bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and predictors of HIV testing among young men in Papua New Guinea: a cross-sectional analysis of a nationally representative sample
Authors: Maviso McKenzie
Published: March 2023

Background

HIV testing is an important component of HIV prevention and serves as a gateway to other HIV-related services. However, the uptake remains suboptimal among young people, particularly in highly prevalent settings such as Papua New Guinea (PNG). This study used nationally representative data to assess the prevalence and determine predictors of HIV testing uptake among young men aged 15–24 years in PNG.

Methods

The 2016–2018 PNG Demographic and Health Survey (PNGDHS) data was used. A total of 1,275 young men aged 15–24 years were included in the final analysis. Descriptive, bivariate, and multivariable logistic regression analyses were performed to determine independent predictors of HIV testing. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported. All analyses were adjusted using survey weights to account for unequal sampling probabilities.

Results

The overall prevalence of HIV testing among young men was 17.2% (95% CI: 15–19). Of those who were tested for HIV, most lived in rural areas (73%), about one-third had a sexual debut at age <15 years (32.9%), and 33.9% inconsistently used condoms during sex. In multivariable analysis, men aged 20–24 years (AOR 1.18, 95% CI: 1.00–2.31), who own mobile phones (AOR 1.43, 95% CI: 1.00– 2.55), who were aware that consistent condom use during sex can reduce HIV risk (AOR 2.18, 95% CI: 1.18–4.04), who had paid for sex (AOR 1.75, 95% CI: 1.01–5.83), and who had two or more sexual partners (AOR 1.37, 95% CI: 1.01–3.14) had increased odds of HIV testing. However, decreased odds of HIV testing were found among men who were never married (AOR 0.51, 95% CI: 0.29–0.88), lived in rural areas (AOR 0.54, 95% CI: 0.32–0.92), and consistently used condoms during sex (AOR 0.59, 95% CI: 0.34–1.01).

Conclusion

The findings show that HIV testing is low among young men in PNG. To increase HIV testing uptake among young men, it is crucial to implement comprehensive youth-friendly HIV/STI education and tailored sensitization programs and enable more accessible and affordable HIV testing services. Also, outreach and community-based testing programs for young men in prioritized areas requiring urgent prevention intervention are feasible options in PNG.
Delivering maternal and child health interventions through the private sector in LMIC: a scoping review of strategies and effective approaches
Authors: Awor Phyllis
Published: March 2023

Despite growing evidence on the role of private health providers, the global public health response to date has primarily focused on the provision of public sector health services for women and children in low and middle income countries (LMIC). Limitations of this approach are well documented and include: shortage of human resources, inefficient institutional frameworks and inadequate quality especially in rural areas. In order to achieve Universal Health Coverage, it is important to strengthen both the public and private sector. The objective was to determine effective strategies for engagement with private health providers for maternal and child health in LMIC.

A scoping review of both published and grey literature from 2000 – 2022 was undertaken, using including all types of papers reporting on: either population level data on the extent of utilization of the private sector for maternal and child health services in more than one country; or interventions for service provision in the private sector using population level results in one or more country; Or both of the above. Aggregate results were extracted, and content analysis was used to identify engagement strategies/themes.

The results confirm that the private sector is the dominant provider of outpatient care for women and children in LMIC, and a significant provider of reproductive and maternal health services including for inpatient care. Effective strategies and recommendations for engagement with private health providers are presented across challenges of private health provider engagement.
Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines – a matched cohort study in France
Authors: Auvigne Vincent , Tamandjou Cynthia , Schaeffer Justine , Vaux Sophie , Parent du Chatelet Isabelle
Published: March 2023

This cohort study aimed to evaluate the protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original (ancestral) monovalent vaccines. Individuals of ≥60 years old who received a booster dose between 03/10/2022 and 06/11/2022, when both the bivalent and monovalent vaccines were used in France, were included. Individuals who received a booster dose with (1) a monovalent Original mRNA vaccine (Pfizer- BioNTech or Moderna) or (2) the bivalent Pfizer-BioNTech Original/BA.4-5 vaccine were matched. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, at least seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136,852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8% [95% CI: 0% - 16%, p=0.045] against symptomatic SARS-CoV-2 infection compared to the monovalent vaccines.
Using natural language processing to study homelessness longitudinally with electronic health record data subject to irregular observations
Authors: Chapman Alec B. , Scharfstein Daniel O. , Montgomery Ann Elizabeth , Byrne Thomas , Suo Ying , Effiong Atim , Velasquez Tania , Pettey Warren , Nelson Richard E.
Published: March 2023

