bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell polarity in ciliates
Authors: Frankel Joseph
Published: November 2023

As pointed by Wolpert (1), the term ‘polarity’ is used by biologists in two different senses (Fig. 1). One is the expression of different spatially segregated qualities or attributes. These might characterize the opposite ends of a system, such as the budding and non-budding poles of a yeast cell (2), or else they might partition the entire system into two relatively homogeneous regions, such as the apical and basolateral domains of an epithelial cell (3). I will call this domain polarity. The other sense embodies the notion of a direction, or vector, that pervades the entire system. It is this latter sense that Crick had in mind when he stated that’a system of polarities … necessarily implies a vector field’ (4, p. 436). I will call this vectorial polarity.
Hybridization At Oligonucleotid Sensitive Electrodes
Authors: Caruana Daren J
Published: November 2023

DNA hybridization on solid surfaces was developed on membranes as a routine biotechnological technique in the 1970s (1). With the invention and refinement of new surface analytical techniques, oligonucleotide detection by surface con-fined hybridization is the fundamental principle behind the function of most oligonucleotide sensitive devices. These devices are capable of high throughput DNA analysis for applications such as sequencing, genetic diagnosis, drug phenotyping, computing, and gene expression analysis.
Genetic Association Between ICAM-1 Gene Variants and Susceptibility to Ischemic Cardiomyopathy
Authors: Naman Tuersunjiang , Abuduhalike Refukaiti , Abudouwayiti Aihaidan , Abudurexiti Muyashaer , Sun Juan , Mahemuti Ailiman
Published: November 2023

The current work was aimed at exploring the association between single nucleotide polymorphisms (SNPs) in the ICAM-1 gene, along with the identification of additional haplotypes and their potential role in the susceptibility to ischemic cardiomyopathy (ICM). The control group underwent a Hardy–Weinberg equilibrium test. The associations of genotypes and alleles with susceptibility to ICM were then analyzed using logistic regression analysis. Subsequently odds ratios (ORs) along with 95% confidence intervals (95% CI) were calculated. Interaction analysis was conducted between these SNPs. Furthermore, linkage disequilibrium analysis and haplotype analysis were performed on SNPs that showed interactions with each other. The incidence of ICM was significantly higher among individuals carrying the T allele of rs3093032 (OR = 2.032, 95% CI, 1.275–3.241, P = 0.003) relative to those with the C allele. In addition, CT genotype carriers had a higher susceptibility to ICM than CC genotype carriers (OR = 2.490, 95% CI, 1.445–4.29, P = 0.001). Furthermore, 3 SNPs (rs3093032, rs923366, rs3093030) exhibited a strong interaction with each other, whereas rs281437 showed no interaction with the other 3 SNPs. Individuals carrying the Crs3093032-Trs923366-Crs3093030 haplotype had an elevated risk of ICM compared with those carrying the Crs3093032-Crs923366-Crs3093030 haplotype (OR = 2.280, 95% CI, 1.568–3.315, P < 0.001). Moreover, individuals carrying the Trs3093032-Crs923366-Crs3093030 haplotype were more susceptible to ICM than those carrying the Crs3093032-Crs923366-Crs3093030 haplotype (OR = 2.388, 95% CI, 1.469–3.880, P < 0.001). Regarding rs3093032, the minor alleles and haplotypes are associated with an increased ICM risk: 3 SNPs (rs3093032, rs923366, rs3093030) in ICAM-1 have strong interaction with each other.
Prevalence and long-term implications of preoperative anemia in patients undergoing elective general surgery – a retrospective cohort study at a university hospital
Authors: Braunschmid Tamara , Graf Alexandra , Eigenbauer Ernst , Schak Gerhard , Sahora Klaus , Baron David M.
Published: November 2023

Objective:

The aim of this retrospective study was to assess the prevalence of anemia in a cohort of patients undergoing elective general surgery at a university hospital. Furthermore, we investigated the influence of anemia on short-term and long-term postoperative outcome.

Background:

Awareness of the negative impact of preoperative anemia on perioperative morbidity and mortality is rising. Anemia is a potentially modifiable factor, and its therapy might improve patient outcome in elective surgery. Nevertheless, patients with preoperative anemia frequently undergo elective surgery without receiving adequate preoperative treatment.

Methods:

In this single-center cohort study, we analyzed 6908 adult patients who underwent elective general surgery. Patients undergoing day-clinic surgery were excluded. In all patients, preoperative hemoglobin (Hb) concentration and hematocrit (Hct) was available.

Results:

Of all patients analyzed, 32.9% were anemic (21.0% mild, 11.8% moderate, 1.1% severe). Median time to last follow up was 5.2 years. During the whole study period, 27.1% of patients died (1.2% died during the hospital stay); median time to death was 1.3 years. Patients with preoperative anemia had significantly higher mortality rates (P<0.001) and a higher probability of postoperative complications (P<0.001). Likewise, receiving blood transfusions was associated with a higher risk of death (P<0.001).

