bluuebunny/crossref_metadata_2025 huggingface dataset:
Miniaturised laboratorial equipment as a solution to implement conservation genetics tools and education in West African countries with limited infrastructures: an application to the study of illegal wildlife trade in Guinea-Bissau
Authors: da Silva Maria Joana Ferreira , Colmonero-Costeira Ivo , Djaló Mohamed , Fernandes Nelson , Camará Tomás , Sá Rui M. , Minhós Tania , Kiebler Angelika , Grethlein Martin , Pikkarainen Netta , Prost Stefan
Published: October 2024

Illegal wildlife trade (IWT) is considered one of the largest global illegal industries that negatively impacts biodiversity and sustainable development worldwide. DNA barcoding coupled with high-throughput sequencing has been shown to be useful in identifying taxa affected by IWT and has been routinely used during the last decades. However, for countries lacking laboratory infrastructures and sequencing units or trained staff, the application of DNA barcoding tools in conservation actions and policies is limited and dependent on slow sample export processes and molecular analyses carried out abroad. Guinea-Bissau (GB) is located on the West-African coast and has one of the lowest human development indices worldwide, while being a biodiversity hotspot facing many conservation challenges due to illegal commercial hunting, and trade in bushmeat and live individuals. Here, we explore the potential of using inexpensive and portable miniaturised laboratory equipment (MLE) to i) identify species illegally traded in GB using DNA barcoding methods and ii) to improve molecular biology and conservation genetic education and training in GB. Our overarching aim is to raise awareness of the current gap between the need to apply conservation genetic technologies in GB and the inability to do so due to a lack of laboratory infrastructures, sequencing units and opportunities for molecular biology training. We show that MLE can be a solution to accelerate the use of DNA barcoding methods to understand IWT and to train students, technicians and staff from governmental agencies dedicated to investigating environmental crimes, ultimately advancing the discipline of conservation genetics in the country.
A comparison of microglial morphological complexity in adult mouse brain samples using 2-dimensional and 3-dimensional image analysis tools
Authors: Murray Colin J. , Tunderman Eva D. , Vecchiarelli Haley A. , González Ibáñez Fernando , Tremblay Marie-Ève
Published: October 2024

Characterizing cell morphology has been an essential aspect of neuroscience for over a century to provide essential insights into cellular function and dysfunction. Microglia, the resident innate immune cells of the central nervous system, undergo drastic changes in morphology in response to various stimuli, with many classifications proposed in recent years. Increased availability of advanced analysis software to study microglial morphology represents a step forward in the field. However, whether the use of advanced analysis tools provides equivalent or varied outcomes remains undetermined. This study re-analyzed raw data, previously processed using a standard 2D microglial morphology analysis method, using 3D analysis methods. The published article observed significant changes in microglial morphology in the mouse ventral hippocampus after administration of a ketogenic diet and exposure to repeated social defeat stress in young adult male mice. Overall, we observed different statistical outcomes in the 3D dataset compared to the previously published 2D results, with both maintained and new findings. This may indicate that the 3D analysis method is better able to capture minute changes in morphology. However, overall conclusions on microglial morphology changes remain consistent between methods. Lastly, we highlight the difference between a nested statistical design, which considers within animal variability, and a non-nested design. Overall, we highlight and discuss differences between 2D and 3D microglial morphology analysis and explore the contribution of individual cell and animal variability to statistical outcomes.

Main Points

3D analysis method generates similar and novel results compared to a 2D method.

verall microglial morphological changes to stimuli are comparable between methods.

nested statistical design produces distinct significant differences.
Autophagic enhancer rescues Tau accumulation in a stem cell model of frontotemporal dementia
Authors: Mirfakhar Farzaneh S. , Marsh Jacob A. , Minaya Miguel A. , Pak Stephen C. , Silverman Gary A. , Perlmutter David H. , Macauley Shannon L. , Karch Celeste M.
Published: October 2024

Tau degradation is disrupted in neurodegenerative tauopathies, such as frontotemporal dementia (FTD), which may contribute to Tau aggregation. The prevailing hypothesis has been that Tau degradation is stymied due to an imbalance in proteostasis that occurs with age. Here, we used Airyscan super resolution imaging to illustrate that a pathogenic FTD mutation in theMAPTgene, which encodes Tau, is sufficient to alter multiple steps of the autophagy lysosomal pathway and impair Tau degradation. We discovered lysosomes clogged with both Tau and phosphorylated Tau, stalled lysosome motility, disrupted molecular motors, enhanced autophagic flux, and slowed cargo degradation in mutant Tau neurons. Treatment of mutant Tau neurons with a small molecule autophagy enhancer drug increases autophagic flux and cargo degradation, reduces phospho-Tau levels, and reduces Tau accumulation in lysosomes without restoring defects in lysosomal motility. This study reveals novel effects of mutant Tau and provides a window through which therapeutic treatments targeting autophagy may promote Tau homeostasis.
Increased CPT1a expression is a critical cardioprotective response to pathological stress that suppresses gene programs for remodeling and enables rescue by gene transfer
Authors: Carley Andrew N. , Maurya Santosh K. , Maurya Chandan K. , Wang Yang , Webb Amy , Challa Azariyas A. , Zhang Zhentao , Zhu Hua , Heydemann Ahlke , Bedi Kenneth C. , Kyriakopoulos Christos P. , Selzman Craig H. , Drakos Stavros G. , Margulies Kenneth B , Lewandowski E. Douglas
Published: October 2024

Text Abstract

Background

Carnitine palmitoyl transferase 1 (CPT1) is a rate-limiting enzyme for long chain fatty acid oxidation (FAO) in cardiac mitochondria. In adult hearts, CPT1b predominates, while CPT1a is co-expressed at lower levels. Pathological stress on the heart induces greater CPT1a expression, and this coincides with a reduction in FAO, yet the role of CPT1a in pathological cardiac remodeling is unknown.

