bluuebunny/crossref_metadata_2025 huggingface dataset:
Chelatococcus albus sp. nov., a bacterium isolated from hot spring microbial mat
Authors: Lv Yi-Qing , Hu Chao-Jian , Xian Wen-Dong , Li Meng-Meng , Liu Lan , Liu Ze-Tao , Tan Sha , Liu Wei-Qiu , Jiao Jian-Yu , Li Wen-Jun
Published: March 2024

A Gram-stain-negative, non-endospore-forming, motile, short rod-shaped strain, designated SYSU G07232T, was isolated from a hot spring microbial mat, sampled from Rehai National Park, Tengchong, Yunnan Province, south-western China. Strain SYSU G07232T grew at 25–50 °C (optimum, 37 °C), at pH 5.5–9.0 (optimum, pH 6.0) and tolerated NaCl concentrations up to 1.0 % (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SYSU G07232T showed closest genetic affinity with Chelatococcus daeguensis K106T. The genomic features and taxonomic status of this strain were determined through whole-genome sequencing and a polyphasic approach. The predominant quinone of this strain was Q-10. Major cellular fatty acids comprised C19 : 0 cyclo ω8c and summed feature 8. The whole-genome length of strain SYSU G07232T was 4.02 Mbp, and the DNA G+C content was 69.26 mol%. The average nucleotide identity (ANIm ≤84.85 % and ANIb ≤76.08  %) and digital DNA–DNA hybridization (≤ 21.9 %) values between strain SYSU G07232T and the reference species were lower than the threshold values recommended for distinguishing novel prokaryotic species. Thus, based on the provided phenotypic, phylogenetic, and genetic data, it is proposed that strain SYSU G07232T (=KCTC 8141T=GDMCC 1.4178T) be designated as representing a novel species within the genus Chelatococcus, named Chelatococcus albus sp. nov.
Anthraquinones against Cryptococcus neoformans sensu stricto: antifungal interaction, biofilm inhibition and pathogenicity in the Caenorhabditis elegans model
Authors: Araújo Géssica dos Santos , Brilhante Raimunda Sâmia Nogueira , Rocha Maria Gleiciane da , Aguiar Lara de , Castelo-Branco Débora de Souza Collares Maia , Guedes Glaucia Morgana de Melo , Sidrim José Júlio Costa , Pereira Neto Waldemiro Aquino , Rocha Marcos Fábio Gadelha
Published: March 2024

Introduction. Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the Caenorhabditis elegans pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of Cryptococcus neoformans sensu stricto.

Hypothesis. Anthraquinones and antifungals are associated with preventing C. neoformans sensu stricto biofilm formation and disrupting these communities. Antraquinones reduced the C. neoformans sensu stricto pathogenicity in the C. elegans model.

Aim. This study aimed to evaluate the in vitro interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of C. neoformans sensu stricto.

Methodology. Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. C. neoformans sensu stricto's pathogenicity was investigated using the nematode C. elegans. Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.

Results. Anthraquinone–antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against C. neoformans sensu stricto biofilms. The C. elegans mortality rate reached 76.7 % after the worms were exposed to C. neoformans sensu stricto for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the C. elegans pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to C. neoformans sensu stricto and these compounds at same time.

Conclusion. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.
Target enrichment improves culture-independent detection of Neisseria gonorrhoeae and antimicrobial resistance determinants direct from clinical samples with Nanopore sequencing
Authors: Street Teresa L. , Sanderson Nicholas D. , Barker Leanne , Kavanagh James , Cole Kevin ,   The GonFast Investigators Group, Llewelyn Martin , Eyre David W.
Published: March 2024

Multi-drug-resistant Neisseria gonorrhoeae infection is a significant public health risk. Rapidly detecting N. gonorrhoeae and antimicrobial-resistant (AMR) determinants by metagenomic sequencing of urine is possible, although high levels of host DNA and overgrowth of contaminating species hamper sequencing and limit N. gonorrhoeae genome coverage. We performed Nanopore sequencing of nucleic acid amplification test-positive urine samples and culture-positive urethral swabs with and without probe-based target enrichment, using a custom SureSelect panel, to investigate whether selective enrichment of N. gonorrhoeae DNA improves detection of both species and AMR determinants. Probes were designed to cover the entire N. gonorrhoeae genome, with tenfold enrichment of probes covering selected AMR determinants. Multiplexing was tested in a subset of samples. The proportion of sequence bases classified as N. gonorrhoeae increased in all samples after enrichment, from a median (IQR) of 0.05 % (0.01–0.1 %) to 76 % (42–82 %), giving a corresponding median improvement in fold genome coverage of 365 times (112–720). Over 20-fold coverage, required for robust AMR determinant detection, was achieved in 13/15(87 %) samples, compared to 2/15(13 %) without enrichment. The four samples multiplexed together also achieved >20-fold genome coverage. Coverage of AMR determinants was sufficient to predict resistance conferred by changes in chromosomal genes, where present, and genome coverage also enabled phylogenetic relationships to be reconstructed. Probe-based target enrichment can improve N. gonorrhoeae genome coverage when sequencing DNA extracts directly from urine or urethral swabs, allowing for detection of AMR determinants. Additionally, multiplexing prior to enrichment provided enough genome coverage for AMR detection and reduces the costs associated with this method.
Assembly collapsing versus heterozygosity oversizing: detection of homokaryotic and heterokaryotic Laccaria trichodermophora strains by hybrid genome assembly
Authors: Ángeles-Argáiz Rodolfo Enrique , Aguirre-Beltrán Luis Fernando Lozano , Hernández-Oaxaca Diana , Quintero-Corrales Christian , Trujillo-Roldán Mauricio A. , Castillo-Ramírez Santiago , Garibay-Orijel Roberto
Published: March 2024

