bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain-state mediated modulation of inter-laminar dependencies in visual cortex
Authors: Das Anirban , Sheffield Alec G. , Nandy Anirvan S. , Jadi Monika P.
Published: February 2023

Spatial attention is a quintessential example of adaptive information processing in the brain and is critical for recognizing behaviorally relevant objects in a cluttered environment. Object recognition is mediated by neural encoding along the ventral visual hierarchy. How the deployment of spatial attention aids these hierarchical computations is unclear. Prior studies point to two distinct mechanisms: an improvement in the efficacy of information directed from one encoding stage to another1–5, and/or a suppression of shared information within encoding stages6,7. To test these proposals, it is crucial to estimate the attentional modulation of unique information flow across and shared information within the encoding stages of the visual hierarchy. We investigated this in the multi-stage laminar network of visual area V4, an area strongly modulated by attention8–10. Using network-based dependency estimation from multivariate data, we quantified the modulation of inter-layer information flow during a change detection task and found that deployment of attention indeed strengthened unique dependencies between the input and superficial layers. Using the partial information decomposition framework11,12, we estimated the modulation of shared dependencies and found that they are reduced specifically in the putative excitatory subpopulations within a layer. Surprisingly, we found a strengthening of unique dependencies within the laminar populations, a finding not previously predicted. Crucially, these modulation patterns were also observed during successful behavioral outcomes (hits) that are thought to be mediated by endogenous brain state fluctuations13–15, and not by experimentally imposed attentive states. Finally, phases of endogenous fluctuations that were optimal for ‘hits’ were associated with reduced neural excitability. A reduction in neural excitability, potentially mediated by diminished shared inputs, suggests a novel mechanism for enhancing unique information transmission during optimal states. By decomposing the modulation of multivariate information, and combined with prior theoretical work16, our results suggest common computations of optimal sensory states that are attained by either task demands or endogenous fluctuations.
McLTP1, a lipid transfer protein isolated from noni seeds induces effective healing of superficial burns
Authors: Kurita Bianca Moreira , de Fátima Pinheiro Rangel Gisele , Rabelo Liviane Maria Alves , de Fátima Goebel de Sousa Tamiris , Macêdo Fernanda Soares , de Carvalho Leitão Renata Ferreira , de Oliveira Hermógenes David , de Alencar Nylane Maria Nunes
Published: February 2023

Burns are health problems that overwhelm the Unified Health System (SUS) in Brazil. Despite the new therapeutic strategies, the costs of treating burns ate still quite high, and there are no effective alternatives for healing the skin. The use of plants with therapeutic potential is popularly used, due to its low cost, easy access and great Brazilian biodiversity.McLTP1, a lipid transfer protein isolated fromMorinda citrifollia(noni) seeds, has shown antinociceptive, anti-inflammatory, antibacterial and antioxidative effects. Therefore, the aim of this study was to investigate the effect of McLTP1 on the healing of superficial burns in mice. The study was approved by CEUA NPDM – UFC (protocol: 02170619-0). The burn was induced by direct contact with a square stainless-steel plate (1.5 cm2). The animals were divided into five experimental groups (n=6-7/grupo) and treated daily with 0.9% NaCl saline solution (Sham), or with topical treatment performed with dermatological creams: Silver sulfadiazine 1% (Sulfa 1%), lanette cream (Vehicle), cream lanette containing 0.25% and 0.5% ofMcLTP1. The animals were euthanized after 14 days.McLTP1 promoted total wound closure after 2 weeks of treatment, reduced histopathological scores at 3rdday, as well as induced the formation of a thicker epithelium and collagens synthesis on 14thday, modulated inflammation by reducing MPO activity, TNF-α, IL-1β and IL-6 levels and increasing IL-10 after 3 days of burn, modulated VEGF production at three times analyzed in this study, increased TGF-β and immunostaining for FGF after 7 days, reduced immunostaining for TNF-α on the 3rdday and exerted an antioxidant function by reducing MDA and nitrite and increasing GSH at day 3. In short,McLTP1 showed an important healing action in this burn model, showing additional anti-inflammatory and antioxidant effects.
Metabolic engineering ofSaccharomyces cerevisiaefor second-generation ethanol production from xylo-oligosaccharides and acetate
Authors: Procópio Dielle Pierotti , Lee Jae Won , Shin Jonghyeok , Tramontina Robson , Ávila Patrícia Felix , Brenelli Lívia Beatriz , Squina Fabio Márcio , Damasio André , Rabelo Sarita Cândida , Goldbeck Rosana , Franco Telma Teixeira , Leak David , Jin Yong-Su , Basso Thiago Olitta
Published: February 2023

