bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial and Pharmacological Approaches for Improving Treatment Adherence and Outcomes in People With Severe Schizophrenia: A 10-Year Follow-up
Authors: Díaz-Fernández Silvia , López-Muñoz Francisco , Fernández-Miranda Juan J.
Published: November 2021

The objective of this study was to understand the psychosocial and pharmacological approaches linked to better treatment adherence and outcomes (psychiatric hospitalizations, clinical severity, and suicide attempts) among patients with schizophrenia receiving the standard treatment in mental health units (MHUs) compared with patients in a community-based, case-managed program (CMP). An observational, prospective (10 y) study was conducted involving patients with severe schizophrenia (N=688). The treatment adherence of patients in the CMP was higher than among those in the MHUs (12.2% vs. 84.3% abandoning treatment; P<0.0001). Hospital admissions and suicide attempts were significantly lower among those treated in the CMP than among those receiving standard care in the MHUs (P<0.001). Scores on the clinical severity scale decreased significantly more in the group in the CMP than in the group in the MHUs (P<0.005). Treatment with long-acting injectable antipsychotic medication was closely linked with higher treatment retention (P<0.001) and fewer hospital admissions and suicide attempts compared with treatment with oral antipsychotics in both patient groups, with the effect greater in the group in the CMP (P<0.001). We highlight how patients with severe schizophrenia treated in a CMP with integrated treatment showed a higher retention rate, fewer psychiatric hospital admissions and suicide attempts, and less clinical severity compared with those receiving standard treatment in MHUs. Treatment with long-acting antipsychotics was also clearly related to these outcomes. A combination of intensive case-managed integrated treatment and treatment with long-acting antipsychotic medication facilitated the achievement of clinical and rehabilitation goals in patients with schizophrenia with severe symptoms and impairment compared with standard care and treatment with oral antipsychotics.
Marinobacter mangrovi sp. nov., isolated from mangrove sediment
Authors: Yi En , Shao Zongze , Li Guizhen , Liang Xiaobo , Zhou Meixian
Published: November 2021

A novel marine bacterium, designated strain CHFG3-1-5T, was isolated from mangrove sediment sampled at Jiulong River estuary, Fujian, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CHFG3-1-5T belonged to the genus

Marinobacter

, with the highest sequence similarity to

Marinobacter segnicrescens

SS011B1-4T (97.6%), followed by

Marinobacter nanhaiticus

D15-8WT (97.5%),

Marinobacter bohaiensis

T17T (97.1%) and

Marinobacter hydrocarbonoclasticus

SP.17T (90.6%). The bacterium was Gram-stain-negative, facultative anaerobic, oxidase- and catalase-positive, rod-shaped and motile with a polar flagellum. Strain CHFG3-1-5T grew optimally at 32–37 °C, pH 6.0–8.0 and in the presence of 2.0–3.0% (w/v) NaCl. The G+C content of the chromosomal DNA was 61.1 mol%. The major respiratory quinone was determined to be Q-9. The principal fatty acids were C16 : 0, summed feature 3 (C16 : 1
ω7c/ω6c), C12 : 0, summed feature 9 (C17 : 1 iso ω9c and/or C16 : 0 10-methyl), C12 : 0 3-OH and summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three phospholipids, one glycolipid and two aminolipids. The average nucleotide identity and digital DNA–DNA hybridization values among the genomes of strain CHFG3-1-5T and the reference strains were 73.4–79.4 and 19.6–22.4%, respectively. Like many other species reported in the genus

Marinobacter

, strain CHFG3-1-5T was able to oxidise iron. The combined genotypic and phenotypic data showed that strain CHFG3-1-5T represents a novel species within the genus

Marinobacter

, for which the name Marinobacter mangrovi sp. nov. is proposed, with the type strain CHFG3-1-5T (=MCCC 1A18306T=KCTC 82398T).
Microbacterium stercoris sp. nov., an indole acetic acid-producing actinobacterium isolated from cow dung
Authors: Zhang Lida , Jiao Yanjie , Ling Ling , Wang Han , Song Wenshuai , Zhao Tianxin , Guo Lifeng , Xiang Wensheng , Zhao Junwei , Wang Xiangjing
Published: November 2021

A novel growth-promoting and indole acetic acid-producing strain, designated NEAU-LLBT, was isolated from cow dung collected from Shangzhi, Heilongjiang Province, PR China. Cells of strain NEAU-LLBT were Gram-stain-positive, non-motile, aerobic and non-spore-forming. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain NEAU-LLBT belonged to the genus

Microbacterium

. Strain NEAU-LLBT had high 16S rRNA sequence similarities of 98.81 and 98.41 % to