Genome assembly and annotation using short-paired reads is challenging for eukaryotic organisms due to their large size, variable ploidy and large number of repetitive elements. However, the use of single-molecule long reads improves assembly quality (completeness and contiguity), but haplotype duplications still pose assembly challenges. To address the effect of read length on genome assembly quality, gene prediction and annotation, we compared genome assemblers and sequencing technologies with four strains of the ectomycorrhizal fungus Laccaria trichodermophora. By analysing the predicted repertoire of carbohydrate enzymes, we investigated the effects of assembly quality on functional inferences. Libraries were generated using three different sequencing platforms (Illumina Next-Seq, Mi-Seq and PacBio Sequel), and genomes were assembled using single and hybrid assemblies/libraries. Long reads or hybrid assemby resolved the collapsing of repeated regions, but the nuclear heterozygous versions remained unresolved. In dikaryotic fungi, each cell includes two nuclei and each nucleus has differences not only in allelic gene version but also in gene composition and synteny. These heterokaryotic cells produce fragmentation and size overestimation of the genome assembly of each nucleus. Hybrid assembly revealed a wider functional diversity of genomes. Here, several predicted oxidizing activities on glycosyl residues of oligosaccharides and several chitooligosaccharide acetylase activities would have passed unnoticed in short-read assemblies. Also, the size and fragmentation of the genome assembly, in combination with heterozygosity analysis, allowed us to distinguish homokaryotic and heterokaryotic strains isolated from L. trichodermophora fruit bodies.
Synaptic weight dynamics underlying memory consolidation: implications for learning rules, circuit organization, and circuit function
Authors: Bhasin Brandon J , Raymond Jennifer L , Goldman Mark S
Published: March 2024

Systems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area. We show that the synaptic dynamics of the circuit during consolidation of an analog memory can be understood as a temporal integration process, by which transient changes in activity driven by plasticity in the early-learning area are accumulated into persistent synaptic changes at the late-learning site. This simple principle naturally leads to a speed-accuracy tradeoff in systems consolidation and provides insight into how the circuit mitigates the stability-plasticity dilemma of storing new memories while preserving core features of older ones. Furthermore, it imposes two constraints on the circuit. First, the plasticity rule at the late-learning site must stably support a continuum of possible outputs for a given input. We show that this is readily achieved by heterosynaptic but not standard Hebbian rules. Second, to turn off the consolidation process and prevent erroneous changes at the late-learning site, neural activity in the early-learning area must be reset to its baseline activity. We propose two biologically plausible implementations for this reset that suggest novel roles for core elements of the cerebellar circuit.

Significance Statement

How are memories transformed over time? We propose a simple organizing principle for how long term memories are moved from an initial to a final site of storage. We show that successful transfer occurs when the late site of memory storage is endowed with synaptic plasticity rules that stably accumulate changes in activity occurring at the early site of memory storage. We instantiate this principle in a simple computational model that is representative of brain circuits underlying a variety of behaviors. The model suggests how a neural circuit can store new memories while preserving core features of older ones, and suggests novel roles for core elements of the cerebellar circuit.
Treatment Heterogeneity of Water, Sanitation, Hygiene, and Nutrition Interventions on Child Growth by Environmental Enteric Dysfunction and Pathogen Status for Young Children in Bangladesh
Authors: Butzin-Dozier Zachary , Ji Yunwen , Coyle Jeremy , Malenica Ivana , Rogawski McQuade Elizabeth T. , Grembi Jessica Anne , Platts-Mills James A. , Houpt Eric R. , Graham Jay P. , Ali Shahjahan , Rahman Md Ziaur , Alauddin Mohammad , Famida Syeda L. , Akther Salma , Hossen Md. Saheen , Mutsuddi Palash , Shoab Abul K. , Rahman Mahbubur , Islam Md. Ohedul , Miah Rana , Taniuchi Mami , Liu Jie , Alauddin Sarah , Stewart Christine P. , Luby Stephen P. , Colford John M. , Hubbard Alan E. , Mertens Andrew N. , Lin Audrie
Published: March 2024

Background

Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments’ effects based on individual pathogen and EED biomarker status with respect to child linear growth.

Methods

We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status. We analyzed treatment (N+WSH, WSH, N, or control) randomly assigned in-utero, child pathogen and EED data at 14 months of age, and child LAZ at 28 months of age. We estimated the difference in mean child length for age Z-score (LAZ) under the treatment rule and the difference in stratified treatment effect (treatment effect difference) comparing children with high versus low pathogen/biomarker status while controlling for baseline covariates.

Results

We analyzed data from 1,522 children, who had median LAZ of -1.56. We found that myeloperoxidase (N+WSH treatment effect difference 0.0007 LAZ, WSH treatment effect difference 0.1032 LAZ, N treatment effect difference 0.0037 LAZ) andCampylobacterinfection (N+WSH treatment effect difference 0.0011 LAZ, WSH difference 0.0119 LAZ, N difference 0.0255 LAZ) were associated with greater effect of all interventions on growth. In other words, children with high myeloperoxidase orCampylobacterinfection experienced a greater impact of the interventions on growth. We found that a treatment rule that assigned the N+WSH (LAZ difference 0.23, 95% CI (0.05, 0.41)) and WSH (LAZ difference 0.17, 95% CI (0.04, 0.30)) interventions based on EED biomarkers and pathogens increased predicted child growth compared to the randomly allocated intervention.

Conclusions

These findings indicate that EED biomarker and pathogen status, particularlyCampylobacterand myeloperoxidase (a measure of gut inflammation), may be related to impact of N+WSH, WSH, and N interventions on child linear growth.
Multi-species co-circulation of adenoviruses identified by next generation sequencing during an outbreak in coastal Kenya in 2023
Authors: Lambisia Arnold W. , Mutunga Martin , Katama Esther N. , Agoti Charles N. , Houldcroft Charlotte J.
Published: March 2024

Background

Although seven human adenovirus (HAdV) species are known to exist,only F (types 40 and 41) and G, are identified as diarrhoeal disease agents. The role of other HAdV species in diarrhoeal disease remains unclear and data of their prevalence is limited. We describe HAdV species and types in hospitalised children with diarrhoea in coastal Kenya.

Methods

329 stool samples collected between June 2022 and August 2023 from children aged <13-years were screened for HAdV using quantitative polymerase chain reaction (qPCR). Positive HAdV cases were genotyped by adenovirus primers from the RespiCoV panel by amplification, next generation sequencing followed by phylogenetic analysis.

Results

65 samples (20%) tested HadV positive from which five HAdV species were identified. Other than HAdV F, other species included A, B, C and D; these were detected as either mono-detections or coinfections. Six HAdV F identified by NGS had been missed by our q PCR typing method. This appeared to be as a result of a 133-nucleotide deletion in the long fiber protein which abrogated a primer and probe binding site. Based on VESIKARI scores grading of diarrheal disease severity, 93% of the HAdV cases presented with severe disease. One child with an HAdV F infection died.

Conclusion

Our study shows the enormous diversity and clinical characteristics of HAdV species in children with diarrhoea in coastal Kenya. These data offers an opportunity to improve current diagnostic assays, increase knowledge of HAdV in Africa for control of outbreaks in the future.
Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer
Authors: Lee Sanghoon , Cho Youngbin , Li Yiting , Li Ruxuan , Brown Daniel , McAuliffe Priscilla , Lee Adrian V , Oesterreich Steffi , Zervantonakis Ioannis K. , Osmanbeyoglu Hatice Ulku
Published: March 2024

Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA-sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors. We found that recombinant S100A11 enhances macrophage infiltration and migration in a dose-dependent manner. Additionally, in 3D models, we showed that S100A11 expression levels in ER+ cancer cells predict macrophage infiltration patterns. Neutralizing S100A11 decreased macrophage recruitment, both in cancer cell lines and in a clinically relevant patient-derived organoid model, underscoring its role as a paracrine regulator of cancer-macrophage interactions in the pro-tumorigenic TME. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.
Altered empathy processing in frontotemporal dementia A task-based fMRI study
Authors: Lindberg Olof , Li Tie-Qiang , Lind Cecilia , Vestberg Susanna , Almkvist Ove , Stiernstedt Mikael , Ericson Anita , Bogdanovic Nenad , Hansson Oskar , Harper Luke , Westman Eric , Graff Caroline , Tsevis Theofanis , Mannfolk Peter , Fischer Håkan , Nilsonne Gustav , Petrovic Predrag , Nyberg Lars , Wahlund Lars-Olof , Santillo Alexander F ,   the Swedish FTD initiative
Published: March 2024

A lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control condition) is an established functional magnetic resonance imaging (fMRI) paradigm used to investigate empathy for pain (EFP; pain condition minus control condition). EFP has been associated with increased blood oxygen level dependent (BOLD) signal in regions known to become atrophic in the early stages in bvFTD, including the anterior insula and the anterior cingulate. We therefore hypothesized that patients with bvFTD would display altered empathy processing in the EFP paradigm. Here we examined empathy processing using the EFP paradigm in 28 patients with bvFTD and 28 sex and age matched controls. Participants underwent structural MRI, task-based and resting-state fMRI. The Interpersonal Reactivity Index (IRI) was used as a measure of different facets of empathic function outside the scanner. The EFP paradigm was analysed at a whole brain level and using two regions-of-interest approaches, one based on a metanalysis of affective perceptual empathy versus cognitive evaluative empathy and one based on the control’s activation pattern. In controls, EFP was linked to an expected increase of BOLD signal that displayed an overlap with the pattern of atrophy in the bvFTD patients (insula and anterior cingulate). Additional regions with increased signal were the supramarginal gyrus and the occipital cortex. These latter regions were the only ones that displayed increased BOLD signal in bvFTD patients. BOLD signal increase under the affective perceptual empathy but not the cognitive evaluative empathy region of interest was significantly greater in controls than in bvFTD patients. The control’s rating on their empathic concern subscale of the IRI was significantly correlated with the BOLD signal in the EFP paradigm, as were an informant’s ratings of the patient’s empathic concern subscale. This correlation was not observed on other subscales of the IRI or when using the patient’s self- ratings. Finally, controls and patients showed different connectivity patterns in empathy related networks during resting-state fMRI, mainly in nodes overlapping the ventral attention network. Our results indicate that reduced neural activity in regions typically affected by pathology in bvFTD is associated with reduced empathy processing, and a predictor of patient’s capacity to experience affective empathy.
Flight performance, activity and behaviour of breeding pied flycatchers in the wild, revealed with accelerometers and machine learning
Authors: Yu Hui , Liang Shujie , Muijres Florian T. , te Lindert Jan Severin , de Knegt Henrik J. , Hedenström Anders , Lamers Koosje P. , Henningsson Per
Published: March 2024

Flight behaviours have been extensively studied from different angles such as their kinematics, aerodynamics and more general their migration pattern. Nevertheless, much is still unknown about the daily flight activity of birds, in terms of their performance, behaviour and the potential differences between males and females. The recent development of miniaturized accelerometers allows us a glimpse into the daily life of a songbird. Here, we tagged 26 pied flycatchers (Ficedula hypoleuca) with accelerometers and analysed using machine learning approaches their flight performance, activity and behaviour during their chick rearing period. We found that during two hours of foraging chick-rearing pied flycatchers were flying 13.7% of the time. Almost all flights (>99%) were short flights lasting less than 10s. Flight activity changed throughout the day and was highest in the morning and lowest in the early afternoon. Male pied flycatcher had lower wing loading than females, and peak flight accelerations were inversely correlated with wing loading. Despite this, we found no significant differences in flight activity and performance between sexes. This suggests that males possess a higher potential flight performance, which they not fully utilized during foraging flights. Our results thus suggest that male and female pied flycatcher invest equally in parental care, but that this comes at a reduced cost by the male, due to their higher flight performance potential.
ParabrachialCalcaneurons mediate second-order conditioning
Authors: Park Sekun , Zhu Anqi , Cao Feng , Palmiter Richard
Published: March 2024

Learning to associate cues, both directly and indirectly, with biologically significant events is essential for survival. Second-order conditioning (SOC) involves forming an association between a previously reinforced conditioned stimulus (CS1) and a new conditioned stimulus (CS2) without the presence of an unconditioned stimulus (US). The neural substrates mediating SOC, however, remain unclear. In the parabrachial nucleus,Calcagene-expressing neurons, which react to the noxious US, also respond to a CS after its pairing with a US. This observation led us to hypothesize their involvement in SOC. To explore this possibility, we established an aversive SOC behavioral paradigm in mice and monitoredCalcaneuron activity via single-cell calcium imaging during SOC and subsequent recall phases. These neurons were activated not only by CS1 following its association with the US but also by CS2 after SOC. Chemogenetically inhibiting these neurons during second-order associations attenuated SOC. These findings suggest that activating the US pathway in response to a learned CS plays an important role in forming the association between the old and a new CS, promoting the formation of second-order memories.
Seeing the piles of the velvet bending under our finger sliding over a tactile stimulator improves the perception of the fabric
Authors: Mouchnino Laurence , Camillieri Brigitte , Faucheu Jenny , Juganaru Mihaela , Moinon Alix , Blouin Jean , Bueno Marie-Ange
Published: March 2024

Using friction modulation to simulate fabrics with a tactile stimulator (i.e. virtual surface) is not sufficient to render fabric touch and even more so for hairy fabrics. We hypothesized that seeing the pile of the velvet darken or lighten depending on changes in the finger movement direction on the virtual surface should improve the velvet fabric rendering. Participants actively rubbed a tactile device or a velvet fabric looking at a screen that showed a synthesized image of a velvet which either remained static (V-static) or darkening/lightening with the direction of touch (V-moving). We showed that in V-moving condition, the touched surface was always perceived rougher, which is a descriptor of a real velvet (Experiment 1). Using electroencephalography and sources localization analyses, we found greater theta band [5-7 Hz] oscillation power in the left inferior posterior parietal lobule (PPC) in the Virtual velvet/V-moving condition as compared to both Real velvet/ V-static and Virtual velvet/V-static conditions(Experiment 2). This result is consistent with studies that give a crucial role to the left PPC for visuo-tactile binding. The greater activity of the lateral occipital area found in the Virtual velvet/V-moving condition could have contributed to the emergence of a velvet more realistic representation.
The refinement paradox and cumulative cultural evolution: collective improvement in knowledge favors conformity, blind copying and hyper-credulity
Authors: Miu Elena , Rendell Luke , Bowles Sam , Boyd Rob , Cownden Daniel , Enquist Magnus , Eriksson Kimmo , Feldman Marcus W. , Lillicrap Timothy , McElreath Richard , Murray Stuart , Ounsley James , Lala Kevin N.
Published: March 2024

Social learning is common in nature, yet cumulative culture (where knowledge and technology increase in complexity and diversity over time) appears restricted to humans. To understand why, we organized a computer tournament in which programmed entries specified when to learn new knowledge and when to refine (i.e. improve) existing knowledge. The tournament revealed a ‘refinement paradox’: refined behavior afforded higher payoffs as individuals converged on a small number of successful behavioral variants, but refining did not generally pay. Paradoxically, entries that refined only in certain conditions did best during behavioral improvement, while simple copying entries thrived when refinement levels were high. Cumulative cultural evolution may be rare in part because sophisticated strategies for improving knowledge and technology are initially advantageous, yet complex culture, once achieved, favors conformity, blind imitation and hyper-credulity.
Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response
Authors: Höfer Stefanie , Frasch Larissa , Putzker Kerstin , Lewis Joe , Sakhteman Amirhossein , The Matthew , Bayer Florian P. , Müller Julian , Hamood Firas , Kuster Bernhard
Published: March 2024

The DNA-damaging agent gemcitabine (GEM) is a first-line treatment for pancreatic cancer but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs including kinase inhibitors but the experimental evidence for such rational is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 140 clinical kinase inhibitors and observed strong synergy for the ATR inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway including phosphorylated pS468 of CHEK1 as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations.
Self-organization of vascularized skeletal muscle from bovine embryonic stem cells
Authors: Sanaki-Matsumiya Marina , Villava Casandra , Rappez Luca , Haase Kristina , Wu Jun , Ebisuya Miki
Published: March 2024

Cultured beef holds promising potential as an alternative to traditional meat options. While adult stem cells are commonly used as the cell source for cultured beef, their proliferation and differentiation capacities are limited. To produce cultured beef steaks, current manufacturing plans often require the separate preparation of multiple cell types and intricate engineering for assembling them into structured tissues. In this study, we propose and report the co-induction of skeletal muscle, neuronal, and endothelial cells from bovine embryonic stem cells (ESCs) and the self-organization of tissue structures in 2- and 3-dimensional cultures. Bovine myocytes were induced in a stepwise manner through the induction of presomitic mesoderm (PSM) from bovine ESCs. Muscle fibers with sarcomeres appeared within 15 days, displaying calcium oscillations responsive to inputs from co-induced bovine spinal neurons. Bovine endothelial cells were also co-induced via PSM, forming uniform vessel networks inside tissues. Our serum-free, rapid co-induction protocols represent a milestone toward self-organizing beef steaks with integrated vasculature and innervation.
Transcriptomics and trans-organellar complementation reveal a limited signaling capacity of 12-cis-oxo-phytodienoic acid in wounded Arabidopsis
Authors: Mekkaoui Khansa , Baral Ranjit , Smith Fiona , Klein Moritz , Feussner Ivo , Hause Bettina
Published: March 2024

12-cis-Oxo-phytodienoic acid (OPDA), the main precursor of the key plant growth and defense hormone jasmonoyl-isoleucine (JA-Ile), is believed to have distinct signaling roles in plant’s responses to stress. In Arabidopsis, insights into OPDA functions have been gained from studying a mutant, which is affected in the conversion of OPDA by missing OPDA REDUCTASE3 (OPR3).opr3mutants, however, accumulate JA-Ile through a cytosolic bypass mediated by OPR2. Therefore, wound-induced transcriptome ofopr2opr3in comparison to wild-type andallene oxide synthasemutant was analyzed to unravel OPDA signaling. Results showed that OPDA lacked a distinct transcriptional signature, whereas known OPDA-response genes were wound-induced independently of OPDA. The application of OPDA toopr2opr3resulted in a distinct transcriptional response compared to the endogenous rise of OPDA in the same mutant, with the activation of the sulfur assimilation pathway genes occurring only with the external application of the compound. These findings suggested a compartmentalization of endogenously produced OPDA, investigated further through trans-organellar complementation. OPR3 complementedopr2opr3mutants in fertility and wound-induced JA-Ile production regardless of its localization. Sincein vitroenzymatic studies revealed OPR3’s activity on both OPDA and 4,5-ddh-JA, conclusions on translocation of OPDA were not unequivocal. Dissecting the conversion of either OPDA or 4,5-ddh-JA by OPR2 and OPR1 organelle variants pointed, however, to a strong OPDA compartmentalization supporting its lacking signaling function.
Shifting Geographical Transmission Patterns: Characterizing the 2023 Fatal Dengue Outbreak in Bangladesh
Authors: Hasan Mohammad Nayeem , Rahman Mahbubur , Uddin Meraj , Ashrafi Shah Ali Akbar , Rahman Kazi Mizanur , Paul Kishor Kumar , Sarker Mohammad Ferdous Rahman , Haque Farhana , Sharma Avinash , Papakonstantinou Danai , Paudyal Priyamvada , Asaduzzaman Md , Zumla Alimuddin , Haider Najmul
Published: March 2024

In 2023, Bangladesh experienced its largest and deadliest outbreak of Dengue virus (DENV), reporting the highest-ever recorded annual cases and deaths. We aimed to characterize the geographical transmission of the DENV in Bangladesh. From 1 Jan – 31 Dec 2023, we extracted and analyzed daily data on dengue cases and deaths from the national Management Information System (MIS). We performed a generalized linear mixed model to identify the associations between division-wise daily dengue counts and various geographical and meteorological covariates. The number of Dengue cases reported in 2023 was 1.3 times higher than the total number recorded in the past 23 years (321,179 vs. 244,246), with twice as many deaths than the total fatalities recorded in the past 23 years (1705 vs. 849). Of the 1705 deaths in 2023, 67.4% (n=1015) expired within one day after hospital admission. The divisions southern to Dhaka had a higher dengue incidence/1000 population (2.30 vs. 0.50, p<0,0.01), and higher mean annual temperatures (27.46 vs. 26.54 °C) than the northern divisions. The average daily temperature (IRR: 1.13, 95% CI: 1.11-1.14), urban and rural population ratio of the divisions (IRR: 1.04, 95% CI: 1.03-1.04), showed a positive, and rainfall (IRR: 0.99, 95% CI: 0.98-0.99) showed a negative association with dengue cases in each division. We observed a major geographical shift of Dengue cases from the capital city Dhaka to different districts of Bangladesh with a higher incidence of dengue in the southern division of Bangladesh, influenced by temperature and urbanization.
Enhancing patient stratification and interpretability through class-contrastive and feature attribution techniques
Authors: Olowu Sharday , Lawrence Neil , Banerjee Soumya
Published: March 2024

Abstract

A crucial component of the treatment of genetic disorders is identifying and characterising the genes and gene modules that drive disease processes. Recent advances in Next-Generation Sequencing (NGS) improve the prospects for achieving this goal. However, many machine learning techniques are not explainable and fail to account for gene correlations. In this work, we develop a comprehensive set of explainable machine learning techniques to perform patient stratification for inflammatory bowel disease. We focus on Crohn’s disease (CD) and its subtypes: CD with deep ulcer, CD without deep ulcer and IBD-controls. We produce an interpretable probabilistic model over disease subtypes using Gaussian Mixture Modelling. We then apply class-contrastive and feature-attribution techniques to identify potential target genes and modules. We modify the widely used kernelSHAP (Shapley Additive Explanations) algorithm to account for gene correlations. We obtain relevant gene modules for each disease subtype. We develop a class-contrastive technique to visually explain why a particular patient is predicted to have a particular subtype of the disease. We show that our results are relevant to the disease through Gene Ontology enrichment analysis and a review of the literature. We also uncover some novel findings, including currently uncharacterised genes. These approaches maybe beneficial, in personalised medicine, to inform decision-making regarding the diagnosis and treatment of genetic disorders. Our approach is model-agnostic and can potentially be applied to other diseases and domains where explainability and feature correlations are important.
Quality of Care at childbirth during the COVID-19 pandemic: findings of the IMAgiNE EURO study in Belgium
Authors: Galle Anna , D’Hauwers Silke , Berghman Helga , Vaerewijck Nele , Valente Emanuelle Pessa , Mariani Ilaria , Bomben Arianna , Vedove Stefano delle , Lazzerini Marza ,   the IMAgiNE EURO Study Group
Published: March 2024

Objectives

To examine quality of maternal and newborn care (QMNC) around childbirth in facilities in Belgium during the COVID-19 pandemic and trends over time.

Design

A cross-sectional observational study.

Setting

Data of the IMAgiNE EURO study in Belgium. Participants

Women giving birth in a Belgian facility from March 1, 2020, to May 1, 2023, responded a validated online questionnaire based on 40 WHO standards-based quality measures organised in four domains: provision of care, experience of care, availability of resources, and organizational changes related to COVID-19.

Primary and secondary outcome measures

Quantile regression analysis was performed to assess predictors of QMNC; trends over time were tested with the Mann-Kendall test.

