bluuebunny/crossref_metadata_2025 huggingface dataset:
The iMab antibody selectively binds to intramolecular and intermolecular i-motif structures
Authors: Ruggiero Emanuela , Marušič Maja , Zanin Irene , Peña Martinez Cristian David , Christ Daniel , Plavec Janez , Richter Sara N
Published: January 2025

i-Motifs (iMs) are quadruplex nucleic acid conformations that form in cytosine-rich regions. Because of their acidic pH dependence, iMs were thought to form only in vitro. The recent development of an iM-selective antibody, iMab, has allowed iM detection in cells, which revealed their presence at gene promoters and their cell cycle dependence. However, recent evidence emerged which appeared to suggest that iMab recognizes C-rich sequences regardless of their iM conformation. To further investigate the selectivity of iMab, we examined the binding of iMab to C-rich sequences, using a combination of pull-down and western blot assays. Here, we observe that the composition of buffers used during binding and washing steps strongly influences the selectivity of antibody binding. In addition, we demonstrate by nuclear magnetic resonance that several of the previously reported C-rich sequences, which were not expected to form iMs, actually form intermolecular iMs which are selectively recognized by iMab. Our results highlight the specificity of the iMab antibody, emphasize the importance of avoiding in vitro artifacts by optimizing DNA concentrations, blocking and washing conditions, and confirm that iMab is selective not only for intramolecular iMs but also for intermolecular iMs, while not affecting the iM conformation.
Energy Expenditure in Chronic Kidney Disease: Affecting Factors and Evaluation Methods
Authors: Şahin Kezban , Acar Tek Nilüfer
Published: January 2025

Chronic kidney disease (CKD) is a chronic health problem whose prevalence is increasing. Nutrition and nutrition-related factors, one of the modifiable risk factors for CKD, are of primary importance. The key to planning optimal nutritional therapy is accurately determining energy requirements and total energy expenditure. Many health problems can accompany CKD, such as protein-energy malnutrition, sarcopenia, etc, and increase the mortality rate. This study aims to present the specific factors affecting energy expenditure specific to CKD in line with the current literature, to discuss the methods used to determine energy expenditure, and to examine these methods according to groups receiving and not receiving renal replacement therapy (hemodialysis, peritoneal dialysis, and renal transplantation).
Ablation of satellite cell‐specific clock gene, Bmal1, alters force production, muscle damage, and repair following contractile‐induced injury
Authors: Kahn Ryan E. , Zhu Pei , Roy Ishan , Peek Clara , Hawley John A. , Dayanidhi Sudarshan
Published: January 2025

Following injury, skeletal muscle undergoes repair via satellite cell (SC)‐mediated myogenic progression. In SCs, the circadian molecular clock gene, Bmal1, is necessary for appropriate myogenic progression and repair with evidence that muscle molecular clocks can also affect force production. Utilizing a mouse model allowing for inducible depletion of Bmal1 within SCs, we determined contractile function, SC myogenic progression and muscle damage and repair following eccentric contractile‐induced injury. At baseline, SC‐Bmal1iKO animals exhibited a ~20–25% reduction in normalized force production (ex vivo and in vivo) versus control SC‐Bmal1Cntrl and SC‐Bmal1iKO untreated littermates (p < .05). Following contractile injury, SC‐Bmal1iKO animals displayed reduced muscle damage and subsequent repair post‐injury (Dystrophinnegative fibers 24 h: SC‐Bmal1Cntrl 199 ± 41; SC‐Bmal1iKO 36 ± 13, p < .05) (eMHC+ fibers 7 day: SC‐Bmal1Cntrl 217.8 ± 115.5; SC‐Bmal1iKO 27.8 ± 17.3; Centralized nuclei 7 day: SC‐Bmal1Cntrl 160.7 ± 70.5; SC‐Bmal1iKO 46.2 ± 15.7). SC‐Bmal1iKO animals also showed reduced neutrophil infiltration, consistent with less injury (Neutrophil content 24 h: SC‐Bmal1Cntrl 2.4 ± 0.4; SC‐Bmal1iKO 0.4 ± 0.2, % area fraction, p < .05). SC‐Bmal1iKO animals had greater SC activation/proliferation at an earlier timepoint (p < .05) and an unexplained increase in activation 7 days post injury. Collectively, these data suggest SC‐Bmal1 plays a regulatory role in force production, influencing the magnitude of muscle damage/repair, with an altered SC myogenic progression following contractile‐induced muscle injury.
Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs
Authors: Khan Naazneen , Gupta Mahesh , Masamha Chioniso Patience
Published: January 2025

