bluuebunny/crossref_metadata_2025 huggingface dataset:
Needlestick and Sharp Injuries Prevalence and Hepatitis B Vaccination Among Healthcare Workers: A cross sectional study in Six District Hospitals (Yaounde, Cameroon)
Authors: Lekeumo Cheuyem Fabrice Zobel , Lyonga Emilia Enjema , Kamga Hortense Gonsu , Mbopi – Keou François – Xavier , Takougang Innocent
Published: April 2023

Introduction

Accidental exposure to blood and body fluids (AEB) in the workplace account for 40 % of contamination by hepatis B virus (HBV) and 2 – 3 % by HIV among healthcare workers (HCW). Developing countries are most affected. The present study sought to determine the prevalence of percutaneous injury and hepatitis B vaccination coverage among HCW.

Methods

A cross-sectional study was carried out from January to April 2022 in six district hospitals in Yaounde using a self - administered questionnaire. Out of the 279 HCW who were solicited, 217 returned completed questionnaires.

Results

More than half of HCW reported an AEB in the last 12 months (53,9 %). The prevalence of AEB varied among hospitals with the Nkolndongo DH reporting the highest prevalence (51.6 %). Healthcare workers were unvaccinated (53 %) or partially vaccinated against HBV (13,2 %); only one third were fully vaccinated (33,9 %). The lowest compliance with vaccination was observed among hygiene personnel (90 %). The high cost of the vaccine was the main reported reason for non - compliance (39 %).

Conclusion

There is an urgent need to set up a monitoring system for the implementation of infection control and prevention in District Hospitals in Cameroon in order to raise awareness of AEB burden among healthcare workers and improve accessibility to HBV vaccine.
A Study of a Deterministic Model for Meningitis Epidemic
Authors: Yaga S. J , Saporu F .W. O
Published: April 2023

A compartmental deterministic model that allows (1) immunity from two stages of infection and carriage, and (2) disease induced death, is used in studying the dynamics of meningitis epidemic process in a closed population. It allows for difference in the transmission rate of infection to a susceptible by a carrier and an infective. It is generalized to allow a proportion (φ) of those susceptibles infected to progress directly to infectives in stage I. Both models are used in this study. The threshold conditions for the spread of carrier and infectives in stage I are derived for the two models. Sensitivity analysis is performed on the reproductive number derived from the next generation matrix. The case-carrier ratio profile for various parameters and threshold values are shown. So also are the graphs of the total number ever infected as influenced byϵandφ. The infection transmission rate (β), the odds in favor of a carrier, over an infective, in transmitting an infection to a susceptible (ϵ) and the carrier conversion rate (ϕ) to an infective in stage I, are identified as key parameters that should be subject of attention for any control intervention strategy. The case-carrier ratio profiles provide evidence of a critical case-carrier ratio attained before the number of reported cases grows to an epidemic level. They also provide visual evidence of epidemiological context, in this case, epidemic incidence (in later part of dry season) and endemic incidence (during rainy season). Results from total proportion ever infected suggest that the model, in whichφ= 0 obtained, can adequately represent, in essence, the generalized model for this study.
Humic substances mitigate adverse effects of elevated temperature with potentially critical repercussions for coral reef resilience
Authors: Stuij T.M. , Cleary D.F.R. , de Voogd N.J. , Rocha R.J.M. , Polonia A.R.M. , Silva D.A.M. , Frommlet J.C. , Louvado A. , Huang Y. M. , van der Windt N. , Gomes N.C.M.
Published: April 2023

Previous observational studies have suggested that terrestrially-derived compounds, most notably humic substances (HS) can protect coral reefs from thermal stress. No study hitherto has, however, tested this hypothesis. In the present study, we used a randomised-controlled microcosm setup to test to what extent HS are able to mitigate the adverse effects of elevated temperature and intense UVB radiation on coral photosynthetic activity, and environmental and host-associated bacterial ercommunities. Our results clearly demonstrate a significant protective effect of HS. Corals in HS-supplemented microcosms had significantly higher photosynthetic activities than those in microcosms subjected to elevated heat and intense UVB radiation. Our results, furthermore, showed that coral reef organisms in HS-supplemented microcosms contained unique bacterial communities enriched with known groups of potentially beneficial bacteria. Our findings have significant repercussions for reef resilience in the face of increasing climate-induced stressors and highlight the importance of restoring coastal forests and the land-sea interface in order to protect coral reefs.
Surface growth ofPseudomonas aeruginosareveals a regulatory effect of 3- oxo-C12-homoserine lactone in absence of its cognate receptor, LasR
Authors: de Oliveira Pereira Thays , Groleau Marie-Christine , Déziel Eric
Published: April 2023

