cargo to be delivered to different cell types. We have investigated the intracellular transport of DNA cargo (of sizes 100 bp, 250 bp and 500 bp) delivered by electrotransfer to non-cancerous and cancerous mammalian cells. We demonstrate that intracellular DNA cargo transport is governed by coexisting ergodic and non ergodic anomalous diffusion for all the tested DNA sizes and cell types. The apparent diffusion coefficient of the electrotransferred DNA cargo in the cytoplasm decreases when the DNA size is increased from 100 bp to 500 bp. Interestingly, the electrotransferred DNA cargo (500 bp) transport is strongly dependent on the cell’s cancer state. Intracellular electrotransferred DNA cargo transport has a higher probability of superdiffusive transport and lower probability of caging in metastatic cells compared to malignant cells followed by benign cells.
DAnIEL: A User-Friendly Web Server for Fungal ITS Amplicon Sequencing Data
Authors: Loos Daniel , Zhang Lu , Beemelmanns Christine , Kurzai Oliver , Panagiotou Gianni
Published: April 2021

Trillions of microbes representing all kingdoms of life are resident in, and on, humans holding essential roles for host development and physiology. The last decade over a dozen online tools and servers, accessible via public domain, have been developed for the analysis of bacterial sequences, however, the analysis of fungi is still in its infancy. Here we present a web server dedicated to the comprehensive analysis of the human mycobiome for (i) translating raw sequencing reads to data tables and high-standard figures; (ii) integrating statistical analysis and machine learning with a manually curated relational database; (iii) comparing the user’s uploaded datasets with publicly available from the Sequence Read Archive. Using 2,048 publicly available ITS samples, we demonstrated the utility of DAnIEL web server on large scale datasets and show the differences in fungal communities between human gut, skin, nasopharynx, and oral body sites.
Acyl Carrier Protein is essential for MukBEF action inEscherichia colichromosome organization-segregation
Authors: Prince Josh P. , Bolla Jani R. , Fisher Gemma L. M. , Mäkelä Jarno , Robinson Carol V. , Arciszewska Lidia K. , Sherratt David J.
Published: April 2021

Structural Maintenance of Chromosomes (SMC) complexes contribute ubiquitously to chromosome organization-segregation. SMC proteins have a conserved architecture, with a dimerization hinge and an ATPase head domain separated by a long antiparallel intramolecular coiled-coil. Dimeric SMC proteins interact with essential accessory proteins, kleisins that bridge the two subunits of an SMC dimer, and HAWK/KITE accessory proteins that interact with kleisins. The ATPase activity of theEscherichia coliSMC protein, MukB, is essential forin vivofunction and is regulated by interactions with its dimeric kleisin, MukF, and KITE, MukE. Here we demonstrate that, in addition, MukB interacts with Acyl Carrier Protein (AcpP) that has essential functions in fatty acid synthesis. We characterize the AcpP interaction site at the joint of the MukB coiled-coil and show that the interaction is essential for MukB ATPase and for MukBEF functionin vivo. Therefore, AcpP is an essential co-factor for MukBEF action in chromosome organization-segregation.
An autonomous tail-beating cycle period expressed by a region- specific swimming pattern generator in theCionalarva
Authors: Hara Takashi , Hasegawa Shuya , Iwatani Yasushi , Nishino Atsuo S.
Published: April 2021

Swimming locomotion in aquatic vertebrates, such as fish and tadpoles, is expressed through orchestrated operations of central pattern generators. These parallel neuronal circuits are ubiquitously distributed and mutually coupled along the spinal cord to express undulation patterns accommodated to efferent and afferent inputs. While such sets of schemes have been shown in vertebrates, the evolutionary origin of those mechanisms along the chordate phylogeny remains unclear. Ascidians, representing a sister group of vertebrates, give rise to tadpole larvae that freely swim in seawater. In this study, we tried to locate the swimming pattern generator in larvae of the ascidianCionaby examining locomotor ability of segmented body fragments. Our experiments demonstrated necessary and sufficient pattern generator activity in a short region (∼10% of the body length as the longest estimation) including the trunk-tail junction but excluding most of the trunk and tail with major sensory apparatuses therein. Moreover, we found that these “mid-piece” body fragments express periodic tail beating bursts with ∼20-s intervals without any exogenous stimuli. Comparisons among temporal patterns of tail beating bursts expressed by the mid-piece fragments and by whole larvae placed under different sensory conditions suggested that the presence of parts other than the critical mid-piece had effects to shorten swimming burst intervals, especially in the dark, and also to expand the variance in burst durations. We propose thatCionalarvae perform swimming as modified representations of autonomous and periodic pattern generator drives, which operate locally in the region of the trunk-tail junction.