Methods

CPT1 isoform expression was assayed in myocardium of human heart failure (HF) patients with nonischemic cardiomyopathy (NICM) and a preclinical mouse model of heart failure. To explore the role of CPT1a upregulation in response to pathological stress, mice were subjected to afterload stress via transverse aortic constriction (TAC) or sham surgery (sham) with cardiac-specific CPT1a knockdown or cardiac-specific, AAV9-mediated CPT1a overexpression (AAV9.cTNTN.Cpt1a), versus empty virus or PBS infusions as controls. MiR370, known to suppress hepatic CPT1a, was assayed and overexpressed to determine if miR370 regulates cardiac CPT1a expression.

Results

CPT1a protein was elevated and miR370 reduced in myocardium of male and female NICM patients (204% vs. non-failing unused donor hearts), as well as in failing mouse hearts. AAV mediated miR370 overexpression in mouse hearts suppressed CPT1a expression and attenuated the response of CPT1a to TAC. Preventing CPT1a upregulation in response to TAC in cardiac specific CPT1a knockout mice (csCPT1a ko) exacerbated adverse remodeling, causing severe dysfunction and increased mortality. In contrast, CPT1a overexpression (2.8 fold), attenuated impaired ejection fraction (EF, by 54%) and fractional shortening (FS, 65%) vs. PBS-infused TAC hearts (p<0.05). Delivery of AAV9.cTnT.Cpt1a 4 wks after TAC surgery, led to significant rescue of EF and FS vs. animals receiving empty virus and mitigated the exacerbated dysfunction of csCPT1a ko hearts at 4 wks TAC. RNA-seq and reverse transcription-quantitative PCR revealed a novel function of CPT1a in suppressing hypertrophic, profibrotic and cell death gene programs in both sham and TAC hearts, irrespective of changes in FAO.

Conclusions

The effects of CPT1a in the heart extend beyond FAO and include a non-canonical regulation of cardiac gene programs. In addition to an animal model of HF, CPT1a upregulation occurs in NICM, and is a critical cardioprotective adaptation to pathological stress.
The expression alteration ofGolim4(Gpp130) and its prognostic value in epithelial ovarian cancer
Authors: Sheida Sadaf Valeh , Gholipour Akram , Bayat Varchaghi Hossein , Mowla Seyed Javad
Published: October 2024

Background

Among common cancers in women, ovarian cancer has the lowest incidence; however, mortality rates are more than other gynecological cancers due to the lack of specific symptoms during early stages and absence of diagnostic markers. Golgi integral membrane protein 4 (GOLIM4) is a member of transporter complex which is located to the cis/medial of Golgi, and its role in tumor is unknown. In this study we aimed to assess the expression ofGolim4(GPP130) in epithelial ovarian cancer (EOC) patients.

Methods

The expression levels ofGolim4in 58 malignant EOC specimens and 11 benign and normal control tissues were determined by real-time RT-PCR. Clinicopathological characteristics were analyzed. Non-parametric survival analysis was estimated by using Kaplan-Meier and log-rank test. Parametric survival analysis was evaluated through multivariate Cox regression analysis and generalized Gamma survival model.

Result

Our findings showed thatGolim4was significantly down-regulated in Serous Papillary type of EOC tissue specimens than in non-cancerous tissues (P<0.001); however; the expression ofGolim4in total EOC tissue specimens revealed non-significant up-regulation. Kaplan-Meier analysis and log-rank test have suggested that EOC patients with lowGolim4expression have shorter overall survival when compared with patients with other expression groups (log-rank test P<0.05). Semi-parametric Cox proportional hazards model indicated that the status ofGolim4were independent predictor of overall survival in patients with EOC. Correlation analysis has been done by Spearman Rank correlation coefficient.
Solid-state esophageal pressure sensor for the estimation of pleural pressure: a bench and first-in-human validation study
Authors: van Oosten Julien P. , Goedendorp Nico , Mousa Amne , Flink Rutger , Schaart Rik , Flinsenberg Merel , Somhorst Peter , Gommers Diederik A.M.P.J. , Heunks Leo , Jonkman Annemijn H.
Published: October 2024

Background

Advanced respiratory monitoring through the measurement of esophageal pressure (Pes) as a surrogate of pleural pressure helps guiding mechanical ventilation in ICU patients. Pes measurement with an esophageal balloon catheter, the current clinical reference standard, needs complex calibrations and a multitude of factors influence its reliability. Solid-state pressure sensors might be able to overcome these limitations.

Objectives

To evaluate the accuracy of a new solid-state Pes transducer (Pessolid). We hypothesized that measurements are non-inferior to those obtained with a properly calibrated balloon catheter (Pesbal).

Methods

Absolute and relative solid-state sensor Pes measurements were compared to a reference pressure in a 5-day bench setup, and to simultaneously placed balloon catheters in 15 spontaneously breathing healthy volunteers and in 16 mechanically ventilated ICU patients. Bland-Altman analysis was performed with nonparametric bootstrapping to estimate bias and upper and lower limits of agreement (LoA).

Results

Bench study: Solid-state pressure transducers had a positive bias (Psolid– Pref) of around 1 cmH2O for the absolute minimal and maximum pressures, and no bias for pressure swings. Healthy volunteers: the solid-state transducer revealed a bias (Pessolid–Pesbal) [upper LoA; lower LoA] of 1.58 [8.19; −5.03], −2.37 [3.96; −8.69] and 3.94 [11.09; −3.20] cmH2O for end-expiratory, end-inspiratory and ΔPes values, respectively. ICU patients: the solid-state transducer showed a bias (Pessolid–Pesbal) [upper LoA; lower LoA] during controlled / assisted ventilation of: −0.15 [1.39; −1.70] / −0.20 [5.02; −5.41], 0.32 [3.35; −2.72] / −0.54 [4.60; −5.68] and 0.47 [3.79; −2.85] / 0.35 [3.88; −3.18] cmH2O for end-expiratory, end-inspiratory and ΔPes values, respectively. LoA were <2cmH2O for static measurements on controlled ventilation.

Conclusions

The novel solid-state pressure transducer showed good accuracy on the bench, in healthy volunteers and in ventilated ICU-patients. This could contribute to the implementation of Pes as advanced respiratory monitoring technique.

Trial registration

Clinicaltrials.govidentifier:NCT05817968(patient study). Registered on 18 April 2023.
Information processing speed modulation by electrical brain stimulation in multiple sclerosis: Towards individually-tailored protocols
Authors: Riemann Steffen , Mittelstädt Michel , Glatzki Maurice , Zilges Carlotta , Wolff Clara , Niemann Filip , Roheger Mandy , Flöel Agnes , Grothe Matthias , Meinzer Marcus
Published: October 2024

Information processing speed (IPS) is a core cognitive process, highly relevant in everyday-life and the most frequent and disabling cognitive symptom in patients with Relapsing Multiple Sclerosis (pwRMS). By using region-specific focalized transcranial direct current stimulation (tDCS) in healthy individuals and pwRMS, we provide causal evidence for superior parietal lobe (SPL) involvement in IPS and identified a clinical predictor of tDCS-response in pwRMS. The study employed a registered, randomized, sham-tDCS controlled, three-way blinded, cross-over trial and a mixed-factors design with eight arms [between-subjects: group (pwRMS, controls); tDCS-polarity (excitatory, inhibitory); within-subjects: stimulation (active-, sham-tDCS)]. Concurrently with tDCS, participants completed a computerized version of the Symbol-Digit-Modalities-Test (SDMT), the current gold standard for quantifying IPS impairment in pwRMS. Bayesian modeling with generalized linear mixed models provided strong evidence for polarity specific modulation of IPS by SPL-tDCS and a double-dissociation of stimulation response in pwRMS and controls. Healthy individuals showed the canonical pattern of significantly enhanced and reduced processing speed during excitatory or inhibitory tDCS. In pwRMS, a reversed pattern was found and tDCS-response was predicted by baseline SDMT performance; i.e., more or less impaired patients benefited from inhibitory or excitatory tDCS, respectively. Our results provide direct causal evidence for SPL involvement in IPS in health and disease and suggest that the degree of IPS impairment in pwRMS reflects compensatory or dysfunctional neuroplastic processes that can be counteracted in a polarity specific way. Identified standardized transition scores for the effectiveness of excitatory or inhibitory tDCS will inform future individually-tailored stimulation protocols in pwRMS.

One Sentence Summary

Polarity-specific modulation of information processing speed in multiple sclerosis.
Determinants of acute malnutrition among children under five in arid regions, Kenya
Authors: Amugsi Dickson A , Sidze Estelle , Thuita Faith , Flax Valerie L. , Wilunda Calistus , Adair Linda , Mwangi Bonventure , Anono Esther , Odhiambo Hazel , Ekiru Stephen , Chepkwony Gillian , Albert Webale , Ng’ang’a Monica , Miller Joshua D. , Sagara Bradley , Kimani-Murage Elizabeth , Lutter Chessa
Published: October 2024

Acute malnutrition, defined as a weight-for-height Z-score below -2 standard deviations of the WHO growth standards, is prevalent among children in low- and middle-income countries. Our study aimed to identify immediate, underlying, and basic determinants of acute malnutrition among children in Turkana and Samburu, two arid and semi-arid regions in Kenya. Data are from a longitudinal study that recruited children under 3 years of age, with follow-up every 4 months over six waves. Generalized estimating equations were used to assess risk factors of acute malnutrition in this population. Among immediate factors, children who recently experienced diarrhea had 19% and 23% higher odds of acute malnutrition and those who consumed animal-source foods had 12% and 22% lower odds of acute malnutrition in Turkana and Samburu, respectively. Among underlying factors, children in Turkana whose caregivers used alcohol had 32% higher odds of acute malnutrition. Among basic factors, children in Turkana whose caregivers had 3-5 or 6 or more children had 39% and 70% higher odds, whereas those in female-headed households had 34% and 81% higher odds of acute malnutrition in Turkana and Samburu, respectively. Children in Turkana’s fisherfolk communities had 36% higher odds of acute malnutrition compared with those in urban or peri-urban areas. Key risk factors for acute malnutrition included child diarrhea, caregiver’s use of alcohol (in Turkana), caregiver’s number of children, female-headed households, and fisherfolk livelihood (in Turkana), while consuming animal-source foods was associated with lower risk. Interventions should target these intersecting factors to reduce acute malnutrition in these counties.