Successful colonization of a multitude of ecological niches by the bacteriumPseudomonas aeruginosarelies on its ability to respond to concentrations of self-produced signal molecules. This intercellular communication system known as quorum sensing (QS) tightly regulates the expression of virulence determinants and a diversity of survival functions, including those required for social behaviours. In planktonic cultures ofP. aeruginosa, the transcriptional regulator LasR is generally considered on top of the QS circuitry hierarchy; its activation relies on binding to 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), a product of the LasI synthase. Transcription oflasIis activated by LasR, resulting in a positive feedback loop. Few studies have looked at the function of QS during surface growth even thoughP. aeruginosatypically lives in biofilm-like communities under natural conditions. Here, we show that surface-grownP. aeruginosareadily produces 3-oxo-C12-HSL in absence of LasR, and that this phenotype is frequent upon surface association in naturally occurring environmental and clinical LasR- defective isolates, suggesting a conserved alternative function for the signal. Indeed, even in the absence of the cognate regulator LasR, 3-oxo-C12-HSL upregulates the autologous expression of pyocyanin and of LasR-controlled virulence determinants in neighboring cells. This highlights a possible role for 3-oxo-C12-HSL in shaping community responses and provides a possible evolutive benefit for mixed populations to carry LasR-defective cells, a common feature of natural ofP. aeruginosa.

IMPORTANCE

The bacteriumPseudomonas aeruginosacolonizes and thrives in many environments, in which it is typically found in surface-associated polymicrobial communities known as biofilms. Adaptation to this social behavior is aided by quorum sensing (QS), an intercellular communication system pivotal in the expression of social traits. Regardless of its importance in QS regulation, the loss of function of the master regulator LasR is now considered a conserved adaptation ofP. aeruginosa, irrespective of the origin of strains. By investigating the QS circuitry in surface-grown cells, we found accumulation of QS signal 3-oxo-C12-HSL in absence of its cognate receptor and activator, LasR. The current understanding of the QS circuit, mostly based on planktonic growing cells, is challenged by investigating the QS circuitry of surface-grown cells. This provides a new perspective on the beneficial aspects that underline the frequency of LasR-deficient isolates.
Learning induces unique transcriptional landscapes in the auditory cortex
Authors: Graham G. , Chimenti M.S. , Knudtson K.L. , Grenard D.N. , Co L. , Sumner M. , Tchou T. , Bieszczad K.M.
Published: April 2023

Learning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days, weeks, or even a lifetime, require learning to inducede novogene expression. Indeed, transcription is the molecular determinant for long-term memories to form with a lasting impact on sound-related behavior. However, auditory cortical genes that support auditory learning, memory, and acquired sound-specific behavior are largely unknown. This report is the first to identify in young adult male rats (Sprague-Dawley) genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie the formation of long-lasting discriminative memory for acoustic frequency cues. Auditory cortical samples were collected from animals in the initial learning phase of a two-tone discrimination sound-reward task known to induce sound-specific neurophysiological and behavioral effects (e.g., Shang et al., 2019). Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identifiedcholinergic synapse (KEGG 04725), extra-cellular matrix receptor interaction (KEGG 04512), andneuroactive ligand-receptor interaction (KEGG 04080)as top biological pathways for auditory discrimination learning. The findings characterize key candidate effectors underlying changes in cortical function that support the initial formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.
Reproducibility of biophysicalin siliconeuron states and spikes from event-based partial histories
Authors: Cudone Evan , Lower Amelia M. , McDougal Robert A
Published: April 2023

Biophysically detailed simulations attempting to reproduce neuronal activity often rely on solving large systems of differential equations; in some models, these systems have tens of thousands of states per cell. Numerically solving these equations is computationally intensive and requires making assumptions about the initial cell states. Additional realism from incorporating more biological detail is achieved at the cost of increasingly more states, more computational resources, and more modeling assumptions. We show that for both point and morphologically-detailed cell models, the presence and timing of future action potentials is probabilistically well-characterized by the relative timings of a small number of recent synaptic events alone. Knowledge of initial conditions or full synaptic input history is not a requirement. While model time constants, etc. impact the specifics, we demonstrate that for both individual spikes and sustained cellular activity, the uncertainty in spike response decreases to the point of approximate determinism. Further, we show cellular model states are reconstructable from ongoing synaptic events, despite unknown initial conditions. We propose that a strictly event-based modeling framework is capable of representing the full complexity of cellular dynamics of the differential-equations models with significantly less per-cell state variables, thus offering a pathway toward utilizing modern data-driven modeling to scale up to larger network models while preserving individual cellular biophysics.
Cryo-EM structure of the folded-back state of human β-cardiac myosin*
Authors: Grinzato Alessandro , Auguin Daniel , Kikuti Carlos , Nandwani Neha , Moussaoui Dihia , Pathak Divya , Kandiah Eaazhisai , Ruppel Kathleen M. , Spudich James A. , Houdusse Anne , Robert-Paganin Julien
Published: April 2023