Microbacterium paludicola

DSM 16915T and

Microbacterium marinilacus

DSM 18904T, and less than 98 % to other members of the genus

Microbacterium

. Chemotaxonomic characteristics showed that MK-11 and MK-12 were detected as the predominant menaquinones. The peptidoglycan contained glutamic acid, aspartic acid, glycine, ornithine and a small amount of alanine, with ornithine as the diagnostic diamino acid. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. The major fatty acids were identified as anteiso-C15 : 0, iso-C16 : 0 and iso-C17 : 0. The genomic DNA G+C content of strain NEAU-LLBT was 70.2 mol%. In addition, the average nucleotide identity values between strain NEAU-LLBT and its reference strains,

M. paludicola

DSM 16915T,

M. marinilacus

DSM 18904T and

M. album

SYSU D8007T, were found to be 81.1, 79.4 and 78.7 %, respectively, and the level of digital DNA–DNA hybridization between them were 23.8, 22.6 and 21.8 %, respectively. Based on the phenotypic, phylogenetic and genotypic data, strain NEAU-LLBT is considered to represent a novel species of the genus

Microbacterium

, for which the name Microbacterium stercoris sp. nov is proposed, with NEAU-LLBT (=CCTCC AA 2018028T=JCM 32660T) as the type strain.
A Campylobacter integrative and conjugative element with a CRISPR-Cas9 system targeting competing plasmids: a history of plasmid warfare?
Authors: van Vliet Arnoud H. M. , Charity Oliver J. , Reuter Mark
Published: November 2021

Microbial genomes are highly adaptable, with mobile genetic elements (MGEs) such as integrative conjugative elements (ICEs) mediating the dissemination of new genetic information throughout bacterial populations. This is countered by defence mechanisms such as CRISPR-Cas systems, which limit invading MGEs by sequence-specific targeting. Here we report the distribution of the pVir, pTet and PCC42 plasmids and a new 70–129 kb ICE (CampyICE1) in the foodborne bacterial pathogens

Campylobacter jejuni

and

Campylobacter coli

. CampyICE1 contains a degenerated Type II-C CRISPR system consisting of a sole Cas9 protein, which is distinct from the previously described Cas9 proteins from

C. jejuni

and

C. coli

. CampyICE1 is conserved in structure and gene order, containing blocks of genes predicted to be involved in recombination, regulation and conjugation. CampyICE1 was detected in 134/5829 (2.3 %)

C

.

jejuni

genomes and 92/1347 (6.8 %)

C

.

coli

genomes. Similar ICEs were detected in a number of non-jejuni/coli

Campylobacter

species, although these lacked a CRISPR-Cas system. CampyICE1 carries three separate short CRISPR spacer arrays containing a combination of 108 unique spacers and 16 spacer-variant families. A total of 69 spacers and 10 spacer-variant families (63.7 %) were predicted to target

Campylobacter

plasmids. The presence of a functional CampyICE1 Cas9 protein and matching anti-plasmid spacers was associated with the absence of the pVir, pTet and pCC42 plasmids (188/214 genomes, 87.9 %), suggesting that the CampyICE1-encoded CRISPR-Cas has contributed to the exclusion of competing plasmids. In conclusion, the characteristics of the CRISPR-Cas9 system on CampyICE1 suggests a history of plasmid warfare in

Campylobacter

.
Using mobile phone data to estimate dynamic population changes and improve the understanding of a pandemic: A case study in Andorra
Authors: Berke Alex , Doorley Ronan , Alonso Luis , Arroyo Vanesa , Pons Marc , Larson Kent
Published: November 2021

Compartmental models are often used to understand and predict the progression of an infectious disease such as COVID-19. The most basic of these models consider the total population of a region to be closed. Many incorporate human mobility into their transmission dynamics, usually based on static and aggregated data. However, mobility can change dramatically during a global pandemic as seen with COVID-19, making static data unsuitable. Recently, large mobility datasets derived from mobile devices have been used, along with COVID-19 infections data, to better understand the relationship between mobility and COVID-19. However, studies to date have relied on data that represent only a fraction of their target populations, and the data from mobile devices have been used for measuring mobility within the study region, without considering changes to the population as people enter and leave the region.

This work presents a unique case study in Andorra, with comprehensive datasets that include telecoms data covering 100% of mobile subscribers in the country, and results from a serology testing program that more than 90% of the population voluntarily participated in. We use the telecoms data to both measure mobility within the country and to provide a real-time census of people entering, leaving and remaining in the country. We develop multiple SEIR (compartmental) models parameterized on these metrics and show how dynamic population metrics can improve the models. We find that total daily trips did not have predictive value in the SEIR models while country entrances did. As a secondary contribution of this work, we show how Andorra’s serology testing program was likely impacted by people leaving the country. Overall, this case study suggests how using mobile phone data to measure dynamic population changes could improve studies that rely on more commonly used mobility metrics and the overall understanding of a pandemic.
An ST131 clade and a Phylogroup A clade bearing a novel Escherichia coli O-antigen cluster predominate among bloodstream E. coli isolates from southwest Nigeria hospitals
Authors: Afolayan Ayorinde O. , Aboderin Aaron O. , Oaikhena Anderson O. , Odih Erkison Ewomazino , Ogunleye Veronica O. , Adeyemo Adeyemi T. , Adeyemo Abolaji T. , Bejide Oyeniyi S. , Underwood Anthony , Argimón Silvia , Abrudan Monica , Egwuenu Abiodun , Ihekweazu Chikwe , Aanensen David M. , Okeke Iruka N.
Published: November 2021