Abstract

Simultaneous intracellular depolymerization of xylo-oligosaccharides (XOS) and acetate fermentation by engineeredSaccharomyces cerevisiaeoffers an advance towards more cost-effective second-generation (2G) ethanol production. As xylan is one of the most abundant polysaccharides present in lignocellulosic residues, the transport and breakdown of XOS in an intracellular environment might bring a competitive advantage for recombinant strains in competition with contaminating microbes, which are always present in fermentation tanks; furthermore, acetic acid is a ubiquitous toxic component in lignocellulosic hydrolysates, deriving from hemicellulose and lignin breakdown. In the present work, the previously engineeredS. cerevisiaestrain, SR8A6S3, expressing NADPH-linked xylose reductase (XR), NAD+-linked xylitol dehydrogenase (XDH) (for xylose assimilation), as well as NADH-linked acetylating acetaldehyde dehydrogenase (AADH) and acetyl-CoA synthetase (ACS) (for an NADH-dependent acetate reduction pathway), was used as the host for expressing of two β-xylosidases,GH43-2andGH43-7, and a xylodextrin transporter,CDT-2, fromNeurospora crassa, yielding the engineered strain SR8A6S3-CDT2-GH432/7. Both β-xylosidases and the transporter were introduced by replacing two endogenous genes,GRE3andSOR1, that encode aldose reductase and sorbitol (xylitol) dehydrogenase, respectively, which catalyse steps in xylitol production. Xylitol accumulation during xylose fermentation is a problem for 2G ethanol production since it reduces final ethanol yield. The engineered strain, SR8A6S3-CDT2-GH432/7, produced ethanol through simultaneous co-utilization of XOS, xylose, and acetate. The mutant strain produced 60% more ethanol and 12% less xylitol than the control strain when a hemicellulosic hydrolysate was used as a mono- and oligosaccharide source. Similarly, the ethanol yield was 84% higher for the engineered strain using hydrolysed xylan compared with the parental strain. The consumption of XOS, xylose, and acetate expands the capabilities ofS. cerevisiaefor utilization of all of the carbohydrate in lignocellulose, potentially increasing the efficiency of 2G biofuel production.

Highlights

Integration of XOS pathway in an acetate-xylose-consumingS. cerevisiaestrain;

Intracellular fermentation of XOS, acetate and xylose improved ethanol production;

Deletion of bothsor1Δ andgre3Δ reduced xylitol production.
An 8-cage imaging system for automated analyses of mouse behavior
Authors: Hernández Thaís Del Rosario , Joshi Narendra R. , Gore Sayali V. , Kreiling Jill A. , Creton Robbert
Published: February 2023

The analysis of mouse behavior is used in biomedical research to study brain function in health and disease. Well-established rapid assays allow for high-throughput analyses of behavior but have several drawbacks, including measurements of daytime behaviors in a nocturnal animal, effects of animal handling, and the lack of an acclimation period in the testing apparatus. We developed a novel 8-cage imaging system, with animated visual stimuli, for automated analyses of mouse behavior in 22-hour overnight recordings. Software for image analysis was developed in two open-source programs, ImageJ and DeepLabCut. The imaging system was used to measure multiple behaviors, including acclimation to the novel cage environment, day and nighttime activity, stretch-attend postures, location in various cage areas, and habituation to animated visual stimuli. These behaviors were summarized in behavioral profiles, which may be used in further studies to examine treatments for neural disorders.
Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics
Authors: Kim Minsoo , McDonald Eli Fritz , Sabusap Carleen Mae P. , Timalsina Bibek , Joshi Disha , Hong Jeong S. , Rab Andras , Sorscher Eric J. , Plate Lars
Published: February 2023

Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX-661) and Elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry (AP-MS) multiplexed with isobaric Tandem Mass Tags (TMT) was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knock-downs sensitize P67L to VX-445 and further enhance the correction of this variant. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize unresponsive CFTR variants to known and available correctors.
Behavioral estimates of mating success corroborate genetic evidence for pre-copulatory sexual selection in maleAnolis sagreilizards
Authors: Bhave Rachana S. , Seears Heidi A. , Reedy Aaron M. , Wittman Tyler N. , Robinson Christopher D. , Cox Robert M.
Published: February 2023

In promiscuous species, fitness estimates obtained from genetic parentage may often reflect both pre- and post-copulatory components of sexual selection. Directly observing copulations can help isolate the role of pre-copulatory selection, but such behavioral data are difficult to obtain in the wild and may also overlook post-copulatory factors that alter the relationship between mating success and reproductive success. To overcome these limitations, we combined genetic parentage analysis with behavioral estimates of size-specific mating in a wild population of brown anole lizards (Anolis sagrei). Males of this species are twice as large as females and multiple mating among females is common, suggesting the scope for both pre- and post-copulatory processes to shape sexual selection on male body size. Our genetic estimates of reproductive success revealed strong positive directional selection for male size, which was also strongly associated with the number of mates inferred from parentage. In contrast, a male’s size was not associated with the fecundity of his mates or his competitive fertilization success. By simultaneously tracking copulations in the wild via the transfer of colored powder to females by males from different size quartiles, we independently confirmed that large males were more likely than small males to mate. We conclude that body size is primarily under pre-copulatory sexual selection in brown anoles, and that post-copulatory processes do not substantially alter this pre-copulatory selection. Our study also illustrates the utility of combining both behavioral and genetic methods to estimate mating success to disentangle pre- and post-copulatory processes in promiscuous species.
Long lifetime and selective accumulation of the A-type lamins accounts for the tissue specificity of Hutchinson-Gilford progeria syndrome
Authors: Hasper John , Welle Kevin , Swovick Kyle , Hryhorenko Jennifer , Ghaemmaghami Sina , Buchwalter Abigail
Published: February 2023

