bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses at various levels of ecological hierarchy indicate acclimation to sequential sublethal heatwaves in a temperate benthic ecosystem
Authors: Ito Maysa , Guy-Haim Tamar , Sawall Yvonne , Franz Markus , Buchholz Björn , Hansen Thomas , Neitzel Philipp , Pansch Christian , Steinhoff Tobias , Wahl Martin , Weinberger Florian , Scotti Marco
Published: July 2024

Marine heatwaves have caused massive mortality in coastal benthic ecosystems, altering community composition. Here, we aim to understand the effects of single and sequential sublethal heatwaves in a temperate benthic ecosystem, investigating their disturbance on various levels of ecological hierarchy, i.e. individual physiology, trophic groups’ biomass and ecosystem carbon fluxes. To do so, we performed a near-natural experiment using outdoor benthic mesocosms along spring/summer, where communities were exposed to different thermal regimes: without heatwaves (0HW), with one heatwave (1HW) and with three heatwaves (3HWs). Gastropods were negatively impacted by one single heatwave treatment, but the exposure to three sequential heatwaves caused no response, indicating ecological stress memory. The magnitude of ecosystem carbon fluxes mostly decreased after 1HW, with a marked negative impact on mesograzers’ feeding, while the overall intensity of carbon fluxes increased after 3HWs. Consumers’ acclimation after the exposure to sequential heatwaves increased grazing activity, representing a threat for the macroalgae biomass. The evaluation of physiological responses and ecological interactions is crucial to interpret variations in community composition and to detect early signs of stress. Our results reveal the spread of heatwave effects along the ecological hierarchical levels, helping to predict the trajectories of ecosystem development.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Neighbourhood benthic configuration reveals hidden co-occurrence social diversity
Authors: Kininmonth Stuart , Ferrando Diana López , Becerro Mikel
Published: July 2024

Ecological interactions among benthic communities are crucial for shaping marine ecosystems. Understanding these interactions is essential for predicting how ecosystems will respond to environmental changes, invasive species, and conservation management. However, determining the prevalence of species interactions at the community scale is challenging. To overcome this challenge, we employ tools from social network analysis, specifically exponential random graph modelling (ERGM). Our approach explores the relationships among animal and plant organisms within their neighbourhoods. Inspired by companion planting in agriculture, we use spatiotemporal co-occurrence as a measure of mixed species interaction. In other words, the variety of community interactions based on co-occurrence defines what we call ‘co-occurrence social diversity’. Our objective is to use ERGM to quantify the proportion of interactions at both the simple paired level and the more complex triangle level, enabling us to measure and compare co-occurrence social diversity. Applying our approach to the Spanish coastal zone across eight sites, five depths, and sunlit/shaded aspects, we discover that 80% of sessile communities, consisting of over a hundred species, exhibit co-occurrence social diversity, with 5% of species consistently forming associations with other species. These organism-level interactions probably have a significant impact on the overall character of the site.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Quantifying stability and resilience of eco-social keystone species complexes for coastal marine ecosystems of the Caribbean Sea and eastern Pacific: applications in conservation and monitoring programmes
Authors: Ortiz Marco , Hermosillo-Núñez Brenda
Published: July 2024

The local stability and resilience of 13 eco-social
keystone species complexes
(eco-social KSCs)—considered as conservation and monitoring units—were quantified in coastal marine ecosystems located in the Caribbean and eastern Pacific. Based on Routh–Hurwitz’s criterion and Levins’ criteria, the eco-social KSCs corresponding to Islas Marietas National Park (Mexico) emerged as the most locally stable and resilient ecosystem. To the contrary, the eco-social KSCs determined for Guala Guala Bay (Chile) and Xcalak Reef National Park (Caribbean) were the least stable and resilient, respectively. In terms of sensitivity, the eco-social KSCs corresponding to El Cobre Bay (Chile) presented the greatest number of sensitive components. The ecological section of the KSCs is formed by a tri-trophic network, dominating self-negative feedbacks. In the case of the socio-economic section, the fisher could exhibit the three types of self-feedbacks, and instead, the demand should be controlled. The identification of eco-social KSCs and the quantification of their stabilities and resiliences allow us to approach ecosystem-based fisheries management under a climate change context. Therefore, we suggest assessing and monitoring the persistence of the eco-social KSCs herein analysed over time, as a way to conserve the fundamental network structure of these ecosystems intervened by fishing.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Collective intelligence facilitates emergent resource partitioning through frequency-dependent learning
Authors: Ogino Mina , Farine Damien R.
Published: July 2024