Escherichia coli bloodstream infections are typically attributed to a limited number of lineages that carry virulence factors associated with invasion and, in recent years, invasive E. coli are increasingly multiply antimicrobial resistant. In Nigeria, E. coli is a common cause of bloodstream infections but the identity of circulating clones is largely unknown and surveillance of their antimicrobial resistance has been limited. We verified and whole genome-sequenced 68 bloodstream E. coli isolates recovered between 2016 and 2018 at three sentinel sites in southwestern Nigeria and susceptibility tested 67 of them. Resistance to antimicrobials commonly used in Nigeria was high, with 67(100%), 62 (92.5%), 53 (79%) and 37(55%) showing resistance to trimethoprim, ampicillin, ciprofloxacin and aminoglycosides, respectively. All the isolates were susceptible to carbapenems and colistin. The strain set included isolates from globally disseminated high risk clones including those belonging to ST12 (n=2), ST131 (n=12) and ST648 (n = 4). Twenty-three (33.82%) of the isolates clustered within two clades. The first of these consisted of ST131 strains, comprised of O16:H5 and O25:H4 sub-lineages. The second was an ST10-ST167 complex clade comprised of strains carrying capsular genes that may have originated in Klebsiella. We additionally determined that four temporally-associated ST90 strains from one sentinel were closely related enough to suggest that at least some of them represented a retrospectively detected outbreak cluster. Our data demonstrate that a broad repertoire of invasive E. coli isolates cause bloodstream infections in southwest Nigeria. In addition to pandemic lineages, particularly ST131, these include a previously undescribed lineage carrying an O-antigen cluster previously only reported from Klebsiella. Genomic surveillance is valuable for tracking these and other clones and for outbreak identification.

Data Summary

Phylogenetic tree, clinical data, and epidemiological data were visualized using Microreact (https://microreact.org/project/hmj3KwxS1dmmFPCKFx6qeA-invasive-escherichia-coli-sw-nigeria-2016-2018). All the sequence data have been deposited in the ENA under the project ID PRJEB29739 (https://www.ebi.ac.uk/ena/browser/view/PRJEB29739). Accessions can be found in Table S6.
Cell Wall Biochemistry Drives Pollen Tube Mechanics and Affects Growth Rate
Authors: Vogler Hannes , Munglani Gautam , Ndinyanka Fabrice Tohnyui , Draeger Christian , Burri Jan T. , Eichenberger Christof , Knox J. Paul , Mollet Jean Claude , Nelson Bradley J. , Herrmann Hans J. , Ringli Christoph , Grossniklaus Ueli
Published: November 2021

Pollen tubes live a life on a razor’s edge. They must maintain cell wall integrity whilst growing towards the ovule at extraordinary speed but explosively burst at just the right moment to release the sperm cells—with fatal consequences for reproduction if things go wrong. The precisely controlled growth of the pollen tube depends on the fine-tuned balance between the expansive force of turgor pressure and the restraining effect of the cell wall. Currently, it is not well understood how the composition of the cell wall affects its mechanical properties. Using Arabidopsis mutants, we have investigated these interactions by combining experimental and simulation techniques to determine instantaneous and time-dependent mechanical parameters. This allowed, for the first time, the quantification of the effects of cell wall biochemistry on turgor pressure and cell wall elasticity and to predict their effects on growth rate. Our systems biology approach is widely applicable to study the implications of mechanical stress on growth.
A novel machine learning-based approach for the detection and analysis of spontaneous synaptic currents
Authors: Pircher Thomas , Pircher Bianca , Feigenspan Andreas
Published: November 2021

Spontaneous synaptic activity is a hallmark of neural networks. A thorough description of these synaptic signals is essential for understanding neurotransmitter release and the generation of a postsynaptic response. However, the complexity of synaptic current trajectories has either precluded an in-depth analysis or it has forced human observers to resort to manual or semi-automated approaches based on subjective amplitude and area threshold settings. Both procedures are time-consuming, error-prone and likely affected by human bias. Here, we present three complimentary methods for a fully automated analysis of spontaneous excitatory postsynaptic currents measured in major cell types of the mouse retina and in a primary culture of mouse auditory cortex. Two approaches rely on classical threshold methods, while the third represents a novel machine learning-based algorithm. Comparison with frequently used existing methods demonstrates the suitability of our algorithms for an unbiased and efficient analysis of synaptic signals in the central nervous system.
Age-Dependent Formation of TMEM106B Amyloid Filaments in Human Brain
Authors: Schweighauser Manuel , Arseni Diana , Huang Melissa , Lövestam Sofia , Shi Yang , Yang Yang , Zhang Wenjuan , Kotecha Abhay , Garringer Holly J. , Vidal Ruben , Hallinan Grace I. , Newell Kathy L. , Tarutani Airi , Murayama Shigeo , Miyazaki Masayuki , Saito Yuko , Yoshida Mari , Hasegawa Kazuko , Lashley Tammaryn , Revesz Tamas , Kovacs Gabor G. , van Swieten John , Takao Masaki , Hasegawa Masato , Ghetti Bernardino , Falcon Benjamin , Murzin Alexey G. , Goedert Michel , Scheres Sjors H.W.
Published: November 2021