The Electronic Health Record (EHR) contains information about social determinants of health (SDoH) such as homelessness. Much of this information is contained in clinical notes and can be extracted using natural language processing (NLP). This data can provide valuable information for researchers and policymakers studying long-term housing outcomes for individuals with a history of homelessness. However, studying homelessness longitudinally in the EHR is challenging due to irregular observation times. In this work, we applied an NLP system to extract housing status for a cohort of patients in the US Department of Veterans Affairs (VA) over a three-year period. We then applied inverse intensity weighting to adjust for the irregularity of observations, which was used generalized estimating equations to estimate the probability of unstable housing each day after entering a VA housing assistance program. Our methods generate unique insights into the long-term outcomes of individuals with a history of homelessness and demonstrate the potential for using EHR data for research and policymaking.
Role of dietary sodium restriction in chronic heart failure. Systematic review and meta-analysis.
Authors: Urban Szymon , Fułek Michał , Błaziak Mikołaj , Fułek Katarzyna , Iwanek Gracjan , Jura Maksym , Grzesiak Magdalena , Szymański Oskar , Stańczykiewicz Bartłomiej , Ptaszkowski Kuba , Zymlinski Robert , Ponikowski Piotr , Biegus Jan Leon
Published: March 2023

Background Dietary sodium restriction remains guidelines-approved lifestyle recommendation for chronic heart failure (CHF) patients. However, its efficacy in clinical outcome improvement is dubious. Methods We performed a systematic review of the following databases: Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition, MEDLINE, Embase, Clinicaltrials.gov and Cochrane Library (trials) to find studies analysing the impact of sodium restriction in the adult CHF population. Both observational and interventional studies were included. Most considerable exclusion criteria included i.e.: sodium consumption assessment based only on natriuresis, in-hospital interventions or mixed interventions - e.g. sodium and fluid restriction in one arm only. The review was conducted following PRISMA guidelines. At least two independent reviewers screened databases and extracted the data. Meta-analysis was performed for the endpoints reported in at least 3 papers. The heterogeneity and sensitivity of the results were assessed. Analyses were conducted in Review Manager (RevMan) Version 5.4.1 The Cochrane Collaboration, 2020. Results Initially, we screened 9175 articles identified in the databases. Backward snowballing revealed 1050 additional articles. Eventually, 9 papers were evaluated in the meta-analysis. All-cause mortality, HF-related hospitalizations, and the composite of mortality and hospitalization were reported in 8, 6 and 3 articles, respectively. Sodium restriction was associated with a higher risk of composite endpoint (OR, 4.12 [95% CI, 1.23 - 13.82]) and did not significantly affect the all-cause mortality (OR, 1.38 [95% CI, 0.76 - 2.49]) or HF hospitalisation (OR, 1.63 [95% CI, 0.69 - 3.88]). Conclusions In a meta-analysis, sodium restriction in CHF patients worsened the prognosis in terms of composite of mortality and hospitalizations and did not influence all-cause mortality and HF hospitalisation rate.
Time-resolved molecular measurements reveal changes in astronauts during spaceflight
Authors: Zheng Minzhang , Charvat Jacqueline , Zwart Sara R. , Mehta Satish , Crucian Brian E. , Smith Scott M. , He Jin , Piermarocchi Carlo , Mias George I.
Published: March 2023

From the early days of spaceflight to current missions, astronauts continue to be exposed to multiple hazards that affect human health, including low gravity, high radiation, isolation during long-duration missions, a closed environment and distance from Earth. Their effects can lead to adverse physiological changes and necessitate countermeasure development and/or longitudinal monitoring. A time-resolved analysis of biological signals can detect and better characterize potential adverse events during spaceflight, ideally preventing them and maintaining astronauts’ wellness. Here we provide a time-resolved assessment of the impact of spaceflight on multiple astronauts (n=27) by studying multiple biochemical and immune measurements before, during, and after long-duration orbital spaceflight. We reveal space-associated changes of astronauts’ physiology on both the individual level and across astronauts, including associations with bone resorption and kidney function, as well as immune-system dysregulation.
Free ferrous ions sustain activity of mammalian stearoyl-CoA desaturase-1
Authors: Shen Jiemin , Wu Gang , Pierce Brad S. , Tsai Ah-Lim , Zhou Ming
Published: March 2023

Mammalian stearoyl-CoA desaturase-1 (SCD1) introduces a double-bond to a saturated long-chain fatty acid and the reaction is catalyzed by a diiron center, which is well-coordinated by conserved histidine residues and is thought to remain with enzyme. However, we find that SCD1 progressively loses its activity during catalysis and becomes fully inactive after nine turnovers. Further studies show that the inactivation of SCD1 is due to the loss of an iron (Fe) ion in the diiron center, and that the addition of free ferrous ions (Fe2+) sustains the enzymatic activity. Using SCD1 labeled with Fe isotope, we further show that free Fe2+is incorporated into the diiron center only during catalysis. We also discover that the diiron center in SCD1 has prominent electron paramagnetic resonance signals in its diferric state, indicative of distinct coupling between the two ferric ions. These results reveal that the diiron center in SCD1 is structurally dynamic during catalysis and that labile Fe2+in cells could regulate SCD1 activity, and hence lipid metabolism.
The energy landscape for R-loop formation by the CRISPR-Cas Cascade complex
Authors: Kauert Dominik J. , Madariaga-Marcos Julene , Rutkauskas Marius , Wulfken Alexander , Songailiene Inga , Sinkunas Tomas , Siksnys Virginijus , Seidel Ralf
Published: March 2023

The discovery1,2and the pioneering applications3of CRISPR-Cas effector complexes have provided powerful gene-editing tools. The effector complexes are guided to the targeted genomic locus by the complementarity of their CRISPR RNA (crRNA)4,5. Recognition of double-stranded DNA targets proceeds via DNA unwinding and base-pairing between crRNA and the DNA target strand resulting in the formation of an R-loop structure5,6. Full R-loop formation is the prerequisite for the subsequent DNA cleavage. While the CRISPR-Cas technology is easy to use, efficient and highly versatile, therapeutic applications are hampered by the off-target effects due to the recognition of unintended sequences with multiple mismatches7. This process is still poorly understood on a mechanistic level8,9. Particularly, the lack of insight into the energetics and dynamics of the R-loop formation hinders a direct modelling of the R-loop formation for off-target prediction.