Changes in protein levels of the mammalian cleavage factor, CFIm25, play a role in regulating pathological processes including neural dysfunction, fibrosis, and tumorigenesis. However, despite these effects, little is known about how CFIm25 (NUDT21) expression is regulated at the RNA level. A potential regulator of NUDT21 mRNA are small non‐coding microRNAs (miRNAs). In general, miRNAs bind to the 3′untranslated regions (3′UTRs) and can target the bound mRNA for degradation or inhibit translation thus affecting the levels of protein in cells. Interestingly, a mechanism known as alternative polyadenylation (APA) enables mRNAs to escape miRNA regulation by generating mRNAs with 3′UTRs of different sizes. As many miRNA target sites are located within the 3′UTR, shortening the 3′UTR allows mRNAs to evade miRNAs targeting this region. The differences in the lengths and the sequence composition of the 3′UTRs may also impact the mRNA's translatability and subcellular localization. APA has been reported to regulate over 70% of protein coding genes, thus increasing the transcript repertoire. Several proteins, including mammalian cleavage factor, CFIm25 (NUDT21), have been shown to regulate APA. In this study we wanted to determine whether CFIm25 (NUDT21), itself a regulator of APA, undergoes APA to evade miRNA regulation. We used the blood cancer mantle cell lymphoma (MCL) cells as a model and showed that in these cells, NUDT21 is relatively stable with a long half‐life. In addition, the NUDT21 pre‐mRNA undergoes alternative APA within the same terminal exon. The three different sized NUDT21 mRNAs have different 3′UTR lengths and they each use a different canonical polyadenylation signal, AAUAAA, for 3′end cleavage and polyadenylation. Use of miRNA mimics and inhibitors showed that miR‐23a, miR‐222, and miR‐323a play a significant role in regulating NUDT21 expression. Hence, these results suggest that NUDT21 mRNA is stable and the different 3′UTRs generated through APA of NUDT21 play an important role in evading miRNA regulation and offers insights into how levels of CFIm25 (NUDT21) may be fine‐tuned as needed under different physiological and pathological conditions.
SKP1‐CUL1‐F‐box: Key molecular targets affecting disease progression
Authors: Zeng Xiangrong , Cao Jiaying , Xu Juan , Zhou Zihua , Long Chen , Zhou Yanhong , Tang Jingqiong
Published: January 2025

The correct synthesis and degradation of proteins are vital for numerous biological processes in the human body, with protein degradation primarily facilitated by the ubiquitin‐proteasome system. The SKP1‐CUL1‐F‐box (SCF) E3 ubiquitin ligase, a member of the Cullin‐RING E3 ubiquitin ligase (CRL) family, plays a crucial role in mediating protein ubiquitination and subsequent 26S proteasome degradation during normal cellular metabolism. Notably, SCF is intricately linked to the pathogenesis of various diseases, including malignant tumors. This paper provides a comprehensive overview of the functional characteristics of SCF complexes, encompassing their assembly, disassembly, and regulatory factors. Furthermore, we discuss the diverse effects of SCF on crucial cellular processes such as cell cycle progression, DNA replication, oxidative stress response, cell proliferation, apoptosis, cell differentiation, maintenance of stem cell characteristics, tissue development, circadian rhythm regulation, and immune response modulation. Additionally, we summarize the associations between SCF and the onset, progression, and prognosis of malignant tumors. By synthesizing current knowledge, this review aims to offer a novel perspective for a holistic and systematic understanding of SCF complexes and their multifaceted functions in cellular physiology and disease pathogenesis.
Influence of remifentanil on the pharmacokinetics and pharmacodynamics of remimazolam in healthy volunteers
Authors: Vellinga Remco , Koomen Jeroen V. , Eleveld Douglas J. , Stöhr Thomas , Pesic Marija , Struys Michel M.R.F. , Colin Pieter J.
Published: January 2025

Background:

Synergistic effects between opioids and remimazolam on bispectral index (BIS) and modified observer’s assessment of alertness and/or sedation (MOAAS) score were previously described. This study aimed to characterize the influence of remifentanil on the sedative properties of remimazolam as measured by MOAAS, BIS, tolerance to laryngoscopy or tetanic stimulation (TOL or TOTS) and to determine target concentrations that maximize MOAAS 2/3.

Methods:

A three-period, cross-over, dose-ranging clinical trial was performed in 24 healthy volunteers. In all periods, remimazolam was administered using a step-up and step-down TCI protocol (50 – 2000 ng/mL). Stable remifentanil target concentrations of 0.5 ng/mL and 0.1 to 4.0 ng/mL were maintained in periods 2 and 3, respectively. Remifentanil, remimazolam and CNS7054 (metabolite) concentrations and, MOAAS, BIS, TOL and TOTS were collected in each step of the TCI protocol. Data were analyzed using non-linear mixed-effects models, where p≤0.01 was considered significant.

Results:

Remifentanil reduced the apparent clearance of CNS7054 with a half-maximum inhibition at 8.0 ng/mL (95% CI 5.5 to 13.4 ng/mL). A pharmacodynamic interaction was detected on all endpoints. Simulations indicate that the probability of observing a MOAAS 2/3 is highest at remimazolam target concentration of 275, 250 or 200 ng/mL combined with 0, 0.1, or 0.5 ng/mL remifentanil resulting in probabilities of 45%, 45% and 44%, respectively. Additionally, simulations indicate that the highest probability of observing TOTS and TOL was 93.3% and 85.5%, respectively, at the highest studied target concentrations.

