bluuebunny/crossref_metadata_2025 huggingface dataset:
Technical Advances Drive the Molecular Understanding of Effectors from Wheat and Barley Powdery Mildew Fungi
Authors: Bilstein-Schloemer Merle , Müller Marion C. , Saur Isabel M. L.
Published: January 2025

Pathogens manipulate host physiology through the secretion of virulence factors (effectors) to invade and proliferate on the host. The molecular functions of effectors inside plant hosts have been of interest in the field of molecular plant-microbe interactions. Obligate biotrophic pathogens, such as rusts and powdery mildews, cannot proliferate outside of plant hosts. In addition to the inhibition of the plant’s immune components, these pathogens are under particular pressure to efficiently extract nutrients from the host. Understanding the molecular basis of infections mediated by obligate biotrophic pathogens is of significance because of their impact in modern agriculture. In addition, powdery mildews serve as excellent models for obligate biotrophic cereal pathogens. Here, we summarise the current knowledge on the effectorome of the barley and wheat powdery mildews and putative molecular virulence functions of effectors. We emphasise the availability of comprehensive genomic, transcriptomic and proteomic resources and discuss the methodological approaches used for identifying candidate effectors, assessing effector virulence traits and identifying effector targets in the host. We highlight established and more recently employed methodologies, discuss limitations and suggest additional strategies. We identify open questions and discuss how addressing them with current available resources will enhance our understanding of Blumeria CSEPs.
Black Shank Official Variety Test, Edgecombe County, North Carolina, 2024
Authors: Ahumada Daisy , Lainfiesta Palomo Maria Fernanda
Published: January 2025

Black shank, caused by the oomycete pathogen Phytophthora nicotianae, is among the most devastating diseases of flue-cured tobacco in tobacco producing regions throughout the world. Symptoms include yellow, wilting, blackening and discing of the pith, and plant death. This report evaluates the resistance of flue-cured varieties to black shank. The trial was conducted in 2024 in a black shank nursery in Rocky Mount, NC. Results from these trials will help advise tobacco growers in developing integrated management programs for this disease.
Commercial sugar beet cultivars evaluated for rhizomania resistance and storability in Idaho, 2023
Authors: Strausbaugh Carl A. , Majumdar Raj , Vincill Eric
Published: January 2025

Rhizomania caused by Beet necrotic yellow vein virus (BNYVV) and storage losses caused by fungal root rots are serious sugar beet production problems. Rhizomania leads to small wine glass shaped roots with excessive root hairs and upright and narrow yellow leaves. The fungal growth of Botrytis, Penicillium, and Athelia-like fungi on the root surface leads to black lesions on the root surface and sucrose loss. Thus, commercial sugar beet cultivars were evaluated for resistance to BNYVV during the 2023 growing season and for storage rots during the subsequent storage season in southern Idaho. The study identified the commercial sugar beet cultivars with resistance to BNYVV and storage rots in order to help growers select the best cultivars for increasing yield and profits.
Evaluation of cotton foliar fungicides against target spot and areolate mildew in North Carolina, 2024
Authors: Ahumada Daisy , Lainfiesta Palomo Maria Fernanda , Phillips Michael
Published: January 2025

Target spot, caused by the fungal pathogen Corynespora cassiicola, and areolate mildew, caused by the fungal pathogen Ramulariopsis gossypii, are two emerging diseases of cotton in cotton production regions of the Southeast United States. While symptoms of target spot are brown, concentric lesions on leaves, and signs of areolate mildew are white, powdery growth on the underside of leaves, both diseases may cause early defoliation when infections are severe. This report evaluates the efficacy of conventional fungicide programs for the management of target spot and areolate mildew. The trial was conducted in 2024 in Rocky Mount, NC. Results from these trials will help advise cotton producers in developing management programs for these diseases.
Defining Successful Radiographic Physeal Arrest: A Comparison Between Ulnar Epiphysiodesis With and Without a Sliding Bone Autograft
Authors: Campbell Tanner R. , Wallace C. Douglas , Curran Patrick F. , Bomar James D. , Edmonds Eric W.
Published: January 2025

Background:

Distal radius physeal injuries can result in growth arrest and progressive deformity in children. Ulnar epiphysiodesis may be used to prevent deformity in the skeletally immature child; however, predicting success may be challenging. The purpose of this study was to (1) develop a method to predict successful ulnar epiphysiodesis, and (2) determine the utility of adding a sliding bone autograft as an adjunct to achieving successful epiphysiodesis.

Methods:

A radiographic assessment of children who underwent isolated ulnar epiphysiodesis for premature radial physeal closure at a single institution was performed, evaluating ulnar variance measurements pre-op, immediate post-op, time of physeal arrest, and final ulnar variance. Surgical technique, including ulnar epiphysiodesis with and without adjunctive sliding bone autograft, was recorded to develop two cohorts to compare the duration of successful physeal closure based on the methodology developed.

