bluuebunny/crossref_metadata_2025 huggingface dataset:
The preparedness and response to COVID-19 in a quaternary Intensive Care Unit in Australia: perspectives and insights from frontline critical care clinicians
Authors: Sundararajan Krishnaswamy , Bi Peng , Milazzo Adriana , Poole Alexis , Reddi Benjamin , Mahmood Mohammad Afzal
Published: November 2021

Objectives

This study was conducted to explore the perspectives and opinions of Intensive Care Unit (ICU) nurses and doctors at a COVID-19 designated pandemic hospital concerning the preparedness and response to COVID-19 and to consolidate the lessons learnt for crisis/disaster management in the future.

Design

A qualitative study using in-depth interviews (IDIs) and focus group discussions (FGDs). Purposeful sampling was conducted to identify participants. A semi-structured guide was utilised to facilitate in-depth interviews with individual participants. Two focus group discussions were conducted, one with the ICU doctors and another with the ICU nurses. Thematic analysis identified themes and subthemes informing about the level of preparedness, response measures, processes, and factors that were either facilitators or those that triggered challenges.

Setting

ICU in a quaternary referral centre affiliated to a university teaching COVID-19 designated pandemic hospital, in Adelaide, South Australia.

Participants

The participants included eight ICU doctors and eight ICU nurses for the in-depth interviews. Another sixteen clinicians participated in focus group discussions.

Results

The study identified six themes relevant to preparedness for, and responses to, COVID-19. The themes included: (1) Staff competence and planning, (2) Information transfer and communication, (3) Education and skills for the safe use of PPE, (4) Team dynamics and clinical practice, (5) leadership, and (6) Managing End-of life situations and expectations of caregivers.

Conclusion

Findings highlight that preparedness and response to the COVID-19 crisis were proportionate to the situation’s gravity. More enablers than barriers were identified. However, opportunities for improvement were recognised in the domains of planning, logistics, self-sufficiency with equipment, operational and strategic oversight, communication, and managing end-of-life care.

ARTICLE SUMMARY

Strengths and limitations of this study

This is the first study that provided insights about clinicians’ perspectives and viewpoints to preparing and responding to COVID-19 in Australia.

The study used qualitative methodological framework allowing participants to provide in-depth accounts of processes and enabling factors and barriers.

Our study provides information on issues that needs to be addressed from a critical care viewpoint and interventions that were effective and efficient

This is a single-center study in a developed country where experience is vastly different from other centers with higher demand and fewer resources

We acknowledge the potential for selection bias because of the qualitative design
ACPA-IgG variable domain glycosylation increases before the onset of rheumatoid arthritis and stabilizes thereafter; a cross-sectional study encompassing over 1500 samples
Authors: Kissel T. , Hafkenscheid L. , Wesemael T.J. , Tamai M. , Kawashiri S.Y. , Kawakami A. , El-Gabalawy H.S. , van Schaardenburg D. , Rantapää-Dahlqvist S. , Wuhrer M. , van der Helm-van Mil A.H.M. , Allaart C.F. , van der Woude D. , Scherer H.U. , Toes R.E.M. , Huizinga T.W.J.
Published: November 2021

Objective

The autoimmune response in rheumatoid arthritis (RA) is marked by anti-citrullinated protein antibodies (ACPA). A remarkable feature of ACPA-IgG is the abundant expression of N-linked glycans in the variable domain. Nonetheless, the presence of ACPA variable domain glycans (VDG) across disease stages and its’ response to therapy is poorly described. To understand its dynamics, we investigated the abundance of ACPA-IgG VDG in 1574 samples from individuals in different clinical disease stages.

Methods

Using liquid chromatography, we analyzed ACPA-IgG VDG profiles of 7 different cohorts from Japan, Canada, the Netherlands and Sweden. We assessed 184 healthy, 228 pre-symptomatic, 277 arthralgia, 305 patients at RA-onset and 117 RA-patients 4, 8 and 12 months after disease onset. Additionally, we measured VDG of 234 samples from RA-patients that did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up.

Results

Our data show that ACPA-IgG VDG significantly increases (p<0.0001) towards disease-onset and associates with ACPA-levels and epitope spreading pre-diagnosis. A slight increase in VDG was observed in established RA and a moderate influence of treatment. Individuals who later achieved DFR displayed reduced ACPA-IgG VDG already at RA-onset.