Many age-dependent neurodegenerative diseases, like Alzheimer’s and Parkinson’s, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β (Aβ), α-synuclein and TDP-43 are the most common. Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in the human brain. We solved cryo-EM structures of TMEM106B filaments from the brains of 22 individuals with neurodegenerative conditions, including sporadic and inherited tauopathies, Aβ-amyloidoses, synucleinopathies and TDP-43opathies, as well as from the brains of two neurologically normal individuals. We observed three different TMEM106B folds, with no clear relationship between folds and diseases. The presence of TMEM106B filaments correlated with that of a 29 kDa sarkosyl-insoluble fragment of the protein on Western blots. The presence of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.
A Transparent Ultrasound Array for Real-time Optical, Ultrasound and Photoacoustic Imaging
Authors: Chen Haoyang , Agrawal Sumit , Osman Mohamed , Minotto Josiah , Mirg Shubham , Liu Jinyun , Dangi Ajay , Tran Quyen , Jackson Thomas , Kothapalli Sri-Rajasekhar
Published: November 2021

Objective and Impact Statement

Simultaneous imaging of ultrasound and optical contrasts can help map structural, functional and molecular biomarkers inside living subjects with high spatial resolution. There is a need to develop a platform to facilitate this multimodal imaging capability to improve diagnostic sensitivity and specificity.

Introduction

Currently, combining ultrasound, photoacoustic and optical imaging modalities is challenging because con-ventional ultrasound transducer arrays are optically opaque. As a result, complex geometries are used to co-align both optical and ultrasound waves in the same field of view.

Methods

One elegant solution is to make the ultrasound transducer transparent to light. Here, we demonstrate a novel transparent ultrasound transducer (TUT) liner array fabricated using a transparent lithium niobate piezoelectric material for real-time multimodal imaging.

Results

The TUT array consisted of 64 elements and centered at ∼ 6 MHz frequency. We demonstrate a quad-mode ultrasound, Doppler ultrasound, photoacoustic and fluorescence imaging in real-time using the TUT array directly coupled to the tissue mimicking phantoms.

Conclusion

The TUT array successfully showed a multimodal imaging capability, and has potential applications in diagnosing cancer, neuro and vascular diseases, including image-guided endoscopy and wearable imaging.
DNA Self-Assembled Plasmonic Nanodiamonds for Biological Sensing
Authors: Liang Le , Zheng Peng , Jia Sisi , Ray Krishanu , Chen Yun , Barman Ishan
Published: November 2021

Nitrogen-vacancy (NV) centers in diamonds are promising solid-state quantum emitters for developing superior biological imaging modalities. They possess desired bio-compatibility, photostability and electronic spin-related photophysical properties that are optically accessible at room temperature. Yet, bare nanodiamond-based imaging modalities are limited by the brightness and temporal resolution due to the intrinsically long lifetime of NV centers. Moreover, it remains a technological challenge using top-down fabrication to create freestanding hybrid nanodiamond imaging probes with enhanced performance. In this study, we leverage the bottom-up DNA self-assembly to develop a hybrid plasmonic nanodiamond construct, which we coin as the plasmon-enhanced nanodiamond (PEN), for biological imaging. The PEN nano-assembly features a closed plasmonic nanocavity that completely encapsulates a single nanodiamond, thus enabling the largest possible plasmonic enhancement to accelerate the emission dynamics of NV centers. Creation of the PEN nano-assembly is size-independent, so is its broadband scattering spectrum that is optimally overlapped with the emission spectrum of NV centers. Study of the structure-property correlation reveals that the optimal condition for emission dynamics modification is causally linked to that for a plasmonic nanocavity. The cellular internalization and cytotoxicity studies further confirm the delivery efficiency and biological safety of PEN nano-assemblies. Collectively, the PEN nano-assembly provides a promising approach for manipulating photophysical properties of solid-state quantum emitters and could serve as a versatile platform to uncover non-trivial quantum effects in biological systems.
PBPK modelling of dexamethasone in patients with COVID-19 and liver disease
Authors: Montanha Maiara Camotti , Cottura Nicolas , Booth Michael , Hodge Daryl , Bunglawala Fazila , Kinvig Hannah , Grañana-Castillo Sandra , Lloyd Andrew , Khoo Saye , Siccardi Marco
Published: November 2021