Here we set up ultrafast DNA unwinding experiments based on plasmonic DNA nanorotors to follow the R-loop formation by the Cascade effector complex in real time, close to base pair resolution. We directly resolve a weak global downhill bias of the energy landscape of the forming R-loop followed by a steep uphill bias for the final base pairs. We furthermore show a modulation of the landscape by base flips and mismatches. These data provide that Cascade-mediated R-loop formation occurs on short time scales in single base pair steps of sub-millisecond duration, but on longer time scales in six–base pair intermediate steps in agreement with the structural periodicity of the crRNA-DNA hybrid. We expect that the knowledge about the energy landscapes of R-loop formation of CRISPR-Cas effector complexes will pave the way for a detailed understanding and prediction of off-target recognition10.
Genetic mapping identifies Homer1 as a developmental modifier of attention
Authors: Gershon Zachary , Bonito-Oliva Alessandra , Kanke Matt , Terceros Andrea , Rankin Genelle , Fak John , Harada Yujin , Iannone Andrew F. , Gebremedhin Millennium , Fabella Brian , De Marco García Natalia V. , Sethupathy Praveen , Rajasethupathy Priya
Published: March 2023

Attention is required for most higher-order cognitive functions. Prior studies have revealed functional roles for the prefrontal cortex and its extended circuits to enabling attention, but the underlying molecular processes and their impacts on cellular and circuit function remain poorly understood. To develop insights, we here took an unbiased forward genetics approach to identify single genes of large effect on attention. We studied 200 genetically diverse mice on measures of pre-attentive processing and through genetic mapping identified a small locus on chromosome 13 (95%CI: 92.22-94.09 Mb) driving substantial variation (19%) in this trait. Further characterization of the locus revealed a causative gene, Homer1, encoding a synaptic protein, where down-regulation of its short isoforms in prefrontal cortex (PFC) during early postnatal development led to improvements in multiple measures of attention in the adult. Subsequent mechanistic studies revealed that prefrontalHomer1down-regulation is associated with GABAergic receptor up-regulation in those same cells. This enhanced inhibitory influence, together with dynamic neuromodulatory coupling, led to strikingly low PFC activity at baseline periods of the task but targeted elevations at cue onset, predicting short-latency correct choices. Notably high-Homer1, low-attentional performers, exhibited uniformly elevated PFC activity throughout the task. We thus identify a single gene of large effect on attention - Homer1 – and find that it improves prefrontal inhibitory tone and signal-to-noise (SNR) to enhance attentional performance. A therapeutic strategy focused on reducing prefrontal activity and increasing SNR, rather than uniformly elevating PFC activity, may complement the use of stimulants to improve attention.
Motor nerves direct the development of the sympathetic nervous system
Authors: Erickson Alek , Motta Alessia , Kastriti Maria Eleni , Edwards Steven , Lallemend Francois , Hadjab Saida , Ruhrberg Christiana , Schwarz Quenten , Fried Kaj , Bonanomi Dario , Adameyko Igor
Published: March 2023

The sympathetic nervous system controls a wide spectrum of bodily functions including operation of vessels, cardiac rhythm, and the “flight or fight response”. Sympathetic neurons, which are neural crest-derived, develop in coordination with presynaptic motor nerves extending from the central nervous system (CNS). By using nerve-selective genetic ablations, we revealed that sympathetic ganglia development depends on CNS-derived motor innervation. In the absence of preganglionic motor nerves, trunk sympathetic chain ganglia were fragmented and smaller in size, while cervical ganglia were severely misshapen. Sympathetic neurons were misplaced along sensory fibers and projected towards abnormal paths, in some cases invading the sensory dorsal root ganglia. The misplaced progenitors of sympathoblasts corresponded to the nerve-associated, neural crest-derived Schwann cell precursors (SCPs). Notably, we found that SCPs activate the autonomic marker PHOX2B while migrating along motor nerves towards the region of the dorsal aorta in wildtype embryos, suggesting that SCP differentiate into sympathetic neurons while still nerve-associated in motor-ablated embryos. Ligand-receptor prediction from single cell transcriptomic data coupled with functional studies identified Semaphorin 3A/3F as candidate motor nerve-derived signals influencing neural crest migration along axons. Thus, motor nerves control the placement of sympathoblasts and their subsequent axonal navigation during critical periods of sympathetic chain development.
Hidden from plain sight: NovelChlamydiotadiversity emerging from screening genomic and metagenomic data
Authors: Davison Helen R. , Hurst Gregory D.D.
Published: March 2023