Key messages

Acute malnutrition in children under 5 years is persistent in East Africa’s arid and semi-arid lands.

Among immediate factors, children who had diarrhea were more likely to have acute malnutrition, while those who consumed animal-source foods were less likely to have acute malnutrition in both counties.

Among underlying factors, children whose caregivers used alcohol were more likely to have acute malnutrition in Turkana only. Household food insecurity and water, sanitation, and hygiene were not directly associated with acute malnutrition.

A variety of basic factors were associated with a higher likelihood of acute malnutrition, including number of children in the household, the household being headed by a female, and fisherfolk livelihood (in Turkana).
Interpreting Health Differences between Self-reported Black and White Children in U.S.: Insights from a Methodological Perspective
Authors: Yang Fan Nils , Duyn Jeff H. , Xie Weizhen
Published: October 2024

Understanding health differences among racial groups in child development is crucial for addressing inequalities that may affect various aspects of a child’s life. However, factors such as household and neighborhood socioeconomic status (SES) often covary with health differences between races, making it challenging to accurately reveal these differences using conventional covariate-control methods such as multiple regression. Alternative methods, such as Propensity Score Matching (PSM), may provide better covariate control. Supporting this notion, we found that PSM is more sensitive than regression-based methods in detecting health differences between self-reported Black and White children across a wide range of behavioral and neural measurements in the ABCD (5636 White, 1350 Black). Puberty status, an index of physical maturation, emerged as the largest difference between races and mediated the health differences between races on the majority of behavioral and neural variables. These findings highlight the importance of controlling for pubertal status and using more effective covariate-control methods to accurately represent health differences between Black and White children.
Rare pathogenic variants in G-protein coupled receptor genes involved in gut-to- host communication are associated with cardiovascular disease risk
Authors: Tavares Leticia Camargo , Muralitharan Rikeish R. , Snelson Matthew , Marques Francine Z.
Published: October 2024

Background

Gut microbial metabolites called short-chain fatty acids (SCFA) confer protective effects against cardiovascular disease and high blood pressure. Proposed mechanisms include anti-inflammatory signalling mediated by SCFA-sensing G-protein-coupled receptors (GPCR), particularly GPR41, GPR43, and GPR109a, as suggested by knockout mouse models. We aimed to determine if rare pathogenic variants (RPVs) affecting GPCR genes in humans increase the risk of hypertension (HTN) and major adverse cardiac events (MACEs), including acute coronary syndrome, heart failure, and ischemic stroke.

Methods

Using UK Biobank whole-exome sequencing data from 393,649 European participants, we identified rare (minor allele frequency <1%) pathogenic variants with predicted high-impact functional consequences in GPCR genes, based on Ensembl Variant Effect Predictor annotations. For missense variants, pathogenicity likelihood scores from AlphaMissense, Mendelian Clinically Applicable Pathogenicity, and Combined Annotation Dependent Depletion were assessed. Multivariable logistic regression models, adjusted for age, sex, BMI, genetic ancestry, and other potential confounders, were conducted to compare RPV prevalence between cases and controls.

Results

We identified a total of 158 RPVs in SCFA-sensing GPCR genes. The prevalence of RPV carriers was significantly higher in patients with HTN (OR=1.12, P=0.014) and MACEs (OR=1.18, P=0.009) than controls. In single GPCR gene analyses, RPVs in the FFAR2 gene (encoding GPR43) were associated with an increased risk of HTN (OR=1.23, P=0.005). RPVs in the HCAR2 gene (encoding GPR109A) were associated with a markedly increased risk of heart failure (OR=1.57, P=0.012).

Conclusions

These findings confirm and extend previous results from knockout animal models in a large population-based cohort, highlighting the potential of GPCRs as therapeutic targets for HTN and cardiovascular diseases in humans.
Gut microbiota and type 2 diabetes associaction: A meta-analysis of 16S studies and their methodological challenges
Authors: Picanço Machado Jéssica Lígia , Schaan Ana Paula , Mamede Izabela , Fernandes Gabriel da Rocha
Published: October 2024

Diabetes mellitus is a prevalent chronic non-communicable disease, and recent studies have explored the link between gut microbiota and its development. Despite some evidence suggesting an association, the influence of gut microbiota on type 2 diabetes DM2 remains unclear. A systematic search of PubMed Janeiro 2016– 10 December 2023 using the keywords “16S” and “diabetes” or “DM2” and “gut microbiota” and “diabetes” or “DM2”. The studies included compared gut microbiome diversity between diabetic and non-diabetic adults using 16S rRNA sequencing, excluding children, interventions, and type 1 diabetes. Alpha diversity indices and bacterial mean abundance were analyzed, with statistical assessments using a random-effects model and I2for heterogeneity. Thirteen studies met the criteria, with the Shannon index being the most commonly used measure. Results showed significant heterogeneity I2>75% and no notable differences between diabetic and non-diabetic groups. Other indices, such as Chao1 and phylogenetic whole tree, similarly showed no consistent differences. Taxonomic analysis also failed to find phyla consistently correlated with DM2, with variability across studies. The relationship between gut microbiota and diabetes remains uncertain due to technical and biological factors that are often overlooked. The inconsistencies across studies highlight the low reproducibility common in microbiota research.
Changes in Myofibril Size, Shape, and Network Connectivity in Aging Muscle
Authors: Ajayi Peter T. , Vue Zer , Hinton Antentor O. , Glancy Brian
Published: October 2024