The aim of the study was to apply Physiologically-Based Pharmacokinetic (PBPK) modelling to predict the effect of liver disease (LD) on the pharmacokinetics (PK) of dexamethasone (DEX) in the treatment of COVID-19. A whole-body PBPK model was created to simulate 100 adult individuals aged 18-60 years. Physiological changes (e.g., plasma protein concentration, liver size, CP450 expression, hepatic blood flow) and portal vein shunt were incorporated into the LD model. The changes were implemented by using the Child-Pugh (CP) classification system. DEX was qualified using clinical data in healthy adults for both oral (PO) and intravenous (IV) administrations and similarly propranolol (PRO) and midazolam (MDZ) were qualified with PO and IV clinical data in healthy and LD adults. The qualified model was subsequently used to simulate a 6 mg PO and 20 mg IV dose of DEX in patients with varying degrees of LD, with and without shunting. The PBPK model was successfully qualified across DEX, MDZ and PRO. In contrast to healthy adults, the simulated systemic clearance of DEX decreased (35% - 60%) and the plasma concentrations increased (170% - 400%) in patients with LD. Moreover, at higher doses of DEX, the AUC ratio between healthy/LD individuals remained comparable to lower doses. The exposure of DEX in different stages of LD was predicted through PBPK modelling, providing a rational framework to predict PK in complex clinical scenarios related to COVID-19. Model simulations suggest dose adjustments of DEX in LD patients are not necessary considering the low dose administered in the COVID-19 protocol.
Pathogens detected using a syndromic molecular diagnostic platform in patients hospitalized with severe respiratory illness in South Africa in 2017
Authors: Moleleki Malefu , du Plessis Mignon , Ndlangisa Kedibone , Reddy Cayla , von Gottberg Anne , Hellferscee Orienka , Mekgoe Omphe , McMorrow Meredith , Walaza Sibongile , Cohen Cheryl , Tempia Stefano , Variava Ebrahim , Wolter Nicole
Published: November 2021

Background

Pneumonia continues to be a leading cause of death globally; however, in >50% of cases, an etiological agent is not identified. We describe the use of a multi-pathogen platform, TaqMan array card (TAC) real-time PCR, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI).

Methods

We conducted prospective hospital-based surveillance for SRI among patients at two sentinel sites in South Africa between January and December 2017. Patients were included in this study if a blood specimen and at least one respiratory specimen (naso- and oro-pharyngeal (NP/OP) swabs and/or sputum) were available for testing. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-squared test.

Results

During 2017, 956 patients were enrolled in SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 NP/OP and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected includedH. influenzae(225/637; 35%),S. pneumoniae(224/637; 35%), rhinovirus (144/637; 23%),S. aureus(129/637; 20%),K. pneumoniae(85/637; 13%),M. tuberculosis(75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (≥2) were co-detected in 57% (364/637) of patients.

Conclusion

While use of a multi-pathogen platform was useful in the detection of a pathogen in the majority of the patients, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions.
What happened when? Brain and behavioral responses to modified structure and content in episodic cueing
Authors: Siestrup Sophie , Jainta Benjamin , El-Sourani Nadiya , Trempler Ima , Wolf Oliver T. , Cheng Sen , Schubotz Ricarda I.
Published: November 2021

Episodic memories are not static but can be modified on the basis of new experiences, potentially allowing us to make valid predictions in the face of an ever-changing environment. Recent research has identified prediction errors during retrieval as a possible trigger for such changes. In the present study, we used modified episodic cues to investigate whether different types of mnemonic prediction errors modulate brain activity and subsequent memory performance. Participants encoded different episodes which consisted of short toy stories. During a subsequent functional magnetic resonance imaging (fMRI) session, participants were then presented videos showing the original episodes, or modified versions thereof. In modified videos, either the order of two subsequent action steps was changed or an object was exchanged for another. Content modifications recruited inferior frontal, parietal, and temporo-occipital areas reflecting the processing of the new object information, while brain responses to structure modifications in right dorsal premotor and inferior frontal areas remained subthreshold. In a post-fMRI memory test, the participants’ tendency to accept modified episodes as originally encoded increased significantly when they had been presented modified versions already during the fMRI session. Our study provides valuable initial insights into the neural processing of different types of episodic prediction errors and their influence on subsequent memory.
Determining the architecture of nuclear ring of Xenopus laevis nuclear pore complex using integrated approaches
Authors: Ren He , Tai Linhua , Zhu Yun , Chan Chun , Zhao Qun , Xu Jiashu , Wang Xiangyang , Ma Xinyao , Zhao Lili , Huang Xiaojun , Yin Guoliang , Jia Mingkang , Zhu Xiaohong , An Yuxin , Zhao Gan , Huang Changxiong , Zhang Lihua , Fan Jun , Sun Fei , Zhang Chuanmao
Published: November 2021