During normal levels of exertion, many cardiac muscle myosin heads are sequestered in an off-state even during systolic contraction to save energy and for precise regulation. They can be converted to an on-state when exertion is increased. Hypercontractility caused by hypertrophic cardiomyopathy (HCM) myosin mutations is often the result of shifting the equilibrium toward more heads in the on-state. The off-state is equated with a folded-back structure known as the interacting head motif (IHM), which is a regulatory feature of all muscle myosins and class-2 non-muscle myosins. We report here the human β-cardiac myosin IHM structure to 3.6 Å resolution. The structure shows that the interfaces are hot spots of HCM mutations and reveals details of the significant interactions. Importantly, the structures of cardiac and smooth muscle myosin IHMs are dramatically different. This challenges the concept that the IHM structure is conserved in all muscle types and opens new perspectives in the understanding of muscle physiology. The cardiac IHM structure has been the missing puzzle piece to fully understand the development of inherited cardiomyopathies. This work will pave the way for the development of new molecules able to stabilize or destabilize the IHM in a personalized medicine approach.

*This manuscript was submitted to Nature Communications in August 2022 and dealt efficiently by the editors. All reviewers received this version of the manuscript before 9208August 2022. They also received coordinates and maps of our high resolution structure on the 18208August 2022. Due to slowness of at least one reviewer, this contribution was delayed for acceptance by Nature Communications and we are now depositing in bioRxiv the originally submitted version written in July 2022 for everyone to see. Indeed, two bioRxiv contributions at lower resolution but adding similar concepts on thick filament regulation were deposited this week in bioRxiv, one of the contributions having had access to our coordinates.

We hope that our data at high resolution will be helpful for all readers that appreciate that high resolution information is required to build accurate atomic models and discuss implications for sarcomere regulation and the effects of cardiomyopathy mutations on heart muscle function.
Neural representations of non-native speech reflect proficiency and interference from native language knowledge
Authors: Brodbeck Christian , Kandylaki Katerina Danae , Scharenborg Odette
Published: April 2023

Learning to process speech in a foreign language involves learning new representations for mapping the auditory signal to linguistic structure. Behavioral experiments suggest that even listeners that are highly proficient in a non-native language experience interference from representations of their native language. However, much of the evidence for such interference comes from tasks that may inadvertently increase the salience of native language competitors. Here we tested for neural evidence of proficiency and native language interference in a naturalistic story listening task. We studied electroencephalography responses of native Dutch listeners to an English short story, spoken by a native speaker of either American English or Dutch. We modeled brain responses with multivariate temporal response functions, using acoustic and language models. We found evidence for activation of Dutch language statistics when listening to English, but only when it was spoken with a Dutch accent. This suggests that a naturalistic, monolingual setting decreases the interference from native language representations, whereas an accent in the listeners’ own native language may increase native language interference, by increasing the salience of the native language and activating native language phonetic and lexical representations. Brain responses suggest that words from the native language compete with the foreign language in a single word recognition system, rather than being activated in a parallel lexicon. We further found that secondary acoustic representations of speech (after 200 ms latency) decreased with increasing proficiency. This may reflect improved acoustic-phonetic models in more proficient listeners.
Comparison of a custom Photogrammetry for Anatomical CarE (PHACE) system with other Low- Cost Facial Scanning Devices
Authors: To Josiah K. , Vu Anderson N. , Ediriwickrema Lilangi S. , Browne Andrew W.
Published: April 2023

Purpose

To compare a custom Photogrammetry for Anatomical CarE (PHACE) system with other cost-effective 3-dimensional (3D) facial scanning systems to objectively characterize morphology and volume of periorbital and adnexal anatomy.

Methods

The imaging systems evaluated include the low-cost custom PHACE system and commercial software product for the iPhone called Scandy Pro (iScandy) application (Scandy, USA), and the mid-priced Einscan Pro 2X (Shining3D Technologies, China) device and Array of Reconstructed Cameras 7 (ARC7) facial scanner (Bellus3D, USA). Imaging was performed on a manikin facemask and humans with various Fitzpatrick scores. Scanner attributes were assessed using mesh density, reproducibility, surface deviation, and emulation of 3D printed phantom lesions affixed above the superciliary arch (brow line).

Results

The Einscan served as a reference for lower cost imaging systems because it qualitatively and quantitatively renders facial morphology with the highest mesh density, reproducibility (0.13 ± 0.10 mm), and volume recapitulation (approximately 2% of 33.5 μL). Compared to the Einscan, the PHACE system (0.35 ± 0.03 mm, 0.33 ± 0.16 mm) demonstrated non-inferior mean accuracy and reproducibility root mean square (RMS) compared to the iScandy (0.42 ± 0.13 mm, 0.58 ± 0.09 mm), and significantly more expensive ARC7 (0.42 ± 0.03 mm, 0.26 ± 0.09 mm). Similarly, the PHACE system showed non-inferior volumetric modeling when rendering a 124 μL phantom lesion compared to the iScandy and more costly ARC7 (mean percent difference from the Einscan: 4.68 ± 3.73%, 9.09 ± 0.94%, and 21.99 ± 17.91% respectively).