Conclusions:

A pharmacokinetic and pharmacodynamic drug-drug interaction between remimazolam and remifentanil was quantified in this clinical trial. Appropriate target concentrations for MOAAS and BIS could be estimated, but, for TOL and TOTS, the trial design did not allow to fully characterize the exposure-response relationship.
A Brief History of Clinical Electrocardiography: A Century After Einthoven’s Nobel Prize
Authors: Zimmerman Franklin H.
Published: January 2025

The invention of the string galvanometer by Willem Einthoven in 1901 ushered in a new era of clinical investigation. Previous instruments were capable only of rudimentary measurements that were of limited utility. Advances in physiology and engineering allowed Einthoven to construct a device that was uniquely capable of recording the minute electrical currents of the heart. Early string galvanometers were massive, immovable machines. Over time, the apparatus became smaller and portable, allowing examinations at the bedside. In the decades that followed, clinicians used the now ubiquitous instrument to evaluate cardiac arrhythmias, coronary artery disease, and conduction abnormalities. The remainder of the century saw the evolution of the contemporary 12-lead electrocardiogram, with standards established regarding technique and nomenclature. Awarded the Nobel Prize in 1924 for “his discovery of the mechanism of the electrocardiogram,” Einthoven’s legacy endures in modern clinical medicine.
Comparison of clinical outcomes in patients with refractory ascites treated with either TIPS, tunneled peritoneal catheter, or ascites pump
Authors: Schütte Sarah L. , Tiede Anja , Mauz Jim B. , Rieland Hannah , Kabelitz Martin , Iker Robin , Richter Nicolas , Meyer Bernhard , Heidrich Benjamin , Wedemeyer Heiner , Maasoumy Benjamin , Tergast Tammo L.
Published: January 2025

Background:

Refractory ascites (RA) remains a serious complication in patients with cirrhosis. Currently, the insertion of a TIPS is considered the standard of care in these patients. To achieve symptom control in those with TIPS contraindications, tunneled peritoneal catheters (PeCa) or ascites pumps were introduced. However, data comparing the available treatment options are scarce. This study aims to compare outcomes among patients with RA treated either with TIPS, PeCa, or ascites pump.

Methods:

All patients with RA and cirrhosis treated at Hannover Medical School between 2009 and 2023 were evaluated. Endpoints included mortality, acute kidney injury (AKI), hyponatremia, peritonitis, and rehospitalization rate. Propensity score matching was conducted to adjust for group differences.

Results:

First, 31 patients with ascites pump were compared to 62 patients with a PeCa after propensity score matching. There were no differences regarding mortality nor incidences of AKI, hyponatremia, or rehospitalization. However, incidences of peritonitis and explantation were lower in those with ascites pump (HR 0.32, 95% CI: 0.15–0.70, and HR 0.32, 95% CI: 0.14–0.71, respectively). Second, 35 ascites pump patients were matched with 70 individuals with TIPS. No differences regarding mortality or peritonitis incidence were observed. Ascites pump patients showed higher incidences of AKI (HR 4.55, 95% CI: 2.53–8.18) and hyponatremia (HR 4.13, 95% CI: 2.08–8.22). Last, 129 patients with TIPS were compared to 129 with PeCa. Mortality was comparable, while incidences of AKI (HR 5.01, 95% CI: 3.36–7.47), hyponatremia (HR 4.64, 95% CI: 3.03–7.12), and peritonitis (HR 2.19, 95% CI: 1.41–3.41) were higher in those with PeCa.

Conclusions:

While ascites pump was associated with lower incidences of device infections and explantations, TIPS was associated with the lowest incidence of clinical complications in patients with RA.
Environmental exposures and the risk of hepatocellular carcinoma
Authors: Rayapati Divya , McGlynn Katherine A. , Groopman John D. , Kim Amy K.
Published: January 2025

The global epidemiology of HCC is shifting due to changes in both established and emerging risk factors. This transformation is marked by an emerging prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) and type 2 diabetes, alongside traditional risks such as viral hepatitis (HBV and HCV), and exposure to chemical agents like aflatoxin, alcohol, tobacco, and air pollution. This review examines how environmental exposures and evolving liver pathology, exacerbated by lifestyle and metabolic conditions, are contributing to the rising worldwide incidence of HCC. Effective prevention strategies must not only address traditional risk factors through vaccination and therapeutic measures but also confront metabolic and socioeconomic disparities through comprehensive public health efforts. As the burden of liver cancer continues to grow, particularly in resource-limited settings, an expansive and inclusive approach is vital for mitigating its impact across diverse populations.
The microbiome mechanism behind depression and treatment prospects of targeting intestinal microbes
Authors: Jiang Kailin , Wang Haisheng , Zeng Zhuoxian , Shi Xueting , Liu Lingyi , Wu Guojun , Tan Yurong
Published: January 2025

Major depressive disorder (MDD) is commonly correlated with gendered, genetic, environmental, or psychological factors. Recently, with an escalating number of depression-related studies, interest has focused on the role of intestinal microbiota in MDD pathogenesis. This research indicates that gut microbiota directly or indirectly influences brain function through diverse mechanisms regulating stress, anxiety, and depression. Studies indicate communication between the intestines and brain via neural, immune, and metabolic pathways. These imply a noteworthy correlation between alterations in gut microbiota and MDD. Hence, the study's potential role in understanding the regulatory mechanism of gut microbiota in MDD occurrence and its relation to probiotic antidepressive mechanisms could deliver a novel therapeutic perspective for treating depression.
Rural Culture and Diabetes Self-Management Beliefs, Behaviors and Health Outcomes
Authors: Pullyblank Kristin
Published: January 2025

Background

Rural populations in the United States face a diabetes mortality penalty. Self-management is a core component of treatment for type 2 diabetes, but there is low uptake of self-management education and support interventions in rural areas. Rural structural barriers to diabetes self-management have been described, yet the role of rural culture has not been extensively explored.