The nuclear pore complexes (NPCs) are large protein assemblies as a physical gate to regulate nucleocytoplasmic transport. Here, using integrated approaches including cryo-electron microscopy, hybrid homology modeling and cell experiment, we determined the architecture of the nuclear ring (NR) from Xenopus laevis oocytes NPC at subnanometer resolution. In addition to the improvement of the Y complex model, eight copies of Nup205 and ELYS were assigned in NR. Nup205 connects the inner and outer Y complexes and contributes to the assembly and stability of the NR. By interacting with both the inner Nup160 and the nuclear envelope (NE), the N-terminal β-propeller and α-solenoid domains of ELYS were found to be essential for accurate assembly of the NPC on the NE.
Deciphering the language of antibodies using self-supervised learning
Authors: Leem Jinwoo , Mitchell Laura S. , Farmery James H.R. , Barton Justin , Galson Jacob D.
Published: November 2021

An individual’s B cell receptor (BCR) repertoire encodes information about past immune responses, and potential for future disease protection. Deciphering the information stored in BCR sequence datasets will transform our fundamental understanding of disease and enable discovery of novel diagnostics and antibody therapeutics. One of the grand challenges of BCR sequence analysis is the prediction of BCR properties from their amino acid sequence alone. Here we present an antibody-specific language model, AntiBERTa, which provides a contextualised representation of BCR sequences. Following pre-training, we show that AntiBERTa embeddings learn biologically relevant information, generalizable to a range of applications. As a case study, we demonstrate how AntiBERTa can be fine-tuned to predict paratope positions from an antibody sequence, outperforming public tools across multiple metrics. To our knowledge, AntiBERTa is the deepest protein family-specific language model, providing a rich representation of BCRs. AntiBERTa embeddings are primed for multiple downstream tasks and can improve our understanding of the language of antibodies.
Non-canonical Function of a Hif-1α Splice Variant Contributes to the Sustained Flight of Locusts
Authors: Ding Ding , Zhang Jie , Du Baozhen , Wang Xuanzhao , Hou Li , Guo Siyuan , Chen Bing , Kang Le
Published: November 2021

The hypoxia inducible factor (Hif) pathway is functionally conserved across metazoans in modulating cellular adaptations to hypoxia. However, the functions of this pathway under aerobic physiological conditions are rarely investigated. Here, we show that Hif-1α2, a locust Hif-1α isoform, does not induce canonical hypoxic responses but functions as a specific regulator of locust flight, which is a completely aerobic physiological process. Two Hif-1α splice variants were identified in locusts, a ubiquitously expressed Hif-1α1 and a muscle-predominantly expressed Hif-1α2. Hif-1α1 that induces typical hypoxic responses upon hypoxia exposure, remains inactive during flight. By contrast, the expression of Hif-1α2, which lacks C-terminal transactivation domain, is less sensitive to oxygen-tension but induced extensively by flying. Hif-1α2 sustains flight endurance by promoting glucose oxidation while simultaneously maintaining redox homeostasis by upregulating the production of a reactive oxygen species (ROS) quencher, DJ-1. Overall, this study reveals a novel Hif-mediated mechanism underlying prolonged aerobic physiological activity.
Mining the microbiota to identify gut commensals modulating neuroinflammation in a mouse model of multiple sclerosis
Authors: Bianchimano Paola , Britton Graham J. , Wallach David S. , Smith Emma M. , Cox Laura M. , Liu Shirong , Iwanowski Kacper , Weiner Howard L. , Faith Jeremiah J. , Clemente Jose C. , Tankou Stephanie K.
Published: November 2021

Background

The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotics effects are not understood. Furthermore, there is no consensus on the gut derived bacterial strains that drive neuroinflammation in multiple sclerosis.

Results

Here we characterized the gut microbiome of untreated and vancomycin treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut and some of them have been implicated in multiple sclerosis includingAnaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found thatAnaerotruncus colihominisameliorates EAE and this is associated with induction of RORγt+regulatory T cells in the mesenteric lymph nodes.

Conclusions

We identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevatedAnaerotruncus colihominisin multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease.
Learning enhances behaviorally relevant representations in apical dendrites
Authors: Benezra Sam E. , Patel Kripa B. , Campos Citlali Pérez , Hillman Elizabeth M.C. , Bruno Randy M.
Published: November 2021

Learning alters cortical representations and improves perception. Apical tuft dendrites in Layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of Layer 5 pyramidal neurons in barrel cortex as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.
Decoupling the molecular regulation of perenniality and flowering in bulbous barley (Hordeum bulbosum)
Authors: Fuerst Dana , Shermeister Bar , Mandel Tali , Hübner Sariel
Published: November 2021

Global crop production is being challenged by rapid population growth, declining natural resources, and dramatic climatic turnovers. These challenges have prompted plant breeders to explore new ventures to enhance adaptation and sustainability in crops. One intriguing approach to make agriculture more sustainable is by turning annual systems into perennial which offers many economic and biodiversity-friendly benefits. Previous attempts to develop a perennial cereal crop employed a classical breeding approach and extended over a long period with limited success. Thus, elucidating the genetic basis of perenniality at the molecular level can accelerate the breeding process.