Across normal aging, striated muscles undergo structural remodeling associated with loss of force production. However, it is unknown how the organization of contractile myofibrillar networks, linked to their efficiency, is modified during aging. Using serial block-face scanning electron microscopy (SBF-SEM), we assess myofibril size, shape, and connectivity across different muscle types in young and geriatric mice and humans. Regardless of skeletal muscle fiber type in mice, age was associated with increased myofibrillar connectivity, with 24 months of age, as compared to 3 months, displaying more sarcomere branches. Distinctive age-related trends in myofibril size and shape were observed among each muscle type. Notably, there was a decrease in myofibril circularity from 3 months of age to 24 months of age in the gastrocnemius muscles of mice, contrasting with an increase in circularity in the soleus muscles during the same time frame. Additionally, while the soleus myofibrils in an aged cohort had a higher cross-sectional area, a reduction was observed in the gastrocnemius muscles. Cardiac muscles displayed no changes in sarcomere connectivity from 3 months to 24 months, although myofibril circularity and cross-sectional area were increased during this time. In human vastus lateralis muscles, sarcomere branching was positively correlated with advanced age. However, there were no consistent changes in myofibril size or shape across a wide age range from 16 to 68 years old. Overall, these data suggest that aging is associated with increased connectivity of the contractile networks within mammalian skeletal muscle.

Graphical Abstract
Super-Resolution Axial Imaging for Quantifying Piconewton Traction Forces in Live-cells
Authors: Wang Dong-Xia , Kong De-Ming , Enderlein Jörg , Chen Tao
Published: October 2024

Cell mechanics play a pivotal role in regulating numerous biological processes. While super-resolution microscopy enables the imaging of cellular forces in the lateral dimension with sub-10-nanometer resolution, achieving comparable resolution along the axial dimension remains a significant challenge. In this study, we combine metal-induced energy transfer (MIET) imaging with novel DNA-hairpin-based molecular tension probes (MIET-MTP) to map integrin-mediated mechanical forces with nanometer precision in the axial direction. MIET-MTP allows for the simultaneous observation of both the plasma membrane and forceexerting molecules in the axial dimension. Using this approach, we mapped axial integrin tension in focal adhesions and podosomes, alongside their corresponding plasma membrane height profiles, offering detailed insights into the structures involved in force transmission.
Integrative physiological plasticity ofAgastache rugosa(Fisch. & C.A.Mey.) Kuntze reveals complex adaptation to light and nutrient gradients
Authors: Rosli Khairul Azree , Misran Azizah , Yazan Latifah Saiful , Megat Wahab Puteri Edaroyati
Published: October 2024

We investigated the physiological plasticity ofAgastache rugosa(Fisch. & C.A.Mey.) Kuntze, in response to different light and nutrient levels, demonstrating complex adaptive strategies. Through comprehensive analysis of leaf traits, photosynthetic parameters, and resource use efficiencies, we uncovered unexpected patterns in Rubisco dynamics and nutrient utilization, particularly in low- light conditions.A. rugosaexhibited subtle thermal regulation, maintaining relatively stable leaf temperatures across treatments through coordinated adjustments in morphology and gas exchange. Multivariate analyses showed distinct clustering of traits, underlining the integrated nature of plant responses to environmental heterogeneity. Leaf area increased under low-light conditions, while leaf mass area was higher in high-light environments, consistent with shade avoidance syndrome and leaf economics spectrum theory. Surprisingly, Rubisco concentration and use efficiency were generally increased under low light, suggesting a compensatory mechanism. Water use efficiency was higher in high-light conditions, but photosynthetic phosphorus and potassium use efficiencies displayed surprising increases under low light. The species exhibited tight coordination between CO2supply and demand, as evidenced by strong correlations between net photosynthesis, stomatal conductance, and carboxylation efficiency. Our findings suggest thatA. rugosaemploys a suite of physiological and morphological adjustments to optimize resource acquisition and utilization that contribute to its ecological success.