Results

897 women were included in the analysis, 67%(n=601) with spontaneous vaginal birth, 13.3%(n=119) with instrumental vaginal birth and 19.7%(n=177) with cesarean section. We found high QMNC scores but also specific gaps in all domains of QMNC. On provision of care, 21.0%(n=166) of women who experienced labor and 14.7%(n=26) of women with a cesarean reported inadequate pain relief; 64.7%(n=74) of women with an instrumental birth reported fundal pressure and 72.3% (n=86) reported that forceps or vacuum cup was used without their consent. On experience of care, 31.1%(n=279) reported unclear communication, 32.9%(n=295) reported that they were not involved in choices,11.5%(n=104) stated not being treated with dignity and 8.1%(n=73) experienced abuse. Related to resources, almost half of the women reported an inadequate number of healthcare professionals (46.2%, n=414). The multivariable analyses showed significantly lower QMNC scores for women with an instrumental vaginal birth. Over time there was a significant increase in QMNC score for ‘experience of care’ and ‘key organizational changes due to COVID-19’.

Conclusions and relevance

Although overall QMNC scores were high, findings also suggest gaps in QMNC. Underlying causes of these gaps should be explored to design appropriate interventions and policies.
Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition
Authors: Thoumas Jean-Louis , Cavaroc Amandine , Sery Damien , Leulier François , Vadder Filipe De
Published: March 2024

Background

Early life, particularly after weaning, is the most rapid period of growth in mammals, and this growth is highly dependent on adequate nutrition. Protein-energy malnutrition (PEM) during this critical window can lead to stunting and wasting, which have long-term health consequences.

Objective

This study aimed to develop a mouse model of juvenile PEM to assess the effects of refeeding with various diets and interventions on growth recovery, including the impact of probiotic supplementation and suboptimal refeeding diets.

Methods

Juvenile C57Bl/6J mice were fed a low-protein diet (LPD, 5% kcal from protein) starting at postnatal day 14 (P14) to induce malnutrition. Following weaning, both male and female mice were refed an optimal diet (Altromin 1310, 27% kcal from protein) at different times ranging from P28 to P56. In a second intervention, male mice were supplemented during refeeding withLactiplantibacillus plantarumWJL (LpWJL), a probiotic known to stimulate growth in malnourished conditions. A final group of malnourished male mice were refed with a Western diet (WD, 34.5% kcal from fat; 15.3% kcal from protein) or a modified Western diet (MWD, 34.2% kcal from fat; 7.5% kcal from protein) to model suboptimal refeeding.

Results

Refeeding with an optimal diet fully restored growth in female mice, but male mice exhibited persistent stunting despite nutritional rehabilitation. LpWJLtreatment during refeeding did not enhance systemic growth in males. In contrast, refeeding with WD or MWD restored body length but impaired glucose metabolism, particularly in mice refed MWD after PEM. LpWJLexacerbated glucose intolerance in the suboptimal refeeding groups.

Conclusion

Sex-dependent differences exist in the recovery from early-life malnutrition, with males showing incomplete growth recovery despite optimal refeeding. Suboptimal diets, while compensating for stunting, impair glucose metabolism, especially when protein intake is insufficient. Probiotic supplementation with LpWJLdid not improve growth outcomes.
Profiling trace organic chemical biotransformation genes, enzymes and associated bacteria in microbial model communities
Authors: Cao Lijia , Garcia Sarahi L. , Wurzbacher Christian
Published: March 2024

Microbial biotransformation of trace organic chemicals (TOrCs) is an essential process in wastewater treatment for eliminating environmental pollution. Understanding of TOrC biotransformation mechanisms, especially at their original concentrations, is important to optimize treatment performance, whereas our current knowledge is limited. Here we investigated the biotransformation of seven TOrCs by 24 model communities. The genome-centric analyses unraveled the biotransformation drivers concerning functional genes and enzymes and responsible bacteria. We obtained efficient model communities for complete removal on ibuprofen, caffeine and atenolol, and the transformation efficiencies for sulfamethoxazole, carbamazepine, trimethoprim and gabapentin were 0-45%. Biotransformation performance was not fully reflected by the presence of known biotransformation genes and enzymes. However, functional similar homologs to existing biotransformation genes and enzymes (e.g., long-chain-fatty-acid-CoA ligase encoded byfadDandfadD13gene, acyl-CoA dehydrogenase encoded byfadE12gene) could play critical roles in TOrC metabolism. Finally, we identified previously undescribed degrading strains, e.g.,Rhodococcus qingshengiifor caffeine, carbamazepine, sulfamethoxazole and ibuprofen biotransformation, and potential transformation enzymes, e.g., SDR family oxidoreductase targeting sulfamethoxazole and putative hypothetical proteins for caffeine, atenolol and gabapentin biotransformation.
System and transcript dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2)
Authors: Silva João M. F. , Oteo Jose Á. , Garay Carlos P. , Elena Santiago F.
Published: March 2024

Statistical laws arise in many complex systems and can be explored to gain insights into their structure and behavior. Here, we investigate the dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) at the system and individual gene levels; and demonstrate that the statistical frameworks used here are robust in spite of the technical noise associated with single-cell RNA sequencing (scRNA-seq) data. A biphasic fit to Taylor’s power law was observed, and it is likely associated with the larger sampling noise inherent to the measure of less expressed genes. The type of the distribution of the system, as assessed by Taylor’s parameters, varies along the course of infection in a cell type-dependent manner, but also sampling noise had a significant influence on Taylor’s parameters. At the individual gene level, we found that genes that displayed signals of punctual rank stability and/or long-range dependence behavior, as measured by Hurst exponents, were associated with translation, cellular respiration, apoptosis, protein-folding, virus processes, and immune response.