Here, we investigated the genetic basis of bulb formation in the barley congener species Hordeum bulbosum by elucidating the transcripts presence/absence variation compared with other annual species in the Poaceae, and a differential expression analysis of meristem tissues. The PAV analysis recaptured the expected phylogeny and indicated that H. bulbosum is enriched with developmental and disease responsive genes that are absent among annual species. Next, the abundance of transcripts was quantified and allowed to identify differentially expressed genes that are associated with bulb formation pathways in addition to major circadian clock genes that regulate flowering. A first model for the bulb formation pathway is suggested and include developmental and starch biosynthesis genes. To the best of our knowledge this is the first transcriptome developed for H. bulbosum and the first attempt to describe the regulation of bulb initiation in cereals at the molecular level.
Generalization of Habituation and Intrinsic Sensitization in the Leech
Authors: Burrell Brian D. , Sahley Christie L.
Published: November 2021

Using the shortening reflex of the medicinal leechHirudo medicinalis we examined stimulus generalization of habituation learning. Preparations received mechanosensory stimulus at two positions on the leech body wall, one site used to carry out habituation training and a second novel site to test for generalization of habituation. After training, the specific mechanosensory neurons activated by each stimulus were assessed using intracellular recordings. As expected, the closer the two sites were to each other, the greater the degree of generalization of habituation at the novel site and the more sensory cells were shared. However, a form of behavioral facilitation was observed at the trained site that resembled behavioral sensitization, but differed from the standard sensitization process in several respects. (1) Facilitation was induced by stimulation of the novel site before habituation training at the trained site, although the stimulus intensity at the novel site was equivalent to the training stimuli and was not the strong, noxious stimuli that normally induce sensitization. (2) The magnitude of the facilitating effect was proportional to the proximity of the novel and trained stimulation sites. (3) Although behavior at the trained site was facilitated, behavior at the novel site was habituated, indicating that the induced behavioral facilitation did not generalize throughout the animal, as normally occurs during sensitization, but was limited to a single stimulus–response pathway.
Target group distribution pattern analysis with bagged convolutional neural networks for UAV distribution pattern identification
Authors: Xu Xin
Published: November 2021

Purpose

The purpose of this study is to address the limitations of existing target group distribution pattern analysis methods and identify subtle distribution differences within and between the groups with no pre-specified distribution features. Classical work generally concentrates on either the group distribution tendency or shape as a whole and simply ignores the subtle distribution differences within the group. Other work is constrained to pre-defined spatial distribution features.

Design/methodology/approach

This study proposes a novel algorithm for target group distribution pattern analysis. This study first transforms the group distribution data with uncertain measurements into a distributional image. Upon that, a bagged convolutional neural network model is constructed to discriminate the delicate group distribution patterns.

Findings

Experimental results indicate that our method is robust to target missing and location variance and scalable with dataset size. Our method has outperformed the benchmark machine learning methods significantly in pattern identification accuracy.

Originality/value

Our method is applicable for complex unmanned aerial vehicle distribution pattern identification.
To create the value of indigenous tourism in multicultural market based on tourists' cultural experience
Authors: Chen Yin-Ju
Published: November 2021

Purpose

Tourism development can reduce the economic disadvantages of indigenous tribes; however, it is also reproached for the destruction of local culture. The challenge for tourism and culture is to reach those diverse audiences through a multicultural marketing perspective for managers to make decisions. Therefore, learning the activity preferences of tourism experiences and creating the value of indigenous tourism by strategies are essential indicators of this research.

Design/methodology/approach

The knowledge lacks cultural understanding and the acceptance of prices concerned with indigenous tourism. This research introduces the value of cultural experience into indigenous tourism experiences and establishes a link between the attributes of tourists' preferences and tourism. The data mining methods are used to analyze relevant indigenous tribal data on the cultural experience.

Findings

By providing a different quality of service for various tourists, it is expected to improve the sustainable tourism of the tribe through the experiential value of different attributes and strategies of push–pull factors.

Research limitations/implications

The experiential activities are based on second-hand data collected from Taitung's indigenous tourism activities, and sample data are the domestic tourism experiences of tourists over the past year. Through empirical analyses, the attributes of tourists' preferences can create the value of the cultural experience for indigenous tourism.

Originality/value

This research explores how indigenous cultural experience can be communicated via learning the value of cultural experience to formulate effective strategies.
Mentoring, research self-efficacy, work–life balance and psychological well-being of doctoral program students
Authors: Haider Zain , Dasti Rabia
Published: November 2021

Purpose

The present correlational research study examined the theoretical and statistical relationship between mentoring, research self-efficacy, work–life balance and the psychological well-being of doctoral program students. The study highlights the positive role of mentoring for uplifting the eudemonic aspects of well-being of doctoral program students of natural sciences.

Design/methodology/approach

A purposive sample (N = 72) of natural sciences doctoral program students was selected from the Higher Education Commission recognized universities of Lahore and Sargodha. Participants' experiences regarding mentoring were operationalized utilizing the Mentorship Effectiveness Scale (Berket al., 2005). Similarly, their levels of research self-efficacy, work–life balance and psychological well-being were operationalized via the Self-Efficacy in Research Measure (Phillips and Russell, 1994), Work–life Balance Scale (Broughet al., 2014) and Psychological Well-Being Scale (Ryff, 1989), respectively.

Findings

Results indicated that mentoring, research self-efficacy, work–life balance and psychological well-being were significantly positively related to one another. The parallel mediation analysis through the process established the path model of mentoring and psychological well-being. The model highlights the importance of mentoring mechanisms in strengthening research self-efficacy and work–life balance and in turn enhancing the psychological well-being of doctoral program students.

Originality/value

This paper highlights the significance of mentoring for the psychological well-being of doctoral program students. It can guide policymakers and mentors to acknowledge and address the research-based needs of these students in terms of improved well-being and productivity.
An appraisal of generic skills for Nigerian built environment professionals in workplace: the unexplored approach
Authors: Ebekozien Andrew , Aigbavboa Clinton Ohis , Thwala Wellington Didibhuku Didibhuku , Aigbedion Marvelous Isibor , Ogbaini Iliye Faith
Published: November 2021

Purpose

Research shows that employers are demanding generic skills from employees to complement disciplinary expertise. Evidence shows that majority of the higher institutions are struggling to meet this demand, especially in developing nations. Hence, these skills may be acquired while in the workplace through training and retraining. Studies concerning the Nigerian built environment professionals (BEP) generic skills in the workplace are scarce. Therefore, the purpose of this paper is to investigate Nigeria’s BEP generic skills in the workplace via an unexplored mechanism and proffer feasible policy solutions that can improve BEP generic skills development.

Design/methodology/approach

The views of BEP were collated via a phenomenology type of qualitative research design across two major Nigerian cities where construction activities are soaring. Virtual interviews were conducted for 20 selected BEP. Data saturation was accomplished and the emerged three themes were analysed through a thematic analysis.

Findings

Findings show that generic skills enhance value for money in construction project delivery. But many of these professionals do not possess these skills in their daily operations. This has raised concerns about the present curriculum for preparing the built environment graduates in today’s profession. Findings categorised the hindrances into employers related-hindrances and employees related-hindrances in Nigeria’s BEP context.

Research limitations/implications

This study is confined to the relevance and hindrances of the generic skills for Nigerian BEP, and proffer feasible policies to promote generic skills in the workplace via a qualitative approach. Future study is needed to investigate the role of the various professional Institutes within Nigeria’s built environment in promoting generic skills.

Practical implications

The paper advanced key stakeholders including BEP Institutes and regulatory bodies to redirect their continuing professional development towards developing professional values and identities as a trajectory to promote the growth of BEP generic skills in the workplace.

Originality/value

The proposed framework can be used to promote the implementation of generic skills for BEP across all levels. This would assist and stir up policymakers and other stakeholders in connection with the implementation of generic skills within the BEP.
Influence of cartoon characters on generation alpha in purchase decisions
Authors: Gupta Ashish , Kumar Jitender , Tewary Tavishi , Virk Nirmaljeet Kaur
Published: November 2021

Purpose

This study aims to understand the influence of cartoon characters on the generation alpha (GA) in purchase decision-making, supported by the theory of planned behaviour.

Design/methodology/approach

Quantitative study was used to collect data from 294 Indian parents on behalf of their children (between 8 and 12 years) using convenience sampling and 20 items Likert scale questionnaire. Partial least squares-structural equation modelling was used to analyse the data and for hypothesis testing.

Findings

The study shows the favourable impact of cartoon characters to influence the behaviour of GA while making the final purchase decision. The likability was found to be significantly related to the recall, willingness to try/buy. The recall was significantly related to willingness to try/buy and purchase intention. Willingness to try/but was significantly related to purchase intention, but it has no significant relation with the final purchase decision, whereas purchase intention had significant relation with the final purchase decision.

Practical implications

The study indicates that generating likability for cartoon characters among GA is important. Managers should recognize that although parents make the final purchase decision, however, children play an influential role. Advertisers should plan their communication accordingly. An emotional connection with cartoons can influence GA, which further impacts recall, willingness to try/buy, purchase intention and decision.

Originality/value

Various studies have been conducted in western countries, but very few studies have been conducted in emerging markets like India, highlighting cartoon characters’ influence on GA’s purchase decision-making, with theoretical underpinnings. The study also explores the importance of GA, an emerging consumer market in today’s digitalized era, which is highly influenced by technological gadgets. It becomes challenging for marketers to promote their products on television to influence GA purchase behaviour.