Conclusions

The affordable PHACE system accurately measures periorbital soft tissue as well as other established mid-cost facial scanning systems. Additionally, the portability, affordability, and adaptability of PHACE can facilitate widespread adoption of 3D facial anthropometric technology as an objective measurement tool in ophthalmology.

Precis

We demonstrate a custom system for facial photogrammetry (Photogrammetry for Anatomical CarE -PHACE) to produce 3D renderings of facial volume and morphology which compares with more expensive alternative 3D scanning technologies.
Prevention of cyclical resurgences of COVID-19-like pandemics in the long term: What are the trade-offs?
Authors: Nakamoto Ichiro
Published: April 2023

Vaccines have facilitated the substantial reduction and containment of COVID-19 transmission in many countries by early 2023. However, the long-term interconnection between vaccines, traits of the pathogen, vaccination strategies, and cases averted/trade-offs of health outcomes is not well understood. Utilizing a compartment-calibrated model, I estimated the aversion/trade-offs effect on six major disease burdens (i.e., total/symptomatic/asymptomatic/hospitalized/ICU/death cases averted) over time conditional on a variety level of scenarios. The findings implied that low-risk immunity profiles of booster doses increased the peak cases averted versus medium- and high-risk counterparts. The effect was most salient for the former paired with enhancing the rollout rate of doses, followed by the medium- and then high-risk scenarios. Positive and temporarily durable aversion effects for the low-risk, in contrast, negative trade-offs and decreasing aversion effects for the suboptimal scenarios were observed. While there are heterogeneities in vaccines, public strategies, social efforts, and other considerations, this work can provide an evidence-based rationale for the long-term trade-off analysis of vaccination.
A systematic review and meta-analysis of participant characteristics in the prevention of gestational diabetes: a summary of evidence for precision medicine
Authors: Lim Siew , Takele Wubet Worku , Vesco Kimberly K , Redman Leanne ,   ADA PMDI GDM prevention working group, Josefson Jami
Published: April 2023

Background and aims

Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with interventions in gestational diabetes mellitus (GDM) prevention.

Methods

We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022.

Results

From 10347 studies, 116 studies (n=40940 women) were included. Physical activity resulted in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Diet and physical activity interventions resulted in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions were more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.22 [0.11, 0.45] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes had no effect.

Conclusions

GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results stratified by participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.

Plain language summary

Precision prevention involves using a group’s unique context to determine their responses to preventive interventions. This study aimed to evaluate the participant characteristics associated with interventions in GDM prevention. We searched medical literature databases to identify lifestyle (diet, physical activity), metformin, myoinositol/inositol and probiotics interventions. A total of 116 studies (n=40903 women) were included. Diet and physical activity interventions resulted in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) and those without a history of GDM. Metformin interventions resulted in greater GDM reduction in participants with PCOS or when started during the preconception period. Future research should include trials starting in the preconception period, and provide results stratified by participant characteristics to predict GDM prevention through interventions.
A neural basis of choking under pressure
Authors: Smoulder Adam L. , Marino Patrick J. , Oby Emily R. , Snyder Sam E. , Miyata Hiroo , Pavlovsky Nick P. , Bishop William E. , Yu Byron M. , Chase Steven M. , Batista Aaron P.
Published: April 2023

Incentives tend to drive improvements in performance. But when incentives get too high, we can “choke under pressure” and underperform when it matters most. What neural processes might lead to choking under pressure? We studied Rhesus monkeys performing a challenging reaching task in which they underperform when an unusually large “jackpot” reward is at stake. We observed a collapse in neural information about upcoming movements for jackpot rewards: in the motor cortex, neural planning signals became less distinguishable for different reach directions when a jackpot reward was made available. We conclude that neural signals of reward and motor planning interact in the motor cortex in a manner that can explain why we choke under pressure.

One-Sentence Summary

In response to exceptionally large reward cues, animals can “choke under pressure”, and this corresponds to a collapse in the neural information about upcoming movements.
Fortuitous events in the evolution of Light-dependent Protochlorophyllide Oxidoreductase
Authors: Vedalankar Pratishtha , Tripathy Baishnab C
Published: April 2023

Light-dependent protochlorophyllide oxidoreductase (LPOR) is a nuclear-encoded photoenzyme in many photosynthetic organisms. LPOR originated in primitive cyanobacterial ancestors during the great oxygenation event that was detrimental to the existence of the oxygen-sensitive LIPOR that prevailed in anoxygenic Earth. Both LIPOR and LPOR catalyse reduction of protochlorophyllide to chlorophyllide in the penultimate step of chlorophyll biosynthesis. Except for angiosperms and gnetophytes several oxygenic phototrophs harbour both LIPOR and LPOR. The coexistence of LIPOR and LPOR in certain phototrophs provides niche spaces for organisms in unconducive environment. The selection pressure of increased O2concentration, changing light quality and quantity at different depths of the ocean, nutrient status of water, gene reorganization during several endosymbiotic events, horizontal gene transfer, LIPOR gene loss and multiple duplication events played a major role in the evolution and diversification of LPOR and its isoforms in photosynthetic and non-photosynthetic organisms. In the absence of LIPOR angiosperms become vulnerable to protochlorophyllide-sensitized and light-induced oxidative stress mediated by singlet oxygen. To overcome the photo-damage PORA was expressed abundantly in the plastids of etiolated plants. PORB evolved to take over the function of vanishing PORA isoform in light. Brassicales evolved PORC to protect plants from high light and other environmental stresses.

Highlights

Protochlorophyllide oxidoreductase is an important photo-enzyme in angiosperms that needs light as a substrate for the synthesis of chlorophylls. Therefore, angiosperms cannot green in dark although several algae and lower green plants can synthesize chlorophyll in dark due to the presence of light-independent protochlorophyllide oxidoreductase (LIPOR).

In response to climate change, during the great oxygenation event light-dependent protochlorophyllide oxidoreductase (LPOR) evolved due to the O2-induced selection pressure that inactivated the oxygen-sensitive LIPOR.

Increased O2concentration, changing light quality and quantity at different depths of ocean, gene reorganization during several endosymbiotic events, selective LIPOR gene loss and multiple duplication events played a major role in the evolution and diversification of LPOR and its isoforms in phototrophs.

Phylogenetic studies indicate that LPOR genes have been overwhelmingly horizontally transferred between phototrophs and also non phototrophic organisms.

Presence of LPOR in non-photosynthetic organisms, Mycobacterium and certain fungi suggests that LPOR may have some other reductive functions in these organisms.
Asymmetric patterns of nucleosome positioning sequences in protein-coding regions
Authors: Kato Hiroaki , Shimizu Mitsuhiro , Urano Takeshi
Published: April 2023

Although nucleosome positioning is key to epigenetic regulation, how the DNA sequence contributes to positioning remains elusive, especially in the context of transcription direction. Analysis of nucleotide bases with respect to the nucleosomal DNA coordinates requires precise nucleosomal mapping information on the genome. However, currently available base-pair-resolution nucleosome maps based on cysteine-mediated chemical cleavage do not fully satisfy the requirement due to method-specific cleavage biases. Here, we generated a chimeric nucleosomal DNA model to achieve less-biased prediction. The model revealed that yeast protein-coding sequences have higher affinity for the promoter-proximal half of nucleosomes than for the distal half. Strikingly, peaks of calculated affinity scores for the promoter-proximal half periodically matched the first few nucleosome positions. Detailed analysis of nucleotide bases revealed that the AA dinucleotide in the left side of the top strand contributes to nucleosome detection frequency in intergenic regions, while the complementary dinucleotide TT is preferred in the other side. In contrast, the sense strand is AA-rich throughout the nucleosome coordinate in protein-coding regions, which is consistent with asymmetric affinity. These data suggest that eukaryotes have evolved DNA sequences with asymmetric affinity for nucleosome formation to maintain epigenetic integrity of protein-coding regions.
Sperm Whales Demographics in the Gulf of Alaska and Bering Sea/Aleutian Islands: An Overlooked Female Habitat
Authors: Posdaljian Natalie , Solsona-Berga Alba , Hildebrand John A. , Soderstjerna Caroline , Wiggins Sean M. , Lenssen Kieran , Baumann-Pickering Simone
Published: April 2023

Sperm whales exhibit sexual dimorphism and sex-specific latitudinal segregation. Females and their young form social groups and are usually found in temperate and tropical latitudes, while males forage at higher latitudes. Historical whaling data and rare sightings of social groups in high latitude regions of the North Pacific, such as the Gulf of Alaska (GOA) and Bering Sea/Aleutian Islands (BSAI), suggest a more nuanced distribution than previously understood. Sperm whales are the most sighted and recorded cetacean in marine mammal surveys in these regions but capturing their demographic composition and habitat use has proven challenging. This study detects sperm whale presence using passive acoustic data from seven sites in the GOA and BSAI from 2010 to 2019. Differences in click characteristics between males and females (i.e., inter-click and inter-pulse interval) was used as a proxy for animal size/sex to derive time series of animal detections. Generalized additive models with generalized estimation equations demonstrate how spatiotemporal patterns differ between the sexes. Social groups were present at all recording sites with the largest relative proportion at two seamount sites in the GOA and an island site in the BSAI. We found that the seasonal patterns of presence varied for the sexes and between the sites. Male presence was highest in the summer and lowest in the winter, conversely, social group peak presence was in the winter for the BSAI and in the spring for the GOA region, with the lowest presence in the summer months. This study demonstrates that social groups are not restricted to lower latitudes and capture their present-day habitat use in the North Pacific. It highlights that sperm whale distribution is more complex than accounted for in management protocol and underscores the need for improved understanding of sperm whale demographic composition to better understand the impacts of increasing anthropogenic threats, particularly climate change.
Oncolytic Newcastle disease virus enhanced apoptosis in colorectal cancer cell lines
Authors: Ginting Teridah Ernala , Hidayat Nur Rahmaniah , Cornelia Vina , Larasati Young Othiwi , Zarkasie Kamaluddin , Yusuf Irawan
Published: April 2023