Objective

The purpose was to examine the relationships among rural culture, diabetes beliefs, self-management behaviors and health outcomes.

Methods

A stratified random sample of 500 adults with type 2 diabetes were recruited from a rural integrated health care system and invited to participate in this non-experimental cross-sectional study. Participants completed a survey that included validated measures of rural identity, self-reliance, perceived diabetes threat, and diabetes self-management behaviors. The most recent A1c was collected from the medical record. Descriptive, bivariate, multivariate and moderation analyses were conducted.

Results

128 participants returned completed surveys. Having an A1c < 8% was associated with better diabetes self-management behaviors, lower perceived threat, being female, and older age. Better diabetes self-management behaviors were associated with lower self-reliance, lower perceived threat, and older age. The combined moderation effect of both self-reliance and rural identity on the relationship between perceived threat and self-management behaviors was significant.

Discussion

Findings highlight the complex relationship between diabetes beliefs and behavior in rural populations and demonstrate that components of the rural culture have both direct and moderating effects on diabetes beliefs and self-management behaviors. These findings have important ramifications for nurses practicing in rural settings.
Diagnosis and Treatment Options for Cirrhosis With Unexplained Upper Gastrointestinal Bleeding: An Observational Study Based on Endoscopic Ultrasonography
Authors: Bai Yuchuan , Wang Zhihong , Shi Chen , Chen Lihong , Mei Xuecan , Kong Derun
Published: January 2025

Objective:

To investigate the role of endoscopic ultrasonography (EUS) in the diagnosis and treatment of upper gastrointestinal bleeding of unknown origin in liver cirrhosis, focusing on patients with recurrent treatment of esophageal and gastric varices who failed to identify the bleeding site under direct endoscopy.

Background:

Esophagogastric variceal bleeding is one of the severe complications of decompensated liver cirrhosis, and serial endoscopic therapy can improve the long-term quality of life of patients. Most acute bleeding can be detected under direct endoscopy with thrombus or active bleeding, but there are still some patients with recurrent bleeding after repeated treatments, and it is difficult to find the bleeding site, especially in gastric variceal bleeding. Therefore, it is of great significance to identify the bleeding site.

Patients and Methods:

A total of 88 patients with liver cirrhosis bleeding diagnosed and treated under EUS were collected in this study, including 26 patients who failed to identify the bleeding site under direct endoscopy. EUS was used to scan the bleeding site, and EUS-guided treatment was performed. The characteristics of the bleeding site under direct endoscopy and EUS and the follow-up results after surgery were analyzed.

Results:

Among the 26 patients, 16 patients (16/26, 61.5%) showed red color signs of gastric fundus mucosa under direct endoscopy, 5 patients (5/26, 19.2%) showed punctate erosion, and the remaining 5 patients (5/26, 19.2%) showed no abnormal mucosal manifestations. All patients could find anechoic blood vessels under EUS, and blood flow signals could be detected within. Among them, 23 patients (23/26, 88.5%) chose EUS-guided treatment, and no rebleeding occurred after surgery. Another 3 patients (3/26, 11.5%) were given endoscopic variceal ligation due to small esophageal and gastric varices and inability to perform intravascular injection. The median follow-up time was 86 days. Adverse reactions included 5 cases of retrosternal pain (5/23, 21.7%), and 1 case of fever (1/23, 4.3%).

Conclusion:

EUS can detect submucosal varices in the gastric mucosa, and these bleeding sites may present as red color signs or punctate erosion under direct endoscopy.
Dorsoventral comparison of intraspecific variation in the butterfly wing pattern using a convolutional neural network
Authors: Amino Kai , Hirakawa Tsubasa , Yago Masaya , Matsuo Takashi
Published: January 2025

Butterfly wing patterns exhibit notable differences between the dorsal and ventral surfaces, and morphological analyses of them have provided insights into the ecological and behavioural characteristics of wing patterns. Conventional methods for dorsoventral comparisons are constrained by the need for homologous patches or shared features between two surfaces, limiting their applicability across species. We used a convolutional neural network (CNN)-based analysis, which can compare images of the two surfaces without focusing on homologous patches or features, to detect dorsoventral bias in two types of intraspecific variation: sexual dimorphism and mimetic polymorphism. Using specimen images of 29 species, we first showed that the level of sexual dimorphism calculated by CNN-based analysis corresponded well with traditional assessments of sexual dissimilarity, demonstrating the validity of the method. Dorsal biases were widely detected in sexual dimorphism, suggesting that the conventional hypothesis of dorsally biased sexual selection can be supported in a broader range of species. In contrast, mimetic polymorphism showed no such bias, indicating the importance of both surfaces in mimicry. Our study demonstrates the potential versatility of CNN in comparing wing patterns between the two surfaces, while elucidating the relationship between dorsoventrally different selections and dorsoventral biases in intraspecific variations.
Growing with dinosaurs: a review of dinosaur reproduction and ontogeny
Authors: Chapelle Kimberley E. J. , Griffin Christopher T. , Pol Diego
Published: January 2025

Since the start of the twenty-first century, there has been a notable increase in annual publications focusing on dinosaur reproduction and ontogeny with researchers using these data to address a range of macroevolutionary questions about dinosaurs. Ontogeny, which is closely tied to osteological morphological variation, impacts several key research areas, such as taxonomic diversity, population dynamics, palaeoecology, macroevolution, as well as the physiological and reproductive factors driving ecological success. While these broad studies have significantly advanced our understanding of dinosaur evolution, they have also revealed important challenges and areas needing further investigation. In this review, we aim to outline some of these challenges in major research areas linked to dinosaur ontogeny, namely reproductive biology, osteohistological growth strategies, morphological osteological variation and the link between ontogeny and macroevolution. We also offer some recommendations for best practices and promising future research directions. These recommendations include increasing sample sizes through fieldwork and exhaustive use of pre-existing fossil collections, using micro-computed tomography (μCT) scanning methods to increase dataset sizes in a non-destructive manner, methodical collection and reposition of μCT scan data, assessing ontogenetic maturity, establishing consistency in terminology and methods and building comprehensive extant comparative datasets.
Transient cognitive impacts of oxygen deprivation caused by catch-and-release angling
Authors: Flink Henrik , Berge Adrian , Leggieri Francesca , Kolm Niclas , Tibblin Petter
Published: January 2025

Vertebrate brain function is particularly sensitive to the effects of hypoxia, with even brief periods of oxygen deprivation causing significant brain damage and impaired cognitive abilities. This study is the first to investigate the cognitive consequences of hypoxia in fish, specifically induced by exhaustive exercise and air exposure, conditions commonly encountered during catch-and-release (C&R) practices in recreational fishing. Angling exerts substantial pressure on inland fish populations, underscoring the need for sustainable practices like C&R. While C&R survival rates are generally high, understanding its sublethal impacts is crucial for evaluating the practice’s ethical and ecological sustainability. We examined the effects of these stressors on the cognitive function of 238 rainbow trout, using the free movement pattern Y-maze method to assess working memory through navigational search patterns during free exploration sessions. Our results showed that air exposure led to short-term (3–4 h post-treatment), but transient impairments in working memory, with no long-term cognitive deficits observed at one week and one month post-treatment. These findings emphasize the high tolerance of fish to hypoxia and support the sustainability of C&R as a tool in fisheries management.
Adaptive behaviour during epidemics: a social risk appraisal approach to modelling dynamics
Authors: O’Gara David , Kasman Matt , Hébert-Dufresne Laurent , Hammond Ross A.
Published: January 2025

The interaction of infectious diseases and behavioural responses to them has been the subject of widespread study. However, limited attention has been given to how broader social context shapes behavioural response. In this work, we propose a novel framework which combines two well-studied dynamic processes into a ‘social risk appraisal’ mechanism. Our proposed framework has both theoretical and empirical support, occupying an important middle ground in the interacting contagions literature. Results indicate that a risk appraisal framework can express a wide range of epidemic outcomes, driven by simple interaction rules. This framework has implications for designing containment strategies in disease outbreaks, as well as equity considerations. Finally, the risk appraisal approach is well-posed to engage with a broad set of literature in epidemic management, decision-making and the adoption of social behaviours.
Finding polarized communities and tracking information diffusion on Twitter: a network approach on the Irish Abortion Referendum
Authors: Pena Caroline B. , MacCarron Pádraig , O’Sullivan David J. P.
Published: January 2025

The analysis of social networks enables the understanding of social interactions, polarization of ideas and the spread of information, and therefore plays an important role in society. We use Twitter data—as it is a popular venue for the expression of opinion and dissemination of information—to identify opposing sides of a debate and, importantly, to observe how information spreads between these groups in our current polarized climate. To achieve this, we collected over 688 000 tweets from the Irish Abortion Referendum of 2018 to build a conversation network from users’ mentions with sentiment-based homophily. From this network, community detection methods allow us to isolate yes- or no-aligned supporters with high accuracy (90.9%). We supplement this by tracking how information cascades spread via over 31 000 retweet cascades. We found that very little information spread between polarized communities. This provides a valuable methodology for extracting and studying information diffusion on large networks by isolating ideologically polarized groups and exploring the propagation of information within and between these groups.
Non-random mating behaviour between diverging littoral and pelagic three-spined sticklebacks in an invasive population from Upper Lake Constance
Authors: Zeidler Tobias , Ros Albert , Roch Samuel , Jacobs Arne , Geist Juergen , Brinker Alexander
Published: January 2025

Adaptive divergence and increased genetic differentiation among populations can lead to reproductive isolation. In Lake Constance, Germany, a population of invasive three-spined stickleback (
Gasterosteus aculeatus
) is currently diverging into littoral and pelagic ecotypes, which both nest in the littoral zone. We hypothesized that assortative mating behaviour contributes to reproductive isolation between these ecotypes and performed a behavioural experiment in which females could choose between two nest-guarding males. Behaviour was recorded, and data on traits relevant to mate choice were collected. Both females of the same and different ecotypes were courted with equal vigour. However, there was a significant interaction effect of male and female ecotypes on the level of aggression in females. Littoral females were more aggressive towards pelagic males, and pelagic females were more aggressive towards littoral males. This indicates rejection of males of different ecotypes in spite of the fact that littoral males were larger, more intensely red-coloured and more aggressive than the pelagic males—all mating traits female sticklebacks generally select for. This study documents the emergence of behavioural barriers during early divergence in an invasive and rapidly diversifying stickleback population and discusses their putative role in facilitating reproductive isolation and adaptive radiation within this species.
Quantifying animal social behaviour with ecological field methods
Authors: Clark Molly A. , Ioannou Christos C.
Published: January 2025

Field studies of social behaviour are challenging due to the need to record or infer interactions between multiple individuals, often under suboptimal environmental conditions or with potential disturbance by observers. Due to the limited field techniques available, we present a novel method to quantify social behaviours in the field by comparing the counts of individuals caught in traps across multiple locations sampled simultaneously. The distribution of individuals between traps gives the extent of aggregation, and phenotypic data allow for inference of non-random assortment. As a case study, we applied this method to populations of three-spined sticklebacks (
Gasterosteus aculeatus
) in freshwater ponds, using minnow traps. As expected, we observed a strong trend for aggregation. We were able to describe the ecological drivers of aggregation, comparing environmental and phenotypic conditions across sites. Aggregation was not related to environmental parameters, but was negatively associated with the proportion of breeding males caught during the breeding season. No evidence for phenotypic assortment based on body size was found. These results demonstrate that widely available ecological equipment can address questions related to social behaviour. This cost-effective approach, avoiding the tagging of individuals and minimizing extended observer disturbance, can be applied across various habitats and species.
Towards carbon neutrality: mapping mass retrofit opportunities in Cambridge, UK
Authors: Mora Humberto , Bardhan Ronita
Published: January 2025

This study proposes a methodology and a proof of concept to target and prioritize mass retrofitting of residential buildings in the UK using open building datasets that combine fabric energy efficiency and fuel poverty to meet the net-zero targets. The methodological framework uses a series of multi-variate statistical and geospatial methods that consider urban, socio-economic and physical attributes. In addition, thermal imaging is implemented to provide insights at the building scale. We define a hard-to-decarbonize (HtD) metric to enable the clustering of different residential types to establish retrofitting priorities. Using Cambridge, UK, as a case study, five neighbourhoods were identified and characterized to help determine decarbonization intervention priorities. We found that one of five clusters of neighbourhoods is HtD and requires more policy support from government for the implementation of retrofit strategies. The achieved framework has the potential to inform policy and decision making. Of relevance, it is applicable to different urban contexts.
Application of a new composite genetic marker semen-specific methylation-microhaplotype in the analysis of semen–vaginal fluid mixtures
Authors: Wen Dan , Xing Hao , Tang Xuan , Wang Yue , Jiang Bowei , Li Jienan , Liu Ying , Zha Lagabaiyila
Published: January 2025

DNA mixtures containing semen and vaginal fluid are common biological samples in forensic analysis. However, the analysis of semen–vaginal fluid mixtures remains challenging. In this study, to solve these problems, it is proposed to combine semen-specific CpG sites and closely related microhaplotype sites to form a new composite genetic marker (semen-specific methylation-microhaplotype). Six methylation-microhaplotype loci were selected. To further improve discrimination power, five methylation-SNP loci were also included. The methylation levels and genotypes of these selected loci were obtained using massively parallel sequencing technology. Except for loci MMH04ZHA019 and MMH17ZHA059, the remaining nine loci were successfully sequenced. For the successfully sequenced loci, they performed well in identifying individuals and body fluids. An allele categorization model was developed using K-nearest neighbour algorithm, which was then used to predict allele types in semen–vaginal fluid mixtures. These loci were able to confirm the presence of semen and link semen to a true donor in semen–vaginal fluid mixtures with mixing ratios of 10:1, 9:1, 5:1, 4:1, 1:1, 1:3, 1:4, 1:8 and 1:9 (semen:vaginal fluid). This preliminary study suggests that this new composite genetic marker has great potential as a supplementary tool to commonly used genetic markers (STR, etc.) for analysing semen–vaginal fluid mixtures.
Awakening not associated with an increased rate of cortisol secretion
Authors: Klaas Samantha , Upton Thomas J. , Zavala Eder , Lawton Michael , Bensing Sophie , Berinder Katarina , Botusan Ileana , Grytaas Marianne , Methlie Paal , Øksnes Marianne , Russell Georgina , Vassiliadi Dimitra A. , Lightman Stafford L.
Published: January 2025

Cortisol is released upon activation of the hypothalamic–pituitary–adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening induces cortisol secretion is limited. We used a mixed effects model with a linear spline fitted to the data to examine tissue-free cortisol measurements obtained from 201 healthy volunteers by automated ambulatory microdialysis before and after awakening in their home environments. We also examined rate of change of cortisol depending on sleep duration and relative timing. We found no evidence for a change in the rate of cortisol increase in the hour after waking when compared with the hour prior to waking. We instead observed substantial interindividual variability in the absolute concentration and rate of change of cortisol levels, and differences in dynamics that may be attributable to duration and relative timing of sleep. Based on these results, we strongly suggest caution is needed when interpreting cortisol measurements solely obtained in the hour after waking.
The hummingbird’s adipostat: can a simple rule explain torpor frequency and duration in hummingbirds?
Authors: Halter Shayne R. , Wolf Blair O. , Martinez del Rio Carlos
Published: January 2025

Because hummingbirds are small and have an expensive mode of locomotion, they have constrained energy budgets. Torpor is used to buffer against these energetic challenges, but its frequency and duration vary. We measured lipid content, metabolic rates and torpor use in two species of migrating hummingbirds, calliope (
Selasphorus calliope
) and rufous hummingbirds (
Selasphorus rufus
) at a stopover site. We constructed a mass-balance model to predict lipid thresholds for torpor entry, torpor duration and minimum morning lipid reserves. Hummingbirds entered torpor if their lipid contents were below a sharply defined threshold. Torpor duration increased as initial lipid content decreased, and birds that entered torpor had relatively constant morning lipid reserves. We propose a minimum morning reserve hypothesis that identifies torpor lipid thresholds and predicts frequency and duration. Several hypotheses were proposed previously to explain torpor’s ultimate function, which can be derived as special cases that result from modifying our mass balance model’s parameters. Torpor entails a balance between energy savings and the non-energetic risks of torpor, such as predation and physiological stress. We assessed energy equivalents of the non-energetic costs of torpor by accounting for the energetic costs and benefits of torpor, and by documenting its occurrence and length.
Distinct retinal ganglion cell types in strictly subterranean, naturally microphthalmic mammals
Authors: Avaroth Bhaskaran Rahul , Vondráčková Zuzana , Koladiya Abhishek , Čapek Martin , Dionigi Francesco , Begall Sabine , Burda Hynek , Peichl Leo , Němec Pavel
Published: January 2025

African mole-rats (Bathyergidae, Rodentia) are subterranean rodents that live in extensive dark underground tunnel systems and rarely emerge aboveground. They can discriminate between light and dark but show no overt visually driven behaviours except for light-avoidance responses. Their eyes and central visual system are strongly reduced but not degenerated. Here, we focus on retinal ganglion cells (RGCs). Sighted mammals have numerous RGC types with distinct morphological and functional properties that encode different aspects of a visual scene. We analysed the morphological diversity of 216 intracellularly dye-injected RGCs in the giant mole-rat (
Fukomys mechowii
) and 48 RGCs in Ansell’s mole-rat (
Fukomys anselli
). Using a hierarchical cluster analysis on 11 morphological parameters, we show that both species possess at least five RGC types with distinct dendritic field sizes and branching patterns. These resemble some RGC types of the mouse and rat, but mole-rat RGCs feature overall sparser and more asymmetric branching patterns. The dendritic trees of most RGCs in all clusters are monostratified in the inner plexiform layer, but bistratified and multistratified/diffuse cells also exist. Thus, although RGC morphologies have become disorganized, the basic retinal organization principle of parallel information processing by distinct RGC types is retained.
Anal Tuberculosis: Diagnostic Challenges and Ambiguities with Crohn's Disease: A case report
Authors: CHRAIBI AMINA , Fellah Sofia , Eddaif Karim , Arjoudane Douae , Bennani Saad , Bentouda Najoua , Goura Hamza , Bnaissa El Mostafa , Benlahlou Yassine , Chadli Mariama
Published: January 2025

Abstract

Tuberculosis is an infectious disease caused by mycobacteria within the tuberculosis complex. Anal tuberculosis is a rare and often underdiagnosed form of extrapulmonary tuberculosis, accounting for approximately 1% of cases.  We present a case of anal tuberculosis in a 40-year-old male with Crohn's disease, who developed anoperineal lesions. The patient was undergoing combination therapy, including an immunosuppressant (azathioprine) and an anti-TNF agent (infliximab). Due to the persistence of symptoms, a GeneXpert test was performed on an anal fistula to detect acid-fast bacilli, yielding a positive result.  Infection in the anorectal region can occur through ingestion of sputum containing the bacilli, direct inoculation via anal skin fissures, or, more rarely, hematogenous dissemination.  Ziehl-Neelsen staining for acid-fast bacilli is not always definitive. Histological examination plays a key role in identifying epithelioid giant-cell granulomas and caseous necrosis. Culturing the bacteria on specialized media can take 2 to 3 months, a delay that is incompatible with the urgent need for treatment. Therefore, the GeneXpert MTB/RIF assay is preferred for its high sensitivity, specificity, speed, and ease of use. The diagnosis of tuberculosis is often complex and relies on a combination of clinical, radiological, histological, and biological evidence, as well as a positive response to antituberculous therapy.

Email addresses

aminaachraibi@gmail.com, sofiafellah96@gmail.com, keddaif@gmail.com, doae.arjoudane@gmail.com, Mr_bennani@outlook.com, najoua1497.bn@gmail.com, hamza.goura@um5s.net.ma, benlahlouyassine@gmail.com benaissaelmostafa2@gmail.com, mariamachadli@gmail.com
Exploring SNP filtering strategies: the influence of strict vs soft core
Authors: Taouk Mona L. , Featherstone Leo A. , Taiaroa George , Seemann Torsten , Ingle Danielle J. , Stinear Timothy P. , Wick Ryan R.
Published: January 2025