Results:

Eighty-seven wrists met the criteria (age 14.1±1.3 y) with an overall radiographic success of 99% with a mean radiographic follow-up of 6.6±5.9 months. Fifty-four wrists had repeat radiographs after defined radiographic physeal closure to confirm that when >50% of the ulnar physis demonstrated bridging bone formation, there was a longitudinal cessation of growth in 100% of these patients. Forty-five children had ulnar epiphysiodesis without bone graft, and 42 had ulnar epiphysiodesis with adjunct sliding bone autograft. Time to radiographic physeal arrest in the sliding bone autograft cohort was 1.3±0.7 (0.6 to 3.7) months compared with those without a bone graft of 2.9±2.2 (0.7 to 8.3) months; P<0.001.

Conclusions:

Greater than 50% of opacity across the ulnar physis reliably indicates a successful arrest following ulnar epiphysiodesis. Although the adjunct of a sliding bone autograft did not significantly change the ability to achieve an arrest, it did reduce the duration of time to achieve the arrest. The metric of 50% opacity as a marker for successful cessation of growth can be adapted to limit additional follow-up radiographs. Ulna epiphysiodesis with adjunct sliding bone autograft can be employed when faster cessation is needed.

Level of Evidence:

Level III—comparative study.
Sodium, the Vascular Endothelium, and Hypertension: A Narrative Review of Literature
Authors: Flores Jackeline , Nugent Kenneth
Published: January 2025

The vascular endothelium and its endothelial glycocalyx contribute to the protection of the endothelial cells from exposure to high levels of sodium and help these structures maintain normal function by regulating vascular permeability due to its buffering effect. The endothelial glycocalyx has negative surface charges that bind sodium and limit sodium entry into cells and the interstitial space. High sodium levels can disrupt this barrier and allow the movement of sodium into cells and extravascular fluid. This can generate reactive oxygen species that inhibit nitric oxide production. This leads to vasospasm and increases intravascular pressures. Overtime vascular remodeling occurs, and this changes the anatomy of blood vessels, their intrinsic stiffness, and their response to vasodilators and results in hypertension. Patients with increased salt sensitivity are potentially at more risk for this sequence of events. Studies on the degradation of the glycocalyx provide insight into the pathogenesis of clinical disorders with vascular involvement, but there is limited information available in the context of higher concentrations of sodium. Data on higher intake of sodium and the imbalance between nitric oxide and reactive oxygen species have been obtained in experimental studies and provide insights into possible outcomes in humans. The current western diet with sodium intake above recommended levels has led to the assessment of sodium sensitivity, which has been used in different populations and could become a practical tool to evaluate patients. This would potentially allow more focused recommendations regarding salt intake. This review will consider the structure of the vascular endothelium, its components, the effect of sodium on it, and the use of the salt blood test mini.
Quantifying Tumor Budding
Authors: Lian Jie , Zhang Wenwen , Wang Chunbao , Zhang Yun , Wang Luyang , Nan Pengfei , Li Xuqi
Published: January 2025

The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6–10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.
Clinicopathologic and Molecular Characterization of Basal Cell Carcinoma Arising at Sun-protected Sites
Authors: Draper Elizabeth , Li Yvonne Y. , Mahadevan Navin R. , Laga Alvaro C. , Hanna John , Russell-Goldman Eleanor
Published: January 2025

Basal cell carcinomas (BCC) are driven primarily by cumulative ultraviolet (UV) radiation exposure resulting in activation of the Hedgehog (Hh) signaling pathway, often as a result of UV-mediated Patched-1 (PTCH1) gene inactivation. Accordingly, BCCs most commonly arise at sun-exposed sites such as the head and neck. Very rarely, BCCs can arise at sun-protected sites such as the genital skin and perianal area. This can pose significant diagnostic challenges not only due to the rarity of BCC at these sites but also due to the potential morphologic overlap with other entities such as basaloid squamous cell carcinoma, trichoblastic carcinoma, and even benign neoplasms such as trichoblastomas. Hh pathway alterations have not yet been described in BCCs arising at genital and perianal sites, and the role of UV radiation is uncertain at these anatomic locations. To address this ambiguity, we report the clinicopathologic features of a cohort of 14 BCCs arising at sun-protected sites (perianal n=7, vulva n=4, scrotum n=3). Furthermore, we use a next-generation DNA sequencing platform to investigate their pathogenesis and compare it to that of a cohort of 8 BCCs arising on sun-exposed skin. We find that BCCs arising on sun-protected sites display a spectrum of morphologic patterns, rarely recur, and do not metastasize. Both sun-protected and sun-exposed BCCs are characterized by recurrent PTCH1 alterations (93% and 100% of cases, respectively), supporting the classification of the tumors arising at sun-protected sites as bona fide BCCs. Notably, in contrast to conventional BCCs, none of the sun-protected BCCs harbored a UV mutation signature, suggesting an alternative mechanism of mutagenesis. Furthermore, the presence of upstream Hh pathway alterations in sun-protected BCCs supports their susceptibility to Hh pathway inhibitors such as vismodegib and sonidegib.
The Role of White Matter Integrity and Neuroplasticity in Stroke Recovery: Insights from DTI and VBM
Authors: Zhang Rongjun , Gong Zhigang , Jiang Wenbing , Su Zhaofeng
Published: January 2025

Background

Stroke is a leading cause of disability, significantly affecting the brain’s white and gray matter. Advanced neuroimaging techniques like Diffusion Tensor Imaging (DTI) and Voxel-Based Morphometry (VBM) offer valuable insights into these structural changes.