Chlamydiotaare an ancient and hyperdiverse Phylum of obligate intracellular bacteria. The best characterized representatives are pathogens or parasites of mammals, but it is thought that their most common hosts are microeukaryotes like Amoebozoa. The diversity in taxonomy, evolution, and function of non-pathogenicChlamydiotaare slowly being described. Here we use data mining techniques and genomic analysis to extend our current knowledge ofChlamydiotadiversity and its hosts, in particular the OrderParachlamydiales. We extract oneRhabdochlamydiaceaeand threeSimkaniaceaegenomes from NCBI Short Read Archive deposits of ciliate and algal genome sequencing projects. We then use these to identify a further 14 and 8 genomes respectively amongst existing, unidentified environmental assemblies. From these data we identify two novel clades with host associated data, for which we propose the names ‘CandidatusSacchlamydia’ (FamilyRhabdochlamydiaceae)and ‘CandidatusAmphrikania’ (FamilySimkaniaceae), as well as a third new clade of environmental MAGs ‘CandidatusAcheromydia’ (FamilyRhabdochlamydiaceae). The extent of uncharacterized diversity within theRhabdochlamydiaceaeandSimkaniaceaeis indicated by 16 of the 22 MAGs being evolutionarily distant from currently characterised genera. Within our limited data, we observe great predicted diversity inParachlamydialesmetabolism and evolution, including the potential for metabolic and defensive symbioses as well as pathogenicity. These data provide an imperative to link genomic diversity in metagenomics data to their associated eukaryotic host, and to develop onward understanding of the functional significance of symbiosis with this hyperdiverse clade.

Graphical Abstract
Structured connectivity in the output of the cerebellar cortex
Authors: Gruver Kim M. , Jiao Jenny W. Y. , Fields Eviatar , Song Sen , Sjöström Per Jesper , Watt Alanna J.
Published: March 2023

Circuits in the brain are built from connections between neurons, where the spatial organization and functional properties of these connections determines circuit function. In the cerebellum, Purkinje cells transmit information to neurons in the cerebellar nuclei, but how Purkinje cell – nuclear neuron connections are organized remains unclear. Here, we explored the connections between Purkinje cells and cerebellar nuclear neurons using whole-cell electrophysiology and optogenetics to produce spatial connectivity maps of cerebellar cortical output. We observed non-random connectivity between Purkinje cells and their target neurons, with inputs to cerebellar nuclear neurons clustering along cerebellar transverse zones. While many nuclear neurons received inputs from a single zone, a number of different connectivity motifs were observed. Neurons receiving inputs from all four zones were more common than predicted by a random model and showed topographic organization in the nucleus. Finally, we observed that small Purkinje cell inputs were sufficient to pause the output of nuclear neurons, suggesting that widespread Purkinje cell synchrony may not be necessary to influence cerebellar output. These findings reveal cerebellar nuclear neurons as an important locus of multimodal cerebellar integration.
Noradrenergic Tone is Not Required for Neuronal Activity-Induced Rebound Sleep in Zebrafish
Authors: Benoit Eleanor , Lyons Declan G , Rihel Jason
Published: March 2023

Sleep pressure builds during wakefulness, but the mechanisms underlying this homeostatic process are poorly understood. One zebrafish model suggests that sleep pressure increases as a function of global neuronal activity, such as during sleep deprivation or acute exposure to drugs that induce widespread brain activation. Given that the arousal-promoting noradrenergic system is important for maintaining heightened neuronal activity during wakefulness, we hypothesised that genetic and pharmacological reduction of noradrenergic tone during drug-induced neuronal activation would dampen subsequent rebound sleep in zebrafish larvae. Unexpectedly, dampening noradrenergic tone with the α2-adrenoceptor agonist clonidine during acute caffeine or pentylenetetrazol treatment enhanced subsequent rebound sleep, while stimulating noradrenergic signalling during caffeine exposure with a cocktail of α1- and β-adrenoceptor agonists did not enhance sleep. Similarly, CRISPR/Cas9-mediated elimination of thedopamine β-hydroxylase(dbh) gene, which encodes an enzyme required for noradrenalin synthesis, enhanced baseline sleep in larvae but did not prevent additional rebound sleep following acute induction of neuronal activity. Across all drug conditions,c-fosexpression immediately after drug exposure varied inversely with noradrenergic tone and correlated strongly with the amount of induced rebound sleep. These results are consistent with a model in which increases in neuronal activity, as reflected by brain-wide levels ofc-fosinduction, drive a sleep pressure signal that promotes rebound sleep independently of noradrenergic tone.
Neural Selectivity for Real-World Object Size In Natural Images
Authors: Luo Andrew F. , Wehbe Leila , Tarr Michael J. , Henderson Margaret M.
Published: March 2023