Author summary

Viruses replicate within susceptible cells by exploiting the cellular machinery. Consequently, cells initiate defenses against the virus and signal other cells, notably immune cells. This ongoing battle prompts significant alterations in the cells’ gene expression patterns throughout the infection process. In this study, we apply statistical principles from complex systems theory to analyze gene expression data from individual cells infected with SARS-CoV-2. Our research aims to elucidate how viral infection impacts cells at both systemic and individual gene levels. Our primary findings are twofold: (i) the virus influences the distribution of gene transcripts over the course of infection, varying depending on cell type. (ii) As the infection progresses, numerous genes associated with critical cellular functions and immunity exhibit signs of punctual instability and/or autocorrelation, indicating their response to viral infection at various stages of the process.
Marine biofilms: cyanobacteria factories for the global oceans
Authors: Zhong Cheng , Yamanouchi Shun , Li Yingdong , Chen Jiawei , Wei Tong , Wang Ruojun , Zhou Kun , Cheng Aifang , Hao Weiduo , Liu Hongbin , Konhauser Kurt O. , Iwasaki Wataru , Qian Pei-Yuan
Published: March 2024

Marine biofilms were newly revealed as a giant microbial diversity pool for global oceans. However, the cyanobacterial diversity in marine biofilms within the upper seawater column and its ecological and evolutionary implications remains undetermined. Here, we reconstructed a full picture of modern marine cyanobacteria habitats by re-analysing 9.3 terabyte metagenomic datasets and 2648 metagenome-assembled genomes (MAGs). The abundance of cyanobacteria lineages exclusively detected in marine biofilms were up to 9-fold higher than those in seawater at similar sample size. Analyses revealed that cyanobacteria in marine biofilms are specialists with strong geographical and environmental constraints on their genome and functional adaption, which in stark contrast to the generalistic features of seawater-derived cyanobacteria. Molecular dating suggests the important diversifications in biofilm-forming cyanobacteria appear to coincide with the Great Oxidation Event (GOE), “boring billion” middle Proterozoic, and the Neoproterozoic Oxidation Event (NOE). These new insights suggest that marine biofilms are large and important cyanobacterial factories for the global oceans.

Importance

Cyanobacteria, highly diverse microbial organisms, play a crucial role in Earth’s oxygenation and biogeochemical cycling. However, their connection to these processes remains unclear, partly due to incomplete surveys of oceanic niches. Our study uncovered significant cyanobacterial diversity in marine biofilms, showing distinct niche differentiation compared to seawater counterparts. These patterns reflect three key stages of marine cyanobacterial diversification, coinciding with major geological events in Earth’s history. Thus, surface-associated biomass within oceanic niches emerges as a pivotal factor in Earth’s evolution.
Adaptive quantum state estimation for two optical point sources
Authors: Kimizu Masataka , Tanaka Fuyuhiko , Fujiwara Akio
Published: March 2024

In classical optics, there is a well-known resolution limit called Rayleigh's curse in the separation of two incoherent optical sources in close proximity. Recently, Tsang [] revealed that this difficulty may be circumvented in the framework of quantum theory. Following their work, various estimation methods have been proposed to overcome Rayleigh's curse, but none of them enables us to estimate the positions of two point sources simultaneously based on single-photon measurements with high accuracy. In this study, we propose a method to estimate the positions of two point sources with the highest accuracy using an adaptive quantum state estimation scheme.

©2024 American Physical Society
2024
American Physical Society
Compilation of a simple chemistry application to quantum error correction primitives
Authors: Blunt Nick S. , Gehér György P. , Moylett Alexandra E.
Published: March 2024

A number of exciting recent results have been seen in the field of quantum error correction. These include initial demonstrations of error correction on current quantum hardware and resource estimates which improve understanding of the requirements to run large-scale quantum algorithms for real-world applications. In this work, we bridge the gap between these two developments by performing careful estimation of the resources required to fault-tolerantly perform quantum phase estimation (QPE) on a minimal chemical example. Specifically, we describe a detailed compilation of the QPE circuit to lattice surgery operations for the rotated surface code, for a hydrogen molecule in a minimal basis set. We describe a number of optimizations at both the algorithmic and error correction levels. We find that implementing even a simple chemistry circuit requires 1000 qubits and 2300 quantum error correction rounds, emphasising the need for improved error correction techniques specifically targeting the early fault-tolerant regime.

Published by the American Physical Society
2024