Deciding where to forage must not only account for variations in habitat quality but also where others might forage. Recent studies have suggested that when individuals remember recent foraging outcomes, negative frequency-dependent learning can allow them to avoid resources exploited by others (indirect competition). This process can drive the emergence of consistent differences in resource use (resource partitioning) at the population level. However, indirect cues of competition can be difficult for individuals to sense. Here, we propose that information pooling through collective decision-making—i.e. collective intelligence—can allow populations of group-living animals to more effectively partition resources relative to populations of solitary animals. We test this hypothesis by simulating (i) individuals preferring to forage where they were recently successful and (ii) cohesive groups that choose one resource using a majority rule. While solitary animals can partially avoid indirect competition through negative frequency-dependent learning, resource partitioning is more likely to emerge in populations of group-living animals. Populations of larger groups also better partition resources than populations of smaller groups, especially in environments with more choices. Our results give insight into the value of long- versus short-term memory, home range sizes and the evolution of specialization, optimal group sizes and territoriality.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
In vitro comparison of viral replication and cytopathology induced by SARS-CoV-2 variants
Authors: Phadke Kruttika S. , Higdon Nathaniel B. A. , Bellaire Bryan H.
Published: July 2024

A myriad of coronaviruses cause diseases from a common cold to severe lung infections and pneumonia. SARS-CoV-2 was discovered to be the etiologic agent of the Coronavirus pandemic and many laboratory techniques were examined for virus culture and basic and applied research. Understanding the replication kinetics and characterizing the effect the virus has on different cell lines is crucial for developing in vitro studies. With the emergence of multiple variants of SARS-CoV-2, a comparison between their infectivity and replication in common cell lines will help give us a clear understanding of their characteristic differences in pathogenicity. In this study we compared the cytopathic effect and replication of Wild-Type (USA/WA1), Omicron (B.1.1.529), and Delta (B.1.617.2) variants on five different cell lines; VeroE6, VeroE6 cells expressing high endogenous ACE2, VeroE6 cells expressing human ACE2 and TMPRSS2, Calu3 cells highly expressing human ACE2 and A549 cells. This data will aid researchers with experimental planning and viral pathogenicity analysis and provide a baseline for testing any future variants.
BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE
Authors: Rojas Rocío , Griñán-Ferré Christian , Castellanos Aida , Griego Ernesto , Martínez Marc , Navarro-López Juan de Dios , Jiménez-Díaz Lydia , Rodríguez-Álvarez José , del Cerro David Soto , Castillo Pablo E , Pallàs Mercè , Fadó Rut , Casals Núria
Published: July 2024

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the liver’s production of ketone bodies, primarily β-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200μM) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and ω-3 docosahexaenoic acid (200μM), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.
Bioadhesive Hydrogel-Coupled and Miniaturized Ultrasound Transducer System for Long-Term, Wearable Neuromodulation
Authors: Tang Kai Wing Kevin , Jeong Jinmo , Hsieh Ju-Chun , Yao Mengmeng , Ding Hong , Wang Wenliang , Liu Xiangping , Pyatnitskiy Ilya , He Weilong , Moscoso-Barrera William D. , Lozano Anakaren Romero , Artman Brinkley , Huh Heeyong , Wilson Preston S. , Wang Huiliang
Published: July 2024

Transcranial focused ultrasound has become a promising non-invasive approach for neuromodulation applications, particularly for neurodegenerative diseases and psychiatric illnesses. However, its implementation in wearable neuromodulation has thus far been limited due to the devices’ large size, which needs external supporting systems for the neuromodulation process. Furthermore, the need for ultrasound gel for acoustic coupling between the device and skin limits the viability for long-term use, due to its inherent susceptibility to dehydration and lack of adhesiveness to form a stable interface. Here, we report a wearable miniaturized ultrasound device with size comparable to standard EEG/ECG electrodes integrated with bioadhesive hydrogel to achieve efficient acoustic intensity upon ultrasound stimulation for long-term, wearable primary somatosensory cortical stimulation. Specifically, air-cavity Fresnel lens (ACFAL) based self-focusing acoustic transducer (SFAT) was fabricated using a lithography-free microfabrication process. Our transducer was able to achieve an acoustic intensity of up to 30.7 W/cm2(1.92 MPa) in free-field with a focal depth of 10 mm. Bioadhesive hydrogel was developed to address the need for long-term stability of acoustic couplant for ultrasound application. The hydrogel demonstrated less than 13% attenuation in acoustic intensity and stable adhesion force of 0.961 N/cm over 35 days. Leveraging our bioadhesive hydrogel-integrated wearable ultrasound transducer, we were able to suppress somatosensory evoked potentials elicited by median nerve stimulation via functional electrical stimulation over 28 days, demonstrating the efficacy of our transducer for long-term, wearable neuromodulation in the brain.
PATJ regulates cell stress responses and vascular remodeling post-stroke
Authors: Zhang Mengqi , Jiang Wei , Arkelius Kajsa , Swanson Raymond A. , Ma Dengke K. , Singhal Neel S.
Published: July 2024

PALS1-associated tight junction (PATJ) protein is linked to metabolic disease and stroke in human genetic studies. Despite the recognized role of PATJ in cell polarization, its specific functions in metabolic disease and ischemic stroke recovery remain largely unexplored. Using a mouse model of stroke, we found post-ischemic stroke duration-dependent increase of PATJ abundance in endothelial cells. PATJ knock-out (KO) HEK293 cells generated by CRISPR-Cas9 suggest roles for PATJ in cell proliferation, migration, mitochondrial stress response, and interactions with the Yes-associated protein (YAP)-1 signaling pathway. Notably,PATJdeletion altered YAP1 nuclear translocation.PATJKO cells demonstrated extensive transcriptional reprograming based on RNA sequencing analysis. Crucially, we identified dysregulation in genes central to vascular development, stress response, and metabolism, includingRUNX1,HEY1,NUPR1, andHK2. These insights offer a new understanding of PATJ’s complex regulatory functions within cellular and vascular physiology and help lay the groundwork for therapeutic strategies targeting endothelial PATJ-mediated pathways for stroke rehabilitation and neurovascular repair.
No evidence that individual alpha frequency (IAF) represents a mechanism underlying motion-position illusions
Authors: Cottier Timothy , Turner William , Chae Violet J. , Holcombe Alex O. , Hogendoorn Hinze
Published: July 2024

Motion-Position Illusions (MPIs) involve the position of an object being misperceived in the context of motion (i.e. when the object contains motion, is surrounded by motion, or is moving). A popular MPI is the flash-lag effect, where a static object briefly presented in spatiotemporal alignment with a moving object, is perceived in a position behind the moving object. Recently, Cottier et al. (2023) observed that there are stable individual differences in the magnitude of these illusions, and possibly even their direction. To investigate the possible neural correlates of these individual differences, the present study explored whether a trait-like component of brain activity, individual alpha frequency (IAF), could predict individual illusion magnitude. Previous reports have found some correlations between IAF and perceptual tasks. Participants (N=61) viewed the flash-lag effect (motion and luminance), Fröhlich effect, flash-drag effect, flash-grab effect, motion-induced position shift, twinkle-goes effect, and the flash-jump effect. In a separate session, five minutes of eyes-open and eyes-closed resting state EEG data was recorded. Correlation analyses revealed no evidence for a correlation between IAF and the magnitude of any MPIs. Overall, these results suggest that IAF does not represent a mechanism underlying MPIs, and that no single shared mechanism underlies these effects. This suggests that discrete sampling at alpha frequency is unlikely to be responsible for any of these illusions.
A temporal gap in sensory streams amplifies the influence of subsequent input on decision making
Authors: Sospedra Alejandro , Canals Santiago , Marcos Encarni
Published: July 2024

Decision making involves evaluating options and predicting their likely outcomes. Traditional laboratory studies of decision making often employ tasks involving the discrimination of perceptual evidence, where sensory information is constant and presented continuously. However, during natural behavior, decision making usually involves intermittent information streams, punctuated by periods with no input. To investigate decision making under such conditions, we designed a perceptual task where participants observed tokens sequentially jumping from a central circle to one of two peripheral targets, disappearing shortly after. Participants were required to report which target they believed would have received most tokens by the trial’s end. Half of the trials included a temporal gap, during which no information was displayed. To better understand decision-making dynamics, we introduced specific patterns of token jumps. We found that participants made choices with less available information and disproportionally weighted the information presented immediately after the gap more heavily than they did when no gap was present. Traditional computational models, which assume uniform or gradual decay or increase of weighting of information over time, could not account for this effect. A control task with randomly presented information further confirmed that the disproportionate weighting of post-gap information is a robust feature of the decision-making process. These findings highlight the importance of studying decision making in environments with intermittent information and temporal gaps, where the timing and structure of inputs critically shape behavior.

Significance statement

Decision making in real-world environments often involves intermittent information, where key evidence might be separated by temporal gaps. Our study demonstrate that people disproportionately rely on information received immediately after such gaps, weighting the same information more heavily than when no gap is present. Traditional decision-making models do not account for this effect, as they lack mechanisms to capture how temporal disruptions shape evidence weighting. By understanding how gaps influence decision making, this research provides insights into how people adapt their decisions in fluctuating environments, with implications for fields ranging from neuroscience to artificial intelligence.
DOG1 prevents AFPs activation by AHG1 to control dormancy separately from ABA core signaling
Authors: Krüger Thorben , Brandt Dennis , Sodenkamp Johanna , Gasper Michael , Romera-Branchat Maida , Ahloumessou Florian , Gehring Elena , Drotleff Julia , Bell Christopher , Kramer Katharina , Eirich Jürgen , Soppe Wim J J , Finkemeier Iris , Née Guillaume
Published: July 2024

Seed dormancy determines germination timing and thereby critically influences seed plant adaptation and overall fitness. DELAY OF GERMINATION1 (DOG1) is a conserved central regulator of dormancy acting in concert with the phytohormone abscisic acid (ABA) through negative regulation of ABA HYPERSENSITIVE GERMINATION (AHG) 1 and AHG3 phosphatases. The current molecular mechanism of DOG1 signaling proposes that it regulates the activation state of central ABA-related SnRK2 kinases. Here, we unveil DOG1’s functional autonomy from the regulation of ABA core signaling components and unravel its pivotal control over the activation of ABSCISIC ACID INSENSITIVE FIVE BINDING PROTEINs (AFPs). Our data revealed a DOG1-AHG1-AFP relay in which AFPs’ genuine activation by AHG1 is contained by DOG1 to prevent the breakdown of maturation-imposed ABA responses independently of ABA-related kinase activation status. This work offers a molecular understanding of how plants fine-tune germination timing, while preserving seed responsiveness to adverse environmental cues, and thus represents a milestone in the realm of conservation and breeding programs.

One-Sentence Summary

Autonomous control of maturation-imposed ABA responses by DOG1 enables seeds to regulate dormancy and stress-reactivity traits independently.
The evolution of local adaptation in long-lived species
Authors: Hablützel Loraine , Mullon Charles , Schmid Max
Published: July 2024

Many species experience heterogeneous environments and adapt genetically to local conditions. The extent of such local adaptation has been shown to depend on a balance between divergent selection and gene flow, but also on other factors such as phenotypic plasticity or the genetic architecture of traits. Here, we explore the role of life history in this process. We develop a quantitative genetics model and run individual-based simulations to contrast the evolution of local adaptation between short- and long-lived species. We show that life history does not have a unidirectional effect on local adaptation. Instead, local adaptation varies with a species’ life cycle and how this cycle modulates the scheduling of selection and dispersal among stage classes. When a longer generation time is associated with more frequent events of selection than dispersal, local adaptation is more pronounced in long-lived than in short-lived species. If otherwise dispersal occurs more frequently than selection, long-lived species evolve weaker local adaptation. Our simulations confirm these findings and further highlight how the scheduling of selection and dispersal shape additive genetic variance, effective dispersal between patches, and the genetic response at quantitative trait loci. Taken together, our results suggest that the effect of longevity on local adaptation depends on the specifics of a species’ life cycle, potentially explaining why current meta-analyses have not consistently detected this effect.
Ascorbic acid and gallic acid mitigate behavioural deficits and loss of cerebellar myelin induced by Bisphenol-A in Wistar rats
Authors: Adigun Kabirat Oluseun , Ehinmowo Michael Ibukun , Folarin Oluwabusayo , Adebiyi Olamide Elizabeth
Published: July 2024

Background

Bisphenol-A (BPA) is a chemical component of plastics, polycarbonates, and epoxy resins making it an environmentally ubiquitous chemical. Its toxicity has been linked to several disorders including neurological disorders. Gallic acid (GA) and Ascorbic acid (AA) are both antioxidants that have been reported to have neuroprotective effects. We therefore investigated the neuroprotective effects of GA and AA on BPA-induced neurotoxicity.

Forty-eight (48) Wistar rats were grouped into Control, BPA, BPA+AA, BPA+GA, AA, and GA groups with eight rats in each group. All treatments were administered via oral gavage for 21 days. Behavioral experiments were conducted to assess forelimb strength (hanging wire test), anxiety (open field and elevated plus maze tests), depression (forced swim test), and spatial memory (Morris water maze). Rats were perfused and brain samples were collected for Luxol fast blue staining. Sera were collected to evaluate the levels of inflammatory cytokines via Enzyme-Linked Immunosorbent Assay.

Results

There was no significant difference in hanging latency between all the groups. There were also no significant changes in the open field test but the elevated plus maze showed an increase in time spent in closed arms in the BPA group indicative of anxiety. GA and AA reduced the duration of immobility that was elevated in the BPA group which suggests they have antidepressant-like effects. Additionally, we observed disruption in the Purkinje cell layer of the cerebellum in the BPA-alone group.

Conclusion

BPA seems to cause anxiety and depressive-like effects which are ameliorated by the gallic acid and ascorbic acid.
Metacommunity theory and metabarcoding reveal the environmental, spatial, and biotic drivers of meiofaunal communities in sandy beaches
Authors: Macher Jan-Niklas , Pichler Maximilian , Creer Simon , Martínez Alejandro , Fontaneto Diego , Renema Willem
Published: July 2024

Sandy beaches are important ecosystems providing coastal protection and recreation, but they face significant threats from human activities and sea level rise. They are inhabited by meiofauna, small benthic invertebrates that are highly abundant and diverse, but are commonly understudied biotic components of beach ecosystems. Here, we investigate the factors shaping meiofaunal metacommunities by employing Generalised Dissimilarity Modelling (GDM) and Joint Species Distribution Modelling (JSDM) to study community turnover and assembly processes. We analysed over 550 meiofauna samples from a >650 km stretch of the southern North Sea coastline using a metabarcoding approach. Our findings reveal that environmental factors, especially Distance from Low Tide and Sediment Grain Size, are important drivers of meiofauna community turnover. This highlights the influence of the gradient from marine to terrestrial habitats and sediment conditions. Spatial factors, which indicate dispersal limitations, also significantly impact community composition, challenging the view that marine meiofauna have broad geographic distributions. The JSDM results show that species sorting by environmental conditions is the dominant process in community assembly with increasing environmental differences between sampling sites, but that biotic associations, or similar environmental preferences, are a major driver of community assembly at sites with similar environmental conditions. Further, we find that spatial factors also significantly influence community assembly across the study region. By facilitating the inference of ecological niches for a high number of meiofaunal taxa, JSDM provides a powerful framework for understanding the ecology of these animals. Our results highlight the importance of considering environmental gradients and dispersal limitations in meiofauna and beach ecosystem research, and future research should aim at adding information on functional traits and biotic interactions under varying environmental conditions to understand meiofauna community dynamics and resilience.
Reward history guides focal attention in whisker somatosensory cortex
Authors: Ramamurthy Deepa L , Rodriguez Lucia , Cen Celine , Li Siqian , Chen Andrew , Feldman Daniel E
Published: July 2024

Prior reward is a potent cue for attentional capture, but the underlying neurobiology is largely unknown. In a novel whisker touch detection task, we show that mice flexibly shift attention between specific whiskers on a trial-by-trial timescale, guided by the recent history of stimulus-reward association. Two-photon calcium imaging and spike recordings revealed a robust neurobiological correlate of attention in the somatosensory cortex (S1), boosting sensory responses to the attended whisker in L2/3 and L5, but not L4. Attentional boosting in L2/3 pyramidal cells was topographically precise and whisker-specific, and shifted receptive fields toward the attended whisker. L2/3 VIP interneurons were broadly activated by whisker stimuli, motion, and arousal but did not carry a whisker-specific attentional signal, and thus did not mediate spatially focused tactile attention. Together, these findings establish a new model of focal attention in the mouse whisker tactile system, showing that the history of stimuli and rewards in the recent past can dynamically engage local modulation in cortical sensory maps to guide flexible shifts in ongoing behavior.
Leveraging Grating-Based Flickers: A Leap Toward Practical, Visually Comfortable, and High-Performance Dry EEG Code-VEP BCI
Authors: Dehais Frédéric , Cabrera Castillos Kalou , Ladouce Simon , Clisson Pierre
Published: July 2024

Abstract

Purpose

Reactive Brain-Computer Interfaces (rBCIs) typically rely on repetitive visual stimuli, which can strain the eyes and cause attentional distraction. To address these challenges, we propose a novel approach rooted in visual neuroscience to design visual Stimuli for Augmented Response (StAR). The StAR stimuli consist of small randomly-orientedGabororRickerpatches that optimize foveal neural response while reducing peripheral distraction.

Methods

In a factorial design study, 24 participants equipped with an 8-dry electrodes EEG system focused on series of target flickers presented under three formats: traditional ’Plain’ flickers,Gabor-based, orRicker-based flickers. These flickers were part of a five-classes Code Visually Evoked Potentials (c-VEP) paradigm featuring low frequency, short, and aperiodic visual flashes.

Results

Subjective ratings revealed thatGaborandRickergratings were visually comfortable and nearly invisible in peripheral vision compared to plain flickers. Moreover,GaborandRicker-based textures achieved higher accuracy (93.6% and 96.3%, respectively) with only 88 seconds of calibration data, compared to plain flickers (65.6%). A follow-up online implementation of this experiment was conducted to validate our findings within the frame of naturalistic operations. During this trial, remarkable accuracies of 97.5% in a cued task and 94.3% in an asynchronous digicode task were achieved, with a mean decoding time as low as 1.68 seconds.

Conclusion

This work demonstrates the potential to expand BCI applications beyond the lab by integrating visually unobtrusive systems with gel-free, low density EEG technology, thereby making BCIs more accessible and efficient. The datasets, algorithms, and BCI implementations are shared through open-access repositories.
Development of 3-in-1 nanotherapeutic strategies for ovarian cancer
Authors: Durocher Emma , McGrath Sean , Gahunia Esha , Matsuura Naomi , Gadde Suresh
Published: July 2024

Among gynecological cancers, ovarian cancer causes the most fatality. Platin-based chemotherapy is the primary therapeutic option, but it is limited by a variety of drug resistance mechanisms. Ovarian cancer is a complex and challenging disease to treat, and combination approaches have shown stronger efficacy than a single drug alone. However, they still need to overcome challenges, such as the non-selective distribution of drugs, and side effects caused by each drug in the combination. To overcome these issues, here we explored a 3-in-1 combination nanotherapeutic approach containing cisplatin, olaparib, and metformin for ovarian cancer. To encapsulate hydrophilic cisplatin and metformin inside the nanoparticle (NP) core, we developed cisplatin polymer prodrugs and metformin derivatives. Our results showed successful development of 3-in-1 NPs containing cisplatin, olaparib, and metformin, and they are stable in the physiological conditions. In vitro evaluation showed each agent in the 3-in-1 NPs is active and exerts therapeutic effects, contributing to ovarian cancer cell killing at lower concentrations. These results provide insight into developing novel nanotherapeutic strategies for improving ovarian cancer treatment.
The N-degron pathway governs autophagy to promote thermotolerance inArabidopsis
Authors: Kim Seu Ha , Park Jun Seok , Lee Myoung-Hoon , Seo Joongyu , Kim Jaekwan , Yang Woo Seok , Park Jihye , Yoo Kwangmin , Choi Jungmin , Seo Jong-Bok , Song Hyun Kyu , Park Ohkmae K.
Published: July 2024

Autophagy is a vital process that enables plants to adapt to various environmental changes. During heat stress (HS), misfolded and denatured proteins accumulate in cells, necessitating autophagy for their removal. Here, we show that a core autophagy component ATG8a is targeted for degradation via the Arg/N-degron pathway.ATG8ais expressed as two alternatively spliced transcripts encoding ATG8a isoforms, namely ATG8a(S) and ATG8a(L), with distinct N-termini. While ATG8a(S) remains stable, ATG8a(L) is N-terminally processed to expose the Arg/N-degron, leading to its degradation. UBR7, identified as an N-recognin, is responsible for ubiquitination and proteasomal degradation of ATG8a(L). Notably,ATG8a(S)andATG8a(L)show dynamic expression patterns, fluctuating ATG8a levels during the HS and recovery periods. Our findings highlight the crucial role of ATG8a turnover in conferring thermotolerance, which is governed by Arg/N-degron-mediated regulation. Understanding the molecular basis of ATG8a stability will provide valuable insights into plant resilience to HS under changing climatic conditions.
AncientBorreliagenomes document the evolutionary history of louse-borne relapsing fever
Authors: Swali Pooja , Booth Thomas , Tan Cedric C.S. , McCabe Jesse , Anastasiadou Kyriaki , Barrington Christopher , Borrini Matteo , Bricking Adelle , Buckberry Jo , Büster Lindsey , Carlin Rea , Gilardet Alexandre , Glocke Isabelle , Irish Joel , Kelly Monica , King Megan , Petchey Fiona , Peto Jessica , Silva Marina , Speidel Leo , Tait Frankie , Teoaca Adelina , Valoriani Satu , Williams Mia , Madgwick Richard , Mullan Graham , Wilson Linda , Cootes Kevin , Armit Ian , Gutierrez Maximiliano G. , van Dorp Lucy , Skoglund Pontus
Published: July 2024

Several disease-causing bacteria have transitioned from tick-borne to louse-borne transmission, a process associated with increased virulence and genome reduction. However, the historical time frame and speed of such evolutionary transitions have not been documented with ancient genomes. Here, we discover four ancient cases ofBorrelia recurrentis, the causative agent of louse-borne relapsing fever, in Britain between ∼600 and 2,300 years ago, and sequence whole genomes up to 29-fold coverage. We estimate a recent divergence from the closest tick-borne ancestor, likely within the last ∼8,000 years. We reconstruct a chronology of gene losses and acquisitions using the pan-genome of related species, and show that almost all of the reductive evolution observed inB. recurrentishad occurred by ∼2,000 years ago, and was thus a rapid process after divergence. Our observations provide a new understanding of the origins ofB. recurrentisand document complex reductive evolution in a specialist vector-borne pathogen.
Optimal thermal niche-tracking buffers wild great tits against climate change
Authors: López-Idiáquez David , Cole Ella F. , Regan Charlotte E. , Sheldon Ben C.
Published: July 2024

Animal and plant populations are responding to climate change by shifting the timing of key seasonal events. However, while measuring responses of natural systems on human calendars provides a standard scale of measurement it reveals little about the underlying biological causes and mechanisms of change. Here, using data from a six decade longitudinal, individual-based, study of great titsParus major, we show that changing the timing of breeding has enabled birds to track specific temperatures at different stages in reproduction. We show, further, that multiple measures of reproductive success are maximised at intermediate, stage-specific, temperatures that correspond to the temperatures tracked while climate has changed in recent decades. Finally, we show that tracking temperatures has allowed great tits to match reproduction with a key food source for nestling development, the winter mothOperophtera brumata. Consequently, phenotypic plasticity in reproductive timing has enabled great tits to track temporal changes in the environmental conditions that maximise individual reproductive success. Shifting our perspective from analysing the phenological timing of life history events under climate change to analysing changes relative to environmental gradients has the potential to shed new light on the causes, mechanisms, and consequences of these shifts.
Systematic identification of Y-chromosome gene functions in mouse spermatogenesis
Authors: Subrini Jeremie , Varsally Wazeer , Balaguer Balsells Irina , Bensberg Maike , Sioutas Georgios , Ojarikre Obah , Maciulyte Valdone , Gylemo Bjorn , Crawley Katharine , Courtis Katherine , de Rooij Dirk G , Turner James MA
Published: July 2024