Methods

This study used Tract-Based Spatial Statistics (TBSS) to evaluate white matter integrity in stroke patients using DTI metrics, including Fractional Anisotropy (FA) and Mean Diffusivity (MD). VBM was employed to assess gray matter volume and cortical thickness. Correlation analyses were performed between imaging metrics and clinical scores, such as the NIH Stroke Scale (NIHSS) and Brunnstrom scores.

Results

TBSS analysis showed significant reductions in FA (globus pallidus: t = −4.71, p < 0.001; caudate nucleus: t = −4.20, p < 0.001) and increases in MD (globus pallidus: t = 3.96, p < 0.001; caudate nucleus: t = 3.85, p < 0.001) in stroke patients compared to controls. These changes correlated significantly with clinical outcomes; higher FA and lower MD were linked to better motor function (Brunnstrom score: r = 0.90, p < 0.001 for FA in globus pallidus) and lower stroke severity (NIHSS score: r = −0.91, p < 0.001 for FA in globus pallidus). VBM analysis revealed significant gray matter volume increases in the anterior cingulate cortex (t = 4.71, p < 0.05, FWE-corrected) and six other regions at p < 0.001.

Conclusion

The study underscores the importance of white matter integrity in post-stroke recovery and highlights neuroplasticity in specific brain regions. Advanced neuroimaging metrics like FA, MD, and gray matter volume are crucial for assessing stroke severity and guiding rehabilitation strategies.
A gut pathobiont regulates circulating glycine and host metabolism in a twin study comparing vegan and omnivorous diets
Authors: Carter Matthew M. , Zeng Xianfeng , Ward Catherine P. , Landry Matthew , Perelman Dalia , Hennings Tayler , Meng Xiandong , Weakley Allison M. , Cabrera Ashley V. , Robinson Jennifer L. , Nguyen Tran , Higginbottom Steven , Maecker Holden T. , Sonnenburg Erica D. , Fischbach Michael A. , Gardner Christopher D. , Sonnenburg Justin L.
Published: January 2025

Metabolic diseases including type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, including vegan diets, are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In a randomized trial involving 21 pairs of identical twins, we investigated the effects of vegan and omnivorous diets on the host metabolome, immune system, and gut microbiome. Vegan diets induced significant shifts in serum and stool metabolomes, cytokine profiles, and gut microbial composition. Despite lower dietary glycine intake, vegan diet subjects exhibited elevated serum glycine levels linked to reduced abundance of the gut pathobiontBilophila wadsworthia. Functional studies demonstrated thatB. wadsworthiametabolizes glycine via the glycine reductase pathway and modulates host glycine availability. RemovingB. wadsworthiafrom a complex microbiota in mice elevated glycine levels and improved metabolic markers. These findings reveal a previously underappreciated mechanism by which diet regulates host metabolic status via the gut microbiota.
Collagen Hydrogel Tube Microbioreactors for Cell and Tissue Manufacturing
Authors: Yang Yakun , Wu Xinran , Pan Ying , Wang Yong , Lian Xiaojun , Dong Cheng , Liu Wansheng , Wang Shue , Lei Yuguo
Published: January 2025

The production of mammalian cells in large quantities is essential for various applications. However, scaling up cell culture using existing bioreactors poses significant technical challenges and high costs. To address this, we previously developed an innovative 3D culture system, known as the AlgTube cell culture system, for high-density cell cultivation. This system involves processing cells into microscale alginate hydrogel tubes, which are suspended in the culture medium within a vessel. These hydrogel tubes shield cells from hydrodynamic stress and maintain the cell mass below 400 µm in diameter, facilitating efficient mass transport and creating a favorable microenvironment for cell growth. Under optimized conditions, AlgTubes supported long-term culture with high cell viability, rapid expansion (1000-fold increase over 9 days per passage), and high yield (5×10⁸ cells/mL), offering significant advantages over conventional methods. Despite these benefits, AlgTubes have critical drawbacks. They are mechanically fragile, with frequent breakage during culture leading to cell leakage and production failures. Additionally, many cell types exhibit poor growth due to the inability to adhere to the alginate surface, making alginate hydrogel microtubes unsuitable for industrial-scale cell production. To overcome these challenges, we developed a novel collagen hydrogel tube-based microbioreactor system in this work. This system provides enhanced robustness and adhesion, enabling scalable, cost-effective, and efficient cell production for a wide range of applications.
Programmable Assembly and Steering of Microbubble Droplets using Ultrasound
Authors: Fonseca Alexia Del Campo , Gautam Kshetri Khemraj , Boev Dimitar , Irniger Nathan , Nama Nitesh , Ahmed Daniel
Published: January 2025