1

Real-world size is a functionally important high-level visual property of objects that supports interactions with our physical environment. Critically, real-world-size is robust over changes in visual appearance as projected onto our retinae such that large and small objects are correctly perceived to have different real-world sizes. To better understand the neural basis of this phenomenon, we examined whether the neural coding of real-world size holds for objects embedded in complex natural scene images, as well as whether real-world size effects are present for both inanimate and animate objects, whether low- and mid-level visual features can account for size selectivity, and whether neural size tuning is best described by a linear, logarithmic, or exponential neural coding function. To address these questions, we used a large-scale dataset of fMRI responses to natural images combined with per-voxel regression and contrasts. Importantly, the resultant pattern of size selectivity for objects embedded in natural scenes was aligned with prior results using isolated objects. Extending this finding, we also found that size coding exists for both animate and inanimate objects, that low-level visual features cannot account for neural size preferences, and size tuning functions have different shapes for large versus small preferring voxels. Together, these results indicate that real-world size is an ecologically significant dimension in the larger space of behaviorally-relevant cortical representations that support interactions with the world around us.
Cryo-EM structure of the human Sirtuin 6-nucleosome complex
Authors: Chio Un Seng , Rechiche Othman , Bryll Alysia R. , Zhu Jiang , Feldman Jessica L. , Peterson Craig L. , Tan Song , Armache Jean-Paul
Published: March 2023

Sirtuin 6 (SIRT6) is a multifaceted protein deacetylase/deacylase and a major target for small-molecule modulators of longevity and cancer. In the context of chromatin, SIRT6 removes acetyl groups from histone H3 in nucleosomes, but the molecular basis for its nucleosomal substrate preference is unknown. Our cryo-electron microscopy structure of human SIRT6 in complex with the nucleosome shows that the catalytic domain of SIRT6 pries DNA from the nucleosomal entry-exit site and exposes the histone H3 N-terminal helix, while the SIRT6 zinc-binding domain binds to the histone acidic patch using an arginine anchor. In addition, SIRT6 forms an inhibitory interaction with the C-terminal tail of histone H2A. The structure provides insights into how SIRT6 can deacetylate both H3 K9 and H3 K56.

Teaser

The structure of the SIRT6 deacetylase/nucleosome complex suggests how the enzyme acts on both histone H3 K9 and K56 residues.
Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1
Authors: Abini-Agbomson Stephen , Gretarsson Kristjan , Shih Rochelle M. , Hsieh Laura , Lou Tracy , Ioannes Pablo De , Vasilyev Nikita , Lee Rachel , Wang Miao , Simon Matthew , Armache Jean-Paul , Nudler Evgeny , Narlikar Geeta , Liu Shixin , Lu Chao , Armache Karim-Jean
Published: March 2023

The intricate regulation of chromatin plays a key role in controlling genome architecture and accessibility. Histone lysine methyltransferases regulate chromatin by catalyzing the methylation of specific histone residues but are also hypothesized to have equally important non-catalytic roles. SUV420H1 di- and tri-methylates histone H4 lysine 20 (H4K20me2/me3) and plays crucial roles in DNA replication, repair, and heterochromatin formation, and is dysregulated in several cancers. Many of these processes were linked to its catalytic activity. However, deletion and inhibition of SUV420H1 have shown distinct phenotypes suggesting the enzyme likely has uncharacterized non-catalytic activities. To characterize the catalytic and non-catalytic mechanisms SUV420H1 uses to modify chromatin, we determined cryo- EM structures of SUV420H1 complexes with nucleosomes containing histone H2A or its variant H2A.Z. Our structural, biochemical, biophysical, and cellular analyses reveal how both SUV420H1 recognizes its substrate and H2A.Z stimulates its activity, and show that SUV420H1 binding to nucleosomes causes a dramatic detachment of nucleosomal DNA from histone octamer. We hypothesize that this detachment increases DNA accessibility to large macromolecular complexes, a prerequisite for DNA replication and repair. We also show that SUV420H1 can promote chromatin condensates, another non-catalytic role that we speculate is needed for its heterochromatin functions. Together, our studies uncover and characterize the catalytic and non-catalytic mechanisms of SUV420H1, a key histone methyltransferase that plays an essential role in genomic stability.
TREM2 and APOE do not modulate phagocytic clearance of dying cells in the live mammalian brain
Authors: Damisah Eyiyemisi C. , Rai Anupama , Hill Robert A. , Tong Lei , Grutzendler Jaime
Published: March 2023

TREM2 and APOE are two major risk factors for Alzheimer’s disease (AD) that have been proposed to play crucial roles in microglia pathophysiology by affecting their ability to phagocytose cellular debris or aggregated proteins. In this study, we investigated for the first time the impact of TREM2 and APOE on the removal of dying neurons in the live brain by implementing a targeted photochemical method for programmed cell death induction combined with high-resolution two-photon imaging. Our findings showed that the deletion of either TREM2 or APOE did not affect the dynamics of microglia engagement with dying neurons or their efficiency in phagocytosing corpses. Interestingly, while microglia that encapsulate amyloid deposits were capable of phagocytosing dying cells without disengaging from plaques or moving their cell bodies; in the absence of TREM2, microglia cell bodies were observed to readily migrate towards dying cells, further disengaging from plaques. Our data suggest that TREM2 and APOE variants are unlikely to increase risk of AD through impaired corpse phagocytosis.