Conclusion:

This retrospective single-center analysis confirmed that preoperative anemia is common, and is a significant risk factor for unfavorable postoperative outcome. As anemia is a modifiable risk factor, the implementation of a PBM concept is crucial to reduce detrimental postoperative events associated with anemia.
Non-invasive prediction of perineural invasion in intrahepatic cholangiocarcinoma by clinicoradiological features and computed tomography radiomics based on interpretable machine learning: a multicenter cohort study
Authors: Liu Ziwei , Luo Chun , Chen Xinjie , Feng Yanqiu , Feng Jieying , Zhang Rong , Ouyang Fusheng , Li Xiaohong , Tan Zhilin , Deng Lingda , Chen Yifan , Cai Zhiping , Zhang Ximing , Liu Jiehong , Liu Wei , Guo Baoliang , Hu Qiugen
Published: November 2023

Background:

Perineural invasion (PNI) of intrahepatic cholangiocarcinoma (ICC) is a strong independent risk factor for tumor recurrence and long-term patient survival. However, there is a lack of non-invasive tools for accurately predicting the PNI status. We develop and validate a combined model incorporating radiomics signature and clinicoradiological features based on machine learning for predicting PNI in ICC, and used the Shapley Additive explanation (SHAP) to visualize the prediction process for clinical application.

Methods:

This retrospective and prospective study included 243 patients with pathologically diagnosed ICC (training, n=136; external validation, n=81; prospective, n=26, respectively) who underwent preoperative contrast-enhanced CT between January 2012 and May 2023 at three institutions (three tertiary referral centers in Guangdong Province, China). The ElasticNet was applied to select radiomics features and construct signature derived from CT images, and univariate and multivariate analyses by logistic regression were used to identify the significant clinical and radiological variables with PNI. A robust combined model incorporating radiomics signature and clinicoradiological features based on machine learning was developed and the SHAP was used to visualize the prediction process. A Kaplan–Meier survival analysis was performed to compare prognostic differences between PNI positive and negative groups and was conducted to explore the prognostic information of the combined model.

Results:

Among 243 patients (mean age, 61.2 y ± 11.0 (SD); 152 men and 91 women), 108 (44.4%) were diagnosed as PNI-positive. The radiomics signature was constructed by seven radiomics features, with areas under the curves (AUCs) of 0.792, 0.748, and 0.729 in the training, external validation, and prospective cohorts, respectively. Three significant clinicoradiological features were selected and combined with radiomics signature to construct a combined model using machine learning. The eXtreme Gradient Boosting (XGBoost) exhibited improved accuracy and robustness (AUCs of 0.884, 0.831, and 0.831, respectively). Survival analysis showed the construction combined model could be used to stratify relapse-free survival (hazard ratio, 1.933; 95% confidence interval (CI): 1.093–3.418; P=0.021).

Conclusions:

We developed and validated a robust combined model incorporating radiomics signature and clinicoradiological features based on machine learning to accurately identify the PNI statuses of ICC, and visualize the prediction process through SHAP for clinical application.
The Medical Impact of Emergent Banning of N-nitrosodimethylamine (NDMA)- contaminated Antihypertensive Drug: A nationwide longitudinal cohort study
Authors: Ahn Juhee , Won Sungho , Park Jong-Heon , Shimbo Daichi , Lee Hae-Young
Published: November 2023

OBJECTIVE

To study the association of NDMA-contaminated generic valsartan with cancer incidence.

DESIGN

Nationwide longitudinal observational cohort study.

SETTING

Claims data from the National Health Insurance Service of South Korea was analyzed using 1:1:1 pairwise propensity score matching (PSM) of NDMA-uncontaminated original, NDMA-contaminated generic, and initially-suspended-but-finally confirmed as NDMA-uncontaminated generic valsartan user-groups. Time-dependent Cox models and dose- response evaluation were used to evaluate carcinogenicity.

PARTICIPANTS

A total of 3,231,212 participants with satisfactory minimal adherence, followed up from January 1, 2013 until December 31, 2020.

INTERVENTIONS

At least one tablet of valsartan.

MAIN OUTCOME MEASURES

The primary outcome was primary cancer incidence and secondary outcome was 12 prevalent organ-specific cancer incidences. All-cause and cardiovascular mortality risks were estimated before and after valsartan withdrawal.

RESULTS

Among participants (mean [standard deviation] age 59.5 [13.1] years; male, 53.5%), new users had adjusted hazard ratios and 95% confidence intervals (CI) of 1.069 (1.054 to 1.085) and 1.142 (1.100 to 1.186) for any cancer in the NDMA-exposed period (versus NDMA-unexposed) before and after 1:1:1 PSM, respectively. Regardless of PSM, lung and prostate cancer risks increased significantly during the NDMA-exposed period whereas, post-PSM, cancer risk did not increase in the eventually-NDMA-uncontaminated group, even in new users. All-cause and cardiovascular mortality did not differ significantly with NDMA exposure before and after emergent banning.