Colorectal cancer (CRC) is a deadly disease with a high prevalence and mortality rate worldwide. Previous investigations have shown that Newcastle disease virus (NDV) exhibits oncolytic activity and antitumor immunostimulation properties on several types of tumor cells but not normal cells. This study aims to examine NDV oncolytic activity against two kinds of human CRC cell lines, i.e., HCT116 and SW620, as well as its ability to induce apoptosis. The results showed that CRC cell lines were susceptible to NDV LaSota strain and the mechanism of death was due to caspase-dependent pathways apoptosis, followed by interferon signaling competence. NDV-induced proinflammatory cytokines in CRC cells might have contributed to apoptosis mechanism. Therefore, further investigation is recommended, using the findings obtained in this study as a basis for an animal CRC model.
Evaluation of nanopore sequencing on polar bodies for routine pre-implantation genetic testing for aneuploidy
Authors: Oberle Anna , Hanzer Franziska , Kokocinski Felix , Ennemoser Anna , Carli Luca , Vaccari Enrico , Hengstschläger Markus , Feichtinger Michael
Published: April 2023

Structured Abstract

BACKGROUND

PGT-A using polar body (PB) biopsy derives a clinical benefit by reducing the number of embryo transfers and miscarriage rates but is currently not cost-efficient. Nanopore sequencing technology opens possibilities by providing cost-efficient, fast sequencing results with uncomplicated sample preparation workflows.

METHODS

In this comparative experimental study, 102 pooled PB samples from 20 patients were analyzed for aneuploidy using nanopore sequencing technology and compared with aCGH results generated as part of the clinical routine. Samples were sequenced on a Nanopore MinION machine for up to 9 hours for 6 pooled PB samples. Whole-chromosome copy-numbers were called by a custom bioinformatic analysis software. Automatically called results were compared to aCGH results.

RESULTS

Overall, 96/99 samples were consistently detected as euploid or aneuploid in both methods (concordance=97.0%, sensitivity = 0.957, specificity = 1.0, PPV = 1.0, NPV = 0.906). On chromosomal level, concordance reached 98.7%. Chromosomal aneuploidies analyzed in this trial covered all 23 chromosomes with 98 trisomies, and 97 monosomies in 70 aCGH samples.

The whole nanopore workflow is feasible in under 5 hours (for one sample) with maximum time of 16 hours (for 12 samples), enabling fresh PB-euploid embryo transfer. Material cost of 150€/sample possibly enable cost-efficient aneuploidy screening.

CONCLUSIONS

This is the first study, systematically comparing nanopore sequencing for aneuploidy of PBs with standard detection methods. High concordance rates confirmed feasibility of nanopore technology for this application. Additionally, the fast and cost-efficient workflow reveals clinical utility of this technology, making PB PGT-A clinically attractive.
Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: the phase I/II first-in-human MATINS trial
Authors: Rannikko Jenna H. , Verlingue Loic , de Miguel Maria , Pasanen Annika , Robbrecht Debbie , Skytta Tanja , Iivanainen Sanna , Shetty Shishir , Ma Yuk Ting , Graham Donna M. , Arora Sukeshi Patel , Jaakkola Panu , Yap Christina , Xiang Yujuan , Mandelin Jami , Karvonen Matti K. , Jalkanen Juho , Karaman Sinem , Koivunen Jussi P. , Minchom Anna , Hollmén Maija , Bono Petri
Published: April 2023

Clever-1 expression in macrophages contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial was designed to investigate the safety and tolerability of Clever-1 blockade in patients with treatment-refractory solid tumors and to assess preliminary anti- tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab was well tolerated with no observed dose limiting toxicities in part I (n=30) and no additional safety signals in part II (n=108). Disease control (DC) rates of 25-40% were observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor positive breast, and biliary tract cancers, which associated with improved survival in a landmark analysis. High pre-treatment intra-tumoral Clever-1 staining and low circulating TNFα correlated with DC. Digital spatial profiling of DC and non-DC tumors with next generation sequencing showed bexmarilimab-induced macrophage activation and robust stimulation of IFNγ and T-cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well-tolerated and show that macrophage targeting can promote tumor control in late stage cancer.