High-resolution two-photon imaging of programmed cell death in the live mouse brain reveals that neither TREM2 nor APOE modulate microglia phagocytosis of neuronal corpses. However, TREM2 regulates microglia migratory behavior towards dying cells in the vicinity of amyloid plaques.
Trinucleotide building blocks enable exponential ribozyme-catalysed RNA replication and open-ended growth of diverse RNA sequence pools
Authors: Attwater James , Augustin Teresa , Curran Joseph F. , Kwok Samantha , Gianni Edoardo , Holliger Philipp
Published: March 2023

RNA replication is considered a crucial stage in the origins of life. However, both enzymatic and non-enzymatic RNA replication cycles are impeded by the “strand separation problem” (SSP), a form of product inhibition arising from the extraordinary stability of RNA duplexes and their rapid kinetics of reannealing. Here we show that RNA trinucleotide triphosphates (triplets) can overcome the SSP by binding to and kinetically trapping dissociated RNA strands in a single-stranded form, while simultaneously serving as substrates for RNA replication by a triplet polymerase ribozyme (TPR). This enabled exponential replication of both (+) and (−) strands of double-stranded RNAs by the TPR when driven by coupled pH and freeze-thaw cycles. We demonstrate replication of a fragment of the ribozyme itself, and open-ended amplification of random RNA sequence pools over >70 cycles, with emergence of partial, distributive TPR self-replication and triplet codon drift towards a primordial genetic code.

One-sentence summary

RNA trinucleotide substrates together with simple physicochemical cycles enable RNA-catalysed replication of double-stranded RNA and partial, distributive self-replication of an RNA polymerase ribozyme.
Metabolic interplay betweenProteus mirabilisandEnterococcus faecalisfacilitates polymicrobial biofilm formation and invasive disease
Authors: Hunt Benjamin C. , Brix Vitus , Vath Joseph , Guterman Beryl L. , Taddei Steven M. , Learman Brian S. , Brauer Aimee L. , Shen Shichen , Qu Jun , Armbruster Chelsie E.
Published: March 2023

Polymicrobial biofilms play an important role in the development and pathogenesis of CAUTI.Proteus mirabilisandEnterococcus faecalisare common CAUTI pathogens that persistently co-colonize the catheterized urinary tract and form biofilms with increased biomass and antibiotic resistance. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution to CAUTI severity. Through compositional and proteomic biofilm analyses, we determined that the increase in biofilm biomass stems from an increase in the protein fraction of the polymicrobial biofilm matrix. We further observed an enrichment in proteins associated with ornithine and arginine metabolism in polymicrobial biofilms compared to single-species biofilms. We show that L-ornithine secretion byE. faecalispromotes arginine biosynthesis inP. mirabilis,and that disruption of this metabolic interplay abrogates the biofilm enhancement we seein vitroand leads to significant decreases in infection severity and dissemination in a murine CAUTI model.
Psychophysical pain encoding in the cingulate cortex predicts responsiveness of electrical stimulation
Authors: Caston Rose M. , Smith Elliot H. , Davis Tyler S. , Singh Hargunbir , Rahimpour Shervin , Rolston John D.
Published: March 2023

Background

The anterior cingulate cortex (ACC) plays an important role in the cognitive and emotional processing of pain. Prior studies have used deep brain stimulation (DBS) to treat chronic pain, but results have been inconsistent. This may be due to network adaptation over time and variable causes of chronic pain. Identifying patient-specific pain network features may be necessary to determine patient candidacy for DBS.

Hypothesis

Cingulate stimulation would increase patients’ hot pain thresholds if non-stimulation 70-150 Hz activity encoded psychophysical pain responses.

Methods

In this study, four patients who underwent intracranial monitoring for epilepsy monitoring participated in a pain task. They placed their hand on a device capable of eliciting thermal pain for five seconds and rated their pain. We used these results to determine the individual’s thermal pain threshold with and without electrical stimulation. Two different types of generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics.

Results

The pain threshold for each patient was determined from the psychometric probability density function. Two patients had a higher pain threshold with stimulation than without, while the other two patients had no difference. We also evaluated the relationship between neural activity and pain responses. We found that patients who responded to stimulation had specific time windows where high-frequency activity was associated with increased pain ratings.

Conclusion

Stimulation of cingulate regions with increased pain-related neural activity was more effective at modulating pain perception than stimulating non-responsive areas. Personalized evaluation of neural activity biomarkers could help identify the best target for stimulation and predict its effectiveness in future studies evaluating DBS.
Pulse trains to percepts: A virtual patient describing the perceptual effects of human visual cortical stimulation
Authors: Fine Ione , Boynton Geoffrey M.
Published: March 2023

The field of cortical sight restoration prostheses is making rapid progress with three clinical trials of visual cortical prostheses underway. However, as yet, we have only limited insight into the perceptual experiences produced by these implants. Here we describe a computational model or ‘virtual patient’, based on the neurophysiological architecture of V1, which successfully predicts the perceptual experience of participants across a wide range of previously published cortical stimulation studies describing the location, size, brightness and spatiotemporal shape of electrically induced percepts in humans. Our simulations suggest that, in the foreseeable future the perceptual quality of cortical prosthetic devices is likely to be limited by the neurophysiological organization of visual cortex, rather than engineering constraints.
An astrocyte-derived cytokine TIMP-1 restores synaptic plasticity in an Alzheimer’s disease model
Authors: Sarkar Sukanya , Gharami Kusumika , Paidi Ramesh Kumar , Srikumar B.N. , Biswas Subhas C.
Published: March 2023