CONCLUSIONS

NDMA-contaminated valsartan increased cancer risk, especially of lung and prostate cancers. All-cause and cardiovascular mortality did not evidently increase following banning. This supports emergent health-policy action against potentially carcinogenic drugs.
ntsm: an alignment-free, ultra low coverage, sequencing technology agnostic, intraspecies sample comparison tool for sample swap detection
Authors: Chu Justin , Rong Jiazhen , Feng Xiaowen , Li Heng
Published: November 2023

Background

Due to human error, sample swapping in large cohort studies with heterogeneous data types (e.g. mix of Oxford Nanopore, Pacific Bioscience, Illumina data,etc.) remains a common issue plaguing large-scale studies. At present, all sample swapping detection methods require costly and unnecessary (e.g. if data is only used for genome assembly) alignment, positional sorting, and indexing of the data in order to compare similarly. As studies include more samples and new sequencing data types, robust quality control tools will become increasingly important.

Findings

The similarity between samples can be determined using indexedk-mer sequence variants. To increase statistical power, we use coverage information on variant sites, calculating similarity using a likelihood ratio-based test. Per sample error rate, and coverage bias (i.e. missing sites) can also be estimated with this information, which can be used to determine if a spatially indexed PCA-based pre-screening method can be used, which can greatly speed up analysis by preventing exhaustive all-to-all comparisons.

Conclusions

Because this tool processes raw data, is faster than alignment, and can be used on very low coverage data, it can save an immense degree of computational resources in standard QC pipelines. It is robust enough to be used on different sequencing data types, important in studies that leverage the strengths of different sequencing technologies. In addition to its primary use case of sample-swap detection, this method provides other useful information useful in QC, such as error rate and coverage bias, as well as population-level PCA ancestry analysis visualization.
Drivers of phenotypic differentiation across rock outcrop sky islands inImpatiensplants
Authors: Rahim Sumayya Abdul , Kulkarni Aboli , Kodandaramaiah Ullasa
Published: November 2023

Habitat specialization can lead to naturally fragmented populations separated by unoccupied habitats that comprise potential barriers to dispersal. Habitat fragmentation can result in phenotypic divergence between populations, and eventual speciation. We investigate trait divergence in a habitat specialist plant species –Impatiens lawii– that is specialized on rock outcrops in the Western Ghats mountains of India. We compare trait divergence in this species with that in a closely related species,I. oppositifolia, which is a continuously distributed habitat generalist that co-occurs with the former species on rock outcrops in addition to being found in intervening regions. As predicted, we found that floral traits were more strongly structured across populations inI. lawiithan inI. oppositifolia, supporting the role of habitat specialization. In both species, floral traits were more strongly structured across populations than were vegetative traits. Interestingly, the population pairs that were significantly differentiated for floral traits differed from those differentiated for vegetative traits. Furthermore, some population pairs differed in vegetative traits but not in floral traits. The incongruence in patterns of floral and vegetative trait differentiation suggests the role of selection. There was no association between floral trait variation and geographic distance in either species. Surprisingly, there was a significant correlation between geographic distance and vegetative trait variation inI. oppositifolia, but not inI. lawii(Fig 4D; Table 2), possibly due to genetic drift. Overall, a combination of habitat specificity, drift and selection best explains trait variation inI. lawii.
Allometry of cell types in planarians by single cell transcriptomics
Authors: Emili Elena , Pérez-Posada Alberto , Christodoulou Maria D. , Solana Jordi
Published: November 2023

Allometry explores the relationship between an organism’s body size and its various components, offering insights into ecology, physiology, metabolism, and disease. The cell is the basic unit of biological systems, and yet, the study of cell type allometry remains relatively unexplored. Single-cell RNA sequencing (scRNA-seq) provides a promising tool for investigating cell type allometry. Planarians, capable of growing and degrowing following allometric scaling rules, serve as an excellent model for such studies. We used scRNA-seq to examine cell type allometry in asexual planarians of different sizes, revealing that they consist of the same basic cell types but in varying proportions. Notably, the gut basal cells are the most responsive to changes in size, suggesting a role in energy storage. We capture the gene regulatory programs of distinct cell types in response to size. This research sheds light on the molecular and cellular aspects of cell type allometry in planarians and underscores the utility of scRNA-seq in such investigations.
Anin vivoplatform to identify pathogenic loci
Authors: Yamada Shigehiro , Ou Tiffany , Nachadalingam Sibani ,   PreMIER Consortium, Yang Shuo , Johnson Aaron N.
Published: November 2023

Rare genetic disease discovery efforts typically lead to the identification of new disease genes. PreMIER (PrecisionMedicine IntegratedExperimentalResources) is a collaborative platform designed to facilitate functional evaluation of human genetic variants in model systems, and to date the PreMIER Consortium has evaluated over 50 variants in patients with genetic disorders. To understand ifDrosophilacould be used to identify pathogenic disease loci as part of the PreMIER Consortium, we used tissue-specific gene knockdown in the fly as a proof of principle experiment. Tissue-specific knockdown of seven conserved disease genes caused significant changes in viability, longevity, behavior, motor function, and neuronal survival arguing a set of defined assays can be used to determine if a gene of uncertain significance (GUS) regulates specific physiological processes. This study highlights the utility of a tissue-specific knockdown platform inDrosophilato characterize GUS, which may provide the first genephenotype correlations for patients with idiopathic genetic disorders
Loss of CTRP10 results in female obesity with preserved metabolic health
Authors: Chen Fangluo , Sarver Dylan C , Saqib Muzna , Velez Leandro M , Aja Susan , Seldin Marcus M. , Wong G. William
Published: November 2023