Phylogenetic analyses are crucial for understanding microbial evolution and infectious disease transmission. Bacterial phylogenies are often inferred from SNP alignments, with SNPs as the fundamental signal within these data. SNP alignments can be reduced to a ‘strict core’ by removing those sites that do not have data present in every sample. However, as sample size and genome diversity increase, a strict core can shrink markedly, discarding potentially informative data. Here, we propose and provide evidence to support the use of a ‘soft core’ that tolerates some missing data, preserving more information for phylogenetic analysis. Using large datasets of Neisseria gonorrhoeae and Salmonella enterica serovar Typhi, we assess different core thresholds. Our results show that strict cores can drastically reduce informative sites compared to soft cores. In a 10 000-genome alignment of Salmonella enterica serovar Typhi, a 95% soft core yielded ten times more informative sites than a 100% strict core. Similar patterns were observed in N. gonorrhoeae. We further evaluated the accuracy of phylogenies built from strict- and soft-core alignments using datasets with strong temporal signals. Soft-core alignments generally outperformed strict cores in producing trees displaying clock-like behaviour; for instance, the N. gonorrhoeae 95% soft-core phylogeny had a root-to-tip regression R
2 of 0.50 compared to 0.21 for the strict-core phylogeny. This study suggests that soft-core strategies are preferable for large, diverse microbial datasets. To facilitate this, we developed Core-SNP-filter (https://github.com/rrwick/Core-SNP-filter), an open-source software tool for generating soft-core alignments from whole-genome alignments based on user-defined thresholds.
The Acceptability of a Tobacco Dependency Treatment for NHS Staff in the North East of England: A Mixed-Methods Study
Authors: Thompson Caitlin , Brennan-Tovey Kerry , Robinson Caitlin , McIlvenna Rachel , Kaner Eileen FS , Ramsay Sheena E , Aquino Maria Raisa Jessica
Published: January 2025

Aims

High smoking rates and deprivation levels in North East of England led to an opportunity to pilot a tobacco dependency treatment offer for NHS Staff who smoke to make a supported quit attempt. The direct and indirect benefits to staff, patients, and NHS organisations are well documented. This study aimed to evaluate the acceptability of the service.

Methods

The service included up to 12 weeks of free Nicotine Replacement Therapy (NRT) and/or a refillable e-cigarette, motivational support, and premium access to the Smoke-Free App. Service evaluation used a mixed-methods design, combining the Theoretical Framework of Acceptability (TFA) questionnaire and semi-structured interviews with staff who had accessed the offer. Quantitative data were analysed using descriptive statistics and qualitative data via thematic analysis.

Results

68 survey responses (Mage= 43.92 years,SD= 12.27; Gender = 27.9% M and 72.1% F) reflected high acceptability (M= 4.59,Mdn= 5.00,SD= 0.72). Eighteen interviews (Mage= 40.67 years,SD= 12.22; Gender = 38.9% M and 81.1% F) revealed four themes relating to service familiarity and ease of access, suitability of the NRT/e-liquid ordering service, the vape kit, and behavioural support.

Conclusions

The service was deemed highly acceptable, and service users’ experiences informed recommendations for improving future tobacco dependency services. This is the first known application of the TFA to an evaluation of a smoking cessation intervention and contributes to a broader body of research on reducing tobacco dependence.
From Flies to Humans: Conserved Roles of CEBPZ, NOC2L, and NOC3L in rRNA Processing and Tumorigenesis
Authors: Rambaldelli Guglielmo , Manara Valeria , Vutera Cuda Andrea , Bertalot Giovanni , Penzo Marianna , Bellosta Paola
Published: January 2025

NOC1, NOC2, and NOC3 are conserved nucleolar proteins essential for regulating ribosomal RNA (rRNA) maturation, a process critical for cellular homeostasis. NOC1, inDrosophilaand yeast, enhances nucleolar activity to sustain rRNA processing, whereas its depletion leads to impaired polysome formation, reduced protein synthesis, and apoptosis. These genes have vertebrate homologs called CEBPZ, NOC2L, and NOC3l. In this study, we demonstrated that the RNA-regulatory functions of CEBPZ are conserved in vertebrates, and we showed that CEBPZ leads to the accumulation of 45S-pre rRNA, with consequent reduction in protein synthesis. Gene Ontology and bioinformatic analyses of CEBPZ, NOC2L, and NOC3L in tumors highlight a significant correlation between their reduction and the processes that regulate rRNA and 60S ribosomal maturation. Comparative analysis of their expression in tumor databases revealed that CEBPZ, NOC2L, and NOC3L exhibit contrasting expression patterns across tumor types. This dual role suggests that their overexpression promotes tumor growth, whereas reduced expression may exert tumor-suppressive effects, uncovering unexpected regulatory functions exerted by these proteins in cancer.
An online GPCR drug discovery resource
Authors: Caroli Jimmy , Andreassen Søren N. , Lorente Javier Sánchez , Xiao Binghan , Pándy-Szekeres Gáspár , Gloriam David E.
Published: January 2025

G protein-coupled receptors (GPCRs) have been targeted across all therapeutic areas, mediate the actions of 516 (36% of all) approved drugs and are being targeted by 337 agents in clinical trials. So far, 121 GPCRs are targets of approved drugs and 30 additional receptors have entered clinical trials and may expand the drugged GPCRome in the coming years. Here, we describe an online resource of GPCR drugs, clinical trial agents, targets and disease indications. This resource offers unique reference data, analysis and visualization, and is availed as a new section, ‘Drugs and Agents in trial’ integrated in the GPCR database, GPCRdb. Furthermore, it includes a target selection tool for prioritization of receptors for future drug discovery. This up-to-date knowledgebase will help identify strategies and trends in current GPCR drug discovery and give insights into which already drugged, or yet untapped targets have the largest potential in specific diseases.