bluuebunny/crossref_metadata_2025 huggingface dataset:
Illuminating evaporating protostellar outflows: ERIS/SPIFFIER reveals the dissociation and ionization of HH 900
Authors: Reiter Megan , Haworth Thomas J , Manara Carlo F , Ramsay Suzanne , Klaassen Pamela D , Itrich Dominika , McLeod Anna F
Published: October 2023

Protostellar jets and outflows are signposts of active star formation. In H ii regions, molecular tracers like CO only reveal embedded portions of the outflow. Outside the natal cloud, outflows are dissociated, ionized, and eventually completely ablated, leaving behind only the high-density jet core. Before this process is complete, there should be a phase where the outflow is partially molecular and partially ionized. In this paper, we capture the HH 900 outflow while this process is in action. New observations from the Enhanced Resolution Imager and Spectrograph/SPIFFIER near-infrared (IR) integral field unit spectrograph using the K-middle filter (λ = 2.06–2.34 μm) reveal H2 emission from the dissociating outflow and Br-γ tracing its ionized skin. Both lines trace the wide-angle outflow morphology but H2 only extends ∼5000 au into the H ii region while Br-γ extends the full length of the outflow (∼12 650 au), indicating rapid dissociation of the molecules. H2 has higher velocities further from the driving source, consistent with a jet-driven outflow. Diagnostic line ratios indicate that photoexcitation, not just shocks, contributes to the excitation in the outflow. We argue that HH 900 is the first clear example of an evaporating molecular outflow and predict that a large column of neutral material that may be detectable with Atacama Large Millimeter Array accompanies the dissociating molecules. Results from this study will help guide the interpretation of near-IR images of externally irradiated jets and outflows such as those obtained with the JWST in high-mass star-forming regions where these conditions may be common.
Evaluating transformative innovation policy in a formative way: Insights from Vinnova’s food mission experiment
Authors: Boni Alejandra , Velasco Diana , Molas-Gallart Jordi , Schot Johan
Published: October 2023

This article presents the insights from an evaluation of a transformative policy experiment, in the food domain, conducted at the Swedish Agency of Innovation (Vinnova). To be consistent with the principles and objectives of these policies, it was necessary to implement a formative evaluation approach developed in the Transformative Innovation Policy Consortium (TIPC), that is supportive of experimental policies designed for highly complex and uncertain environments. The article presents the main characteristics of this approach and its differences and similarities with other proposals to assess transformative innovation policies. Next, the article describes how the evaluation was conducted in Vinnova during a 2-year engagement. Subsequently, the main insights gleaned from the process are highlighted in terms of (1) understanding the expectations of actors; (2) what has been learned by doing, from a technical and organizational point of view; and (3) the constraints that emerged during the engagement. It is then argued that the TIPC- formative evaluation approach challenges the role of evaluators, stretching them, and requires different attitudes from those that are common in evaluation practice.
Review of Lumbosacral MR Neurography
Authors: George Valerie , Ismail Mohammed , Tilmans Luke , Ajam Amna , Nguyen Xuan
Published: October 2023

Magnetic resonance neurography (MRN) is increasingly used for the evaluation of lumbosacral plexopathy and peripheral neuropathy.1 Although clinical evaluation and electroclinical studies are helpful in evaluating function, they are limited in their ability to characterize the underlying pathology. Electromyography is very sensitive for nerve injury but lacks specificity and cannot depict the level of anatomic detail often needed to localize the nerve lesion and for treatment planning.1 Furthermore, conventional imaging studies, such as MRI or CT, have a role in evaluating extrinsic structural abnormalities that may compress the nerves, such as retroperitoneal hematomas or pelvic abscesses, but are unable to adequately depict the lumbosacral plexus and peripheral nerves due to limited imaging contrast between neural tissue and adjacent soft tissues.2 With advances in MR technology and acquisition technique, MRN has become a frequently requested advanced imaging modality for the detection of lumbosacral plexopathy and muscles and nonneural structures in the lumbar spine and pelvis.1
,
3
Associations between parental adherence to healthy lifestyles and cognitive performance in offspring: A prospective cohort study in China
Authors: Lv Rongxia , Huang Yuhui , Huang Siyi , Wu Shiyi , Wang Siwen , Hu Guangyu , Ma Yanan , Song Peige , Chavarro Jorge E. , Subramanian S.V. , Lu Chunling , Li Zhihui , Yuan Changzheng
Published: October 2023

Background:

Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring's cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring's cognitive performance during adolescence and young adulthood in China.