Gas-filled microbubbles have been extensively used as contrast agents for ultrasound therapies and have recently been explored as microrobots. When exposed to an intense acoustic wave, microbubbles oscillate and scatter the sound field, leading to assembly and manipulation behaviors. Although traditional microbubbles demonstrated promising potential for manipulation in physiological environments, we recognized the need for improved assembly selectivity and acoustically directed propulsion. For this, we developed a new microbubble design using microfluidics. We engineered microbubbles with an outer oil droplet encapsulating a gas core, allowing the gas to move freely within the oil. When the gas reaches the droplet’s periphery, the oil attenuates the scattered wave, ensuring that scattering or acoustic amplification is concentrated near the droplet’s edge. This approach enabled us to control the organized assembly of microbubbles and direct their acoustic navigation. We believe this approach will open new possibilities for using gas-filled microbubbles as safer drug carriers or for micro-interventions in biomedical settings.
Effects of a temperate heatwave on diel rhythms of insect activity: a comparison across habitats
Authors: Carter J.A. , Davies R.G. , Nash W.J. , Morris R.K.A.
Published: January 2025

The increasing frequency and intensity of heatwave events in temperate climates threatens to alter behavioural rhythms of ectothermic animals, such as insects. However, it is poorly understood how heatwaves affect daily activity patterns of insects, and whether shaded microclimates can moderate these responses.

We investigated impacts of a heatwave on the diel profile of insect activity, comparing effects across open, tree-covered and hedged habitats. Using yellow pan traps, insect activity was monitored from 07:00 to 19:00 on ten non-consecutive days, including two during a heatwave.

Insect counts exhibited a unimodal relationship with temperature.

During heatwave days, open habitat exhibited a significant (∼81.9%) reduction in counts compared to two ‘non-heatwave’ field-days, one before and one after the heatwave. Smaller, non-significant reductions were observed in the tree-covered (38.3%) and hedged (17.8%) habitats.

The diel activity profile on non-heatwave days approximated to a unimodal relationship, with GLMM-estimated counts peaking around 15:00; by contrast, heatwave days exhibited a bimodal profile, with predicted counts highest in the morning and evening.

Such heatwave-induced deformations of activity patterns, modelled as interactions between heatwave and time-of-day, were significant across all three habitat types.

The findings suggest that temperate heatwaves can markedly decrease insect activity levels, and that whilst shade-providing vegetational features may reduce this effect, diel patterns of activity are affected landscape-wide. As heatwaves become more frequent, preservation of trees and hedges in temperate landscapes is likely crucial to support resilience of insect activity and wider ecosystem functioning.
Correlation between circadian and photoperiodic latitudinal clines inDrosophila littoralis
Authors: Manoli Giulia , Lankinen Pekka , Bertolini Enrico , Helfrich-Förster Charlotte
Published: January 2025

Insects can survive harsh conditions, including Arctic winters, by entering a hormonally induced state of dormancy, known as diapause. Diapause is triggered by environmental cues such as shortening of the photoperiod (lengthening of the night). The time of entry into diapause depends on the latitude of the insects’ habitat, and this applies even within a species: populations living at higher latitudes enter diapause earlier in the year than populations living at lower latitudes. A long-standing question in biology is whether the internal circadian clock, which governs daily behaviour and serves as a reference clock to measure night length, shows similar latitudinal adaptations. To address this question, we examined the onset of diapause and various behavioural and molecular parameters of the circadian clock in the cosmopolitan fly,Drosophila littoralis,a species distributed throughout Europe from the Black Sea (41°N) to arctic regions (69°N). We found that all clock parameters examined showed the same correlation with latitude as the critical night length for diapause induction. We conclude that the circadian clock has adapted to the latitude and that this may result in the observed latitudinal differences in the onset of diapause.
Experimental validation of genome-environment associations in Arabidopsis
Authors: Luo Yuxin , Lorts Claire , Lawrence-Paul Erica , Lasky Jesse
Published: January 2025

Identifying the genetic basis of local adaptation is a key goal in evolutionary biology. Allele frequency clines along environmental gradients, known as genotype-environment associations (GEA), are often used to detect potential loci causing local adaptation, but GEA are rarely followed by experimental validation. Here, we tested loci identified in three different moisture-related GEA studies on Arabidopsis. We studied 44 GEA-identified genes using t-DNA knockout lines under drought and tested for effects on flowering time, an adaptive trait, and genotype-by-environment (GxE) interactions on performance and fitness. We found that wrky38 mutants had significant GxE effects for fitness; lsd1 plants had a significant GxE effect for flowering time, while 11 genes showed flowering time effects with no drought interaction. However, most GEA candidates did not exhibit GxE. In the follow-up experiments we found wrky38 caused decreased stomatal conductance and specific leaf area under drought, indicating potentially adaptive drought avoidance. Additionally, we found that GEA identified natural putative LoF variants of WRKY38 associated with dry environments, as well as alleles associated with variation in LSD1 expression. While only a few GEA putative drought-adapted genes were validated for GxE interactions for fitness under drought, we likely overlooked some genes because experiments might not well represent natural environments and t-DNA insertions might not well represent natural alleles. Nevertheless, GEAs apparently identified some genes contributing to local adaptation. GEA and follow-up experiments are straightforward to implement in model systems and thus demonstrate prospects for GEA discovery of new local adaptations.
Host avoidance and resistance vary independently and are specific to parasite genotype
Authors: Amoroso Caroline R. , Lockwood-Shabat Adianna , Kamali Andreas , Gibson Amanda K.
Published: January 2025