Summary statement

Mid-piece fragments of tadpole larvae of the ascidianCiona, lacking most of the anterior trunk and posterior tail, autonomously and periodically express tail beating bursts.
Do female executives and CEO tenure matter for corporate cash holdings? Insight from a Southeast Asian country
Authors: Suherman Suherman , Usman Berto , Mahfirah Titis Fatarina , Vesta Renhard
Published: April 2021

Purpose

This paper aims to investigate the relationship between female executives, chief executive officer (CEO) tenure and corporate cash holdings in the context of the developing Southeast Asian capital market (Indonesia).

Design/methodology/approach

The sample was screened from 231 publicly listed companies in the Indonesian Stock Exchange. The period of observation was 2011–2017. Two measures were applied for corporate cash holdings: the ratio of cash and cash equivalent to total assets and cash and cash equivalent to net assets. Three surrogate indicators were used for female executives: female CEO, the proportion of female members in the board of management and the number of female members in the board of management. CEO tenure is the length of time a CEO has been a member of the board of management. This study uses panel data regression analysis, including the fixed effect model with clustered standard errors.

Findings

The empirical evidence indicates that female executives and CEO tenure are positively and negatively associated with corporate cash holdings, respectively, and both are significantly related. Additional analysis using lagged independent variables remains consistent with the main analysis, suggesting that corporate cash holding becomes higher as a female presence in the board of management increases.

Research limitations/implications

Empirical tests set in Indonesia suggest that female executives are more conservative and risk-averse, thereby holding more cash with a precautionary motive. The findings also imply that CEOs with long tenure focus on long-term performance such as increasing research and development investments or capital expenditure, thus holding less cash. Accordingly, policymakers and regulators should promote diversity issues proportionally and advance to the board level.

Originality/value

This study contributes to the field of executive and CEO studies by enriching the empirical findings in related topics. In addition, to the best of the authors’ knowledge, this is one of the first studies applying two measures of cash holdings in the setting of a developing Southeast Asian capital market (Indonesia).
Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox‐LDL‐induced endothelial dysfunction in atherosclerosis by functioning as a miR‐876‐3p sponge
Authors: Gao Yanhui , Li Guangnan , Fan Shasha , Wang Yu , Wei Hong , Li Mingyang , Li Xueqi
Published: April 2021

Circular RNAs (circRNAs) are widely expressed in mammals and act as regulatory targets in the atherogenesis. The objective of this study was to research the biological role and molecular mechanism of circ_0093887 in oxidized low‐density lipoprotein (ox‐LDL)‐induced atherosclerosis (AS) of human aortic endothelial cells (HAECs). Cell viability detection was performed by CCK‐8 assay. Inflammatory molecules were examined using ELISA. Flow cytometry was used to measure cell‐cycle progression and cell apoptotic rate. Caspase 3 activity was determined using caspase 3 activity assay. The expression levels of circ_0093887, miR‐876‐3p, CCND2 and SUCNR1 were assayed by quantitative real‐time polymerase chain reaction (qRT‐PCR). Dual‐luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull‐down assays were used for the target analysis. EdU assay, wound healing assay/transwell assay and tube formation assay were, respectively, used to assess the effects of circ_0093887/miR‐876‐3p axis on cell proliferation, migration and tube formation. Oxidized low‐density lipoprotein inhibited cell viability and cell‐cycle progression but induced the inflammatory response and cell apoptosis. Circ_0093887 was downregulated and miR‐876‐3p was upregulated in AS patients and ox‐LDL‐treated HAECs. Functionally, the overexpression of circ_0093887 abrogated the cell injury of HAEC exposed to ox‐LDL. For the functional mechanism, we found that circ_0093887 was a sponge for miR‐876‐3p and miR‐876 targeted CCND2 or SUCNR1. The reverted experiment indicated that the function of circ_0093887 was achieved by sponging miR‐876‐3p. Meanwhile, miR‐876‐3p inhibitor relieved the inhibitory regulation of circ_0093887 knockdown in cell proliferation, migration and tube formation. Downregulation of miR‐876‐3p also alleviated the ox‐LDL‐induced cell injury by upregulating the expression of CCND2 or SUCNR1. Furthermore, circ_0093887 was validated to regulate the levels of CCND2 and SUCNR1 via the sponge effect on miR‐876‐3p. The protective effects of circ_0093887 on HAECs from ox‐LDL were also ​alleviated by repressing the CCND2 and SUCNR1 levels. These findings suggested that circ_0093887 protected HAEC against the ox‐LDL‐induced inflammatory and apoptotic damages by targeting the miR‐876‐3p/CCND2 or miR‐876/SUCNRA axis. Circ_0093887 could act as a potential therapeutic biomarker for AS patients.