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologous in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.
Astrocytes are active: An information theoretic approach reveals differences in Ca2+ signaling patterns among distinct astrocyte subtypes
Authors: Mennona Nicholas J. , Barile Barbara , Kang Hoony , Benfenati Valentina , Nicchia Grazia P. , O’Neill Kate M. , Losert Wolfgang
Published: November 2023

The discovery that astrocytes are an active, rather than a passive, component of the brain has ushered in a paradigm shift in thinking about how the brain processes information. Although the mechanisms by which astrocytes integrate information from neurons are still debated, such discourse should not distract from the importance of more completely understanding how astrocytes communicate via signals amongst themselves. This work aims to study how different astrocytes signal within their own networks. We investigate group calcium (Ca2+) dynamics in polygonal, stellate, and reactive astrocytes. These distinct and important astrocyte subtypes are present in the brain to varying degrees at different physiological states. We use an information-theoretic framework to quantify the dynamics embedded in the Ca2+ traces within astrocyte networks; specifically, we employ the Hurst exponent, cross-correlation, mutual information, and partitioned entropy to assess differences in the astrocyte signals across subtypes. To gain insights into the ability of astrocyte networks to respond to changes in the extracellular environment, we probe the networks with perturbations affecting their cytoskeletal dynamics (Latrunculin B) and energetic levels (Adenosine triphosphate). Overall, these three classes of astrocytes behave differently and respond idiosyncratically to their extracellular environment. We find that polygonal astrocytes are not quiescent, stellate astrocytes respond most strongly to ATP, and reactive astrocytes are uniquely perturbed by Latrunculin B. Interestingly, despite these distinct differences in behaviors, we find a uniform speed of information transport regardless of subtype or perturbation; this uniformity is maintained when using both cross-correlation and mutual information to assess this speed. We conclude that the differential ways astrocytes signal within our measured framework yield important insights into how astrocytes communicate and contribute to this pressing issue of understanding astrocyte information processing.
Cryo-EM structure of Slo1 with the auxiliary γ1 subunit suggests mechanism of depolarization-independent activation
Authors: Redhardt Milena , Raunser Stefan , Raisch Tobias
Published: November 2023

Mammalian Ca2+-dependent Slo K+channels are expressed with β and γ auxiliary subunits that greatly influence voltage- and Ca2+-induced gating, thereby fundamentally altering the behavior of the channel. The four γ subunits reduce the need for voltage-dependent activation, allowing Slo to open in the absence of an action potential. The mechanism of this activation has, however, remained elusive. Here, we present the cryo-EM structure of Slo1 in complex with γ1/LRRC26, revealing how the transmembrane helix of γ1 binds and presumably stabilizes the active conformation of the voltage-sensor domain. This effect is further enhanced by a polybasic stretch on the intracellular side of the membrane which locally changes the charge gradient across the membrane. Sequence differences explain why the four γ subunits possess different activation efficiencies. Simultaneous binding of γ and the unrelated β subunits is structurally possible, as both binding sites do not overlap and the γ1 LRR domains are partially flexible. Thus, our data provide a possible explanation for Slo1 regulation by γ subunits, and furthermore suggest a novel mechanism of activation of voltage-gated ion channels by auxiliary subunits and add to the growing knowledge of their complex regulation.
Local Ecological Knowledge enhances our capacity to document potential climate sentinels: a loggerhead sea turtle (Caretta caretta) case study
Authors: Early-Capistrán Michelle María , Crane Nicole L. , Crowder Larry B. , Garibay-Melo Gerardo , Seminoff Jeffrey A. , Johnston David
Published: November 2023

Climate change is inducing rapid transformations in marine ecosystems, with a pronounced effect on top predators like loggerhead sea turtles (Caretta caretta). Loggerheads’ responsiveness to temperature fluctuations underscores their significance as a climate sentinel species. We present the first record of a loggerhead sea turtle in Monterey Bay, California, USA, documented through Local Ecological Knowledge (LEK) and community or citizen science (CS), highlighting the pivotal role of these approaches in documenting species occurrences beyond anticipated habitats during climatic anomalies. In rapidly changing conditions, rigorously documented CS and LEK offer a crucial complement to conventional scientific methods, providing high-quality data with extensive coverage— especially for elusive species—and yielding insights into emerging phenomena.
Pervasive relaxed selection in termite genomes
Authors: Ewart Kyle M. , Ho Simon Y. W. , Chowdhury Al-Aabid , Jaya Frederick R. , Kinjo Yukihiro , Bennett Juno , Bourguignon Thomas , Rose Harley A. , Lo Nathan
Published: November 2023

The genetic changes that enabled the evolution of eusociality have long captivated biologists. In recent years, attention has focussed on the consequences of eusociality on genome evolution. Studies have reported higher molecular evolutionary rates in eusocial hymenopteran insects compared with their solitary relatives. To investigate the genomic consequences of eusociality in termites, we sequenced genomes from three of their non-eusocial cockroach relatives. Using a phylogenomic approach, we found that termite genomes experienced lower rates of synonymous mutations than those of cockroaches, possibly as a result of longer generation times. We identified higher rates of nonsynonymous mutations in termite genomes than in cockroach genomes, and identified pervasive relaxed selection in the former (24–31% of the genes analysed) compared with the latter (2–4%). We infer that this is due to a reduction in effective population size, rather than gene-specific effects (e.g., indirect selection of caste-biased genes). We found no obvious signature of increased genetic load in termites, and postulate efficient purging at the colony level. Additionally, we identified genomic adaptations that may underpin caste formation, such as genes involved in post-translational modifications. Our results provide insights into the evolution of termites and the genomic consequences of eusociality more broadly.
Activation of the Maternal Genome Through Asymmetric Distribution of Oocyte-Genome-Associated Histone H3.3
Authors: Wen Duancheng , Rosenwaks Zev
Published: November 2023

Upon fertilization, the typically silent and epigenetically repressed oocyte genome undergoes activation, yet the precise mechanism remains unclear. The histone variant H3.3 is evenly distributed throughout the oocyte genome, suggesting its involvement in repression. This study reveals that oocyte-genome-associated H3.3 (oH3.3) undergoes asymmetric segregation among four-cell stage blastomeres, persisting in only two blastomeres through the blastocyst stage. These oH3.3-retaining blastomeres maintain a repressive state characterized by high levels of the chromatin marker H3K9me2. Intriguingly, single-cell RNA-seq analysis revealed asymmetric transcriptional activation between paternal and maternal genomes, with the maternal genome being considerably less active. We propose a model wherein oH3.3 and associated oocyte DNA co-segregate during mitosis, allowing two blastomeres to inherit oH3.3 and a strand of oocyte DNA from maternal chromatids. Meanwhile, the other blastomeres acquire newly synthesized DNA associated with the nascent histone H3, which lacks oocyte-specific repressive modifications. Consequently, full maternal genome activation occurs in two of the four-cell stage blastomeres, while the remaining two, which retain oH3.3, remain partially repressed. This study uncovers a previously unrecognized H3.3 mediated mechanism for maternal genome activation.
Complete phylogeny ofMicrathenaspiders suggests multiple dispersal events among Neotropical rainforests, islands, and landmasses, and indicates Andean orogeny promotes speciation
Authors: Magalhaes Ivan L. F. , Martins Pedro H. , Faleiro Bárbara T. , Vidigal Teofânia H. D. A. , Santos Fabrício R. , Carvalho Leonardo S. , Santos Adalberto J.
Published: November 2023

The Neotropical region is the most diverse on the planet, largely due to its mosaic of tropical rainforests. Multiple tectonic and climatic processes have been hypothesized to play a role in generating this diversity; these include Andean orogeny, closure of the Panama Isthmus, the hypothesized GAARlandia land bridge, and putative historical connections among currently isolated forests.Micrathenaspiny spiders (Araneidae) include ∼120 species distributed mostly in forests from Mexico to Argentina, including the Antilles. Here, we use it as a model to study the biogeographic history of Neotropical rainforests by estimating a complete, dated phylogeny using morphological data for all species and molecular data for a subsample of 79 species. This resulted in a phylogeny that is mostly robust and supports most of the previously recognized species groups, although with uncertainty in the phylogenetic position of some species, especially those lacking sequences. The genus began diversifying about 25 million years ago. We use an event-based approach and biogeographic stochastic mapping to estimate ancestral distributions and the timing and direction of dispersal events, and to identify areas where diversity was generated, while accounting for phylogenetic uncertainty. Andean cloud forests generated the majority of species through in-situ speciation, but the Amazon was the major source of species for adjacent areas through dispersal; on the other extreme, the Dry Diagonal received species from other areas but generated very little diversity. Species exchange between Central and South America was intense, with ∼23 dispersal events beginning at least 20 million years ago, indicating thatMicrathenadispersed between these continents before closure of the Isthmus of Panama. We also inferred ∼4 over-water dispersal events from Central and North America to the Antilles, which happened in the last 20 million years, and thus much after the proposed age of the GAARlandia land bridge. We identified an important species exchange route between the Amazon and the Atlantic forests. Sampling all species of the genus was fundamental to some of the conclusions above, especially in identifying the Andes as the area that generated the majority of species. This study highlights the importance of a solid and complete taxonomic sampling in biogeographic studies.
Intra-breath oscillometry detects ventilation inhomogeneity in Cystic Fibrosis children
Authors: Blake Tamara L , Robinson Paul D , Deery Maddison T , Wainwright Claire E , Hantos Zoltan , Sly Peter D
Published: November 2023

Background

Ventilation inhomogeneity (VI) is measured in patients with Cystic Fibrosis (CF) by lung clearance index (LCI) using the Multiple Breath Washout (MBW). In young children, feasibility is often low within busy clinical settings. Intra-breath oscillometry (IB-OSC) measures respiratory system reactance (Xrs), which is determined by the same physiological principles. Given the high feasibility of IB-OSC in young children (>80%), we aimed to explore whether Xrs variables reflected VI as measured by LCI.

Methods

Paired measurements of IB-OSC (TremoFLO C-100, 10Hz signal) and Nitrogen (N2) MBW (Exhalyzer D) were performed in 97 children with CF. Abnormal LCI was defined as ≥7.1. IB-OSC Xrs variables at end-expiration (XeE), end-inspiration (XeI), volume-dependence of Xrs (ΔX) and ΔX corrected for tidal volume (ΔX/VT) were compared between those with normal and abnormal LCI. Receiver operator characteristic (ROC) analysis was performed to identify cut-off values to detect abnormal LCI.

Results

115 acceptable paired IB-OSC and MBW measurements were achieved by 85 children (male 61%, median age 7.8yrs [25th-75th% 5.8-11.9]). 52 (45%) measurements of LCI were abnormal. All Xrs variables where significantly decreased (more negative) in children with abnormal LCI compared to normal (XeE -2.98v-0.81; XeI -2.10v-1.00; ΔX -0.25v0.12; ΔX/VT -0.54v0.22; all p<0.001). Cut-off values for ΔX and ΔX/VT provided the best sensitivity and specificity for detecting abnormal LCI.

Conclusion

These results suggest that novel IB-OSC variables can detect abnormal VI as measured by N2MBW-LCI. This technique may allow us to detect and monitor early changes to lung function in busy CF clinics more easily.
On theindependent irritabilityof goldfish eggs and embryos – a living communication on the rhythmic yolk contractions in goldfish
Authors: Layague Sanchez Paul Gerald , Wang Chen-Yi , Li Ing-Jia , Ota Kinya G.
Published: November 2023

Rhythms play an important role in the precise spatiotemporal regulation of biological processes during development and patterning of embryos. We here investigate the rhythmic contractions of the yolk during early development of the goldfishCarassius auratus. We quantify these contractions and record robust and persistent rhythmic yolk movements that are not seen in closely-related species (common carpCyprinus carpioand zebrafishDanio rerio). We report that yolk contractions are an intrinsic emergent property of the egg, i.e. goldfish eggs are independently irritable / excitable. These contractions do not require sperm entry / fertilization nor cell division, and they notably emerge at a precise time — suggesting that goldfish eggs are able to measure elapsed time from what we infer to be egg activation. We further show that these rhythmic contractions persist even in yolk in isolation. As the yolk itself is known to confer critical cues for early dorsoventral (DV) patterning of teleost embryos, we hypothesize that its contractions in goldfish may influence the patterning process of this species. Indeed, we find that embryos of the naturally more ventralized twin-tail goldfish strainOrandadisplay altered yolk contraction dynamics (i.e. faster contractions). We also present that the period of yolk contractions is independent ofChdS, a key gene involved in DV pattening and linked to the twin-tail phenotype, but is instead a trait that is maternal in origin. We aim to uncover whether the yolk contractions happening during early development of domesticated goldfish are the licensing process which permit the emergence of novel patterning phenotypes naturally-observed in this species (e.g. twin-tail and dorsal-finless strains) and which instead have not been found among closely-related species (e.g. common carp) whose yolks do not contract.

This manuscript is here published as a living communication (as described in Gnaiger (2021)). The authors intend to share findings when they are available, encourage feedback and discussion, and invite knowledge exchange and collaboration.
Emergent functional behaviors of ribozymes in oxychlorine brines indicate Mars could host a unique niche for molecular evolution
Authors: Hoog Tanner G. , Pawlak Matthew R. , Gaut Nathaniel J. , Baxter Gloria C. , Bethel Thomas A. , Adamala Katarzyna P. , Engelhart Aaron E.
Published: November 2023

Mars is a particularly attractive candidate among known astronomical objects to potentially host life. Results from space exploration missions have provided insights into Martian geochemistry indicating oxychlorine species, particularly perchlorate, are ubiquitous features of the Martian geochemical landscape. Perchlorate presents potential obstacles for known forms of life due to its toxicity. However, it can also provide potential benefits, such as producing brines by deliquescence, like those thought to exist on present-day Mars. Here we show perchlorate brines support folding and catalysis of functional RNAs, while inactivating representative protein enzymes. Additionally, we show perchlorate and other oxychlorine species enable new ribozyme functions, including homeostasis-like regulatory behavior, copying of structured RNAs, and the first ribozyme-catalyzed chlorination of organic molecules. We suggest nucleic acids are uniquely well-suited to hypersaline Martian environments. Furthermore, Martian near-or subsurface oxychlorine brines, and brines found in potential lifeforms, could provide a unique niche for biomolecular evolution.
ReptiLearn: A Smart Home Cage for Behavioral Experiments in Reptiles
Authors: Eisenberg Tal , Shein-Idelson Mark
Published: November 2023