Conclusion

The abundance of ACPA-IgG VDG rises towards RA-onset and correlates with maturation of the ACPA-response. Although, ACPA-IgG VDG levels are rather stable in established disease, a lower degree at RA-onset correlates with DFR. Even though the underlying biological mechanisms are still elusive, our data support the concept that VDG relates to an expansion of the ACPA-response pre-disease and contributes to disease-development.
Recurrent urinary tract infection and estrogen shape the taxonomic ecology and functional potential of the postmenopausal urobiome
Authors: Neugent Michael L. , Kumar Ashwani , Hulyalkar Neha V. , Lutz Kevin C. , Nguyen Vivian H. , Fuentes Jorge L. , Zhang Cong , Nguyen Amber , Sharon Belle M. , Kuprasertkul Amy , Arute Amanda P. , Ebrahimzadeh Tahmineh , Natesan Nitya , Li Qiwei , Xing Chao , Shulaev Vladimir , Zimmern Philippe E. , Palmer Kelli L. , De Nisco Nicole J.
Published: November 2021

Community-acquired urinary tract infection (UTI) is among the most common bacterial infections observed in humans. Postmenopausal women are a rapidly growing and underserved demographic group who are severely affected by recurrent UTI (rUTI) with a >50% recurrence rate. In this population, rUTI can persist for years, reducing quality of life and imposing a significant healthcare burden. rUTI is most often treated by antibiotics, but development of antibiotic resistance and allergy limit therapeutic options. The female urinary microbiome (urobiome) has been identified as a key component of the urogenital environment. However, compositional and functional changes in the urobiome underlying rUTI susceptibility in postmenopausal women are not well understood. Here, we used a controlled, cross-sectional cohort of postmenopausal women, to interrogate changes in urobiome structure and function linked to rUTI susceptibility by whole genome metagenomic sequencing (WGMS), advanced urine culture, estrogen metabolite profiling, and antibiotic sensitivity testing. Overall, we detected 276 bacterial, archaeal, and fungal species representing 106 genera. We find a putative commensal population consisting of species known to protect against bacterial vaginosis, such as Lactobacillus crispatus, within the urobiome of postmenopausal women who do not experience UTI. Integration of clinical metadata detected an almost exclusive enrichment of lactobacilli, including L. crispatus and L. vaginalis, in women taking estrogen hormone therapy (EHT). Integrating quantitative metabolite profiling of urinary estrogens with WGMS, we observed robust correlations between urobiome taxa, such as Bifidobacterium breve and L. crispatus, and urinary estrogen conjugate concentrations in women with no history of UTI that were absent in women with rUTI history. We further used functional metagenomic profiling and patient-derived isolate phenotyping to identify microbial metabolic pathways, antimicrobial resistance genes (ARGs), and clinically relevant antimicrobial resistance phenotypes enriched between disease-states. Our data indicate that distinct urobiome metabolic and ARG signatures are associated with current rUTI status and history. Importantly, we observed that rUTI history leaves an imprint of enriched ARGs even in women not currently experiencing UTI. Taken together, our data suggests that rUTI history and estrogen strongly shape the functional and taxonomic composition of the urobiome in postmenopausal women.
Coffee, smoking and aspirin are associated with age at onset and clinical severity in idiopathic Parkinson’s disease
Authors: Gabbert Carolin , König Inke R. , Lüth Theresa , Kolms Beke , Kasten Meike , Vollstedt Eva-Juliane , Balck Alexander ,   Fox Insight Study, Grünewald Anne , Klein Christine , Trinh Joanne
Published: November 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene-environment interactions have been found to modify PD risk and disease progression. The objective of this study was to evaluate the association of smoking, caffeine and anti-inflammatory drugs with age at onset (AAO) and clinical severity in a large PD cohort. A total of 35,963 American patients with idiopathic PD (iPD) from the Fox Insight Study responded to health and lifestyle questionnaires. We compared the median AAO between different groups using the non-parametric Mann-Whitney U test. Non-parametric Spearman correlation was used for correlation assessments and regression analysis was used to assess interaction between variables. Reported p-values remain descriptive because they are not corrected for multiple testing and results are exploratory. We found that smoking (r=0.08, p<0.0001), coffee drinking (r=0.69, p<0.0001) and aspirin intake (r=0.23, p<0.0001) show an exploratory association with AAO in iPD. However, the effect of aspirin diminished as an independent predictor after including comorbidities (heart diseases and arthritis). Smoking was associated with higher (more severe) motor scores, while coffee drinking was linked to lower (less severe) motor scores (p<0.05). In addition, smokers reported anxiety, depression and other non-motor symptoms such as unexplained pains and problems remembering (p<0.05). The association of aspirin with PD AAO was replicated in another cohort (EPIPARK) (n=237 patients with PD), although again the effect diminished after including age in the regression model. Future longitudinal studies are warranted to investigate the clinical severity over time.
Listening to mental health crisis needs at scale: using Natural Language Processing to understand and evaluate a mental health crisis text messaging service
Authors: Liu Zhaolu , Peach Robert L. , Lawrance Emma L. , Noble Ariele , Ungless Mark A. , Barahona Mauricio
Published: November 2021

Abstract

The current mental health crisis is a growing public health issue requiring a large-scale response that cannot be met with traditional services alone. Digital support tools are proliferating, yet most are not systematically evaluated, and we know little about their users and their needs. Shout is a free mental health text messaging service run by the charity Mental Health Innovations, which provides support for individuals in the UK experiencing mental or emotional distress and seeking help. Here we study a large data set of anonymised text message conversations and post-conversation surveys compiled through Shout. This data provides an opportunity to hear at scale from those experiencing distress; to better understand mental health needs for people not using traditional mental health services; and to evaluate the impact of a novel form of crisis support. We use natural language processing (NLP) to assess the adherence of volunteers to conversation techniques and formats, and to gain insight into demographic user groups and their behavioural expressions of distress. Our textual analyses achieve accurate classification of conversation stages (weighted accuracy = 88%), behaviours (1-hamming loss = 95%) and texter demographics (weighted accuracy = 96%), exemplifying how the application of NLP to frontline mental health data sets can aid with post hoc analysis and evaluation of quality of service provision in digital mental health services.
The effect of notification window length on the epidemiological impact of COVID-19 contact tracing mobile applications
Authors: Leng Trystan , Hill Edward M. , Keeling Matt J. , Tildesley Michael J. , Thompson Robin N.
Published: November 2021

1

The reduction in SARS-CoV-2 transmission from contact tracing applications (apps) depends both on the number of contacts notified and on the probability that those contacts quarantine after notification. Referring to the number of days preceding a positive test that contacts are notified as an app’s notification window, we use an epidemiological model of SARS-CoV-2 transmission that captures the profile of infection to consider the trade-off between notification window length and active app-usage. We focus on 5-day and 2-day windows, the lengths used by the NHS COVID-19 app in England and Wales before and after 2nd August 2021, respectively. Short windows can be more effective at reducing transmission if they are associated with higher levels of active app usage and adherence to isolation upon notification, demonstrating the importance of understanding adherence to control measures when setting notification windows for COVID-19 apps.
A multiscale computational study of the conformation of the full-length intrinsically disordered protein MeCP2
Authors: Chávez-García Cecilia , Hénin Jérôme , Karttunen Mikko
Published: November 2021

The malfunction of the Methyl CpG binding protein 2 (MeCP2) is associated to the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modelling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and TRD domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent accessible, and having 4.1% of α-helix content, compared to the 4% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.
Towards a structurally resolved human protein interaction network
Authors: Burke David F. , Bryant Patrick , Barrio-Hernandez Inigo , Memon Danish , Pozzati Gabriele , Shenoy Aditi , Zhu Wensi , Dunham Alistair S , Albanese Pascal , Keller Andrew , Scheltema Richard A. , Bruce James E. , Leitner Alexander , Kundrotas Petras , Beltrao Pedro , Elofsson Arne
Published: November 2021

All cellular functions are governed by complex molecular machines that assemble through protein-protein interactions. Their atomic details are critical to the study of their molecular mechanisms but fewer than 5% of hundreds of thousands of human interactions have been structurally characterized. Here, we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human interactions. We show that higher confidence models are enriched in interactions supported by affinity or structure-based methods and can be orthogonally confirmed by spatial constraints defined by cross-link data. We identify 3,137 high confidence models, of which 1,371 have no homology to a known structure, from which we identify interface residues harbouring disease mutations, suggesting potential mechanisms for pathogenic variants. We find groups of interface phosphorylation sites that show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple interactions as signalling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies. Accurate prediction of protein complexes promises to greatly expand our understanding of the atomic details of human cell biology in health and disease.
Open Access publishing in Medicine: lights and shadows
Authors: Bernabò Nicola , Valbonetti Luca , Ordinelli Alessandra , Ciccarelli Rosa , Barboni Barbara
Published: November 2021

The widespread use of internet has had enormous consequences in changing the way of accessing to scientific literature in all domains of knowledge and, in particular, in medicine. One of the most important related factors is the idea of making research output freely available: the so-called Open Access (OA) option. OA is considered very important in spreading of knowledge, breaking down barriers in benefit of research, and increasing the impact of research outputs within the scientific community.

Here, we carried out a comparison between Non-Open Access (NOA) and OA medical Journals in terms of growing rate, geographical distribution, and the impact on scientific community.

We collected the bibliometric data on the scientific Journals indexed in Scopus starting from 2001 to 2016 published either as NOA or OA. Then, we analysed the number of Journals, their geolocalization, their impact on the scientific community, and the parameters as SJR, H index, and cites for document (2 years).

As a result, we found that while the number of NOA Journals is virtually stable, that of OA is dramatically increasing, with a growing rate higher than 400% in 2016. Then, the majority of OA Journals are published in developing Countries (Brazil, India, South Africa, South Korea, New Zealand, Serbia, and Poland) and their impact within researchers is lower compared to the NOA Journals.

In conclusion, our data provide an updated and unprecedented picture of OA adoption in medical field, with its lights and shadows.

Article Highlights

We are seeing in medicine a huge increase in the number of Journals that use OA;

This trend is mainly due to the increase in publishing Journals in Countries with emergent economies;

The use of OA for Journals in the medical field, did not guarantee a vantage in term of bibliometric parameters.

