bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatally acquired cytomegalovirus infection among preterm infants
Authors: Puopolo Karen M.
Published: August 2024

Purpose of review

Although there are multiple benefits of mother's own milk feeding for very-low birth weight, low gestation infants, those born to cytomegalovirus (CMV)-seropositive mothers are at risk for acquiring postnatal CMV infection. This review will describe the risk and consequences of postnatal CMV infection among very preterm infants.

Recent findings

Postnatal CMV may manifest as clinically silent infection or as mild to severe and occasionally fatal disease. The risk of disease is balanced by the health benefits of human milk feeding to preterm infants. Postnatal CMV infection has been associated with increased risks of multiple preterm morbidities such as bronchopulmonary dysplasia, necrotizing enterocolitis and neurodevelopmental impairment, but current evidence is limited by the selection bias inherent to reporting in case series and retrospective cohort studies.

Knowledge gaps exist regarding the risk–benefit balance of pasteurization to inactivate CMV in fresh breast milk, as well as the optimal dosing, duration and efficacy of treating infected infants with antiviral medications. Multicenter, prospective studies are urgently needed to accurately determine the true burden that postnatal CMV infection presents to very preterm infants. Such studies will inform the need for preventive strategies and treatment guidance.
68Ga-DOTA-IBA PET/CT and 18F-FDG PET/CT in Ewing Sarcoma
Authors: Xiang Feifan , Liu Huipan , Tan Xiaoqi , Ma Wenzhe , Chen Yue
Published: August 2024

A 29-year-old man with Ewing sarcoma in the right ankle underwent 68Ga-DOTA-IBA PET/CT and 18F-FDG PET/CT, both of which showed high radiotracer activity for the primary tumor. Interestingly, bone metastases were detected early using 68Ga-DOTA-IBA PET/CT for the sixth thoracic vertebrae and with 18F-FDG PET/CT for the bilateral humerus. Higher uptake of 68Ga-DOTA-IBA was found in both primary and metastatic sites of Ewing sarcoma. 177Lu-DOTA-IBA may be one of the possible therapies for metastatic or recurrent Ewing sarcoma.
Hidden rivals: the negative impacts of dolphinfish on seabird foraging behaviour
Authors: Koyama Shiho , Goto Yusuke , Furukawa Seishiro , Maekawa Takuya , Yoda Ken
Published: August 2024

Marine predators often aggregate at the air–sea boundary layer to pursue shared prey. In such scenarios, seabirds are likely to benefit from underwater predators herding fish schools into tight clusters thereby enhancing seabirds’ prey detectability and capture potential. However, this coexistence can lead to competition, affecting not only immediate foraging strategies but also their distribution and interspecies dynamics. We investigated both the longitudinal relationships and instantaneous interactions between streaked shearwaters (
Calonectris leucomelas
) and common dolphinfish (
Coryphaena hippurus
), both preying on Japanese anchovy (
Engraulis japonicus
). Using GPS data from 2011 to 2021, we calculated behavioural parameters for streaked shearwaters as an index of time spent and distance travelled. Despite the abundance of Japanese anchovies, we found that streaked shearwaters might increase their foraging time in the presence of underwater predators. Moreover, video loggers provided direct evidence of streaked shearwaters and common dolphinfish attacking the same fish schools, potentially interfering with bird foraging by dolphinfish. Our results suggest that the presence of underwater predators in a given patch might increase the time spent by seabirds foraging without affecting the distance travelled. This highlights the need for future studies that consider the potential adverse effects of other top predators on seabird prey availability.
Do risk-prone behaviours compromise reproduction and increase vulnerability of fish aggregations exposed to fishing?
Authors: Karkarey Rucha , Boström Einarsson L , Graham Nicholas A. J. , Mukrikkakudi Ibrahim , Bilutheth Mohammed Nowshad , Chekkillam Abdul Riyas , KK Idrees Babu , Keith Sally A.
Published: August 2024

Human disturbances can prompt natural anti-predator behaviours in animals, affecting how energy is traded off between immediate survival and reproduction. In our study of male squaretail groupers (
Plectropomus areolatus
) in India’s Lakshadweep archipelago, we investigated the impact of fishing pressure on anti-predatory responses and reproductive behaviours by comparing a fished and unfished spawning aggregation site and tracking responses over time at the fished site. Using observational sampling and predator exposure experiments, we analysed fear responses (flight initiation distance, return time), as well as time spent in vigilance, courtship and territorial defence. Unpaired males at fished sites were twice as likely to flee from simulated predators and took longer to return to mating territories. In contrast, paired males at both sites took greater risks during courtship, fleeing later than unpaired males, but returned earlier at the unfished site compared with the fished site. Our findings suggest that high fishing pressure reduces reproductive opportunities by increasing vigilance and compromising territorial defence, potentially affecting mate selection cues. Altered behavioural trade-offs may mitigate short-term capture risk but endanger long-term population survival through altered reproductive investment. Human extractive practices targeting animal reproductive aggregations can have disruptive effects beyond direct removal, influencing animal behaviours crucial for population survival.
Transiently restricting individual amino acids protects
Drosophila melanogaster
against multiple stressors
Authors: Fulton Tahlia L. , Johnstone Joshua N. , Tan Jing J. , Balagopal Krithika , Dedman Amy , Chan Andrea Y. , Johnson Travis K. , Mirth Christen K. , Piper Matthew D. W.
Published: August 2024

Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect
Drosophila melanogaster
against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.
Decolonizing global AI governance: assessment of the state of decolonized AI governance in Sub-Saharan Africa
Authors: Ayana Gelan , Dese Kokeb , Daba Nemomssa Hundessa , Habtamu Bontu , Mellado Bruce , Badu Kingsley , Yamba Edmund , Faye Sylvain Landry , Ondua Moise , Nsagha Dickson , Nkweteyim Denis , Kong Jude Dzevela
Published: August 2024

Global artificial intelligence (AI) governance must prioritize equity, embrace a decolonial mindset, and provide the Global South countries the authority to spearhead solution creation. Decolonization is crucial for dismantling Western-centric cognitive frameworks and mitigating biases. Integrating a decolonial approach to AI governance involves recognizing persistent colonial repercussions, leading to biases in AI solutions and disparities in AI access based on gender, race, geography, income and societal factors. This paradigm shift necessitates deliberate efforts to deconstruct imperial structures governing knowledge production, perpetuating global unequal resource access and biases. This research evaluates Sub-Saharan African progress in AI governance decolonization, focusing on indicators like AI governance institutions, national strategies, sovereignty prioritization, data protection regulations, and adherence to local data usage requirements. Results show limited progress, with only Rwanda notably responsive to decolonization among the ten countries evaluated; 80% are ‘decolonization-aware’, and one is ‘decolonization-blind’. The paper provides a detailed analysis of each nation, offering recommendations for fostering decolonization, including stakeholder involvement, addressing inequalities, promoting ethical AI, supporting local innovation, building regional partnerships, capacity building, public awareness, and inclusive governance. This paper contributes to elucidating the challenges and opportunities associated with decolonization in SSA countries, thereby enriching the ongoing discourse on global AI governance.
Novel phylogenomic inference and ‘Out of Asia’ biogeography of cobras, coral snakes and their allies
Authors: Weinell Jeffrey L. , Burbrink Frank T. , Das Sunandan , Brown Rafe M.
Published: August 2024

Estimation of evolutionary relationships among lineages that rapidly diversified can be challenging, and, in such instances, inaccurate or unresolved phylogenetic estimates can lead to erroneous conclusions regarding historical geographical ranges of lineages. One example underscoring this issue has been the historical challenge posed by untangling the biogeographic origin of elapoid snakes, which includes numerous dangerously venomous species as well as species not known to be dangerous to humans. The worldwide distribution of this lineage makes it an ideal group for testing hypotheses related to historical faunal exchanges among the many continents and other landmasses occupied by contemporary elapoid species. We developed a novel suite of genomic resources, included worldwide sampling, and inferred a robust estimate of evolutionary relationships, which we leveraged to quantitatively estimate geographical range evolution through the deep-time history of this remarkable radiation. Our phylogenetic and biogeographical estimates of historical ranges definitively reject a lingering former ‘Out of Africa’ hypothesis and support an ‘Out of Asia’ scenario involving multiple faunal exchanges between Asia, Africa, Australasia, the Americas and Europe.
Climatic temperature and precipitation jointly influence body size in species of western rattlesnakes
Authors: Meik Jesse M. , Watson Jessica A. , Schield Drew R. , Perry Blair W. , Francioli Yannick , Guss Hannah , Mackessy Stephen P. , Castoe Todd A.
Published: August 2024

Both the metabolic theory of ecology and dynamic energy budget theory predict that climate influences body size through its effects on first-order determinants of energetics: reactive temperatures, carbon resources and oxygen availability. Although oxygen is seldom limiting in terrestrial systems, temperature and resources vary spatially. We used redundancy analyses and variation partitioning to evaluate the influence of climatic temperature, precipitation and their seasonalities on multivariate body size across the distributions of four species of the western rattlesnake group in North America (
Crotalus pyrrhus
,
C. scutulatus
,
C. oreganus
and
C. viridis
). Most species showed a pattern of increased body size in cooler, mesic climates and decreased body size in warmer, xeric climates. Exceptions to the pattern provided additional context through climatic idiosyncrasies in the distributions of each species. For example, the general pattern of a negative influence of temperature on body size was not apparent for
C. oreganus
, which ranges across the mildest climates overall among the four species. In contrast to previous studies, we found that seasonality had negligible effects on body size. We suggest that precipitation gradients correlate positively with resource availability in driving intraspecific body size and that temperature compounds this gradient by increasing baseline metabolic demands and restricting activity in particularly warm or otherwise extreme climates.
Trophic guilds differ in blood glucose concentrations: a phylogenetic comparative analysis in birds
Authors: Szarka Endre Z. , Lendvai Ádám Z.
Published: August 2024

Glucose is a central metabolic compound used as an energy source across all animal taxa. There is high interspecific variation in glucose concentration between taxa, the origin and the consequence of which remain largely unknown. Nutrition may affect glucose concentrations because carbohydrate content of different food sources may determine the importance of metabolic pathways in the organism. Birds sustain high glucose concentrations that may entail the risks of oxidative damage. We collected glucose concentration and life-history data from 202 bird species from 171 scientific publications, classified them into seven trophic guilds and analysed the data with a phylogenetically controlled model. We show that glucose concentration is negatively associated with body weight and is significantly associated with trophic guilds with a moderate phylogenetic signal. After controlling for allometry, glucose concentrations were highest in carnivorous birds, which rely on high rates of gluconeogenesis to maintain their glycaemia, and lowest in frugivorous/nectarivorous species, which take in carbohydrates directly. However, trophic guilds with different glucose concentrations did not differ in lifespan. These results link nutritional ecology to physiology and suggest that at the macroevolutionary scale, species requiring constantly elevated glucose concentrations may have additional adaptations to avoid the risks associated with high glycaemia.
Enhanced Cell Wall Mechanics in VirtualLeaf Enable Realistic Simulations of Plant Tissue Dynamics
Authors: Großeholz Ruth , van Nieuwenhoven Richard W. , Mele Bruno Hay , Merks Roeland M.H.
Published: August 2024

Computational modelling has become increasingly important in advancing our understanding of biological systems, necessitating the development of new computational approaches and software. VirtualLeaf, in particular, is a modelling framework for plant tissues that accounts for the biophysical mechanics of plant cell interactions. The plant cell wall plays a pivotal role in plant development and survival, with younger cells generally having thinner, more flexible (primary) walls than older cells. Signalling processes in growth and pathogen infection also affect cell wall stability. This article presents an updated version of VirtualLeaf with improved cell wall mechanics and morphing behaviour. These are crucial for ultimately understanding plant tissue dynamics and essential signalling processes during growth, tissue formation and pathogen defence. The updated version of VirtualLeaf enables detailed modelling of variations in cell wall stability to the level of individual cell wall elements. These improvements lay the groundwork for using VirtualLeaf to address new research questions, including the structural implications of pathogen infection and growth.
A flexible model for thermal performance curves
Authors: Cruz-Loya Mauricio , Mordecai Erin A , Savage Van M
Published: August 2024

Temperature responses of many biological traits—including population growth, survival, and development—are described by thermal performance curves (TPCs) with phenomenological models like the Briere function or mechanistic models related to chemical kinetics. Existing TPC models are either simple but inflexible in shape, or flexible yet difficult to interpret in biological terms. Here we present flexTPC: a model that is parameterized exclusively in terms of biologically interpretable quantities, including the thermal minimum, optimum, and maximum, and the maximum trait value. FlexTPC can describe unimodal temperature responses of any skewness and thermal breadth, enabling direct comparisons across populations, traits, or taxa with a single model. We apply flexTPC to various microbial and entomological datasets, compare results with the Briere model, and find that flexTPC often has better predictive performance. The interpretability of flexTPC makes it ideal for modeling how thermal responses change with ecological stressors or evolve over time.
Genomic prediction of cereal crop architecture traits using models informed by gene regulatory circuitries from maize
Authors: Bertolini Edoardo , Manjunath Mohith , Ge Weihao , Murphy Matthew D. , Inaoka Mirai , Fliege Christina , Eveland Andrea L. , Lipka Alexander E.
Published: August 2024

Plant architecture is a major determinant of planting density, which enhances productivity potential for crops per unit area. Genomic prediction is well-positioned to expedite genetic gain of plant architecture traits since they are typically highly heritable. Additionally, the adaptation of genomic prediction models to query predictive abilities of markers tagging certain genomic regions could shed light on the genetic architecture of these traits. Here, we leveraged transcriptional networks from a prior study that contextually described developmental progression during tassel and leaf organogenesis in maize (Z. mays) to inform genomic prediction models for architecture traits. Since these developmental processes underlie tassel branching and leaf angle, two important agronomic architecture traits, we tested whether genes prioritized from these networks quantitatively contribute to the genetic architecture of these traits. We used genomic prediction models to evaluate the ability of markers in the vicinity of prioritized network genes to predict breeding values of tassel branching and leaf angle traits for two diversity panels in maize, and diversity panels from sorghum (S. bicolor) and rice (O. sativa). Predictive abilities of markers near these prioritized network genes were similar to those using whole-genome marker sets. Notably, markers near highly connected transcription factors from core network motifs in maize yielded predictive abilities that were significantly greater than expected by chance in not only maize but also closely related sorghum. We expect that these highly connected regulators are key drivers of architectural variation that are conserved across closely related cereal crop species.
Transcriptional and Metabolic Mechanism of Carbon Dots Enhancing Rice Growth and Resistance by Promoting Root
Authors: Li Yadong , Xu Ronghua , Qi Jingyi , Lei Shang , Han Qianying , Ma Congli , Ru Yunlong , Wang Hongjie
Published: August 2024

Increasing climate change and pollutant discharge induce constant challenges to crops, while crops are vulnerable to environmental and pollutant stresses. In this study, a carbon dots (CDs) was developed that significantly increased rice seedling growth, and successfully reduced the inhibition of heavy metal cadmium (Cd), salt (NaCl), and herbicide 2,4-D stresses on rice seedling growth by pre-spraying. The root of rice seedlings responded specifically to CDs exposure, with significant improvements in root biomass, architecture, cell wall thickness, mechanical strength, and metabolic vitality. Metabolomics and transcriptomics were combined to reveal the regulatory mechanism of CDs in rice seedlings. Transcriptome analysis indicated that CDs upregulated genes related to cytokinin, jasmonic acid, salicylic acid, MAPK signaling pathway, calcium homeostasis, and peroxidase, and downregulated those related to auxin, abscisic acid, and ethylene. Metabolomic analysis suggested CDs improved the metabolites related to antioxidant (betalain, ascorbate, aldarate, and glutathione), formation of cell wall, plasma membrane, xylem, and root cortex (phenylpropanoids biosynthesis, stilbenoid, diarylheptanoid and gingerol biosynthesis, and sphingolipid), and energy metabolism (nicotinate, nicotinamide, glyoxylate, dicarboxylate, and nitrate cycle) in rice seedlings. Therefore, pre-spraying CDs reprogrammed stress signaling pathways and enhanced adaptive responses in rice seedlings, ultimately increasing growth potential and stress resistance. This study presents a promising nano-bio-stimulant of CDs for crop resilience in the context of increasing climate change and contributes to sustainable agriculture.
Pregnancy Reduces Il33+ Hybrid Progenitor Accumulation in the Aged Mammary Gland
Authors: Olander Andrew , Ramirez Cynthia M , Acosta Veronica Haro , Medina Paloma , Kaushik Sara , Jonsson Vanessa D , Sikandar Shaheen S
Published: August 2024

Aging increases breast cancer risk while an early first pregnancy reduces a woman’s life-long risk. Several studies have explored the effect of either aging or pregnancy on mammary epithelial cells (MECs), but the combined effect of both remains unclear. Here, we interrogate the functional and transcriptomic changes at single cell resolution in the mammary gland of aged nulliparous and parous mice to discover that pregnancy normalizes age-related imbalances in lineage composition, while also inducing a differentiated cell state. Importantly, we uncover a minority population ofIl33-expressing hybrid MECs with high cellular potency that accumulate in aged nulliparous mice but is significantly reduced in aged parous mice. Functionally, IL33 treatment of basal, but not luminal, epithelial cells from young mice phenocopies aged nulliparous MECs and promotes formation of organoids withTrp53knockdown. Collectively, our study demonstrates that pregnancy blocks the age-associated loss of lineage integrity in the basal layer through a decrease inIl33+hybrid MECs, potentially contributing to pregnancy-induced breast cancer protection.
Transmission of Mixed Convergent Signals at the Mouse Retinogeniculate Synapse
Authors: Sonoda Takuma , Jiang Qiufen , Ledesma Héctor Acarón , Wei Wei , Chen Chinfei
Published: August 2024

There are two broad modes of information transfer in the brain: the labeled line model, where neurons relay inputs they receive, and the mixed tuning model, where neurons transform and integrate different inputs. In the visual pathway, information transfer between retinal ganglion cells (RGCs) and the dorsal lateral geniculate nucleus (dLGN) neurons is primarily viewed as a labeled line. However, recent work in mice has demonstrated that different RGC types, encoding distinct visual features, can converge onto a dLGN neuron, raising the fundamental question of whether the dLGN transforms visual information. Using optogenetics we activated distinct RGC populations and assessed spiking output of dLGN neurons byin vivorecordings. We found that visual response properties of dLGN neurons driven by a specific RGC population largely matched properties of the activated RGCs. Furthermore,in vitrodual-opsin experiments demonstrate that strong functional convergence from distinct RGC types rarely occurs. Thus, retinogeniculate information transfer in mice largely adheres to a labeled line model.
Cleavage of the vascular matrix attracts glioblastoma cells to infiltrate the brain parenchyma
Authors: Perryman Lara , Høye Anette M , Cox Thomas R , Baker Ann-Marie , Strøbech Jan , Leonte Lidia , Singh Lukram B , Popov Sergey , Lorentzen Lasse G , Reuten Raphael , Skovgaard Poulsen Hans , Davies Michael J , Jones Chris , Erler Janine T
Published: August 2024

Background

Glioblastoma is a highly aggressive brain cancer and, unlike many other cancers types, the median survival for patients after treatment (14.6 months) has barely improved in the last 20 years. Infiltrative growth into the surrounding brain parenchyma facilitates tumor recurrence and ultimately the death of the patient - novel therapies targeting this process are desperately needed. Lysyl oxidase inhibition has been shown to decrease invasive growth in a variety of solid tumours and is a potential therapy for glioblastoma patients.

Methods

Genes highly expressed in the mesenchymal subtype of glioblastoma were analyzed in a data set from the Cancer Genome Atlas and tissue microarrays. Two patient-derived human glioblastoma stem cell lines were used to assess the involvement of lysyl oxidase (LOX). The effect of LOX on infiltration was examined in an organotypic brain slice assay and in an orthotopic mouse model. Chemotactic assays, protease and cleavage arrays were used to assess the underlying mechanism behind LOX-mediated infiltration. The orthotopic model was used to evaluate potential clinical utility of targeting LOX in glioblastoma.

Results

LOX is overexpressed in the mesenchymal glioblastoma subtype and strongly associated with poor patient survival. LOX expression upregulates MMP7 expression, which subsequently cleaves the vascular matrix resulting in increased chemotaxis of glioblastoma cells.

Conclusions

We have uncovered a novel mechanism of glioblastoma infiltration and suggest that targeting LOX represent an effective therapeutic approach blocking glioblastoma infiltration.

Importance of the study

The ability of glioblastoma cells to infiltrate the surrounding normal brain tissue facilitates their evasion of current therapies, leading to tumor recurrence and ultimately the death of the patient. To improve targeted therapies for glioblastoma patients we need to understand the molecular mechanisms of glioblastoma cell infiltration and how cells interact with the unique microenvironment of the brain. We have identified a novel mechanism whereby tumor-derived LOX mediates chemotaxis of glioblastoma cells to the laminin rich perivascular niche, enabling infiltrative growth. Inhibiting this infiltrative pathway is a potential anti-invasive therapy that is desperately needed for glioblastoma patients.
Head down tilt 15° increases cerebral perfusion before recanalization in acute ischemic stroke. A pre-clinical MRI study
Authors: Beretta Simone , Carone Davide , Cho Tae-Hee , Viganò Martina , Diamanti Susanna , Mariani Jacopo , Pedrazzini Francesco Andrea , Bianchi Elisa , Pini Cristiano , Bolbos Radu , Wiart Marlene , Ferrarese Carlo , Chauveau Fabien
Published: August 2024

We investigated the therapeutic effect of head down positioning at −15° (head down tilt; HDT15) on cerebral collateral flow and infarct growth in a rat model of large vessel occlusion (LVO) stroke, using multi-modal MRI. Twenty-eight Wistar rats were randomly assigned to HDT15 or flat position for 60 minutes, starting 30 minutes after occlusion of the middle cerebral artery, followed by reperfusion. The perfusion shift analysis, comparing post- versus pre-treatment voxel-level changes in time-to-peak perfusion maps, showed a significant increase in cerebral perfusion in the HDT15 group (common odds ratio 1.50; 95% CI 1.41-1.60; p < 0.0001), but not in the flat group (common odds ratio 0.97; 95% CI 0.92-1.03; p = 0.3503). Infarct growth at 24 hours was + 31.4% in the flat group (343 versus 250 mm3; 95% CI 2.4 to 165.1; p = 0.0447) and + 15.4% in the HDT15 group (224 versus 192 mm3; 95% CI -26.9 to 85.9; p = 0.2272). Our findings indicate that HDT15 acutely increases cerebral perfusion in LVO acute ischemic stroke and provides a tissue-saving effect before recanalization. Further research is needed to develop HDT15 as an emergency therapy to acutely increase collateral flow in ischemic stroke prior to recanalization therapy.
RF Channel-Based Adaptive Beamforming for 3D Ultrasound Localization Microscopy
Authors: Chabouh Georges , Pialot Baptiste , Denis Louise , Dumas Raphael , Couture Olivier , Seya Pauline Muleki , Varray François
Published: August 2024

Ultrasound Localization Microscopy (ULM) has been applied in various preclinical settings and in the clinic to reveal the microvasculature in deep organs. However, most ULM images employ standard Delay-and-Sum (DAS) beamforming. In standard ULM conditions, lengthy acquisition times are required to fully reconstruct small vessels due to the need for spatially isolated microbubbles, resulting in low temporal resolution. When microbubbles are densely packed, localizing a point spread function with significant main and side lobes becomes challenging due to matrix arrays’ low signal-to-noise ratio and spatial resolution. In this work, we applied adaptive beamforming such as high order DAS known as (pDAS), Coherence Factor (CF), Coherence Factor with Gaussian Filtering (CFGF), and statistical interpretation of beamforming (iMAP) to provide a more complete 3D ULM mapsin vitroandin vivo(rat kidney). Specifically, the CF and 1MAP adaptive beamformers achieved higher resolution (32.9 microns and 27.2 microns respectively), as measured by the Fourier Shell Correlation (FSC), compared to the standard DAS beamformer, which had an FSC value of 38.6 microns.
Regularly updated benchmark sets for statistically correct evaluations of AlphaFold applications
Authors: Dobson Laszlo , Tusnady Gabor E. , Tompa Peter
Published: August 2024

AlphaFold2 changed structural biology by providing high-quality structure predictions for all possible proteins. Since its inception, a plethora of applications were built on AlphaFold2, expediting discoveries in virtually all areas related to protein science. In many cases, however, optimism seems to have made scientists forget about data leakage, a serious issue that needs to be addressed when evaluating machine learning methods. Here we provide a rigorous benchmark set that can be used in a broad range of applications built around AlphaFold2/3.
Conservation of animal genome structure is the exception not the rule
Authors: Lewin Thomas D. , Liao Isabel Jiah-Yih , Luo Yi-Jyun
Published: August 2024

Species from diverse animal lineages have retained groups of orthologous genes together on the same chromosomes for over half a billion years since their last common ancestor. However, by examining interchromosomal rearrangements across all major bilaterian groups, we show that cases of high-fidelity genome structure conservation are unexpectedly rare. Large-scale genome restructuring events are pervasive, correlate with increased rates of protein sequence evolution, and may contribute to adaptation and animal diversity.
Plectin-mediated cytoskeletal crosstalk as a target for inhibition of hepatocellular carcinoma growth and metastasis
Authors: Outla Zuzana , Oyman-Eyrilmez Gizem , Korelova Katerina , Prechova Magdalena , Frick Lukas , Sarnova Lenka , Bisht Piyush , Novotna Petra , Kosla Jan , Bortel Patricia , Borutzki Yasmin , Bileck Andrea , Gerner Christopher , Rahbari Mohammad , Rahbari Nuh , Birgin Emrullah , Kvasnicova Bibiana , Galisova Andrea , Sulkova Katerina , Bauer Andreas , Jobe Njainday , Tolde Ondrej , Sticova Eva , Rosel Daniel , O’Connor Tracy , Otahal Martin , Jirak Daniel , Heikenwälder Mathias , Wiche Gerhard , Meier-Menches Samuel M. , Gregor Martin
Published: August 2024

The most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/AKT signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.
Monitoring free-living honeybee colonies in Germany: Insights into habitat preferences, survival rates, and Citizen Science reliability
Authors: Rutschmann Benjamin , Remter Felix , Roth Sebastian
Published: August 2024

Our understanding of the western honeybee (Apis mellifera) predominantly stems from studies conducted within beekeeping environments, leaving the presence and characteristics of honeybees outside managed settings largely unexplored. This study examined the habitats, nesting sites, and survival rates of free-living colonies through personal monitoring of nest sites in Munich (N=107) and the coordination of Citizen Science monitoring across Germany (N=423). Within seven years we collected 2,555 observations on 530 colonies from 311 participants. Nesting preferences differed between urban, rural, and forested areas. Overall, we found that 31% of the occupied nest sites were in buildings and 63% in mature trees, with clear preferences for specific tree species. On average, only 12% of the personal monitored colonies in Munich survived annually, a figure that aligns well with other published studies but contrasts sharply with the significantly higher survival rates reported by Citizen Science (29%). We found that Citizen Science yielded significantly fewer updates per colony, underreported abandoned sites, and that 46% of overwintering reports overlapped with the swarming season and had to be excluded. To gain reliable survival data in Citizen Science projects, consistency and timing of reports need particular attention and regional swarming should be monitored too. This study enhances our understanding of the ecological dynamics, liminal state, and conservation needs of free-living honeybee cohorts, addresses potential monitoring biases, and suggests standardized data collection protocols for future monitoring projects.
Molecular hydrogen can minimize negative effects of heat stress on the hard coral genusAcropora
Authors: Ostendarp Malte , de Breuyn Mareike , El-Khaled Yusuf C. , Garcias-Bonet Neus , Carvalho Susana , Peixoto Raquel S. , Wild Christian
Published: August 2024

Coral reefs are increasingly threatened by mass bleaching events due to global ocean warming. Novel management strategies are urgently needed to support coral survival until global efforts can mitigate ocean warming. Given the strong antioxidant, anti-inflammatory and anti-apoptotic properties of molecular hydrogen, our study explores its potential to alleviate the negative effects of heat stress on corals. We investigated the ecophysiological responses of two common hard corals (Acroporaspp. andPocillopora verrucosa) from the Central Red Sea under ambient (26 °C) and elevated seawater temperatures (32 °C), with and without hydrogen addition (∼ 150 µM H2) over 48 h. Our results showed that at 32 °C without hydrogen addition,P. verrucosaexhibited high temperature tolerance, whereasAcroporaspp. showed significant reductions in photosynthetic efficiency and maximum electron transport rate compared to the ambient condition (26 °C). The addition of hydrogen at 32 °C increased the maximum electron transport rate ofAcroporaspp. by 28 %, maintaining it at levels compared to those at 26 ° C. This suggests that molecular hydrogen benefits specific coral species under heat stress in the short-term. This study provides the foundation for future long-term and in-situ studies, potentially guiding the development of new management strategies aiming at enhancing coral resilience to ocean warming.
Resting-state causal brain connectivity in youth female athletes suggest sex-related differences following subacute concussion
Authors: McLeod Julianne , Sattari Sahar , Hristopulos Dionissios T. , Thanjavur Karun , Virji-Babul Naznin
Published: August 2024