Highlight

This study reveals complex adaptive strategies inA. rugosaunder varying light and nutrient levels, showing unexpected patterns in Rubisco dynamics and nutrient use efficiencies while maintaining subtle thermal regulation across environments.
Coordinated control of genome-nuclear lamina interactions by Topoisomerase 2B and Lamin B receptor
Authors: Manzo Stefano G , van Schaik Tom , de Haas Marcel , Breda Jeremie , Magnitov Mikhail , de Wit Elzo , Manjon Anna G , Medema Rene H , Buckle Adam J , Naughton Catherine , Gilbert Nick , van Steensel Bas
Published: October 2024

Lamina-associated domains (LADs) are megabase-sized genomic regions anchored to the nuclear lamina (NL). Factors controlling the interactions of the genome with the NL have largely remained elusive. Here, we identified DNA topoisomerase 2 beta (TOP2B) as a regulator of these interactions. TOP2B binds predominantly to inter-LAD (iLAD) chromatin and its depletion results in a partial loss of genomic partitioning between LADs and iLADs, suggesting that its activity might protect specific iLADs from interacting with the NL. TOP2B depletion affects LAD interactions with lamin B receptor (LBR) more than with lamins. LBR depletion phenocopies the effects of TOP2B depletion, despite the different positioning of the two proteins in the genome. This suggests a complementary mechanism for organising the genome at the NL. Indeed, co-depletion of TOP2B and LBR causes partial LAD/iLAD inversion, reflecting changes typical of oncogene-induced senescence. We propose that a coordinated axis controlled by TOP2B in iLADs and LBR in LADs maintains the partitioning of the genome between the NL and the nuclear interior.

Highlights

LADs and iLADs differ in supercoiling state

TOP2B controls genome partitioning between nuclear lamina and nuclear interior

TOP2B depletion preferentially affects genome interactions with LBR

Similar impact of TOP2B depletion and LBR depletion on genome-NL interactions

Co-depletion of TOP2B and LBR recapitulates LAD reshaping typical of oncogene-induced senescence.
Verifying the concordance between motion corrected and conventional MPRAGE for pediatric morphometric analysis
Authors: Gal-Er Barat , Brackenier Yannick , Bonthrone Alexandra F , Casella Chiara , Price Anthony , Arulkumaran Sophie , Chew Andrew TM , Nosarti Chiara , Cleri Michela , Di Cio Pierluigi , Egloff Collado Alexia , Rutherford Mary , O'Muircheartaigh Jonathan , Tomi-Tricot Raphael , Malik Shaihan , Cordero-Grande Lucilio , Hajnal Joseph V , Counsell Serena J
Published: October 2024

Purpose: To validate a retrospective motion correction technique, Distributed and Incoherent Sample Orders for Reconstruction Deblurring using Encoding Redundancy (DISORDER), for pediatric brain morphometry. Methods: Two T1-weighted MPRAGE 3D datasets were acquired at 3T in thirty-seven children, median age 7.75 years; one with conventional linear phase encoding and one using DISORDER. MPRAGE images were scored as motion-free or motion-corrupt. Cortical morphometry and regional brain volumes were measured with FreeSurfer, subcortical grey matter (GM) with FSL-FIRST, and hippocampal volumes with HippUnfold. Intraclass correlation coefficient (ICC) was used to determine agreement between the 2 MPRAGE acquisitions. Mann-Whitney U was used to test the difference between measures obtained using DISORDER and (i) motion-free and (ii) motion-corrupt conventional MPRAGE data. Results: ICC measures were good/excellent for most subcortical GM (motion-free, 0.75-0.96; motion-corrupt, 0.62-0.98) and regional brain volumes (motion-free 0.47-0.99; motion-corrupt, 0.54-0.99) between conventional MPRAGE and DISORDER data, except for the amygdala and nucleus accumbens (motion-free, 0.38-0.65; motion-corrupt, 0.1-0.42). However, these values were less consistent for motion-corrupt conventional MPRAGE data for hippocampal volumes (motion-free 0.65-0.99; motion-corrupt, 0.11-0.91) and cortical measures (motion-free 0.76-0.98; motion-corrupt, 0.09-0.74). Mann-Whitney U showed percentage differences in measures obtained with motion-corrupt conventional MPRAGE compared to DISORDER data were significantly greater than in those obtained using motion-free conventional MPRAGE data in 22/58 structures. Conclusion: In the absence of motion, morphometric measures obtained using DISORDER are largely consistent with those from conventional MPRAGE data, whereas improved reliability is obtained by DISORDER for motion-degraded scans. This study validates DISORDER for brain morphometric studies in children.
Social facilitation of risky habitats in woodland caribou: responses to fire and roads
Authors: Hendrix Jack Graham , Brown Carissa D , Gosse John , Vander Wal Eric
Published: October 2024

Habitat change and subsequent trophic effects remain the dominant hypothesis for woodland caribou (Rangifer tarandus) population declines. Boreal forests are undergoing rapid changes, including expanding linear features and climate-induced increased wildfire activity. Within these landscapes caribou habitat selection and movement ought to maximize benefits while mitigating costs, e.g. predation risk, but spatial locations are likely not fixed in their cost-benefit ratio. For caribou, costs and benefits may vary seasonally and by social context. To test the effects of season and social context on caribou movement and selection of potentially risky habitats, we used a socially informed integrated step selection analysis (iSSA). We tested responses to two forms of risk in Terra Nova National Park, NL: roads and areas burned 2 - 75 years prior. Caribou avoided areas near roads irrespective of season. Burned area avoidance varied by season and burn age. Caribou avoided roads less and selected burns more in a social context. Social facilitation may permit the use of areas that were functionally unavailable to animals that were not in groups. As the most at-risk populations of woodland caribou exist at low density in highly disturbed landscapes, our results highlight the importance of considering sociality in maintaining access to resources.
UBR-1 deficiency leads to ivermectin resistance inC. elegans
Authors: Li Yi , Gong Long , Wu Jing , Hung Wesley , Zhen Mei , Gao Shangbang
Published: October 2024

Resistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance inCaenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in variousubr-1mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes ofubr-1is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+activity is diminished inubr-1. Additionally, enhancing glutamate uptake inubr-1mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance inC. elegans.
Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses
Authors: Baillet Julie , Klich John H. , Ou Ben S. , Meany Emily L. , Yan Jerry , Bruun Theodora U. J. , Utz Ashley , Jons Carolyn K. , Lecommandoux Sebastien , Appel Eric A.
Published: October 2024

The threat of future coronavirus pandemics requires developing cost-effective vaccine technologies that provide broad and long-lasting protection against diverse circulating and emerging strains. Here we report a multivalent liposomal hydrogel depot vaccine technology comprising the receptor binding domain (RBD) of up to four relevant SARS and MERS coronavirus strains non-covalently displayed on the surface of the liposomes within the hydrogel structure. The multivalent presentation and sustained exposure of RBD antigens improved the potency, neutralizing activity, durability, and consistency of antibody responses across homologous and heterologous coronavirus strains in a naïve murine model. When administrated in animals previously exposed to the wild-type SARS-CoV-2 antigens, liposomal hydrogels elicited durable antibody responses against the homologous SARS and MERS strains for over 6 months and elicited neutralizing activity against the immune-evasive SARS-CoV-2 variant Omicron BA.4/BA.5. Overall, the tunable antigen-decorated liposomal hydrogel platform we report here generates robust and durable humoral responses across diverse coronaviruses, supporting global efforts to effectively respond to future viral outbreaks.

Progress and Potential

Rapidly mutating infectious diseases such as influenza, HIV, and COVID-19 pose serious threats to human health. Yet, most vaccines still do not mount durable protection against mutagenic viruses and fail to induce broad responses to protect against emergent strains. Materials approaches to vaccine design, such as employing sustained delivery approaches or decorating nanoparticle constructs with multiple antigens, have shown promise in improving the breadth and potency of vaccines. Yet, these approaches typically require cumbersome chemistries and have not been explored in pre-exposed populations over clinically relevant time scales. Here, we report the development of an injectable liposomal hydrogel depot technology capable of prolonged presentation of multiple coronavirus antigens non-covalently coordinated on the surface of the liposomes forming the hydrogel structure. These hydrogels improve the potency, durability and breadth of vaccine response and are easy to fabricate, enabling the rapid design of next generation vaccines that confer protection against rapidly evolving pandemics.
Function of the alternative electron transport chain in theCryptosporidium parvummitosome
Authors: Deng Silu , Sibley L. David
Published: October 2024

Cryptosporidium parvum and C. hominispossess a remanent mitochondrion called the mitosome, which lacks DNA, the tricarboxylic acid cycle, a conventional electron transport chain, and ATP synthesis. The mitosome retains ubiquinone and iron sulfur cluster biosynthesis pathways, both of which require protein import that relies on the membrane potential. It was previously proposed that the membrane potential is generated by electrons transferred through an alternative respiratory pathway coupled to a transhydrogenase (TH) that pumps hydrogens out of the mitosome. This pathway relies on an alternative oxidase (AOX) and type II NADH dehydrogenase (NDH2), which also exists in plants, some fungi, and several protozoan parasites. To examine this model, we determined the location and function of AOX and NDH2 inC. parvum. Surprisingly, we observed that NDH2 was localized to parasite surface membranes instead of the mitosome. Furthermore, a Δndh2knockout (KO) strain was readily obtained, indicating that this protein is not essential for parasite growth. Although, AOX exhibited a mitosome-like staining pattern, we readily obtained an Δaoxknockout strain, indicating that AOX is also dispensable for parasite growth. The growth of the Δaoxstrain was inhibited by the AOX inhibitors SHAM and 8-HQ to the same extent as wild type, indicating that AOX is not the target of these inhibitors inC. parvum. Collectively, our studies indicate that NDH2 and AOX are non-essential genes inC. parvum, necessitating an alternative mechanism for maintaining the mitosome membrane potential.

Importance

Cryptosporidiosis is the leading cause of diarrhea in young children and immunocompromised individuals, particularly AIDS/HIV patients. The only FDA approved drug against cryptosporidiosis, nitazoxanide, has limited effectivity in immunocompromised patients and is not approved for usage in children under 1 year old. Genomic analysis and previous studies proposed an alternative respiration pathway involving alternative oxidase (AOX) and type II NAD(P)H dehydrogenase (NDH2), which are thought to generate the mitosome membrane potential inC. parvum. Additionally, AOX and NDH2 were nominated as potential drug targets, based on their absence in mammalian hosts and sensitivity of parasite growth to known inhibitors of AOX. However, our study demonstrated that NDH2 is not localized in mitosome, AOX non-essential for parasite growth, and knockout lines lacking this enzyme are equally sensitive to AOX inhibitors. These findings indicate that AOX and NDH2 are not ideal candidates for future drug development against cryptosporidiosis and force a re-evaluation for models of how the mitosome generate its membrane potential.
Epigenome profiling identifies H3K27me3 regulation of extra-cellular matrix composition in human corticogenesis
Authors: Ditzer Nora , Senoglu Ezgi , Schütze Theresa M. , Nikolaidi Aikaterina , Kolodziejczyk Annika , Sameith Katrin , Dietz Sevina , Derihaci Razvan P. , Birdir Cahit , Eugster Anne , Karl Mike O. , Dahl Andreas , Wimberger Pauline , Baenke Franziska , Peitzsch Claudia , Albert Mareike
Published: October 2024

Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodelling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass cytometry-based approach for the simultaneous single cell analysis of more than 30 epigenetic marks. We identify H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), as the modification with the strongest cell type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation towards differentiation. Cell type- specific profiling of H3K27me3 not only identified neuronal differentiation genes in the human neocortex, but also extra-cellular matrix (ECM) genes. PRC2 inhibition resulted in increased production of the proteoglycan Syndecan 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.
Synthetic cell-based tissues for bottom-up assembly of artificial lymphatic organs
Authors: Burgstaller Anna , Lopez Lopez Erick Angel , Staufer Oskar
Published: October 2024

Synthetic cells have emerged as novel biomimetic materials for studying fundamental cellular functions and enabling new therapeutic approaches. However, replicating the structure and function of complete tissues as self-organized 3D collectives has remained challenging. Here, we engineer lymph node-mimicking 3D lymphatic bottom-up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization based on individual synthetic cells. We demonstrate that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. By tuning the lymphBUT micro-organization and metabolic activity, we induce theex vivoexpansion of therapeutic CD8+T cells with an IL-10+/IL-17+regulatory phenotype. Our study highlights the functional integration of living and non-living matter, advancing synthetic cell engineering toward 3D tissue structures.
A fucose-binding superlectin fromEnterobacter cloacaewith high Lewis and ABO blood group antigen specificity
Authors: Beshr Ghamdan , Sikandar Asfandyar , Gläser Julia , Fares Mario , Sommer Roman , Wagner Stefanie , Köhnke Jesko , Titz Alexander
Published: October 2024

Bacteria frequently employ carbohydrate-binding proteins, so-called lectins, to colonize and persist in a host. Thus, bacterial lectins are attractive targets for the development of new antiinfectives. To find new potential targets for antiinfectives against pathogenic bacteria, we searched for homologs ofPseudomonas aeruginosalectins and identified homologs of LecA inEnterobacterspecies. Here, we recombinantly produced and biophysically characterized a homolog that comprises one LecA domain and one additional novel protein domain. This protein was termedEnterobacter cloacaelectin A (EclA) and found to bind L-fucose. Glycan array analysis revealed a high specificity for the LewisA antigen and the type II H-antigen (blood group O) for EclA, while related antigens LewisX, Y, and B as well as blood group A or B were not bound. We developed a competitive binding assay to quantify blood group antigen binding specificity in solution. Finally, the crystal structure of EclA could be solved in complex with methyl α-L-selenofucoside. It revealed the unexpected binding of the carbohydrate ligand to the second domain, which comprises a novel fold that dimerizes via strand-swapping resulting in an intertwined beta sheet.
Arthropod Diversity at Two Sites with Different Disturbance Levels at the Texas A&M International University
Authors: Siller Eduardo
Published: October 2024

This research aimed to measure arthropod species richness in two different sites with different disturbance levels in the Texas A&M International University campus to determine the overall biological diversity of the two sites and compare these measurements. As part of the research and methods, the Paleontological Statistics (PAST) software was used to calculate statistical indices in ecology that can help determine the difference between East and South sites. Some indices employed were the Shannon’s Diversity Index or the Simpson’s Index of Diversity, the Bray-Curtis matrix, and the iNaturalist app. Results showed that the abundance of arthropods differed significantly from one site to the other, with the South site having a greater quantity, which was the site with less degradation created by humans. The site with the degraded ecosystem (East site) did not show a clear disadvantage regarding the diversity of arthropods. Thus, this article is relevant considering abundance and diversity to discover which is more important in each location. Finally, the study provides more insight into the arthropod community in the South Texas region, which can help with land and ecosystem management.
Trafficking and translation of mRNA in osteocyte dendrites
Authors: Mazur Courtney M. , Kotsalidis Parthena E. , Castro Andrade Christian D. , Wu Mingrui , Wang Xiao , Taliaferro J. Matthew , Wein Marc N.
Published: October 2024

Osteocyte dendrites extend great distances through canaliculi in bone supported by an extensive cytoskeletal network. The formation and maintenance of osteocyte dendrites is closely linked to bone health, yet the mechanisms regulating these processes are poorly understood. Here we tested the hypothesis that osteocytes transport mRNA to their dendrites for local translation as a mechanism of regulating the formation and maintenance of these subcellular structures. Using molecular and imaging approaches, we demonstrated that a subset of mRNAs are enriched in Ocy454 osteocyte-like cell dendrites. To understand how certain mRNAs are directed to dendrites, we performed a massively parallel reporter assay with 7115 oligonucleotide sequences designed from the 3’ untranslated regions of eight dendrite-enriched transcripts. We identified localization sequences within some 3’UTRs that were both sufficient and necessary for trafficking to osteocyte dendrites, indicating that localization directions are specifically encoded in enriched transcripts. Furthermore, we found that dendrites contain the elements necessary for local translation, and trafficked transcripts were engaged in active translation within dendrites. Together this work describes a molecular regulatory mechanism novel to osteocyte biology with many potential consequences for the spatiotemporal control of the cytoskeleton and dendrites.