Understanding behavior and its evolutionary underpinnings is crucial for unraveling the complexities of brain function. Traditional approaches strive to reduce behavioral complexity by designing short-term, highly constrained behavioral tasks with dichotomous choices in which animals respond to defined external perturbation. In contrast, natural behaviors evolve over multiple time scales and under minimally constrained conditions in which actions are selected through bi-directional interactions with the environment and without human intervention. Recent technological advancements have opened up new possibilities for more natural experimental designs by replacing stringent experimental control with accurate multidimensional behavioral analysis. However, these approaches have been tailored to fit only a small number of species. This specificity limits the experimental opportunities offered by species diversity. Further, it hampers comparative analyses which are essential for extracting overarching behavioral principles and for examining behavior from an evolutionary perspective. To address this limitation, we developed ReptiLearn - a versatile, low-cost, Python-based solution, optimized for conducting automated long-term experiments in the home cage of reptiles, without human intervention. In addition, this system offers unique features such as precise temperature measurement and control, live prey reward dispensers, engagement with touch screens, and remote control through a user-friendly web interface. Finally, ReptiLearn incorporates low-latency closed-loop feedback allowing bi-directional interactions between animals and their environments. Thus, ReptiLearn provides a comprehensive solution for researchers studying behavior in ectotherms and beyond, bridging the gap between constrained laboratory settings and natural behavior in non-conventional model systems. We demonstrate the capabilities of ReptiLearn by automatically training the lizardPogona vitticepson a complex spatial learning task requiring association learning, displaced reward learning and reversal learning.
Seven-up acts in neuroblasts to specify adult central complex neuron identity and initiate neuroblast decommissioning
Authors: Dillon Noah R. , Manning Laurina , Hirono Keiko , Doe Chris Q.
Published: November 2023

An open question in neurobiology is how diverse neuron cell types are generated from a small number of neural stem cells. In theDrosophilalarval central brain, there are eight bilateral Type 2 neuroblast (T2NB) lineages that express a suite of early temporal factors followed by a different set of late temporal factors and generate the majority of the central complex (CX) neurons. The early-to-late switch is triggered by the orphan nuclear hormone receptor Seven-up (Svp), yet little is known about this Svp-dependent switch in specifying CX neuron identities. Here, we (i) birthdate the CX neurons P-EN and P-FN (early and late, respectively); (ii) show that Svp is transiently expressed in all early T2NBs; and (iii) show that loss of Svp expands the population of early born P-EN neurons at the expense of late born P-FN neurons. Furthermore, in the absence of Svp, T2NBs fail decommissioning and abnormally extend their lineage into week-old adults. We conclude that Svp is required to specify CX neuron identity, as well as to initiate T2NB decommissioning.

Seven-up acts in Type 2 neuroblasts to specify adult central complex columnar neuron identity and to initiate neuroblast decommissioning.
The pH-responsive SmrR-SmrT system modulatesC. difficileantimicrobial resistance, spore formation, and toxin production
Authors: Wetzel Daniela , Carter Zavier A. , Monteiro Marcos P. , Edwards Adrianne N. , McBride Shonna M.
Published: November 2023

Clostridioides difficileis an anaerobic gastrointestinal pathogen that spreads through the environment as dormant spores. To survive, replicate, and sporulate in the host intestine,C. difficilemust adapt to a variety of conditions in its environment, including changes in pH, the availability of metabolites, host immune factors, and a diverse array of other species. Prior studies showed that changes in intestinal conditions, such as pH, can affectC. difficiletoxin production, spore formation, and cell survival. However, little is understood about the specific genes and pathways that facilitate environmental adaptation and lead to changes inC. difficilecell outcomes. In this study, we investigated two genes,CD2505andCD2506,that are differentially regulated by pH to determine if they impactC. difficilegrowth and sporulation. Using deletion mutants, we examined the effects of both genes (hereinsmrRandsmrT) on sporulation frequency, toxin production, and antimicrobial resistance. We determined that SmrR is a repressor ofsmrRTthat responds to pH and suppresses sporulation and toxin production through regulation of the SmrT transporter. Further, we showed that SmrT confers resistance to erythromycin and lincomycin, establishing a connection between the regulation of sporulation and antimicrobial resistance.

IMPORTANCE

C. difficileis a mammalian pathogen that colonizes the large intestine and produces toxins that lead to severe diarrheal disease.C. difficileis a major threat to public health due to its intrinsic resistance to antimicrobials and its ability to form dormant spores that are easily spread from host to host. In this study, we examined the contribution of two genes,smrRandsmrTon sporulation, toxin production, and antimicrobial resistance. Our results indicate that SmrR repressessmrTexpression, while production of SmrT increases spore and toxin production, as well as resistance to antibiotics.
Membrane potential mediates the cellular response to mechanical pressure
Authors: Mukherjee Avik , Huang Yanqing , Elgeti Jens , Oh Seungeun , Abreu Jose G. , Neliat Anjali Rebecca , Schüttler Janik , Su Dan-Dan , Dupre Christophe , Benites Nina Catherine , Liu Xili , Peshkin Leonid , Barboiu Mihail , Stocker Hugo , Kirschner Marc W. , Basan Markus
Published: November 2023

Mechanical forces have been shown to influence cellular decisions to grow, die, or differentiate, through largely mysterious mechanisms. Separately, changes in resting membrane potential have been observed in development, differentiation, regeneration, and cancer. We now demonstrate that membrane potential is the central mediator of cellular response to mechanical pressure. We show that mechanical forces acting on the cell change cellular biomass density, which in turn alters membrane potential. Membrane potential then regulates cell number density in epithelia by controlling cell growth, proliferation, and cell elimination. Mechanistically, we show that changes in membrane potential control signaling through the Hippo and MAPK pathways, and potentially other signaling pathways that originate at the cell membrane. While many molecular interactions are known to affect Hippo signaling, the upstream signal that activates the canonical Hippo pathway at the membrane has previously been elusive. Our results establish membrane potential as a central regulator of growth and tissue homeostasis.
The effect of head motion on brain age prediction using deep convolutional neural networks
Authors: Vakli Pál , Weiss Béla , Rozmann Dorina , Erőss György , Nárai Ádám , Hermann Petra , Vidnyánszky Zoltán
Published: November 2023

Deep learning can be used effectively to predict participants’ age from brain magnetic resonance imaging (MRI) data, and a growing body of evidence suggests that the difference between predicted and chronological age—referred to as brain-predicted age difference (brain-PAD)—is related to various neurological and neuropsychiatric disease states. A crucial aspect of the applicability of brain-PAD as a biomarker of individual brain health is whether and how brain-predicted age is affected by MR image artifacts commonly encountered in clinical settings. To investigate this issue, we trained and validated two different 3D convolutional neural network architectures (CNNs) from scratch and tested the models on a separate dataset consisting of motion-free and motion-corrupted T1-weighted MRI scans from the same participants, the quality of which were rated by neuroradiologists from a clinical diagnostic point of view. Our results revealed a systematic increase in brain-PAD with worsening image quality for both models. This effect was also observed for images that were deemed usable from a clinical perspective, with brains appearing older in medium than in good quality images. These findings were also supported by significant associations found between the brain-PAD and standard image quality metrics indicating larger brain-PAD for lower-quality images. Our results demonstrate a spurious effect of advanced brain aging as a result of head motion and underline the importance of controlling for image quality when using brain-predicted age based on structural neuroimaging data as a proxy measure for brain health.

Highlights

Two 3D CNNs trained from scratch and validated to predict age from T1-w brain MRI

Testing on motion-free and motion-corrupted scans from the same participants

Image quality assessed by neuroradiologists and using standard image quality metrics

Systematic increase in brain-predicted age difference with worsening image quality

Spurious advanced brain aging effect in scans deemed usable for clinical diagnostics
Distress symptoms of old age and mild cognitive impairment are two distinct dimensions in older adults without major depression: effects of adverse childhood experiences and negative life events
Authors: Tran-Chi Vinh-Long , Maes Michael , Nantachai Gallayaporn , Hemrungrojn Solaphat , Solmi Marco , Tunvirachaisakul Chavit
Published: November 2023

Background

Studies in old adults showed bidirectional interconnections between amnestic mild cognitive impairment (aMCI) and affective symptoms and that adverse childhood experiences (ACE) may affect both factors. Nevertheless, these associations may be confined to older adults with clinical depression.

Aims

To delineate the relationship between clinical symptoms of aMCI and affective symptoms in older adults without major depression (MDD) or dysfunctions in activities of daily living (ADL).

Methods

This case-control study recruited 61 participants with aMCI (diagnosed using Petersen’s criteria) and 59 older adults without aMCI and excluded subjects with MDD and ADL dysfunctions.

Results

We uncovered 2 distinct dimensions, namely distress symptoms of old age (DSOA) comprising anxiety, depression, perceived stress and neuroticism scores, and mild cognitive dysfunctions (mCoDy) comprising episodic memory test scores, and the total Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. A large part of the variance (37.9%) in DSOA scores was explained by ACE, negative life events (health and financial problems), a subjective feeling of cognitive decline, and education (all positively). While ACE and NLE have a highly significant impact on the DSOA, they are not associated with the mCoDy scores. Cluster analysis showed that the diagnosis of aMCI is overinclusive because some subjects with DSOA symptoms may be incorrectly classified as aMCI.

Conclusions

The clinical impact is that clinicians should carefully screen older adults for DSOA after excluding MDD. DSOA might be misinterpreted as aMCI.
Characterization of highly active mutational signatures in tumors from a large Chinese population
Authors: Chevalier Aaron , Guo Tao , Gurevich Natasha Q. , Xu Jingwen , Yajima Masanao , Campbell Joshua D.
Published: November 2023

The majority of mutational signatures have been characterized in tumors from Western countries and the degree to which mutational signatures are similar or different in Eastern populations has not been fully explored. We leveraged a large-scale clinical sequencing cohort of tumors from a Chinese population containing 25 tumor types and found that the highly active mutational signatures were similar to those previously characterized1,2. The aristolochic acid signature SBS22 was observed in four soft tissue sarcomas and the POLE-associated signature SBS10 was observed in a gallbladder carcinoma. In lung adenocarcinoma, the polycyclic aromatic hydrocarbon (PAH) signature SBS4 was significantly higher in males compared to females but not associated with smoking status. The UV-associated signature SBS7 was significantly lower in cutaneous melanomas from the Chinese population compared to a similar American cohort. Overall, these results add to our understanding of the mutational processes that contribute to tumors from the Chinese population.