Objective

Youth male athletes show changes in resting-state causal brain connectivity following subacute concussion; however, little is known about how concussion alters causal brain connectivity in female youth. In this study, we compared resting-state causal brain connectivity in healthy and subconcussed females.

Materials and methods

Data from 11 concussed and 15 healthy control female athletes were included in this study. Five minutes of resting state eyes-closed EEG data were collected from all participants. SCAT5 data were also collected from all concussed participants. Causal connectivity was calculated from EEG source data. Network topology was evaluated using the degree assortativity coefficient, a summary statistic describing network structure of information flow between source locations.

Results

We observed three main results: 1) a qualitative difference in the spatial pattern of the most active connections, marked by posterior connectivity shifting in the concussed group, 2) an increase in the magnitude of connectivity in the concussed group, and 3) no significant difference in degree assortativity between the concussed and control groups.

Conclusion

Causal connectivity changes following concussion in females do not follow the same trends reported in males. These findings suggest a potential sex difference in injury response and may have implications for recovery.
Individual alpha frequency tACS reduces functional connectivity across the default mode network
Authors: Carrasco-Gómez Martín , García-Colomo Alejandra , Cabrera-Álvarez Jesús , del Cerro-León Alberto , Gómez-Ariza Carlos J. , Santos Andrés , Maestú Fernando
Published: August 2024

Structured Abstract

Objectives

Research on the influence of transcranial alternating current stimulation over alpha functional connectivity (FC) is scarce, and at the same time poses as a potential treatment for various diseases. This study aimed to investigate the effects of individualized alpha frequency tACS (IAF-tACS) on FC within the default mode network (DMN) in healthy individuals, particularly focusing on the precuneus (PCU) as a major hub within the network.

Materials and Methods

27 healthy participants were recruited, which underwent a 20-minute IAF-tACS session and three magnetoencephalography (MEG) recordings: two pre-stimulation and one post-stimulation. Participants were randomly assigned to either the stimulation or sham group. FC was evaluated through the corrected imaginary phase locking value (ci-PLV) and leakage corrected amplitude envelope correlation (AEC-c). Statistical analyses compared both Pre-Post FC ratio between groups through ratio t-tests and intragroup FC changes through repeated measures t-tests, with FDR correction applied to account for multiple comparisons. An additional analysis simulated the influence of the cortical folding on the effect of tACS over FC.

Results

IAF-tACS significantly decreased AEC-c within the PCU and DMN in the stimulation group compared to the sham group, especially influencing antero-posterior links between hubs of the DMN. No significant changes were observed in ci-PLV connectivity metrics. Negative correlations were found between AEC-c FC changes and power alterations in posterior DMN areas, suggesting a complex interaction between cortical folding and electric field direction.

Conclusions

Against our initial hypothesis, IAF-tACS reduced FC in the DMN, possibly due to phase disparities introduced by cortical gyrification. These findings suggest that tACS might modulate FC in a more complex manner than previously thought, highlighting the need for further research into the personalized application of neuromodulation techniques, as well as its potential therapeutic implications for conditions like Alzheimer’s disease.
Effects of Aging, Fitness, and Cerebrovascular Status on White Matter Microstructural Health
Authors: Clements Grace M. , Camacho Paul , Bowie Daniel C. , Low Kathy A. , Sutton Bradley P. , Gratton Gabriele , Fabiani Monica
Published: August 2024

White matter (WM) microstructural health declines with increasing age, with evidence suggesting that improved cardiorespiratory fitness (CRF) may mitigate this decline. Specifically, higher fit older adults tend to show preserved WM microstructural integrity compared to their lower fit counterparts. However, the extent to which fitness and agingindependentlyimpact WM integrity across the adult lifespan is still an open question, as is the extent to which cerebrovascular health mediates these relationships. In a large sample (N = 125, aged 25-72), we assessed the impact of age and fitness on fractional anisotropy (FA, derived using diffusion weighted imaging, DWI) and probed the mediating role of cerebrovascular health (derived using diffuse optical tomography of the cerebral arterial pulse, pulse-DOT) in these relationships. After orthogonalizing age and fitness and computing a PCA on whole brain WM regions, we found several WM regions impacted by age that were independent from the regions impacted by fitness (hindbrain areas, including brainstem and cerebellar tracts), whereas other areas showed interactive effects of age and fitness (midline areas, including fornix and corpus callosum). Critically, cerebrovascular health mediatedbothrelationships suggesting that vascular health plays a linking role between age, fitness, and brain health. Secondarily, we assessed potential sex differences in these relationships and found that, although females and males generally showed the same age-related FA declines, males exhibited somewhat steeper declines than females. Together, these results suggest that age and fitness impact specific WM regions and highlight the mediating role of cerebrovascular health in maintaining WM health across adulthood.
The Dichoptic Contrast Ordering Test: A method for measuring the depth of binocular imbalance
Authors: Baldwin Alex S , Lorenzini Marie-Céline , Fan Annabel Wing-Yan , Hess Robert F , Reynaud Alexandre
Published: August 2024

Abstract

In binocular vision, the relative strength of the input from the two eyes can have significant functional impact. These inputs are typically balanced, however in some conditions (e.g. amblyopia) one eye will dominate over the other. To quantify imbalances in binocular vision, we have developed the Dichoptic Contrast Ordering Test (DiCOT). Implemented on a tablet device, the program uses rankings of perceived contrast (of dichoptically-presented stimuli) to find a scaling factor that balances the two eyes. We measured how physical interventions (applied to one eye) affect the DiCOT measurement. These were: i) neutral density filters, ii) Bangerter filters, and iii) optical blur introduced by a +3 D lens. The DiCOT results were compared to those from the Dichoptic Letter Test (DLT). Both the DiCOT and the DLT showed excellent test-retest reliability, however the magnitude of the imbalances introduced by the interventions was greater in the DLT. To find consistency between the methods, rescaling the DiCOT results from individual conditions gave good results. However, the adjustments needed for the +3 D lens condition were quite different from those for the ND and Bangerter filter. Our results indicate that the DiCOT and DLT measure partially separate aspects of binocular imbalance. This supports the simultaneous use of both measures in future studies.
Resting-State EEG Reveals Regional Brain Activity Correlates in Alzheimer’s and Frontotemporal Dementia
Authors: Azargoonjahromi Ali , Nasiri Hamide , Abutalebian Fatemeh
Published: August 2024

Resting-state EEG records brain activity when awake but not engaged in tasks, analyzing frequency bands linked to cognitive states. Recent studies on Alzheimer’s disease (AD) and frontotemporal dementia (FTD) have found a link between EEG activity, MMSE scores, and age, though some findings are conflicting. This study aimed to explore EEG regional differences among AD and FTD, thereby improving diagnostic strategies. We analyzed EEG recordings from 88 participants in OpenNeuro Dataset ds004504, collected at AHEPA General Hospital using a Nihon Kohden 2100 EEG device. The study used preprocessed recordings, classification algorithms, and cognitive function assessments (MMSE) to identify significant predictors and correlations between EEG measures and cognitive variables. The study revealed that cognitive function, age, and brain activity show distinct relationships in AD and FTD. In AD, MMSE scores significantly predicted brain activity in regions like C3, C4, T4, and Fz, with better cognitive performance linked to higher EEG power in frontal and temporal areas. Conversely, age had a major influence on brain activity in FTD, particularly in regions like C3, P3, O1, and O2, while MMSE scores did not significantly predict brain activity. In FTD, higher EEG power in regions like P3, P4, Cz, and Pz correlated with lower cognitive function. Thus, the findings suggest that EEG biomarkers can enhance diagnostic strategies by highlighting different patterns of brain activity related to cognitive function and age in AD and FTD.
The molecular basis of lamin-specific chromatin interactions
Authors: Wang Baihui , Kronenberg-Tenga Rafael , Rosti Valentina , Di Patrizio Soldateschi Emanuele , Luo Qiang , Pinet Louise , Eibauer Matthias , Boujemaa-Paterski Rajaa , Schuler Benjamin , Lanzuolo Chiara , Medalia Ohad
Published: August 2024

In the cell nucleus, chromatin is anchored to the nuclear lamina, a network of lamin filaments and binding proteins that underly the inner nuclear membrane. The nuclear lamina is involved in chromatin organisation through the interaction of lamina-associated domains (LADs) within the densely packed heterochromatin regions. Employing cryo-focused ion beam (cryo-FIB) milling in conjunction with cryo-electron tomography (cryo-ET), we analysed the distribution of nucleosomes at the lamin-chromatin interface. Depletion of lamin A/C reduced the concentration of nucleosomes at the nuclear periphery, suggesting that lamins are directly involved in the interaction with chromatin. Using cryo-electron microscopy (cryo-EM), we then identified the specific binding motif of the lamin A tail domain that interacts with nucleosomes, distinguishing it from the other lamin isoforms. Furthermore, we examined chromatin structure dynamics using a genome-wide analysis that revealed lamin-dependent macroscopic-scale alterations in gene expression and chromatin remodelling. Our findings provide detailed insights into the dynamic and structural interplay between lamin isoforms and chromatin, molecular interactions which are shaping chromatin architecture and epigenetic regulation.