MCS

92C99

JEL

I30
Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways
Authors: Ibanez Kristen R , McFarland Karen N , Phillips Jennifer , Allen Mariet , Lessard Christian , Zobel Lillian , De La Cruz Elsa Gonzalez , Shah Shivani , Vo Quan , Wang Xue , Quicksall Zach , Ryu Daniel , Funk Cory , Ertekin-Taner Nilufer , Prokop Stefan , Golde Todd E , Chakrabarty Paramita
Published: November 2021

The S209F variant of Abelson Interactor Protein 3 (ABI3) increases risk for Alzheimer’s disease (AD), but little is known about ABI3 function. RNAscope showed Abi3 is expressed in microglial and non-microglial cells, though its increased expression appears to be driven in plaque-associated microglia. Here, we evaluated Abi3-/- mice and document that both Abi3 and its overlapping gene, Gngt2, are disrupted in these mice. Expression of Abi3 and Gngt2 are tightly correlated, and elevated, in rodent models of AD. RNA-seq of the Abi3-Gngt2-/- mice revealed robust induction of an AD-associated neurodegenerative signature, including upregulation of Trem2, Plcg2 and Tyrobp. In APP mice, loss of Abi3-Gngt2 resulted in a gene dose- and age-dependent reduction in Aβ deposition. Additionally, in Abi3-Gngt2-/- mice, expression of a pro-aggregant form of human tau exacerbated tauopathy and astrocytosis. Further, the AD-associated S209F mutation alters the extent of ABI3 phosphorylation. These data provide an important experimental framework for understanding the role of Abi3-Gngt2 function in AD. Our studies also demonstrate that manipulation of glial function could have opposing effects on amyloid and tau pathology, highlighting the unpredictability of targeting such pathways in AD.
Transcription modulates chromatin dynamics and locus configuration sampling
Authors: Forte Giada , Buckle Adam , Boyle Shelagh , Marenduzzo Davide , Gilbert Nick , Brackley Chris A.
Published: November 2021

In living cells the 3D structure of gene loci is dynamic, but this is not revealed by 3C and FISH experiments in fixed samples, leaving a significant gap in our understanding. To overcome these limitations we applied the “highly predictive heteromorphic polymer” (HiP-HoP) model, validated by experiments, to determine chromatin fibre mobility at the Pax6 locus in three mouse cell lines with different transcription states. While transcriptional activity minimally affects the movement of 40 kbp regions, we observed that the motion of smaller 1 kbp regions depends strongly on local disruption to chromatin fibre structure marked by H3K27 acetylation. This also significantly influenced locus configuration dynamics by modulating promoter-enhancer loops associated with protein bridging. Importantly these simulations indicate that chromatin dynamics are sufficiently fast to sample all possible conformations of loci within minutes, generating wide dynamic variability of gene loci structure within single cells. Experiments inhibiting transcription change chromatin fibre structure subtly, yet we predict they should substantially affect mobility. This combination of simulation and experimental validation provide a novel insight and mechanistic model to explain how transcriptional activity influences chromatin structure and gene dynamics.
High Throughput Intact Protein Analysis for Drug Discovery Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry
Authors: Pu Fan , Ugrin Scott A. , Radosevich Andrew J. , Chang-Yen David , Sawicki James W. , Talaty Nari N. , Elsen Nathaniel L. , Williams Jon D.
Published: November 2021

Mass spectrometry (MS) is the primary analytical tool used to characterize proteins within the biopharmaceutical industry. Electrospray ionization (ESI) coupled to liquid chromatography (LC) is the current gold standard for intact protein analysis. However, inherent speed limitations of LC/MS prevent analysis of large sample numbers (>1000) in a day. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI-MS), an ambient ionization MS technology, has recently been established as a platform for high throughput small molecule analysis. Here we report the applications of such a system for the analysis of intact proteins commonly performed within the drug discovery process. A wide molecular weight range of proteins 10 – 150 kDa was detected on the system with improved tolerance to salts and buffers compared to ESI. With high concentrations and model proteins, a sample rate up to 22 Hz was obtained. For proteins at low concentrations and in buffers used in commonly employed assays, robust data at a sample rate of 1.5 Hz was achieved, which is ∼ 22x faster than current technologies used for high throughput ESI-MS-based protein assays. In addition, two multiplexed plate-based high throughput sample cleanup methods were coupled to IR-MALDESI-MS to enable analysis of samples containing excessive amounts of salts and buffers without fully compromising productivity. Example experiments, which leverage the speed of the IR-MALDESI-MS system to monitor NISTmAb reduction, protein autophosphorylation and compound binding kinetics in near real-time, are demonstrated.

Graphical Abstract
Ubiquitination of stalled ribosomes enables mRNA decay via HBS-1 and NONU-1in vivo
Authors: Monem Parissa C. , Vidyasagar Nitin , Piatt Audrey L. , Sehgal Enisha , Arribere Joshua A.
Published: November 2021

As ribosomes translate the genetic code, they can encounter a variety of obstacles that hinder their progress. If ribosomes stall for prolonged times, cells suffer due to the loss of translating ribosomes and the accumulation of aberrant protein products. Thus to protect cells, stalled ribosomes experience a series of reactions to relieve the stall and degrade the offending mRNA, a process known as No-Go mRNA Decay (NGD). While much of the machinery for NGD is known, the precise ordering of events and factors along this pathway has not been tested. Here, we deployC. elegansto unravel the coordinated events comprising NGD. Utilizing a novel reporter and forward and reverse genetics, we identify the machinery required for NGD. Our subsequent molecular analyses define a functional requirement for ubiquitination on at least two ribosomal proteins (eS10 and uS10), and we show that ribosomes lacking ubiquitination sites on eS10 and uS10 fail to perform NGDin vivo. We show that the nuclease NONU-1 acts after the ubiquitin ligase ZNF-598, and discover a novel requirement for the ribosome rescue factors HBS-1/PELO-1 in mRNA decay via NONU-1. Taken together, our work demonstrates mechanisms by which ribosomes signal to effectors of mRNA repression, and we delineate links between repressive factors working toward a well-defined NGD pathway.

AUTHOR SUMMARY

Ribosomes are large molecular machines entrusted with the essential task of reading mRNAs and building proteins. It is critical that ribosomes proceed with their work undeterred, so as to avoid traffic jams between ribosomes on mRNAs; however, they sometimes experience challenges which make traffic jams unavoidable. In these cases, cells have evolved machinery to clean up stalled ribosomes and remove offending mRNAs. Much of this machinery is now identified, but the relationships between factors has yet to be tested. Here, inC. eleganswe identify the machinery that responds to stalls, and we order factors relative to one another. We find that ribosomes must be tagged by ubiquitin to signal mRNA decay, as ribosomes lacking ubiquitin sites fail to elicit mRNA decay. Furthermore, we find that these ubiquitin signals recruit an enzyme which cuts mRNA, and we present evidence that ribosome rescue factors are required for the mRNA decay reaction as well. Overall, our work provides new connections between factors orchestrating the elimination of problematic mRNAs that stall ribosomes.
Context-dependent inversion of the response in a single sensory neuron type reverses olfactory preference behavior
Authors: Khan Munzareen , Hartmann Anna H. , O’Donnell Michael P. , Piccione Madeline , Chao Pin-Hao , Dwyer Noelle D. , Bargmann Cornelia I. , Sengupta Piali
Published: November 2021

The valence and salience of individual odorants are modulated by an animal’s innate preferences, learned associations, and internal state, as well as by the context of odorant presentation. The mechanisms underlying context-dependent flexibility in odor valence are not fully understood. Here we show that the behavioral response of C. elegans to bacterially-produced medium-chain alcohols switches from attraction to avoidance when presented in the background of a subset of additional attractive chemicals. This context-dependent reversal of odorant preference is driven by cell-autonomous inversion of the response to alcohols in the single AWC olfactory neuron pair. We find that while medium-chain alcohols inhibit the AWC olfactory neurons to drive attraction, these alcohols instead activate AWC to promote avoidance when presented in the background of a second AWC-sensed odorant. We show that these opposing responses are driven via engagement of different odorant-directed signal transduction pathways within AWC. Our results indicate that context-dependent recruitment of alternative intracellular signaling pathways within a single sensory neuron type conveys opposite hedonic valences, thereby providing a robust mechanism for odorant encoding and discrimination at the periphery.
Ciliary Generation of a Peptidergic Sexual Signal
Authors: Luxmi Raj , Mains Richard E. , Eipper Betty A. , King Stephen M.
Published: November 2021

Peptidergic intercellular communication occurs throughout the eukaryotes, and regulates a wide range of physiological and behavioral responses. Cilia are sensory and secretory organelles that both receive information from the environment and transmit signals. Cilia derived vesicles (ectosomes), formed by outward budding of the ciliary membrane, carry enzymes and other bioactive products; this process represents an ancient mode of regulated secretion. Our previous study revealed the presence of the peptide amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), in cilia and its key role in ciliogenesis. Furthermore, PAM and its amidated products are released in ciliary ectosomes from the green alga Chlamydomonas reinhardtii. One amidated product (GATI-amide) serves as a chemotactic modulator for C. reinhardtii gametes, attracting minus gametes while repelling plus gametes. Here we dissect the complex processing pathway that leads to formation of this amidated peptidergic sexual signal specifically on the ectosomes of plus gametes. We also identify a potential prohormone convertase that undergoes domain rearrangement during ectosomal secretion as a substrate for PAM. Analysis of this pathway affords insight into how single-celled organisms lacking dense core vesicles engage in regulated secretion, and provides a paradigm for understanding how amidated peptides that transmit sexual and other signals through cilia are generated.
The predictive brain: temporal coincidence and temporal order in synaptic learning mechanisms.
Authors: Montague P R , Sejnowski T J
Published: November 2021