Hosts can reduce the negative fitness effects of parasite infection by avoiding contact with parasites or by resisting infection after contact. Because of their shared outcome, avoidance and resistance have been hypothesized to trade off with one another. Assuming these defenses carry fitness costs, hosts are expected to have high levels of one defense or the other, but not both. Alternatively, avoidance and resistance may covary positively, if, for example, they complement one another or are genetically or mechanistically linked. Testing these hypotheses requires measuring avoidance and resistance independently, which is challenging because they are functionally linked. In this study, we separated avoidance and resistance of the hostC. elegansagainst the bacterial parasiteS. marcescensand tested for a correlation between them. We phenotyped a panel of 12 genetically divergent hosts using two distinct bacterial strains and multiple experimental contexts. We found no evidence of a correlation between avoidance and resistance. This result suggests that avoidance and resistance can covary independently. Moreover, we found strong genetic specificity not only for resistance, but also for a measure of avoidance, motivating further research to examine the coevolutionary dynamics of avoidance.
Flipping the switch on some of the slowest mutating genomes: Direct measurements of plant mitochondrial and plastid mutation rates inmsh1mutants
Authors: Broz Amanda K. , Hodous Mychaela M. , Zou Yi , Vail Patricia C. , Wu Zhiqiang , Sloan Daniel B.
Published: January 2025

Plant mitochondrial and plastid genomes have exceptionally slow rates of sequence evolution, and recent work has identified an unusual member of theMutSgene family (“plantMSH1”) as being instrumental in preventing point mutations in these genomes. However, the eXects of disruptingMSH1-mediated DNA repair on “germline” mutation rates have not been quantified. Here, we usedArabidopsis thalianamutation accumulation (MA) lines to measure mutation rates inmsh1mutants and matched wild type (WT) controls. We detected 124 single nucleotide variants (SNVs: 49 mitochondrial and 75 plastid) and 668 small insertions and deletions (indels: 258 mitochondrial and 410 plastid) inmsh1MA lines. In striking contrast, we did not find any organelle mutations in the WT MA lines, and reanalysis of data from a much larger WT MA experiment also failed to detect any variants. The observed number of SNVs in themsh1MA lines corresponds to estimated mutation rates of 6.1ξ10-7and 3.2 ξ10-6per bp per generation in mitochondrial and plastid genomes, respectively. These rates exceed those of species known to have very high mitochondrial mutation rates (e.g., nematodes and fruit flies) by an order of magnitude or more and are on par with estimated rates in humans despite the generation times ofA. thalianabeing nearly 100-fold shorter. Therefore, disruption of a single plant-specific genetic factor inA. thalianais suXicient to erase or even reverse the enormous diXerence in organelle mutation rates between plants and animals.
SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway
Authors: Yang Hua , Cheung Pak-Hin Hinson , Wu Li
Published: January 2025

Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) inhibits HIV-1 replication in non-dividing cells by reducing the intracellular dNTP pool. SAMHD1 enhances spontaneous apoptosis in cells, but its effects on HIV-1-induced apoptosis and the underlying mechanisms remain unknown. Here we uncover a new mechanism by which SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells through the mitochondrial pathway. We found that endogenous SAMHD1 enhances apoptosis levels induced by HIV-1 infection in dividing THP-1 cells. Mechanistically, SAMHD1 expression decreases the mitochondrial membrane potential and promotes cytochrome c release induced by HIV-1 infection in THP-1 cells, thereby enhancing mitochondrial apoptotic pathway. SAMHD1-enhanced apoptosis is associated with increased expression of the pro-apoptotic protein BCL-2-interacting killer (BIK) in cells. We further demonstrated that BIK contributes to SAMHD1-enhanced apoptosis during HIV-1 infection. Overall, our results reveal an unappreciated regulatory mechanism of SAMHD1 in enhancing HIV-1-induced apoptosis via the mitochondrial pathway in monocytic cells.
Determinants of contraceptive use and intention to use among youth 15-24 years in Karamoja, Uganda
Authors: Ojanduru Lillian , Siu Godfrey , Bukenya Justine , Tumwesigye Nazarius. M.
Published: January 2025

Background

Globally, contraceptive use among young people aged 15-24 years is low with a prevalence lower than 21% yet contraceptive use reduces the likelihood of high-risk and unintended pregnancies. In Uganda, nearly a quarter (24%) of girls aged 15-19 years have either been pregnant or given birth, mainly attributed to non-use of contraceptives which is so low at 10% in Karamoja. In response the study aimed to assess determinants of contraceptive use and intention to use in Karamoja region

Methods

This was a quantitative study with a sample size of 448 youth (women and men 15-24 years). Of these,409 were sexually active (had sex within the last 12 months) and included in our analysis. Modified Poisson model that incorporated sampling weights was used to establish the factors associated with contraceptive use, and intention to use.

Results

About 41.6% (49.3% males and 32.6% females) had ever used a contraceptive. only 11.0% (16.3% women and 6.4% men) were currently using a contraceptive and about 72.4% (84% males and 59% females) intended to use contraception. Youths with secondary education had higher prevalence rate for ever use of contraceptives by 32% and 25% for females and males respectively than those with no education. Females who had a paid job were 4.5 times (APR=4.51, 95%CI: 3.80-5.36) and males were 1.6 times (APR=1.6, 95% CI: 1.26-1.92) more likely to use contraceptives while the prevalence of intention to use was higher among those who had a job by 5.7 times (APR=5.75, 95%CI: 4.94-6.69) for females and 2.3 times (APR=2.25, 95%CI: 1.76-2.89) for males. Never married females were 3.1 times (APR=3.09, 95%CI: 2.39-3.99) more likely to use contraceptives than married females. Females who had children 1.6 times (APR=1.46, 95% CI: 1.18-1.81) and males 7.4 times (APR=7.4, 95% CI: 4.74-11.69) more like to have ever used a contraceptive.

Conclusion

The factors positively associated with use of contraceptives and intention to use were age (being older, 20-24 year), marital status, having biological children, attaining secondary education level, living with biological parents and having a job and all these varied by gender. The study recommends improving access to education and employment opportunities for youth, involving parents in young people’s SRH, and targeting male youth with interventions to improve contraceptive use.
Extracellular matrix mechanical cues (dys)regulate metabolic redox homeostasis due to impaired autophagic flux
Authors: Gerardo Heloísa , Lourenço Tânia , Torres Júlio , Ferreira Manuela , Aveleira Célia , Simões Susana , Ferreira Lino , Cavadas Cláudia , Oliveira Paulo J. , Teixeira José , Grãos Mário
Published: January 2025

Extracellular matrix (ECM) stiffness is increasingly recognized as a critical regulator of cellular behavior, governing processes such as proliferation, differentiation, and metabolism. Neurodegenerative diseases are characterized by mitochondrial dysfunction, oxidative stress, impaired autophagy, and progressive softening of the brain tissue, yet research into how mechanical cues influence cellular metabolism in this context remains scarce. In this study, we evaluated the long-term effects of brain-compliant, soft ECM on mitochondrial bioenergetics, redox balance, and autophagic capacity in neuronal cells. Using human neuroblastoma (SH-SY5Y) and mouse hippocampal (HT22) cell lines, as well as primary mouse neurons, we observed that prolonged exposure to soft ECM resulted in mitochondrial bioenergetic dysfunction, redox imbalance, and disrupted autophagic flux. These findings were consistently validated across both human and mouse neuronal cells. Our data indicate a decreased maximal autophagic capacity in cells exposed to long-term soft ECM, potentially due to an imbalance in autophagosome formation and degradation, as demonstrated by decreased LC3 II levels following chloroquine-induced autophagic flux inhibition. This impairment in autophagy was coupled with increased cellular oxidative stress, further indicating metabolic alterations. These findings emphasize the critical role of ECM stiffness in regulating neuronal cell metabolism and suggest that prolonged exposure to soft ECM may mimic key aspects of neurodegenerative disease pathology, thereby enhancing the physiological relevance ofin vitromodels. This study underscores the necessity for further research into ECM mechanics as a contributing factor in neurodegenerative disease progression and as a potential target for therapeutic strategies.
Optimizing dsRNA sequences for RNAi in pest control and research with the dsRIP Web-Platform
Authors: Cedden Doga , Güney Gözde , Rostás Michael , Bucher Gregor
Published: January 2025

Background

RNA interference (RNAi) is a tool for studying gene function and has emerged as a promising eco-friendly alternative to chemical pesticides. RNAi relies on delivering double-stranded RNA (dsRNA), which is processed into small interfering RNA (siRNA) to silence genes. However, so far, knowledge and tools for optimizing the dsRNA sequences for maximum efficacy are based on human data, which might not be optimal for insects and pest control.

Results

Here, we systematically tested different siRNA sequences in the red flour beetleTribolium castaneumto identify sequence features that correlated with high efficacy using pest control as a study case. Thermodynamic asymmetry, the absence of secondary structures, and Adenine at the 10thposition in antisense siRNA were most predictive of insecticidal efficacy. Interestingly, we also found that in contrast to results from human data, high, rather than low GC content from the 9thto 14thnucleotides of antisense was associated with high efficacy. Consideration of these features for the design of insecticidal dsRNAs targeting essential genes in three insect species improved the efficacy of the treatment. The improvement was associated with a higher ratio of the antisense, rather than sense, siRNA strand bound to the RNA-induced silencing complex. Finally, we developed a web-platform named dsRIP (https://dsrip.uni-goettingen.de), which offers tools for optimizing dsRNA sequences, identifying effective RNAi target genes for pest control, and minimizing risk to non-target species.

Conclusions

The identified sequence features and the dsRIP web-platform allow optimizing dsRNA sequences for both application of RNAi for pest control and research.
TFBSFootprinter: a multiomics tool for prediction of transcription factor binding sites in vertebrate species
Authors: Barker Harlan R. , Parkkila Seppo , Tolvanen Martti E.E.
Published: January 2025

Background

Transcription factor (TF) proteins play a critical role in the regulation of eukaryotic gene expression via sequence-specific binding to genomic locations known as transcription factor binding sites (TFBSs). Accurate prediction of TFBSs is essential for understanding gene regulation, disease mechanisms, and drug discovery. These studies are therefore relevant not only in humans but also in model organisms and domesticated and wild animals. However, current tools for the automatic analysis of TFBSs in gene promoter regions are limited in their usability across multiple species. To our knowledge, no tools currently exist that allow for automatic analysis of TFBSs in gene promoter regions for many species.

Methodology and Findings

The TFBSFootprinter tool combines multiomic transcription-relevant data for more accurate prediction of functional TFBSs in 124 vertebrate species. In humans, this includes vertebrate sequence conservation (GERP), proximity to transcription start sites (FANTOM5), correlation of expression between target genes and TFs predicted to bind promoters (FANTOM5), overlap with ChIP-Seq TF metaclusters (GTRD), overlap with ATAC-Seq peaks (ENCODE), eQTLs (GTEx), and the observed/expected CpG ratio (Ensembl).

TFBSFootprinter analyses are based on the Ensembl transcript ID for simplicity of use and require minimal setup steps. Benchmarking of the TFBSFootprinter on a manually curated and experimentally verified dataset of TFBSs produced superior results when using all multiomic data (average area under the receiver operating characteristic curve, 0.881), compared with DeepBind (0.798), FIMO (0.817) and traditional PWM (0.854). The results were further improved by selecting the best overall combination of multiomic data (0.910). Additionally, we determined combinations of multiomic data that provide the best model of binding for each TF. TFBSFootprinter is available as Conda and Python packages.
Memory engram synapse 3D molecular architecture visualized by cryoCLEM-guided cryoET
Authors: Lovatt Charlie , O'Sullivan Thomas J. , Ortega-de San Luis Clara , Ryan Tomas J. , Frank Rene A. W.
Published: January 2025

Memory is incorporated into the brain as physicochemical changes to engram cells. These are neuronal populations that form complex neuroanatomical circuits, are modified by experiences to store information, and allow for memory recall. At the molecular level, learning modifies synaptic communication to rewire engram circuits, a mechanism known as synaptic plasticity. However, despite its functional role on memory formation, the 3D molecular architecture of synapses within engram circuits is unknown. Here, we demonstrate the use of engram labelling technology and cryogenic correlated light and electron microscopy (cryoCLEM)-guided cryogenic electron tomography (cryoET) to visualize the in-tissue 3D molecular architecture of engram synapses of a contextual fear memory within the CA1 region of the mouse hippocampus. Engram cells exhibited structural diversity of macromolecular constituents and organelles in both pre- and postsynaptic compartments and within the synaptic cleft, including in clusters of membrane proteins, synaptic vesicle occupancy, and F-actin copy number. This "engram to tomogram" approach, harnessing in vivo functional neuroscience and structural biology, provides a methodological framework for testing fundamental molecular plasticity mechanisms within engram circuits during memory encoding, storage and recall.
Why Accuracy Metrics Fall Short in Comparing Phenomic and Genomic Prediction Models
Authors: Wang Fangyi , Feldmann Mitchell J , Runcie Daniel E
Published: January 2025

Phenomic Selection is a new paradigm in plant breeding that uses high-throughput phenotyping technologies and machine learning models to predict traits of new individuals and make selections. This can allow breeders to evaluate more plants in higher throughput more accurately, resulting in faster rates of gain and reduced labor costs. However, Phenomic Prediction models are frequently benchmarked against Genomic Prediction models using cross-validation to demonstrate their usefulness to breeders. We argue that this is inappropriate for two reasons: 1) Differences in the accuracy statistic measured by cross-validation do not reliably indicate differences in the accuracy parameter of the breeder’s equation, and 2) Accuracy alone is insufficient to compare breeding schemes using Phenomic vs. Genomic Prediction because these tools differentially influence other parameters of the breeder’s equation. We show analytically and through re-analysis of data from three representative Phenomic Prediction studies that conclusions about the superiority of Phenomic Prediction over Genomic Prediction change if compared using consistent methods. We conclude that Phenotypic Selection may be useful, but comparisons of accuracy between Genomic Prediction and Phenotypic Prediction models are not.
A Murine Database of Structural Variants Enables the Genetic Architecture of a Spontaneous Murine Lymphoma to be Characterized
Authors: Ren Wenlong , Fang Zhuoqing , Dolzhenko Egor , Saunders Christopher T. , Cheng Zhuanfen , Popic Victoria , Peltz Gary
Published: January 2025

A more complete map of the pattern of genetic variation among inbred mouse strains is essential for characterizing the genetic architecture of the many available mouse genetic models of important biomedical traits. Although structural variants (SVs) are a major component of genetic variation, they have not been adequately characterized among inbred strains due to methodological limitations. To address this, we generated high-quality long-read sequencing data for 40 inbred strains; and designed a pipeline to optimally identify and validate different types of SVs. This generated a database for 40 inbred strains with 573,191SVs, which included 10,815 duplications and 2,115 inversions, that also has 70 million SNPs and 7.5 million insertions/deletions. Analysis of this SV database led to the discovery of a novel bi-genic model for susceptibility to a B cell lymphoma that spontaneously develops in SJL mice, which was initially described 55 years ago. The first genetic factor is a previously identified endogenous retrovirus encoded protein that stimulates CD4 T cells to produce the cytokines required for lymphoma growth. The second genetic factor is a newly found deletion SV, which ablates a protein whose promotes B lymphoma development in SJL mice. Characterizing the genetic architecture of SJL lymphoma susceptibility could provide new insight into the pathogenesis of a human lymphoma that has similarities with this murine lymphoma.
Absolute Quantification of Lysosomal Proteins by Multiple Reaction Monitoring Mass Spectrometry and QconCAT Protein Standards
Authors: Mosen Peter Robert , Moharana Biswajit , Fajardo-Callejon Sofía , Kaade Edgar , Rösel Norbert , Omidi Maryam , Sakson Roman , Ruppert Thomas , Pohl Sandra , Gieselmann Volkmar , Winter Dominic
Published: January 2025

Lysosomes are membrane-enclosed organelles that play a crucial role in the degradation of intra- and extracellular substrates and the regulation of metabolic signaling. These functions are carried out by a variety of proteins, of which > 150 are currently known to be located in the lysosomal lumen or to be embedded in its membrane. These proteins are typically low abundant, necessitating organelle enrichment experiments to enable their investigation by unbiased mass spectrometry-based proteomics analyses. Enrichment strategies have been applied in a plethora of studies to gain a deeper understanding of lysosomal composition and relative changes of lysosomal proteome abundance in a variety of pathological conditions. Such experiments are restricted, however, to selected cell lines and tissues and do not allow a direct analysis of the lysosomal proteome from whole cell or tissue lysates. Furthermore, they do not provide absolute quantities. We developed a multiple reaction monitoring mass spectrometry-based assay for the highly sensitive and reproducible absolute quantification of 143 mouse lysosomal proteins from any type of sample following the QconCAT strategy. We applied our approach to the investigation of mouse embryonic fibroblast whole cell lysates and lysosome-enriched fractions, providing absolute copy numbers per cell/lysosome for lysosomal hydrolases and membrane proteins. These data reveal a dynamic range of more than three orders of magnitude in protein expression and strong differences in the subcellular distribution of individual lysosomal proteins. Furthermore, we applied our strategy to the investigation of four primary cell types (macrophages, lung fibroblasts, osteoblasts, and osteoclasts), demonstrating pathway-specific heterogeneity of individual lysosomal protein classes and indicating protein-specific post-transcriptional regulation of expression levels.
The carrying capacity of a fragmented landscape depends on the home-range size of a species
Authors: Pereira Henrique M. , Daily Gretchen C.
Published: January 2025

Population models have not considered the problem of home-range settlement when the grain of the landscape is smaller than the home-range size. We present an individual-based model addressing this problem that combines age-structured population dynamics, optimal foraging and habitat selection. During home-range settlement each juvenile tries to maximize her fitness, which depends on the proportion of high-quality habitat in her home range. We assume that home ranges do not overlap, which can happen because the home range is defended as a territory or because individuals avoid areas used by conspecifics. We show that the population supported by the landscape at equilibrium, the carrying capacity of the landscape, decreases with the amount of low-quality habitat cover. However, this decrease is non-linear, the carrying capacity starts to decline only below a critical habitat threshold. Furthermore, when the home-range size is larger than the grain of the landscape, the carrying capacity declines faster when the habitat is fragmented. Therefore species with small home-ranges persist in instances where species with large home-ranges go deterministically extinct. Species with large population growth rates have low critical habitat sizes, and are more resilient to habitat conversion.
OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies
Authors: Wang Qinglong , Wang Yiqi , Jiang Yi Da Douglas , Donahue Ryan , Cao Gaby , Yan Weixuan , Guo Hong , Hao Jin , Lu Yi , Wang Qianbin , Tian Feng
Published: January 2025

Optineurin (OPTN) is a crucial component of the homeostatic pathway, playing a pivotal role in regulating a number of essential signaling pathways including NF-κB, interferon, autophagy, and vesicular trafficking. The dysfunction of OPTN has been implicated in the pathogenesis of several diseases, such as primary open angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia, and Paget’s disease of bone. Interestingly, mutations in OPTN are implicated as gain-of-function in glaucoma pathology and loss-of-function in ALS. However, the role of loss-of-function OPTN in glaucoma pathology remains unclear. Here, we demonstrate that OPTN dysfunction contributes to chronic neuroinflammation, leading to sustained RGC death, which may represent a shared pathological mechanism in both normal tension glaucoma (NTG) and high-tension glaucoma (HTG). Retinal conditioned OPTN knockout contributes to short-term astrogliosis and long-term microglia activation, with the propagation of microglia activation spreading to the optic nerve. Moreover, OPTN loss of function does not further exacerbate RGC death in the ocular hypertension mouse model induced by viscobead injection. Combined with the downregulation of OPTN in glaucoma patients, we have revealed an IOP-independent mechanism of glaucoma pathogenesis. Furthermore, we found that OPTN-driven NPY upregulation may suppress the CHOP-associated neurodegeneration. Our findings reveal a neuroprotective role for the OPTN-NPY signaling pathway, and its dysfunction promotes RGC loss in glaucoma pathology. The OPTN-NPY-mediated neuroinflammatory pathway provides a potential therapy for IOP-resistant glaucoma and highlights a druggable target for CHOP-associated neurodegeneration.