The mammalian Y chromosome is essential for male fertility, but how individual Y genes regulate spermatogenesis is poorly understood. To resolve this question, we generate a deletion series of the mouse Y chromosome, creating thirteen Y-deletant mouse models and conducting exhaustive reproductive phenotyping. Eight Y genes, including several that are deeply conserved and exhibit testis-specific expression, are dispensable for spermatogenesis. For others, we uncover novel functions, including a role for Uty in establishment and differentiation of spermatogonia, and for Zfy2 in ensuring meiotic pairing and reciprocal recombination between the sex chromosomes. We also generate the first mouse equivalent of the human infertility AZFa deletion, revealing cumulative detrimental effects of Y-gene loss on spermatogenesis. We use single nuclei RNAseq to identify candidate mechanisms by which Y genes regulate the germ cell transcriptome and reveal an unexpected impact of Y genes on testis supporting cells. Our study represents a paradigm for the complete functional dissection of a mammalian Y chromosome and advances our knowledge of human infertility and Y-chromosome evolution.
The evolutionary ancient MEIS transcription factors actuate lineage-specific transcription to establish cardiac fate
Authors: Darieva Zoulfia , Zarrineh Peyman , Phillips Naomi , Mallen Joshua , Mora Araceli Garcia , Donaldson Ian , Bridoux Laure , Douglas Megan , Dias Henriques Sara F , Schulte Dorothea , Birket Matthew J , Bobola Nicoletta
Published: July 2024

Control of gene expression is commonly mediated by distinct combinations of transcription factors (TFs). This cooperative action allows multiple biological signals to be integrated at specific regulatory elements, resulting in highly specific gene expression patterns in space and time. It is unclear whether combinatorial binding is also necessary to bring together TFs with distinct biochemical functions, which collaborate to effectively recruit and activate RNA polymerase II. Using a cardiac differentiation model, we find that the largely ubiquitous, evolutionary ancient homeodomain proteins MEIS are essential for activating a cardiac-specific gene expression program. MEIS TFs act asactuators, fully activating transcriptional programs selected by lineage-restricted TFs to drive the dynamic progression of cardiac differentiation. Combinatorial binding of MEIS with lineage-enriched TFs, GATA and HOX, provides selectivity, guiding MEIS to function at cardiac-specific enhancers. In turn, MEIS TFs promote accumulation of the methyltransferase KMT2D to initiate lineage-specific enhancer commissioning. MEIS combinatorial binding dynamics, dictated by the changing dosage of its partners, drive cells into progressive stages of cardiac differentiation. Our results uncover tissue-specific transcriptional activation as the result of ubiquitousactuator TFsharnessing general transcriptional coactivators at tissue-specific enhancers, to which they are directed by binding with lineage- and domain-specific TFs.
The distribution of the hemlock woolly adelgid in Canada
Authors: MacQuarrie Chris J K , Gray Meghan , Bullas-Appleton Erin , Kimoto Troy , Mielewczyk Nicole , Neville Ron , Ogden Jeffrey B , Fidgen Jeffrey G , Turgeon Jean J.
Published: July 2024

The hemlock woolly adelgid,Adelges tsugaeAnnand (Hemiptera: Adelgidae) has distinct native and invasive populations in Canada. On Canada’s west coast the adelgid is a native insect feeding on western hemlock,Tsuga heterophylla(Raf.) Sarg. and mountain hemlock,Tsuga mertensiana(Bong.) Carrière (Pinaceae). In eastern Canada, the adelgid is an invasive species that attacks and kills eastern hemlock,Tsuga canadensis(L.) Carrière (Pinaceae). We obtained all records ofA. tsugaein institutional and public databases and develop updated range maps, phenologies and dispersal estimates for the species in British Columbia and eastern Canada In British ColumbiaA. tsugae’s distribution is centred around the lower mainland and on Vancouver Island but with populations in the interior and along the Pacific coast that have been poorly explored and which could be sources of biological control agents to manage invasive populations in the east. In eastern Canada, the adelgid has invaded all of southern Nova Scotia, portions of the Niagara region in Ontario as far west as Hamilton, and at least one site on the north shore of Lake Ontario. No populations have been found in New Brunswick, Quebec or Prince Edward Island. Finaly, we estimated the rate of spread in Nova Scotia at 12.6 ± 8.2 to 20.5 ± 27.21 km/year.
Frequency coding of multisensory integration in the local field potentials of the medial pulvinar
Authors: Vittek Anne-Laure , Juan Cécile , Gaillard Corentin , Mercier Manuel , Girard Pascal , Ben Hamed Suliann , Cappe Céline
Published: July 2024

The pulvinar is a posterior thalamic nucleus, with a heterogeneous anatomo-functional organization. It is divided into four parts, including the medial pulvinar, which is densely connected with primary unisensory and multisensory cortical regions, and subcortical structures, including the superior colliculus. Based on this connectivity, the medial pulvinar may play an important role in sensory processing and multisensory integration. However, its contribution to multisensory integration has rarely been directly investigated. To fill this knowledge gap, two macaque monkeys were trained on a fixation task, during which auditory, visual and audiovisual stimuli were presented. We characterize local field potentials of the medial pulvinar associated with these stimuli. In the temporal domain, we describe an early and a late period showing multisensory integration, both dominated by sub-additive processes (the audiovisual response is inferior to the sum of the unisensory responses). In the frequency domain, multisensory integration, mostly sub-additive, is predominant in the lower frequencies (90% of recorded signals in 4.5-8.5Hz and 96% in 8.5-20Hz). Prevalence largely decreases in high frequencies (54% in 35-60Hz, 37% in 60-120Hz). This suggests that the medial pulvinar is a multisensory hub, integrating visual and auditory information in different frequency bands and contributing to cortico-pulvino-cortical multisensory computational loops.
Adolescent choices and caregiver roles: Understanding individual and interpersonal influences on sexual decision-making in South Africa
Authors: Makkan Heeran , Machira Yvonne Wangui , Mthembu Funeka , Masibi Omphile , Molefe Thuso , Maenetje Pholo , Muturi-Kioi Vincent , Price Matt A. , Edward Vinodh Aroon , Chetty-Makkan Candice
Published: July 2024

South African adolescents are at-risk for HIV infection. Understanding the factors influencing sexual decision-making is crucial for developing effective HIV prevention strategies. We conducted a qualitative study with adolescents and caregivers in Rustenburg, South Africa to explore individual and interpersonal factors that influence adolescent sexual decision-making. Focus Group Discussions (FGDs) were conducted in English and Setswana with 17 adolescents (13 females and 4 males) and 19 caregivers (17 females and 2 males) between April and July 2018. Thematic analysis revealed that while adolescents had access to sexual education from various sources, where the knowledge does not translate into healthy sexual decision-making. A contributing barrier was the lack of effective communication and support between caregivers and adolescents in discussing topics related to sexual activity. Although adolescents expressed a strong need to be understood and supported by caregivers regarding their sexual activity, there was perceived distrust, judgemental attitude from caregivers, poor role models of a father figure, and the traditional taboo of having these discussions with caregivers. While female adolescents and female caregivers discussed sensitive matters, this type of communication was limited with adolescent males. Male adolescents were uncomfortable communicating with either caregiver, fearing caregiver judgemental attitudes and being misunderstood. Female caregivers perceived male caregiver roles to be absent and non-engaging when it came to adolescent education and support in sexual matters. Caregivers desired to support their children, yet they seemed to doubt their skills. Communication tools and guidance on how adolescents and caregivers could communicate about sensitive matters could create enabling environments for adolescents to make informed, healthy decisions regarding their risky sexual behaviours. To address adolescent intention-behaviour gap, future interventions could consider gain-framed messaging within intervention packages to promote healthy sexual choices.
Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake
Authors: Klemets Annabel , Reppo Ingrid , Krigul Kertu Liis , Volke Vallo , Aasmets Oliver , Org Elin
Published: July 2024

Context

The gut microbiome has been shown to be in a bidirectional interaction with type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described.

Objective

We investigate the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyze whether the pre-treatment gut microbiome can predict the treatment efficacy.

Methods

Gut microbiome fecal samples donated at four timepoints (Baseline, Month 1, Month 3; Month 12) were studied using 16S ribosomal RNA gene sequencing and analysis. Subjects additionally donated plasma and urine samples for quantitative measurement of clinical markers before treatment initiation and at Months 3 and 12. Repeated measures ANOVA paired with paired t-tests were used to analyze the effects of drug initiation on the gut microbiome. Pearson correlation was used to identify microbial features associated with the change in clinical parameters.

Results

Semaglutide and empagliflozin use is associated with changes in the gut microbiome after treatment initiation, but changes in microbial diversity were not detected. The baseline gut microbiome predicted changes in glycohemoglobin for semaglutide and empagliflozin users.

Conclusion

Our findings suggest that semaglutide and empagliflozin impact the gut microbial community during treatment. In addition, the baseline gut microbiome can predict semaglutide treatment effects.
Introduction of Dengue Virus Serotype 3 in the Afar Region, Ethiopia
Authors: Mekonnen Feleke , Khan Bilal A. , Nibret Endalkachew , Munshea Abaineh , Tsega Daniel , Endalamaw Demeke , Tadesse Senait , Yismaw Gizachew , Lankir Damtie , Ali Jemal , Ulinici Mariana , Orsini Emanuele , Susnjar Ursa , Carletti Tea , Licastro Danilo , Bitew Molalegne , Giovanetti Marta , Marcello Alessandro
Published: July 2024

The genetic analysis of the Dengue virus circulating in Ethiopia’s Afar region, in 2023, identified three distinct introductions with spatiotemporal clustering linked to genomes from Asia and Italy. These findings are crucial for enhancing prevention and control strategies, reinforcing the necessity to provide sustainable tools for genomic epidemiology in Africa.