Some forms of synaptic plasticity depend on the temporal coincidence of presynaptic activity and postsynaptic response. This requirement is consistent with the Hebbian, or correlational, type of learning rule used in many neural network models. Recent evidence suggests that synaptic plasticity may depend in part on the production of a membrane permeant-diffusible signal so that spatial volume may also be involved in correlational learning rules. This latter form of synaptic change has been called volume learning. In both Hebbian and volume learning rules, interaction among synaptic inputs depends on the degree of coincidence of the inputs and is otherwise insensitive to their exact temporal order. Conditioning experiments and psychophysical studies have shown, however, that most animals are highly sensitive to the temporal order of the sensory inputs. Although these experiments assay the behavior of the entire animal or perceptual system, they raise the possibility that nervous systems may be sensitive to temporally ordered events at many spatial and temporal scales. We suggest here the existence of a new class of learning rule, called a predictive Hebbian learning rule, that is sensitive to the temporal ordering of synaptic inputs. We show how this predictive learning rule could act at single synaptic connections and through diffuse neuromodulatory systems.
Hippocampal formation size in normal human aging: a correlate of delayed secondary memory performance.
Authors: Golomb J , Kluger A , de Leon M J , Ferris S H , Convit A , Mittelman M S , Cohen J , Rusinek H , De Santi S , George A E
Published: November 2021

Although mild progressive memory impairment is commonly associated with normal human aging, it is unclear whether this phenomenon can be explained by specific structural brain changes. In a research sample of 54 medically healthy and cognitively normal elderly persons (ages 55-87, x = 69.0 +/- 7.9), magnetic resonance imaging (MRI) was used to derive head-size-adjusted measurements of the hippocampal formation (HF) (dentate gyrus, hippocampus proper, alveus, fimbria, subiculum), the superior temporal gyrus (STG), and the subarachnoid cerebrospinal fluid (CSF) (to estimate generalized cerebral atrophy). Subjects were administered tests of primary memory (digit span) and tests of secondary memory with immediate and delayed recall components (paragraph, paired associate, list recall; facial recognition). Separate composite scores for the immediate and delayed components were created by combining, with equal weighting, the subtests of each category. The WAIS vocabulary subtest was used as a control measure for language and intelligence. A highly significant correlation (P < 0.001), independent of age, gender, and generalized cerebral atrophy was found between HF size and delayed memory performance. No significant correlations were found between HF size and primary or immediate memory performance. STG size was not significantly correlated with any of the composite memory variables. These results suggest that HF atrophy may play an important independent role in contributing to the memory loss experienced by many aging adults.
Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization.
Authors: Huang Y Y , Kandel E R
Published: November 2021

To study how the late phase of long-term potentiation (LTP) in hippocampus arises, we examined the resulting LTP for its time course and its dependence on protein synthesis and different second-messenger kinases by applying various conditioning tetani. We find that one high-frequency train (100 Hz) produces a form of LTP that lasts longer than 1 hr but less than 3 hr (the early phase of LTP, or E-LTP). It is blocked by inhibitors of calcium/calmodulin kinase II (Cam kinase II) but is not affected by an inhibitor of cAMP-dependent protein kinase [protein kinase A (PKA) and the protein synthesis inhibitor anisomycin] nor is it occluded by the cAMP activator forskolin. In contrast, when three high-frequency trains are used, the resulting potentiation persists for at least 6-10 hr. The L-LTP induced by three trains differs from the E-LTP in that it requires new protein synthesis, is blocked by an inhibitor of cAMP-dependent protein kinase, and is occluded by forskolin. These results indicate that the two mechanistically distinctive forms of LTP, a transient, early component (E-LTP) and a more enduring form (L-LTP), can be recruited selectively by changing the number of conditioning tetanic trains. Repeated tetani induce a PKA and protein synthesis-dependent late component that adds to the amplitude and duration of the potentiation induced by a single tetanus.
Temporal and spatial regulation of the expression of BAD2, a MAP kinase phosphatase, during seizure, kindling, and long-term potentiation.
Authors: Qian Z , Gilbert M , Kandel E R
Published: November 2021

Recent studies indicate that stimulation of NMDA receptors in cultured hippocampal cells activates MAP kinase. Although the pathway whereby MAP kinase is activated has been been characterized, little is known about the mechanisms that shut off MAP kinase. In the course of analyzing several immediate-early genes identified previously by differential screen as inducible by seizure activity, we found that one of them, BAD2, encodes dual purpose, threonine/tyrosine phosphates with specific activity directed against MAP kinase (MKP-1). In situ hybridization of BAD2 demonstrates that stimuli that produce seizure, kindling, and long-term potentiation cause a rapid increase in BAD2 mRNA (within 0.5-1 hr after stimulation) that has, in each case, a distinctive pattern of expression in the brain. In these regions, the induction of a MAP kinase-specific phosphatase may provide a negative feedback control associated with long-term synaptic changes.
Evaluation of access to electricity and the socioeconomic effects in rural and urban expanses of Nigeria
Authors: Ogunro Toluwalope , Afolabi Luqman
Published: November 2021

Purpose

Recently, multidimensional aspects of poverty has been increasingly focused on which includes education, economy and health, while access to modern energy such as stable electricity is also one of the possible solution; thus, this article aims to divulge the relation between access to electricity and progression in socioeconomic status in urban and rural areas of Nigeria in an attempt to propose a sustainable framework for access to electricity.