Highlights

Targeting Clever-1 with bexmarilimab is well tolerated

Disease control in late stage cancer can be achieved with bexmarilimab monotherapy

Low baseline immune activation associates with bexmarilimab benefit

Bexmarilimab converts intratumoral macrophages to support adaptive immune responses
Associations betweenin vitro,in vivoandin silicocell classes in mouse primary visual cortex
Authors: Wei Yina , Nandi Anirban , Jia Xiaoxuan , Siegle Joshua H. , Denman Daniel , Lee Soo Yeun , Buchin Anatoly , Geit Werner Van , Mosher Clayton P. , Olsen Shawn , Anastassiou Costas A.
Published: April 2023

The brain consists of many cell classes yetin vivoelectrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modalin vitroproperties from experiments within vivorecorded units via computational modeling and optotagging experiments. We found two one-channel and six multi-channel clusters in mouse visual cortex with distinctin vivoproperties in terms of activity, cortical depth, and behavior. We used biophysical models to map the two one- and the six multi-channel clusters to specificin vitroclasses with unique morphology, excitability and conductance properties that explain their distinct extracellular signatures and functional characteristics. These concepts were tested in ground-truth optotagging experiments with two inhibitory classes unveiling distinctin vivoproperties. This multi-modal approach presents a powerful way to separatein vivoclusters and infer their cellular properties from first principles.
Ancient diversity in host-parasite interaction genes in a model parasitic nematode
Authors: Stevens Lewis , Martinez-Ugalde Isaac , King Erna , Wagah Martin , Absolon Dominic , Bancroft Rowan , Gonzalez de la Rosa Pablo , Hall Jessica L , Kieninger Manuela , Kloch Agnieszka , Pelan Sarah , Robertson Elaine , Pedersen Amy B , Abreu-Goodger Cei , Buck Amy H , Blaxter Mark
Published: April 2023

Host-parasite interactions exert strong selection pressures on the genomes of both host and parasite. These interactions can lead to increased fitness of rare alleles, resulting in negative frequency-dependent selection, a form of balancing selection that is hypothesised to explain the high levels of polymorphism seen in many host immune and parasite antigen loci. Despite their economic and ecological importance, there is limited evidence for balancing selection in parasitism-relevant genes in parasitic nematodes. Here, we sequenced the genomes of several individuals ofHeligmosomoides bakeri, a parasite of house mice that is a well-established model parasitic nematode, andHeligmosomoides polygyrus, a closely related parasite of wood mice. We combined our single nematode genome assemblies with chromatin conformation capture (Hi-C) libraries derived from pools of individuals to generate chromosome-level reference genomes for both species. AlthoughH. bakeriis commonly referred to asH. polygyrusin the literature, their genomes show levels of divergence that are consistent with millions of years of independent evolution. We found that theH. bakerigenome, which we expected to be highly homozygous through inbreeding, contained hundreds of hyper-divergent haplotypes, similar to those recently reported in free-living nematodes. Within these haplotypes, we found an enrichment of protein families that interact with the host immune response, including protease inhibitors and transthyretin-related proteins. We also found that many of these haplotypes originated prior to the divergence betweenH. bakeriandH. polygyrus, suggesting that they have been maintained since the last common ancestor of the two species by long-term balancing selection. Together, our results suggest that selection pressures exerted on parasites by their hosts have led to unexpected modes and levels of genetic diversity in the genomes of these economically and ecologically important species.
A weaponized phage suppresses competitors in historical and modern metapopulations of pathogenic bacteria
Authors: Backman Talia , Latorre Sergio M. , Symeonidi Efthymia , Muszyński Artur , Bleak Ella , Eads Lauren , Martinez-Koury Paulina I. , Som Sarita , Hawks Aubrey , Gloss Andrew D. , Belnap David M. , Manuel Allison M. , Deutschbauer Adam M. , Bergelson Joy , Azadi Parastoo , Burbano Hernán A. , Karasov Talia L.
Published: April 2023

Bacteriophages, the viruses of bacteria, are proposed to drive bacterial population dynamics, yet direct evidence of their impact on natural populations is limited. Here we identified viral sequences in a metapopulation of wild plant-associatedPseudomonasspp. genomes. We discovered that the most abundant viral cluster does not encode an intact phage but instead encodes a tailocin - a phage-derived element that bacteria use to kill competitors for interbacterial warfare. Each pathogenicPseudomonassp. strain carries one of a few distinct tailocin variants, which target variable polysaccharides in the outer membrane of co-occurring pathogenic strains. Analysis of historic herbarium samples from the last 170 years revealed that the same tailocin and receptor variants have persisted in thePseudomonaspopulations for at least two centuries, suggesting the continued use of a defined set of tailocin haplotypes and receptors. These results indicate that tailocin genetic diversity can be mined to develop targeted “tailocin cocktails” for microbial control.

One-Sentence Summary

Bacterial pathogens in a host-associated metapopulation use a repurposed prophage to kill their competitors.
Histone divergence inTrypanosoma bruceiresults in unique alterations to nucleosome structure
Authors: Deák Gauri , Wapenaar Hannah , Sandoval Gorka , Chen Ruofan , Taylor Mark R. D. , Burdett Hayden , Watson James A. , Tuijtel Maarten W. , Webb Shaun , Wilson Marcus D.
Published: April 2023