Mutations to theLMNAgene cause laminopathies including Hutchinson-Gilford progeria syndrome (HGPS) that severely affect the cardiovascular system. The origins of tissue specificity in these diseases are unclear, as the A-type Lamins are abundant and broadly expressed proteins. We show that A-type Lamin protein and transcript levels are uncorrelated across tissues. As protein-transcript discordance can be caused by variations in protein lifetime, we applied quantitative proteomics to profile protein turnover rates in healthy and progeroid tissues. We discover that tissue context and disease mutation each influence A-type Lamin protein lifetime. Lamin A/C has a weeks-long lifetime in the aorta, heart, and fat, where progeroid pathology is apparent, but a days-long lifetime in the liver and gastrointestinal tract, which are spared from disease. The A-type Lamins are insoluble and densely bundled in cardiovascular tissues, which may present an energetic barrier to degradation and promote long protein lifetime. Progerin is even more long-lived than Lamin A/C in the cardiovascular system and accumulates there over time. Progerin accumulation interferes broadly with protein homeostasis, as hundreds of abundant proteins turn over more slowly in progeroid tissues. These findings indicate that potential gene therapy interventions for HGPS will have significant latency and limited potency in disrupting the long-lived Progerin protein. Finally, we reveal that human disease alleles are significantly over-represented in the long-lived proteome, indicating that long protein lifetime may influence disease pathology and present a significant barrier to gene therapies for numerous human diseases.

Significance statement

Many human diseases are caused by mutations to broadly expressed proteins, yet disease mysteriously manifests only in specific tissues. An example of this is Hutchinson-Gilford progeria syndrome (HGPS), which is caused by a mutation to the Lamin A/C protein. We show that this mutation slows the turnover of Lamin A/C proteins in disease-afflicted tissues, causing the mutant “Progerin” protein to accumulate over time and interfere with the normal turnover of hundreds of other proteins. Because Progerin is a long-lived protein, effective therapies for this disease will need to attack the protein and not just the gene that encodes it.
Endogenous Tenocyte Activation Underlies the Regenerative Capacity of Adult Zebrafish Tendon
Authors: Tsai Stephanie L. , Villasenor Steffany , Shah Rishita , Galloway Jenna L.
Published: February 2023

Tendons are essential, frequently injured connective tissues that transmit forces from muscle to bone. Their unique highly ordered, matrix-rich structure is critical for proper function. While adult mammalian tendons heal after acute injuries, endogenous tendon cells, or tenocytes, fail to respond appropriately, resulting in the formation of disorganized fibrovascular scar tissue with impaired function and increased propensity for re-injury. Here, we show that unlike mammals, adult zebrafish tenocytes activate upon injury and fully regenerate the tendon. Using a full tear injury model in the adult zebrafish craniofacial tendon, we defined the hallmark stages and cellular basis of tendon regeneration through multiphoton imaging, lineage tracing, and transmission electron microscopy approaches. Remarkably, we observe that the zebrafish tendon can regenerate and restore normal collagen matrix ultrastructure by 6 months post-injury (mpi). We show that tendon regeneration progresses in three main phases: inflammation within 24 hours post-injury (hpi), cellular proliferation and formation of a cellular bridge between the severed tendon ends at 3-5 days post-injury (dpi), and re-differentiation and matrix remodeling beginning from 5 dpi to 6 mpi. Importantly, we demonstrate that pre-existing tenocytes are the main cellular source of regeneration. Collectively, our work debuts the zebrafish tendon as one of the only reported adult tendon regenerative models and positions it as an invaluable comparative system to identify regenerative mechanisms that may inspire new tendon injury treatments in the clinic.
The representational geometry of cognitive maps under dynamic cognitive control
Authors: Park Seongmin A. , Zolfaghar Maryam , Russin Jacob , Miller Douglas S. , O’Reilly Randall C , Boorman Erie D.
Published: February 2023

Recent work has shown that the brain abstracts non-spatial relationships between entities or task states into representations called cognitive maps. Here, we investigated how cognitive control enables flexible top-down selection of goal-relevant information from multidimensional cognitive maps retrieved from memory. We examined the relationship between cognitive control and representational geometry by conducting parallel analyses of fMRI data and recurrent neural network (RNN) models trained to perform the same task. We found both stable map-like representations in a medial temporal lobe and orbitofrontal cortical network that reflected both task-relevant and irrelevant dimensions and dynamic, orthogonal representations of only relevant task dimensions in a frontoparietal network. These representational motifs also emerged with distinct temporal profiles over the course of training in the RNN, with map-like representations appearing first. We further show that increasing control demands due to incongruence (conflicting responses) between current task-relevant and irrelevant dimensions impact the geometry of subjective representations, and the degree of this effect further accounts for individual differences in cognitive control. Taken together, our findings show how complementary representational geometries balance stability and behavioral flexibility, and reveal an intricate bidirectional relationship between cognitive control and cognitive map geometry.
Effort cost of harvest affects decisions and movement vigor of marmosets during foraging
Authors: Hage Paul , Jang In Kyu , Looi Vivian , Fakharian Mohammad Amin , Orozco Simon P. , Pi Jay S. , Sedaghat-Nejad Ehsan , Shadmehr Reza
Published: February 2023

Our decisions are guided by how we perceive the value of an option, but this evaluation also affects how we move to acquire that option. Why should economic variables such as reward and effort alter the vigor of our movements? In theory, both the option that we choose and the vigor with which we move contribute to a measure of fitness in which the objective is to maximize rewards minus efforts, divided by time. To explore this idea, we engaged marmosets in a foraging task in which on each trial they decided whether to work by making saccades to visual targets, thus accumulating food, or to harvest by licking what they had earned. We varied the effort cost of harvest by moving the food tube with respect to the mouth. Theory predicted that the subjects should respond to the increased effort costs by choosing to work longer, stockpiling food before commencing harvest, but reduce their movement vigor to conserve energy. Indeed, in response to an increased effort cost of harvest, marmosets extended their work duration, but slowed their movements. These changes in decisions and movements coincided with changes in pupil size. As the effort cost of harvest declined, work duration decreased, the pupils dilated, and the vigor of licks and saccades increased. Thus, when acquisition of reward became effortful, the pupils constricted, the decisions exhibited delayed gratification, and the movements displayed reduced vigor.

Significance statement

Our results suggest that as the brainstem neuromodulatory circuits that control pupil size respond to effort costs, they alter computations in the brain regions that control decisions, encouraging work and delaying gratification, and the brain regions that control movements, reducing vigor and suppressing energy expenditure. This coordinated response suggests that decisions and actions are part of a single control policy that aims to maximize a variable relevant to fitness: the capture rate.
Extended fractional-polynomial generalizations of diffusion and Fisher-KPP equations on directed networks: Modeling neurodegenerative progression
Authors: Rahimabadi Arsalan , Benali Habib
Published: February 2023

In a variety of practical applications, there is a need to investigate diffusion or reaction-diffusion processes on complex structures, including brain networks, that can be modeled as weighted undirected and directed graphs. As an instance, the celebrated Fisher-Kolmogorov-Petrovsky-Piskunov (Fisher-KPP) reaction-diffusion equation are becoming increasingly popular for use in graph frameworks by substituting the standard graph Laplacian operator for the continuous one to study the progression of neurodegenerative diseases such as tauopathies including Alzheimer’s disease (AD). However, due to the porous structure of neuronal fibers, the spreading of toxic species can be governed by an anomalous diffusion process rather than a normal one, and if this is the case, the standard graph Laplacian cannot adequately describe the dynamics of the spreading process. To capture such more complicated dynamics, we propose a diffusion equation with a nonlinear Laplacian operator and a generalization of the Fisher-KPP reaction-diffusion equation on undirected and directed networks using extensions of fractional polynomial (FP) functions. A complete analysis is also provided for the extended FP diffusion equation, including existence, uniqueness, and convergence of solutions, as well as stability of equilibria. Moreover, for the extended FP Fisher-KPP reaction-diffusion equation, we derive a family of positively invariant sets allowing us to establish existence, uniqueness, and boundedness of solutions. Finally, we conclude by investigating nonlinear diffusion on a directed one-dimensional lattice and then modeling tauopathy progression in the mouse brain to gain a deeper understanding of the potential applications of the proposed extended FP equations.
Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration
Authors: Liu Wei , Lu Jia-Yin , Wang Ya-Jun , Xu Xin-Xin , Chen Yu-Chen , Yu Sai-Xi , Xiang Xiao-Wei , Chen Xue-Zhu , Jiu Yaming , Gao Hai , Sheng Mengyao , Chen Zheng-Jun , Hu Xinyao , Li Dong , Maiuri Paolo , Huang Xinxin , Ying Tianlei , Xu Guo-Liang , Pang Dai-Wen , Zhang Zhi-Ling , Liu Baohong , Liu Yan-Jun
Published: February 2023

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, high-resolution dynamics and mechanisms underlying this type of cell migration remain unclear. Here, we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo EMT-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-induced mesenchymal migration is highly dependent on the actin cytoskeleton and RhoA signaling, which is responsible for the depolymerization of robust actin stress fibers, the leading-edge protrusion formation, and the rear-edge recontraction. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.
Network-based molecular subtyping of acral melanoma
Authors: Mingzhu Yin , Zhang Yiding , Wang Wenhua , Zhao Shuang , Su Juan , Li Shao , Chen Xiang
Published: February 2023

Acral melanoma is more biologically aggressive with a worse prognosis compared with other melanoma subtypes. However, the molecular basis underlying the biological and clinical behavior of this cancer is still unclear. Here, using the combination of multi-omics data analysis and network-based disease gene prediction algorithm, we first demonstrate the existence of two acral melanoma subtypes which greatly differed in clinical performance, cellular and molecular mechanisms, and discovered a biomarker panel (EREG, VSIG4, FCGR3A, RAB20) that accurately distinguished these two subtypes with the AUC of 0.946, which has been verified by clinical samples. Subtype I has thinner Breslow with a better prognosis. On the contrary, subtype II is a high-risk subtype that is easier to invade the dermis. We further analyzes the intrinsic biological mechanism of the two subtypes from the cellular level, and reveals the important role of macrophages subgroups in the molecular typing of acral melanoma. Feature genes of subtype I are enriched in FCN1+ macrophages that promote inflammatory and immune responses. In contrast, feature genes of subtype II are enriched in SPP1+ macrophages which ha the greatest impact on tumor cells. The identification of the two subtypes opens up important biological and clinical perspectives for acral melanoma.
High-Quality Nuclei Isolation from Postmortem Human Heart Muscle Tissues for Single-Cell Studies
Authors: Araten Sarah , Mathieu Ronald , Jetly Anushka , Shin Hoon , Hilal Nazia , Zhang Bo , Morillo Katherine , Nandan Deepa , Sivankutty Indu , Chen Ming Hui , Choudhury Sangita
Published: February 2023

Single-cell approaches have become an increasingly popular way of understanding the genetic factors behind disease. Isolation of DNA and RNA from human tissues is necessary to analyze multi-omic data sets, providing information on the single-cell genome, transcriptome, and epigenome. Here, we isolated high-quality single-nuclei from postmortem human heart tissues for DNA and RNA analysis. Postmortem human tissues were obtained from 106 individuals, 33 with a history of myocardial disease, diabetes, or smoking, and 73 controls without heart disease. We demonstrated that the Qiagen EZ1 instrument and kit consistently isolated genomic DNA of high yield, which can be used for checking DNA quality before conducting single-cell experiments. Here, we provide a method for single-nuclei isolation from cardiac tissue, otherwise known as the SoNIC method, which allows for the isolation of single cardiomyocyte nuclei from postmortem tissue by nuclear ploidy status. We also provide a detailed quality control measure for single-nuclei whole genome amplification and a pre-amplification method for confirming genomic integrity.
Nomadic ungulate movements under threat: Declining mobility of Mongolian gazelles in the Eastern Steppe
Authors: Mendgen Philipp , Dejid Nandintsetseg , Olson Kirk , Buuveibaatar Bayarbaatar , Calabrese Justin M. , Chimeddorj Buyanaa , Dalannast Munkhnast , Fagan William F. , Leimgruber Peter , Müller Thomas
Published: February 2023

Increasing habitat fragmentation and disturbance threaten long distance movements of ungulates. While the effects of impermeable barriers on ungulate migrations have been well researched, quantitative evidence for gradual and long-term changes of mobility in response to anthropogenic disturbance remains relatively rare.

We investigated changes in movement behavior of Mongolian gazelleProcapra gutturosa, a nomadic ungulate species native to the Mongolian steppe. Using GPS tracking data collected from 62 gazelle individuals between 2007 and 2021, we quantified 16-day displacement distances for each individual as a metric for long-distance movements. We used generalized linear mixed models, generalized additive models and additive quantile mixed models to assess how anthropogenic and environmental factors affected gazelle movement behavior.

Long distance 16-day movements decreased significantly by up to 36 %, from 142 km in 2007 to 92 km in 2021. Changes in gazelle mobility were affected by the increasing number of vehicles in Mongolia, but could not be explained by concurrent changes in other environmental factors like temperature, precipitation or vegetation greenness that often drive ungulate migration behavior. Moreover, we found that gazelle movement decreased close to roads, and that gazelles stayed further away from roads during the snow-free season, when vehicular traffic likely is most intense.

Conserving landscape permeability is essential for maintaining populations of highly mobile species. Our study provides evidence for a gradual decline in gazelle mobility over fifteen years as a response to increasing anthropogenic impact. To date, the transportation infrastructure permeating the Eastern Steppe does not pose physical barriers, yet our findings suggest that increasing traffic volume may create semipermeable barriers to gazelle movement. As human activity is increasing throughout the Eastern Steppe, interactions between ungulates and vehicle traffic need to be closely monitored in order to identify, localize, and mitigate semipermeable barrier effects before landscape permeability is severely altered.
Interactive Bioacoustic Playback as a Tool for Detecting and Exploring Nonhuman Intelligence: “Conversing” with an Alaskan Humpback Whale
Authors: McCowan Brenda , Hubbard Josephine , Walker Lisa , Sharpe Fred , Frediani Jodi , Doyle Laurance
Published: February 2023

Here we report on a rare and opportunistic acoustic “conversation” with an adult female humpback whale, known as Twain, in Southeast Alaska. Post hoc acoustic and statistical analyses of a 20-minute acoustic exchange between the broadcast of a recorded contact call, known as a ‘whup/throp’, with call responses by Twain revealed an intentional human-whale acoustic (and behavioral) interaction. Our results show that Twain participated both physically and acoustically in three phases of interaction (Phase 1: Engagement, Phase 2: Agitation, Phase 3: Disengagement), independently determined by blind observers reporting on surface behavior and respiratory activity of the interacting whale. A close examination of both changes to the latency between Twain’s calls and the temporal matching to the latency of the exemplar across phases indicated that Twain was actively engaged in the exchange during Phase 1 (Engagement), less so during Phase 2 (Agitation), and disengaged during Phase 3 (Disengagement). These results, while preliminary, point to several key considerations for effective playback design, namely the importance of salient, dynamic and adaptive playbacks, that should be utilized in experimentation with whales and other intelligent nonhuman species.
A novel lethal cuticular structural protein, AaCPR100A and its upstream interaction protein, G12-like, function in cuticle and egg shell formation in the yellow fever mosquito,Aedes aegypti
Authors: Chen Jing , Wu Yuchen , Lu Haoran , Cheng Gong , Tu Zhijian Jake , Liao Chenghong , Han Qian
Published: February 2023

AaCPR100A is a structural protein, found in the soft cuticle ofAe. Aegypti. RNAi ofAaCPR100Aresulted in high mortality inAe. Aegyptiand abnormal egg development in the surviving mosquitoes. Over thirty proteins that could interact with AaCPR100A were screened out by yeast two-hybrid assay, and subsequently, further verification by hybrid and GST pull-down assays identified that G12-like had the strongest interaction with AaCPR100A. RNAi ofG12-likesuggested it may be related to larva development. Interestingly, the adults in which theG12-likegenewasknocked down were sensitive to low temperature, and their egg shell formation, production, and hatching were affected.G12-likehas the opposite effect in the upstream expression ofAaCPR100A, promotingAaCPR100Afunction in the larval stage and inhibitingAaCPR100Ain the adult stage. In all, functional studies of AaCPR100A and its interaction protein G12-like provide insight into its involvement in cuticle development and formation and egg shell formation.
A simple cognitive model explains movement decisions during schooling in zebrafish
Authors: Oscar Lital , Li Liang , Gorbonos Dan , Couzin Iain D. , Gov Nir S.
Published: February 2023

While moving, animals must frequently make decisions about their future travel direction, whether they are alone or in a group. Here we investigate this process for zebrafish (Danio rerio), which naturally move in cohesive groups. Employing state-of-the-art virtual reality, we study how real fish follow one or several moving, virtual conspecifics. These data are used to inform, and test, a model of social response that includes a process of explicit decision-making, whereby the fish can decide which of the virtual conspecifics to follow, or to follow some average direction. This approach is in contrast with previous models where the direction of motion was based on a continuous computation, such as directional averaging. Building upon a simplified version of this model [Sridhar et al., 2021], which has been shown to exhibit a spontaneous symmetry-breaking transition from moving along a “compromise” (average) direction, to deciding on following one of the virtual fish. This previously published simplified version was limited to a one-dimensional projection of the fish motion, while here we present a model that describes the motion of the real fish as it swims freely in two-dimensions. Here, we extend our proposed Ising-like model, which inherently describes a spontaneous symmetry-breaking transition from moving along a “compromise” (average) direction, to deciding on following one of the virtual fish. Motivated by experimental observations, the swim speed of the fish in this model uses a burst-and-coast swimming pattern, with the burst frequency being dependent on the distance of the fish from the followed conspecific(s). We demonstrate that this model is able to explain the observed spatial distribution of the real fish behind the virtual conspecifics in the experiments, as a function of their average speed and number. In particular, the model naturally explains the observed critical bifurcations for a freely swimming fish, which appear in the spatial distributions whenever the fish makes a decision to follow only one of the virtual conspecifics, instead of following them as an averaged group. This model can provide the foundation for modeling a cohesive shoal of swimming fish, while explicitly describing their directional decision-making process at the individual level.
Nano-structured Hydrotrope-Caged Cytochrome c with Boosted Stability in Harsh Environments: A Molecular Insight
Authors: Bharadwaj Pranav , Sarkar Dheeraj Kumar , Bisht Meena , Shet Sachin M. , Kotrappanavar Nataraj Sanna , Lokesh Veeresh , Franklin Gregory , Brezovsky Jan , Mondal Dibyendu
Published: February 2023

Green and nano-structured catalytic media are vital for bio-catalysis to attenuate the denaturation tendency of biocata-lysts under severe reaction conditions. Hydrotropes with multi-faceted physiochemical properties represent promising systems for sustainable protein packaging. Herein, the suitability of adenosine-5’-triphosphate (ATP) and cholinium sa-licylate ([Cho][Sal]) ionic liquid (IL) to form nano-structures and to nano-confine Cytochrome c (Cyt c) were demonstrat-ed to enhance the stability and activity under multiple stressors. Experimental and computational analyses were under-taken to explain the nano-structured phenomenon of ATP and IL, structural organizations of nano-confined Cyt c, and site-specific interactions that stabilize the protein structure. Both ATP and IL form nano-structures in aqueous media and could cage Cyt c via multiple nonspecific soft interactions. Remarkably, the engineered molecular nano-cages of ATP (5-10 mM), IL (300 mg/mL), and ATP+IL surrounding Cyt c resulted in 9-to-72-fold higher peroxidase activity than native Cyt c with exceptionally high thermal tolerance (110oC). The polar interactions with the cardiolipin binding site of Cyt c, mediated by hydrotropes, were well correlated with the increased peroxidase activity. Furthermore, higher activity trends were observed in the presence of urea, GuHCl, and trypsin without any protein degradation. Specific binding of hy-drotropes in highly mobile regions of Cyt c (Ω 40-54 residues) and enhanced H-bonding with Lys and Arg offered excel-lent stability under extreme conditions. Additionally, ATP effectively counteracted reactive oxygen species (ROS)-induced denaturation of Cyt c, which was enhanced by the [Sal] counterpart of IL. Overall, this study explored the robustness of nano-structured hydrotropes to have a higher potential for protein packaging with improved stability and activity under extreme conditions. Thus, the present work highlights a novel strategy for real-time industrial bio-catalysis to protect mitochondrial cells from ROS-instigated apoptosis.

Suitability of ATP and [Cho][Sal] ionic liquid to form nanostructured hydrotropes and their utility in protein packaging in extreme conditions are discussed. Both ATP and IL form nanostructures in aqueous media and could cage Cyt c via multiple nonspecific soft interactions. The engineered molecular nanocages surrounding Cyt c resulted in 9-to-72-fold higher peroxidase activity than native Cyt c with exceptionally high thermal tolerance (110°C) and stability in the presence of urea, GuHCl, and trypsin without any protein degradation.
Differential expression of some termite neuropeptides and insulin/IGF-related hormones and their plausible functions in growth, reproduction and caste determination
Authors: Veenstra Jan A.
Published: February 2023

Background

Insulin-like growth factor (IGF) and other Insulin-like peptides (ilps) are important hormones regulating growth and development in animals. Whereas most animals have a single female and male adult phenotype, in some insect species the same genome may lead to different final forms. Perhaps the best known example is the honeybee where females can either develop into queens or workers. More extreme forms of such polyphenism occur in termites, where queens, kings, workers and soldiers coexist. Both juvenile hormone and insulin-like peptides are known to regulate growth and reproduction as well as polyphenism. In termites the role of juvenile hormone in reproduction and the induction of the soldier caste is well known, but the role of IGF and other ilps in these processes remains largely unknown. Here the various termite ilps are identified and hypotheses regarding their functions suggested.

Methods

Genome assemblies and transcriptome short read archives (SRAs) were used to identify insulin-like peptides and neuropeptides in termites and to determine their expression in different species, tissues and castes.

Results and Discussion

Termites have seven different ilps,i.e. gonadulin, IGF and an ortholog ofDrosophilainsulin-like peptide 7 (dilp7), which are commonly present in insects, and four smaller peptides, that have collectively been called short IGF-related peptides (sirps) and individually atirpin, birpin, cirpin and brovirpin. Gonadulin is lost from the higher termites which have however amplified the brovirpin gene, of which they often have two or three paralogs. Based on differential expression of these genes it seems likely that IGF is a growth hormone and atirpin an autocrine tissue factor that is released when a tissue faces metabolic stress. Birpin seems to be responsible for growth and in the absence of juvenile hormone this may lead to reproductive adults or, when juvenile hormone is present, to soldiers. Brovirpin is expressed both by the brain and the ovary and likely stimulates vitellogenesis, while the function of cirpin is less clear.
Neutral models ofde novogene emergence suggest that gene evolution has a preferred trajectory
Authors: Iyengar Bharat Ravi , Bornberg-Bauer Erich
Published: February 2023