Methods:

We included 2531 adolescents aged 10–15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0–5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring's fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).

Results:

Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29–0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16–0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring's healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring's cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring's overall crystallized intelligence.

Conclusions:

Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring's cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.
A framework for untangling the consequences of artificial light at night on species interactions
Authors: Seymoure Brett , Dell Anthony , Hölker Franz , Kalinkat Gregor
Published: October 2023

Although much evidence exists showing organismal consequences from artificial light at night (ALAN), large knowledge gaps remain regarding ALAN affecting species interactions. Species interactions occur via shared spatio-temporal niches among species, which may be determined by natural light levels. We review how ALAN is altering these spatio-temporal niches through expanding twilight or full Moon conditions and constricting nocturnal conditions as well as creating patches of bright and dark. We review literature from a database to determine if ALAN is affecting species interactions via spatio-temporal dynamics. The literature indicates a growing interest in ALAN and species interactions: 58% of the studies we analysed have been published since 2020. Seventy-five of 79 studies found ALAN altered species interactions. Enhancements and reductions of species interactions were equally documented. Many studies revealed ALAN affecting species interactions spatially, but few revealed temporal alterations. There are biases regarding species interactions and ALAN—most studies investigated predator–prey interactions with vertebrates as predators and invertebrates as prey. Following this literature review, we suggest avenues, such as remote sensing and animal tracking, that can guide future research on the consequences of ALAN on species interactions across spatial and temporal axes.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Part-night exposure to artificial light at night has more detrimental effects on aphid colonies than fully lit nights
Authors: Heinen Robin , Sanchez-Mahecha Oriana , Martijn Bezemer T. , Dominoni Davide M. , Knappe Claudia , Kollmann Johannes , Kopatsch Anton , Pfeiffer Zoë A. , Schloter Michael , Sturm Sarah , Schnitzler Jörg-Peter , Corina Vlot A. , Weisser Wolfgang W.
Published: October 2023

Artificial light at night (ALAN) threatens natural ecosystems globally. While ALAN research is increasing, little is known about how ALAN affects plants and interactions with other organisms. We explored the effects of ALAN on plant defence and plant–insect interactions using barley (
Hordeum vulgare
) and the English grain aphid (
Sitobion avenae
). Plants were exposed to ‘full’ or ‘part’ nights of 15–20 lux ALAN, or no ALAN ‘control’ nights, to test the effects of ALAN on plant growth and defence. Although plant growth was only minimally affected by ALAN, aphid colony growth and aphid maturation were reduced significantly by ALAN treatments. Importantly, we found strong differences between full-night and part-night ALAN treatments. Contrary to our expectations, part ALAN had stronger negative effects on aphid colony growth than full ALAN. Defence-associated gene expression was affected in some cases by ALAN, but also positively correlated with aphid colony size, suggesting that the effects of ALAN on plant defences are indirect, and regulated via direct disruption of aphid colonies rather than via ALAN-induced upregulation of defences. Mitigating ecological side effects of ALAN is a complex problem, as reducing exposure to ALAN increased its negative impact on insect herbivores.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Long-term exposure to experimental light affects the ground-dwelling invertebrate community, independent of light spectra
Authors: Spoelstra Kamiel , Teurlincx Sven , Courbois Matthijs , Hopkins Zoë M. , Visser Marcel E. , Jones Therésa M. , Hopkins Gareth R.
Published: October 2023

Our planet endures a progressive increase in artificial light at night (ALAN), which affects virtually all species, and thereby biodiversity. Mitigation strategies include reducing its intensity and duration, and the adjustment of light spectrum using modern light emitting diode (LED) light sources. Here, we studied ground-dwelling invertebrate (predominantly insects, arachnids, molluscs, millipedes, woodlice and worms) diversity and community composition after 3 or 4 years of continued nightly exposure (every night from sunset to sunrise) to experimental ALAN with three different spectra (white-, and green- and red-dominated light), as well as for a dark control, in natural forest-edge habitat. Diversity of pitfall-trapped ground-dwelling invertebrates, and the local contribution to beta diversity, did not differ between the dark control and illuminated sites, or between the different spectra. The invertebrate community composition, however, was significantly affected by the presence of light. Keeping lights off during single nights did show an immediate effect on the composition of trapped invertebrates compared to illuminated nights. These effects of light on species composition may impact ecosystems by cascading effects across the food web.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
How artificial light at night may rewire ecological networks: concepts and models
Authors: Sanders Dirk , