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Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments
The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis, a complex process involving hundreds of proteins and RNAs. The proper execution of ribosome biogenesis likely depends on the material properties of the nucleolus. However, these material properties remain poorly understood due to the challenges of in vivo measurements. Here, we use micropipette aspiration (MPA) to directly characterize the viscoelasticity and interfacial tensions of nucleoli within transcriptionally active Xenopus laevis oocytes. We examine the major nucleolar subphases, the outer granular component (GC) and the inner dense fibrillar component (DFC), which itself contains a third small phase known as the fibrillar center (FC). We show that the behavior of the GC is more liquid-like, while the behavior of the DFC/FC is consistent with that of a partially viscoelastic solid. To determine the role of ribosomal RNA in nucleolar material properties, we degrade RNA using RNase A, which causes the DFC/FC to become more fluid-like and alters interfacial tension. Together, our findings suggest that RNA underlies the partially solid-like properties of the DFC/FC and provide insights into how material properties of nucleoli in a near-native environment are related to their RNA-dependent function.
From waste to feed: In vitro assessment of spent silkworm by-products and manure-raised housefly as soybean meal substitutes in ruminant feed
Viral and host network analysis of the human cytomegalovirus transcriptome in latency
The human cytomegalovirus (HCMV) UL135 and UL138 genes play opposing roles regulating latency and reactivation in CD34 + human progenitor cells. We designed an RNA sequencing study to compare the transcriptional profile of HCMV infection in the presence and absence of these genes using the Tohoku Hospital Pediatrics-1 (THP-1) monocytic cell line model for latency. Relative to primary cell models, THP-1 cells offer the strength of a homogenous population that uniformly silences gene expression and will synchronously reexpress viral genes following stimulation to differentiate, which models early phases of viral reactivation. The loss of UL138 resulted in elevated levels of viral gene expression and in spontaneous adhesion of distinct cell populations that support HCMV gene expression and genome synthesis. The loss of UL135 resulted in diminished viral gene expression during an initial burst that occurs as latency is established and in no expression of eleven viral genes from the UL b ′ region even following differentiation and reexpression of viral genes. Transcriptional network analysis revealed host transcription factors (TFs) with potential to regulate the UL b ′ genes in coordination with pUL135. We show that the cellular TF peroxisome proliferator-activated receptor gamma binds to the viral genome and influences the expression of UL133-UL138 locus genes. Our results define roles for UL135 and UL138 in regulation of patterns of viral gene expression for the establishment of latency and reexpression of viral genes for reactivation and reveal insights into differentiation-linked mechanisms of transcriptional control of the HCMV genome.
Comparison of triglyceride-glucose related indices in prediction of cardiometabolic disease incidence among US midlife women
Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling
Interleukin (IL)-23 is a validated therapeutic target in inflammatory bowel disease. While antibodies targeting IL23 demonstrate clinical efficacy, they face challenges such as high costs, safety risks, and the necessity of parenteral administration. Here, we present a workflow to simultaneously enhance the affinity and protease stability of an inhibitory anti-IL23R VHH for oral use. Cocrystal structure analysis reveals that the anti-IL23R VHH employs both CDR and framework residues to achieve picomolar affinity for IL23R. The engineered VHH remains stable for over 8 h in intestinal fluid and 24 h in fecal samples. Oral administration of this VHH achieves deep pathway inhibition in a murine colitis model. Furthermore, a single pill provides sustained IL23R inhibition in nonhuman primate blood for over 24 h. With high potency, gut stability, high production yield, and favorable drug-like properties, oral VHHs offer a promising approach for inflammatory bowel diseases.
Leveraging Africa’s underutilized crops to combat climate change, water scarcity, and food insecurity in South Africa
Abstract This study aims to integrate underutilized crops (UCs) into the food system to address climate change impacts, and food -water insecurity. UCs have immense potential to mitigate food shortages, yet their role remains largely unexplored in mainstream agricultural and food security strategies. A multidisciplinary approach using social psychology, resource-based theory (RBT), and a new ecological paradigm was used to investigate factors influencing UCs adoption and their potential contribution to water and food insecurity in South Africa. The water poverty index (WPI) and household food insecurity access score (HFIAS) were used to determine the water and food insecurity status of rural households. The study found that UCs cultivation was driven by awareness, access to extension advisory services, and climate information. The findings indicate that adopting UCs significantly improves water and food insecurity in South Africa. Consequently, households that integrated UCs into their farming systems experienced higher WPI scores, reflecting improved water availability and conservation, as UCs require less water than conventional crops. Likewise, lower HFIAS values suggest that UCs enhance food insecurity by diversifying diets, stabilizing food access, and reducing seasonal hunger. Statistically, households in Limpopo, Mpumalanga, and North-West provinces who adopted UCs saw 25.18 (21%), 31.03 (26%), and 28.77 (24%) rise in WPI and HFIAS compared to those who did not embrace UCs, respectively. These results highlight the potential of UCs as climate-resilient crops that mitigate water scarcity and food insecurity, making them a viable strategy for enhancing rural livelihoods amid climate change. Therefore, prioritizing UCs cultivation could build more resilient agricultural systems, address water scarcity and improve food security.