Eukaryotes have a multitude of diverse mechanisms for organising and using their genomes, but the histones that make up chromatin are highly conserved. Unusually, histones from kinetoplastids are highly divergent. The structural and functional consequences of this variation are unknown. Here, we have biochemically and structurally characterised nucleosome core particles (NCPs) from the kinetoplastid parasiteTrypanosoma brucei. A structure of theT. bruceiNCP reveals that global histone architecture is conserved, but specific sequence alterations lead to distinct DNA and protein interaction interfaces. TheT. bruceiNCP is unstable and has weakened overall DNA binding. However, dramatic changes at the H2A-H2B interface introduce local reinforcement of DNA contacts. TheT. bruceiacidic patch has altered topology and is refractory to known binders, indicating that the nature of chromatin interactions inT. bruceimay be unique. Overall, our results provide a detailed molecular basis for understanding evolutionary divergence in chromatin structure.
CamoTSS: analysis of alternative transcription start sites for cellular phenotypes and regulatory patterns from 5’ scRNA-seq data
Authors: Hou Ruiyan , Hon Chung-Chau , Huang Yuanhua
Published: April 2023

Five-prime single-cell RNA-seq (scRNA-seq) has been widely employed to profile cellular transcriptomes, however, its power of analysing transcription start sites (TSS) has not been fully utilised. Here, we present a computational method suite, CamoTSS, to precisely identify TSS and quantify its expression by leveraging the cDNA on read 1, which enables effective detection of alternative TSS usage. With various experimental data sets, we have demonstrated that CamoTSS can accurately identify TSS and the detected alternative TSS usages showed strong specificity in different biological processes, including cell types across human organs, the development of human thymus, and cancer conditions. As evidenced in nasopharyngeal cancer, alternative TSS usage can also reveal regulatory patterns including systematic TSS dysregulations.
Impact of light pollution at night on male reproductive success in Japanese medaka (Oryzias latipes)
Authors: Closs Lauren E. , Royan Muhammad Rahmad , Sayyari Amin , Mayer Ian , Weltzien Finn-Arne , Baker Dianne M. , Fontaine Romain
Published: April 2023

Environmental light is perceived and anticipated by organisms to synchronize their biological cycles. Therefore, exposure to artificial light at night could disrupt diurnal and seasonal rhythmicity. Reproduction is a complex physiological process involving integration of environmental signals by the brain, and release of endocrine signals by the pituitary that regulate gametogenesis and spawning. In addition, males from many species form a dominance hierarchy that, through a combination of aggressive and protective behavior, influences their reproductive success. In this study, we investigated the effect of different light regimes, including light pollution at night and continuous light, on the fitness of male fish within a dominance hierarchy using a model fish, the Japanese medaka. In normal light/dark rhythm conditions, we observed that dominant males are more aggressive, remain closer to the female, and spend ten-fold more time spawning than subordinates. By using males with different genotypes, we determined the paternity of the progeny and found that even though subordinate males spend less time with the females, they are equally successful at fertilizing eggs in normal light conditions due to an efficient sneaking behavior. However, when exposed to light at night, dominant males fertilize more eggs. We indeed found that when exposed to nocturnal light pollution, dominant males produce higher quality sperm than subordinate males. Surprisingly, we did not find differences in circulating sex steroid levels, pituitary gonadotropin levels, or gonadosomatic index between dominant and subordinate males, neither in control nor night light condition. Continuous light was found to completely inhibit establishment of male hierarchy. This study is the first to report an effect of light pollution on sperm quality with an impact on male fertilization success in any vertebrate. It has broad implications for fish ecology in urban areas with potential impacts on the genetic diversity of these fish populations.

GRAPHICAL ABSTRACT:

Highlights:

In a triadic relationship, subordinate medaka show sneaking behavior during female spawning, allowing them to produce about 50% of the offspring.

Continuous light inhibits establishment of male hierarchy.

Light pollution at night shifts the balance of reproductive efficiency between dominant and subordinate males, benefiting dominant males.

Exposure to light pollution at night improves sperm quality in dominant fish relative to subordinates, but does not clearly affect reproductive hormone levels.
Colocalization of Protein and microRNA Markers Reveals Unique Extracellular Vesicle Sub-Populations for Early Cancer Detection
Authors: Li Zongbo , Guo Kaizhu , Gao Ziting , Chen Junyi , Ye Zuyang , Wang Shizhen Emily , Yin Yadong , Zhong Wenwan
Published: April 2023

Extracellular vesicles (EVs) play important roles in cell-cell communication but they are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm thus encapsulates very limited amounts of cargos. We report the technique of NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) that utilizes NOBs, which are superparamagnetic nanorods easily handled by a magnet or a rotating magnetic field, to act as isolated “islands” for EV immobilization and cargo confinement. NOBEL-SPA permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, and can assess the colocalization of selected protein/microRNA (miRNA) pairs in the EVs produced by various cell lines or present in clinical sera samples. Specific EV sub-populations marked by the colocalization of unique protein and miRNA combinations have been revealed by the present work, which can differentiate the EVs by their cells or origin, as well as to detect early-stage breast cancer (BC). We believe NOBEL-SPA can be expanded to analyze the co-localization of other types of cargo molecules, and will be a powerful tool to study EV cargo loading and functions under different physiological conditions, and help discover distinct EV subgroups valuable in clinical examination and therapeutics development.