The influence of astrocyte-secreted cytokines on neuronal health in Alzheimer’s disease (AD) is poorly understood, despite their increasing recognition as potential molecules for therapeutic targeting. Recently, we demonstrated that an anti-inflammatory cytokine, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is robustly secreted by astrocytes early in response to amyloid-β (Aβ) but is reduced in its prolonged presence. Here, we found strikingly diminished levels of TIMP-1 in the brain of six-month-old 5xFAD mice concomitant with high levels of Aβ, versus wild-type mice. Intracerebroventricular injection of TIMP-1 in 5xFAD mice ameliorated their cognitive functions. TIMP-1 not only ensured neuronal viability against apoptosis and aberrant autophagy in the AD model by binding to neuronal CD63 receptors, but also conferred synapse–specific effects. Synaptosomal analysis revealed TIMP-1 elevates dendritic spine size and protein levels, likely by promoting post-synaptic long-term potentiation in hippocampus, independent of pre-synaptic activity. TIMP-1 induced brain-derived neurotrophic factor (BDNF) and BDNF-mediated post-synaptic signaling. Therefore, we identify TIMP-1 as a multifunctional cytokine with distinct protective mechanisms-of-action on neurons and propose it as a promising therapeutic candidate in AD.

GRAPHICAL ABSTRACT
Sensorimotor memories influence movement kinematics but not associated tactile processing
Authors: Beyvers Marie C. , Voudouris Dimitris , Fiehler Katja
Published: March 2023

When interacting with objects, we often rely on visual information. However, vision is not always the most reliable sense for determining relevant object properties. For example, when the mass distribution of an object cannot be inferred visually, humans may rely on predictions about the object’s dynamics. Such predictions may not only influence motor behavior but also associated somatosensory processing, as sensorimotor predictions lead to reduced tactile sensitivity during movement. We examined whether predictions based on sensorimotor memories influence grasping kinematics and associated tactile processing. Participants lifted an object of unknown mass distribution and reported whether they detected a tactile stimulus on their grasping hand during the lift. In Experiment 1, the mass distribution could change from trial to trial, whereas in Experiment 2, we intermingled longer with shorter parts of constant and variable mass distributions, while also providing implicit or explicit information about the trial structure. In both experiments, participants grasped the object by predictively choosing contact points that would compensate the mass distribution experienced in the previous trial. Tactile suppression during movement, however, was invariant across conditions. These results suggest that predictions based on sensorimotor memories can influence movement kinematics but may not affect associated tactile perception.

Public significance statement

To perform a goal-directed movement, such as grasping an object, humans combine the available sensory information with predictions about the prevailing dynamics. Sensorimotor predictions also lead to a decrease of movement-related tactile signals, a phenomenon termed tactile suppression. Tactile suppression is supposed to rely on a dynamic weighting of sensory feedback and predictive signals. When sensory feedback is not reliable, reliance on memory-based predictions may be desired. Here we show that motor behavior is influenced by predictions based on sensorimotor memories, but associated tactile processing appears to be robust.
Investor reaction to ESG news sentiment: evidence from South Africa
Authors: Nyakurukwa Kingstone , Seetharam Yudhvir
Published: March 2023

Purpose

Utilising a database that distinctly classifies firm-level ESG (environmental, social and governance) news sentiment as positive or negative, the authors examine the information flow between the two types of ESG news sentiment and stock returns for 20 companies listed on the Johannesburg Stock Exchange between 2015 and 2021.

Design/methodology/approach

The authors use Shannonian transfer entropy to examine whether information significantly flows from ESG news sentiment to stock returns and a modified event study analysis to establish how stock prices react to changes in the two types of ESG sentiment.

Findings

Using Shannonian transfer entropy, the authors find that for the majority of the companies studied, information flows from the positive ESG news sentiment to stock returns while only a minority of the companies exhibit significant information flow from negative ESG news sentiment to returns. Furthermore, the study’s findings show significantly positive (negative) abnormal returns on the event date and beyond for both upgrades and downgrades in positive ESG news sentiment.

Originality/value

This study is among the first in an African context to investigate the impact of ESG news sentiment on stock market returns at high frequencies.
Ten years after the Jasmine Revolution: do social audits matter for investment and credit-granting decision-making?
Authors: Arfaoui Feten , Kammoun Ines , Ben Slimene Imen
Published: March 2023

Purpose

This research aims to explore the perceived usefulness of audited social information in making economic decisions, in the eyes of both Tunisian financial analysts and bankers.

Design/methodology/approach

The authors conduct an exploratory qualitative study using twelve semi-structured interviews: seven are carried out with financial analysts, and five are performed among bankers.