New protein coding genes can emerge from genomic regions that previously did not contain any genes, via a process calledde novogene emergence. To synthesize a protein, DNA must be transcribed as well as translated. Both processes need certain DNA sequence features. Stable transcription requires promoters and a polydenylation signal, while translation requires at least an open reading frame (ORF). We develop mathematical models based on mutation probabilities, and the assumption of neutral evolution, to find out how quickly genes emerge and are lost. We also investigate the effect of the order by which DNA features evolve, and if sequence composition is biased by mutation rate. We rationalize how genes are lost much more rapidly than they emerge, and how genes with long ORFs preferentially arise in regions that are already transcribed. Our study not only answers some fundamental questions on the topic ofde novoemergence but also provides a modeling framework for future studies.
DiscoTope-3.0 - Improved B-cell epitope prediction using AlphaFold2 modeling and inverse folding latent representations
Authors: Høie Magnus Haraldson , Gade Frederik Steensgaard , Johansen Julie Maria , Würtzen Charlotte , Winther Ole , Nielsen Morten , Marcatili Paolo
Published: February 2023

Accurate computational identification of B-cell epitopes is crucial for the development of vaccines, therapies, and diagnostic tools. However, current structure-based prediction methods face limitations due to the dependency on experimentally solved structures. Here, we introduce DiscoTope-3.0, a markedly improved B-cell epitope prediction tool that innovatively employs inverse folding structure representations and a positive-unlabelled learning strategy, and is explicitly adapted for both solved and predicted structures. Our tool demonstrates a considerable improvement in performance over existing methods, accurately predicting linear and conformational epitopes across multiple independent datasets. Most notably, DiscoTope-3.0 maintains high predictive performance across solved, relaxed and predicted structures, alleviating the need for experimental validation and extending the general applicability of accurate B-cell epitope prediction by more than 3 orders of magnitude. DiscoTope-3.0 is made widely accessible on two web servers, processing over 100 structures per submission, and as a downloadable package. In addition, the servers interface with RCSB and AlphaFoldDB, facilitating large-scale prediction across over 200 million cataloged proteins. DiscoTope-3.0 is available at:https://services.healthtech.dtu.dk/service.php?DiscoTope-3.0
Improving selection efficiency inC. americana×C. avellanainterspecific hybrids through the development of an indel-based genetic map
Authors: Brainard S.H. , Fischbach J.A. , Braun L.C. , Dawson J.C.
Published: February 2023

This study reports a genetic map created using a progeny family descended from the interspecific hazelnut crossCorylus avellana×Corylus americana. This research represents a critical step in the development of genomic tools that enable the deployment of next-generation sequencing methods in the breeding of hazelnut, specifically the improvement of well-adapted Midwestern hazelnut varieties. To produce this map, we first developed high-density molecular markers using short-read Illumina sequencing of genotype-by-sequencing libraries. By aligning reads to a newly assembled reference genome forC. americana, we were able to identify over 75,000 high-quality indel-based polymorphisms across an F1experimental population. These markers exhibited both high allele depth coverage, and low linkage disequilibrium, making them well-suited to genetic map development. We constructed such a map using 95 individuals from a single F1 family, demonstrating the utility of next-generation sequencing to efficiently and accurately generate high-density genetic maps. This research will improve the efficiency of breeding efforts, both through the validation of specific molecular markers that are associated with agronomically-relevant traits in breeding populations of interest.
Implicit auditory memory in older listeners: from encoding to 6-month retention
Authors: Bianco Roberta , Hall Edward T. R. , Pearce Marcus. T. , Chait Maria
Published: February 2023

Any listening task, from sound recognition to sound-based communication, rests on auditory memory which is known to decline in healthy ageing. However, how this decline maps onto multiple components and stages of auditory memory remains poorly characterised. In an online unsupervised longitudinal study, we tested ageing effects on implicit auditory memory for rapid tone patterns. The test required participants (younger, aged 20-30, and older adults aged 60-70) to quickly respond to rapid regularly repeating patterns emerging from random sequences. Patterns were novel in most trials (REGn), but unbeknownst to the participants, a few distinct patterns reoccurred identically throughout the sessions (REGr). After correcting for processing speed, the response times (RT) to REGn should reflect the information held in echoic and short-term memory before detecting the pattern; long-term memory formation and retention should be reflected by the RT advantage (RTA) to REGr vs REGn which is expected to grow with exposure. Older participants were slower than younger adults in detecting REGn and exhibited a smaller RTA to REGr. Computational simulations using a model of auditory sequence memory indicated that these effects reflect age-related limitations both in early and long-term memory stages. In contrast to ageing-related accelerated forgetting of verbal material, here older adults maintained stable memory traces for REGr patterns up to 6 months after the first exposure. The results demonstrate that ageing is associated with reduced short-term memory and long-term memory formation for tone patterns, but not with forgetting, even over surprisingly long timescales.