Laser-induced graphene points to sustainable electronics
Climate, biogeography, and human resilience in the demographic history of the Canary Islands during the Amazigh period
Allelic variations and gene cluster modularity act as nonlinear bottlenecks for cholera emergence
The underlying factors that lead to specific strains within a species to emerge as human pathogens remain mostly enigmatic. The diarrheal disease cholera is caused by strains from a phylogenetically confined group within the Vibrio cholerae species, the pandemic cholera group (PCG), making it an ideal model system to tackle this puzzling phenomenon. Comprehensive analyses of over 1,840 V. cholerae genomes, including environmental isolates from this study, reveal that the species consists of eleven groups, with the PCG belonging to the largest and located within a lineage shared with environmental strains. This hierarchical classification provided us with a framework to unravel the ecoevolutionary dynamics of the genetic determinants associated with the emergence of toxigenic V. cholerae . Our analyses indicate that this phenomenon is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. We determined that certain PCG-associated alleles are essential for successful colonization whereas others provide a nonlinear competitive advantage, acting as a critical bottleneck that clarifies the isolated emergence of PCG. For instance, toxigenic strains encoding non-PCG alleles of a) tcpF or b) a sextuple allelic exchange mutant for genes tcpA , toxT , VC0176 , VC1791 , rfbT, and ompU , lose their ability to colonize the intestine. Interestingly, these alleles do not play a role in the colonization of newly established model environmental reservoirs. Our study uncovers the evolutionary roots of toxigenic V. cholerae offering a tractable approach for investigating the emergence of pathogenic clones within an environmental population.
Soil and cherry bacterial communities predict flavor on coffee farms
Abstract Coffee (Coffea arabica) is a popular beverage worldwide with increasing value placed on sensory qualities as specialty markets grow. Plant-associated microbiomes have emerged as a potential but poorly understood driver of coffee flavor that may interact with other environmental and farm management factors. To determine if coffee plant-associated bacteria are linked with flavor, we collected 320 soil and 320 coffee cherry samples from 22 farms in Cundinamarca, Colombia that varied in farm management system (shade vs. sun-grown) and in flavor (presence vs. absence of a specialty flavor profile). We found, using amplicon sequencing, that soil and cherry bacterial communities differed between sun and shade farms and between farms that did and did not produce specialty flavored coffee, with shade + flavor farms notably distinct. Flavor presence was predicted by the abundance of multiple bacterial strains in soils and cherries, but correlations with flavor differed between sun and shade systems. These bacterial taxa correlated with coffee flavor may guide future efforts to optimize farms for specialty quality characteristics. Overall, the observed complex relationships between plant-associated bacteria and coffee flavor will likely require that initiatives seeking to optimize microbiomes for quality outcomes be tailored to individual farm systems and local conditions.
Specialized molecular pathways drive the formation of light-scattering assemblies in leucophores
Pigmentation plays a vital role in the survival of organisms, supporting functions such as camouflage, communication, and mate attraction. In vertebrates, these functions are mediated by specialized pigment cells known as chromatophores of which, uric acid crystal–forming leucophores remain the least understood, with little known about their molecular mechanisms. A key question in pigment cell biology is whether different crystal chemistries require distinct molecular pathways, or whether similar cellular processes drive the formation of diverse crystals. This study was designed to unravel the uncharacterized process of uric acid crystallization in leucophores and compare them to guanine crystal formation in iridophores and pterin formation in xanthophores. The results of our transcriptomic, ultrastructural, and metabolomic analyses, demonstrate that leucophores share molecular pathways with iridophores, particularly those connected to organelle organization and purine metabolism, but express discrete genes involved in uric acid biosynthesis and storage. Additionally, leucophores share intracellular trafficking and pterin biosynthesis genes with xanthophores, suggesting universally conserved processes. Ultrastructural studies reveal star-like fibrous structures in leucosomes, which likely serve as scaffolds for unique one-dimensional uric acid assemblies that radiate from the core and act as efficient light scatterers. These findings provide insights into leucophore cell biology and the specialized mechanisms driving molecular crystalline assembly, and reveal that while some cellular processes are conserved, the specific chemistry of each crystal type drives the evolution of distinct molecular pathways.
Cross-National variations in mental health: A cross-sectional study on depression, anxiety, and stress among university staff and students in Sub-Saharan African
Purpose Mental health disorders are global concerns, but their impact varies across regions. In sub-Saharan Africa (SSA), the influence of country-specific factors on mental health is under-researched. This study investigates the influence of country of origin on the prevalence and severity of mental health conditions among university students and staff across select SSA countries. Method A cross-sectional, web-based survey using the Depression, Anxiety, and Stress Scale-21 (DASS-21) was conducted from 16 April to 18 November 2024. The survey was distributed online through multiple African social networks, reaching students and staff from different universities across Africa. Prevalence estimates for anxiety, depression, and stress were based on binomial distribution with Clopper-Pearson confidence intervals, while country-level differences were assessed using univariate odds ratios and multiple logistic regression. Results Of the 3221 participants, aged 25.3 ± 8.6 (mean±SD), the majority (1850, 57.3%) were females. Findings revealed that Nigerians reported the highest prevalence of severe and extremely severe mental health conditions, while Ghanaians recorded the lowest levels across all mental health categories. Multivariable analysis revealed that, compared to Ghanaians, respondents from Malawi had the strongest odds for mental health challenges followed by Mozambique and Nigeria. The adjusted odds ratios (AORs) for Malawi were 4.39 (95% CI: 3.28–5.89), 3.86 (95% CI: 2.81–5.29) and 4.51 (95% CI: 3.33–6.11) for depression, anxiety, and stress, respectively. Conclusions This study found significant differences in mental health outcomes between participants from Ghana, Malawi, Mozambique, and Nigeria. Malawi had the greatest risk for depression, anxiety, stress, and combinations of those conditions while Ghana reported the lowest risks. The findings emphasize the importance of considering contextual factors, such as education levels, gender, and country of origin, in understanding mental health risks. Overall, these findings underscore the critical mental health burden in sub-Saharan Africa and the need for increased access to mental health resources and targeted interventions.
Measurement of spatial heterogeneity in street restorative perceptions and street refinement design
Nanoimmunomodulation of the Aβ-STING feedback machinery in microglia for Alzheimer’s disease treatment
Imbalanced production and clearance of amyloid-β (Aβ) is a hallmark pathological feature of Alzheimer’s disease (AD). While several monoclonal antibodies targeting Aβ have shown reductions in amyloid burden, their impact on cognitive function remains controversial, with the added risk of inflammatory side effects. Dysregulated stimulator of interferon genes (STING) signaling is implicated in neurodegenerative disorders, yet the biological interaction between this pathway and Aβ, as well as their combined influence on AD progression, is poorly understood. Here, we show that while microglia play a protective role in clearing extracellular Aβ, excessive Aβ engulfment triggers the cytosolic leakage of mitochondrial DNA for cGAS–STING cascade. This creates a negative feedback loop that not only exacerbates neuroinflammation but also impairs further Aβ clearance. To address this, we present a nanomedicine approach termed “Aβ-STING Synergistic ImmunoSilencing Therapy (ASSIST)”. ASSIST comprises STING inhibitors encapsulated within a blood–brain barrier (BBB)-permeable polymeric micelle that also serves as an Aβ scavenger. Through a multivalent interaction mechanism, ASSIST efficiently destabilizes Aβ plaques and prevents monomer aggregation, subsequently promoting the engulfment of the dissociated Aβ by microglia rather than neurocytes. Furthermore, the STING signaling induced by excessive Aβ uptake is blocked, reducing inflammation and restoring microglial homeostatic functions involved in Aβ clearance. Intravenous administration of ASSIST significantly reduces Aβ burden and improves cognition in AD mice, with minimal cerebral amyloid angiopathy or microhemorrhages. We provide a proof-of-concept nanoengineering strategy to target the maladaptive immune feedback loop arising from conventional immunotherapy for AD treatment.
Use peripheral blood leukocyte parameters combined with inflammatory indicators in diagnosis and severity assessment of mycoplasma pneumoniae pneumonia in children
Background Mycoplasma pneumoniae is a common cause of pneumonia in children over 5 years of age. Cell Population Data (CPD) is valuable for screening various diseases, including certain infections and myeloproliferative disorders, but less used in the diagnosis of children mycoplasma pneumoniae pneumonia (MPP). Aims To improve the diagnostic efficacy and severity assessment of MPP in children by combining CPD with inflammatory markers. Methods This study was conducted at the Gansu Provincial Maternity and Child-care Hospital, China. The data was accessed on 01.10.2024 for the purpose of research. A retrospective study from 01.10. 2022–01.01.2024 included three groups of children aged 5–9 years: 1) those with MPP (n = 240), of which 73 were mild, 167 were severe; 2) those with bacterial pneumonia (n = 52); and 3) those with health check-ups (n = 340). CPD indicators were measured by Sysmex XN-9000 (Kobe, Japan) hematology analyzer. Inflammatory markers included PCT (procalcitonin), LDH (lactate dehydrogenase), CK-MB (creatine kinase isoenzyme), CRP (c-reactive protein), SAA (serum amyloid A), APTT (activated partial thromboplastin time), FIB (fibrinogen). The differences and correlation of parameters between three groups were analyzed and receiver operating characteristic (ROC) analysis was performed. Results Most of the leukocyte parameter indices showed statistically significant differences between the MPP group and the healthy physical examination group (p < 0.05). Compared with bacterial pneumonia group, inflammatory markers were not correlated with the occurrence of MPP (p > 0.05), while LY-X and NE-WY were negatively correlated with the occurrence of MPP (p < 0.05). ROC analysis showed that the areas under the curve (AUC) for LY-X and NE-WY were 0.707 and 0.736, respectively. Additionally, LY-WY and MO-WZ are positively correlated with the severity of MPP (p < 0.05), and the AUC for MO-WZ was 0.709. Among the inflammatory markers, the AUC for SAA was 0.828, and combining SAA with MO-WZ increased the AUC to 0.861 in distinguishing mild from severe MPP. Conclusion Peripheral blood leukocyte parameters may have clinical application value for the early diagnosis and disease progression assessment of MPP.
A machine learning approach to carbon emissions prediction of the top eleven emitters by 2030 and their prospects for meeting Paris agreement targets
Host complement C3 promotes malaria transmission by killing symbiotic bacteria in the mosquito midgut
Host-derived factors ingested during mosquito blood feeding are poorly understood modulators of malaria transmission. Here, we demonstrated that host complement C3, acquired by mosquitoes during Plasmodium infection, significantly enhanced rodent malaria infection in laboratory-reared mosquitoes. This effect was recapitulated in field-caught Anopheles sinensis mosquitoes, confirming its relevance to malaria transmission in a more natural setting. Moreover, host-derived C3 significantly reduced the efficacy of anti-Pfs25 antibodies in blocking malaria transmission. Mechanistically, host-derived C3 lyses the mosquito midgut symbiont Elizabethkingia anophelis ( E. anophelis )—a bacterium that intrinsically suppresses parasite development by blocking the zygote-to-ookinete transition. Strikingly, host-derived C3 in mosquitoes appears to be activated by the alternative pathway, and inhibiting Factor B with Iptacopan (LNP023) reduced Plasmodium falciparum ( P. falciparum ) infection, while increased the efficacy of anti-Pfs25 antibodies to blocking P. falciparum transmission in the standard membrane-feeding assay. Therefore, this study describes a strategy of the malaria parasite to utilize host complement C3 to promote its transmission and provides us with an avenue to block malaria transmission and improve the blocking efficacy of anti-Pfs25 antibodies by the inhibition of C3 activation.
Identifying clinical skill gaps of healthcare workers using a digital clinical decision support algorithm during outpatient pediatric consultations in primary health centers in Rwanda
Digital clinical decision support algorithms (CDSAs) that guide healthcare workers during consultations can enhance adherence to guidelines and the resulting quality of care. However, this improvement depends on the accuracy of inputs (symptoms and signs) entered by healthcare workers into the digital tool, which relies mainly on their clinical skills, often limited, especially in resource-constrained primary care settings. This study aimed to identify and characterize potential clinical skill gaps based on CDSA data patterns and clinical observations. We retrospectively analyzed data from 20,085 pediatric consultations conducted using an IMCI-based CDSA in 16 primary health centers in Rwanda. We focused on clinical signs with numerical values: temperature, mid-upper arm circumference (MUAC), weight, height, z-scores (MUAC for age, weight for age, and weight for height), heart rate, respiratory rate and blood oxygen saturation. Statistical summary measures (frequency of skipped measurements, plausible and implausible values) and their variation in individual health centers compared to the overall average were used to identify 10 health centers with irregular data patterns signaling potential clinical skill gaps. We subsequently observed 188 consultations in these health centers and interviewed healthcare workers to understand potential error causes. Observations indicated basic measurements not being assessed correctly in most children; weight (70%), MUAC (69%), temperature (67%), height (54%). These measures were predominantly conducted by minimally trained non-clinical staff in the registration area. More complex measures, done by healthcare workers in the consultation room, were often skipped: respiratory rate (43%), heart rate (37%), blood oxygen saturation (33%). This was linked to underestimating the importance of these signs in child management, especially in context of high patient loads at primary care level. Addressing clinical skill gaps through in-person training, eLearning and regular personalized mentoring tailored to specific health center needs is imperative to improve quality of care and enhance the benefits of CDSAs.