Findings

This study’s results reveal that financial analysts and bankers paid little attention to the audited social information in making investment/credit granting decisions. The authors also show that the low perceived usefulness of social audit is due to many reasons related to political, economic, regulatory, educational, cultural and cognitive factors.

Originality/value

This study contributes to the current literature in several ways. First, it enriches the knowledge about the perceived usefulness of social audit. To the authors’ knowledge, this is the first study to explore the perception of financial analysts and bankers to audited social information and its usefulness for decision-making. Second, the focus on the Tunisian context is interesting as it was marked, since the outbreak of the Jasmine Revolution, by the uncertainty and the instability of political, economic and social conditions. Third, this research goes further by exploring the most important factors affecting the perceiveness of social auditing.
The influence of personality traits on investment decision-making: a moderated mediation approach
Authors: Sachdeva Muskan , Lehal Ritu
Published: March 2023

Purpose

Behavioral finance proposes that psychology of the individual plays a vital role in investment decisions. Therefore, this study aims to examine the influence of one of the important disciplines of psychology, i.e. personality on investment decision-making by incorporating financial satisfaction as an intervening variable and gender as a moderator.

Design/methodology/approach

The data of 406 valid responses were collected through structured questionnaires from individual investors of Indian stock market and analyzed using structural equation modeling. Several invariance tests were also conducted to perform the multigroup analysis of gender on the mediated model.

Findings

The results revealed that extraversion, agreeableness, conscientiousness and neuroticism significantly influence investment decision-making through financial satisfaction. While financial satisfaction significantly mediates the indirect relationships between personality traits and investment decision-making for both males and females, no significant differences among males and females were found in the mediated model.

Research limitations/implications

The current study covers a limited geographical area of North India. In addition to this, it is cross-sectional in nature and incorporates only limited factors for predicting investment decisions.

Practical implications

The study possesses numerous significant implications for financial practitioners, advisors, investors, academicians and researchers in the field of behavioral finance.

Originality/value

This study suggests a moderated mediation approach, which incorporates financial satisfaction as a mediator and gender as a moderator. To the best of the authors’ knowledge, so far, no study has been conducted in this context, and it will enhance the understanding of investment decisions of individual investors.
Determinants of the financial wellbeing of individuals in an emerging economy: an empirical study
Authors: Kumar Jitender , Rani Vinki , Rani Garima , Sarker Tapan
Published: March 2023

Purpose

The current study aims to identify the impact of financial literacy, financial risk-tolerance, financial socialization, financial stress, socio-demographic factors and financial behavior on the individual financial wellbeing residing in India's National Capital Region (NCR) region. Understanding financial wellbeing is crucial as it helps individuals understand personal finance better and develop a more favorable financial attitude. The information can depict individuals' financial skills, knowledge and attitudes toward achieving financial wellbeing in emerging economies.

Design/methodology/approach

Through self-administered survey questionnaires, data are obtained using convenience sampling from 420 (394) respondents regarding individual financial wellbeing levels in India. The survey responses were collected between May 2022 and July 2022. The authors use the “partial least squares structural equation modeling” (PLS-SEM) technique to test the research hypotheses.

Findings

The present study's outcome confirms that five determinants, such as financial literacy, financial risk-tolerance, financial socialization, financial stress and socio-demographic factors, significantly influence the financial behavior of individuals. Further, financial behavior, financial literacy, financial risk-tolerance and financial socialization significantly influence financial wellbeing. However, financial stress and socio-demographic factors have statistically insignificant impacts on financial wellbeing.

Originality/value

The present study is exclusive in which an effort is being made to acquire relative importance on financial behavior and an individual's financial wellbeing. The present paper will help the government, financial services providers, and policymakers in offering innovative economic schemes and designing policies that may enhance the financial wellbeing of individuals. Finally, this article provides the road map for future research in this field.
Women’s employment in rural Senegal: what can we learn from non-farm diversification strategies?
Authors: Diallo Thierno Malick , Mazu Amoudath Adebomi , Araar Abdelkrim , Dieye Abdoulaye
Published: March 2023

Purpose

As rural nonfarm activities grow in developing countries, less attention is being paid to the opportunities they may provide for women. The purpose of this study is to examine the gender-differentiated impact of nonfarm diversification strategies in rural Senegal.

Design/methodology/approach

This study uses data collected from the Senegalese poverty monitoring survey and employs an instrumental variable (IV) approach and a multinomial endogenous treatment model to investigate the extent to which diversification strategies lead to improved outcomes for rural women and their households.

Findings

While nonfarm diversification is a male-dominated livelihood strategy, rural women make the most of it, regardless of whether they diversify into low- or high-return nonfarm activities. At the individual level, diversification improves rural women’s well-being through large income-increasing effects and higher empowerment but has no effect on rural men’s well-being. At the household level, the authors find that, when only women diversify, households have lower per capita income but are less likely to be food insecure than when only men or both genders diversify.

Research limitations/implications

This study is based on cross-sectional data, making it impossible to examine the dynamic effects of nonfarm diversification strategies on well-being outcomes.

Originality/value

This study contributes to the current literature on rural livelihood diversification. While much attention has been paid to the feminization of agriculture, remarkably little is known about the expanding role of rural women in the nonfarm sector.