Design/methodology/approach

Demographic and health survey data are collected using four categories of model of questionnaires. A standard questionnaire was designed to gather information on features of the household's dwelling element and attributes of visitors and usual residents between the 2018 period. Biomarker questionnaire was used to gather biomarker data on men, women and children. Logistic model estimation technique was employed to estimate the socioeconomic factors affecting access to electricity in Nigeria.

Findings

These studies discovered that there are diverse set of factors affecting access to electricity in Nigeria especially in the rural areas. However, respondent residing in rural areas are still largely deprived access to electricity; most importantly, households with no access to electricity are more likely to use self-generating sets as revealed. Additionally, empirical findings indicated that the higher the level of your education and wealth, the higher the likelihood of having access to electricity in Nigeria. These factors included political will to connect the rural areas to the national grid, development of other infrastructures in those deprived areas and others.

Practical implications

The problem confronting access to electricity in Nigeria has three components. The first is the significance of those deprived access to electricity in the rural areas and the physical resources needed to connect them to the national grid. The second is the political willingness of the government to have equitable distribution of public goods evenly between rural and urban areas especially on electricity access which will go a long way in reducing poverty in Nigeria. The third is lack of robust national development plans and strategy to tackle the problems facing electricity access in Nigeria.

Social implications

As the rate of socioeconomic status/development increases, access to electricity is anticipated to rise up in Nigeria.

Originality/value

The findings can be used by the policy makers to address problems facing access to electricity in Nigeria.
Key skills and competencies of LIS professionals in the digital library environment: a content analysis of job advertisements
Authors: Yadav Akhilesh K.S.
Published: November 2021

Purpose

The main purpose of this research study is to identify the essential skills and competencies sought by prospective employers for library and information science (LIS) positions in India. The research study aims to find out various designated positions in job advertisements.

Design/methodology/approach

The data were collected from a major weekly job journal “Employment News” in India over five years from 2016 to 2020. The Employment News provides the latest job vacancies of central/state governments, public sector undertakings and autonomous bodies in India. Each issue of Employment News was carefully scanned and searched for job advertisements in the field of LIS. The researcher analyzed various posts on permanent, deputation and short-term contracts to gain insights into the job’s skills.

Findings

The findings highlight that public sector academic and school libraries are the top employers of LIS professionals. One of the most frequent demands of employers is profession-related work experience. Results show that employers place the strongest emphasis on library administration, computer knowledge, technical skills, managerial skills and soft skills. Library management, library supervision and procurement of journals and books are the primary job responsibilities for top-level positions.

Research limitations/implications

The weekly job journal, Employment News, is the largest source of LIS jobs in publicly funded organizations and institutions in India. It does not cover private educational institutes, industries and corporates. Job-related data were collected solely from this journal for the duration of 2016–2020. Therefore, this research study does not fully represent the LIS job market with regard to private educational institutes and corporate organizations.

Practical implications

The research findings can help LIS professionals prepare themselves according to market needs and demands. The LIS school should integrate these required skills and competencies into the course curriculum for preparing professionals in the digital age.

Originality/value

The results are benchmarked to guide and evaluate LIS course curricula in India. LIS schools may emphasize soft skills in future curriculum design, which employers frequently seek.
Integrated solid-state wearable sweat sensor system for sodium and potassium ion concentration detection
Authors: Zhang Haowei , Sun Lili , Song Chengli , Liu Ying , Xuan Xueting , Wang Fei , Zhong Jing , Sun Li
Published: November 2021

Purpose

Design, fabricate and evaluate all-solid-state wearable sensor systems that can monitor ion concentrations in human sweat to provide real time health analysis and disease diagnosis capabilities.

Design/methodology/approach

A human health monitoring system includes disposable customized flexible electrode array and a compact signal transmission-processing electronic unit.

Findings

Patterned rGO (reduced-graphene oxide) layers can replace traditional metal electrodes for the fabrication of free-standing all solid film sensors to provide improved flexibility, sensitivity, selectivity, and stability in ion concentration monitoring. Electrochemical measurements show the open circuit potential of current selective electrodes exhibit near Nernst responses versus Na+ and K+ ion concentration in sweat. These signals show great stability during a typical measurement period of 3 weeks. Sensor performances evaluated through real time measurements on human subjects show strong correlations between subject activity and sweating levels, confirming high degree of robustness, sensitivity, reliability and practicality of current sensor systems.

Originality/value

In improving flexibility, stability and interfacial coherency of chemical sensor arrays, rGO films have been the developed as a high-performance alternative to conventional electrode with significant cost and processing complexity reduction. rGO supported solid state electrode arrays have been found to have linear potential response versus ion concentration, suitable for electrochemical sensing applications. Current sweat sensor system has a high degree of integration, including electrode arrays, signal processing circuits, and data visualization interfaces.
A simulated crime scene footwear impression database for teaching and research purposes
Authors: Lin En‐Tni , DeBat Tabitha , Speir Jacqueline A.
Published: November 2021

Community‐shared open‐source forensic footwear databases are relatively rare, although it is generally agreed that access to such resources can support a multitude of research and teaching/training goals. The objective of this technical report is to detail the creation of such a dataset that includes both high‐quality exemplars and simulated crime scene impressions. To achieve this goal, a variety of shoe makes, models, sizes, substrates, matrices, lifting methods, and enhancement (chemical/digital) techniques were employed and are fully described. The result is an open‐source dataset available for download, and comprised of 214 high‐quality impressions (87 right outsoles × 2 replicates + 40 left (close non‐mated) outsoles), 138 dust impressions (46 outsoles × 3 replicates), and 73 blood impressions (24 outsoles × 3 replicates = 72 + 1 additional replicate). Of the 138 dust impressions, 117 are provided in a digitally enhanced form (via Adobe® Photoshop and/or Photoshop Camera Raw software), and 120 are provided in an unenhanced form for a total of 237 images. For the blood impressions, all 73 are provided in both unenhanced and chemically enhanced forms for a total of 146 images. Thus, in addition to the outsole scans, a total of 597 simulated crime scene and/or known test impressions are included and fully documented.
Invasion and defense of the basic social unit in a nonhuman primate society leads to sexual differences in the gut microbiome
Authors: XIA Wancai , ZHAO Mei , WANG Dali , WANG Fan , CHEN Hua , LIU Guoqi , ZHU Lifeng , LI Dayong
Published: November 2021

Multilevel society is one of the most complex social systems in natural ecosystems and is a typical feature among some primates. Given the potential connection between social behavior and gut microbiome composition, the multilevel social system could affect the primate gut microbiome. Here, based on long‐term observation (e.g. social unit dynamics, transfer, and behavior), we investigated this potential integrating 16S rRNA gene amplicon sequencing and behavior data in Yunnan snub‐nosed monkeys (Rhinopithecus bieti), which possess a multilevel social group based on one male units (OMUs, each unit with several breeding females and their offspring) and all‐male unit (AMU, several bachelor males residing together). We found that the mean unweighted Unifrac distance between adult males from different OMUs was significantly lower than that between adult females from different OMUs (paired Wilcoxon test, P = 0.007). There was no significant difference in the mean unweighted Unifrac distance between females within the same OMU or between females from different OMUs. These findings indicated the potential connection between the defense and invasion of social units and the gut microbiome community in wild Yunnan snub‐nosed monkeys. We speculated that the resident males of OMUs displaying a significantly higher similarity in the gut microbial community than that of adult females in separate OMUs might be associated with the sexual differences in their interactions and from previously having cohabitated together in the AMU. Therefore, this study suggested that multilevel societies might have an effect on the gut microbial community in this wild nonhuman primate species.
Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: A case‐control study
Authors: Yu Songcheng , Feng Yinhua , Qu Chenling , Yu Fei , Mao Zhenxing , Wang Chongjian , Li Wenjie , Li Xing
Published: November 2021

Background

Physical activity and vitamin D receptor (VDR) have been associated with type 2 diabetes mellitus (T2DM). However, the associations of VDR methylation with T2DM and physical activity remained unknown. We aimed to investigate whether VDR methylation was a link between physical activity and T2DM.

Methods

A 1:1 matching case‐control study was designed based on the Henan Rural Cohort Study, including 272 pairs of T2DM patients and nonpatients. Physical activity level was assessed using the International Physical Activity Questionnaire. The high‐resolution melt method was applied to determine the methylation level of the promoter region of VDR. The association between physical activity and T2DM was analyzed with a conditional logistic regression model. The effect modification of VDR methylation levels on the association between physical activity and T2DM was conducted. A multivariate correlation analysis model was applied to investigate correlations of VDR methylation with insulin sensitivity.

Results

Physical activity level was associated with T2DM risk (crude model: odds ratio [OR] 0.611; 95% CI, 0.416‐0.897; adjusted model: OR 0.619; 95% CI, 0.418‐0.917). In effect modification analysis, the effects of physical activity on T2DM were stronger for low VDR methylation levels than for high (P = .025). Moreover, VDR methylation levels were associated with insulin (r = −0.089, P = .039) as well as homeostatic model assessment of insulin resistance (r = −0.098, P = .022).

Conclusions

The methylation status of the VDR promoter is associated with the secretion and sensitivity of insulin. VDR methylation attenuates the association between physical activity and T2DM, indicating that proactively physical activity may reduce the risk of T2DM, especially in people with low VDR methylation level.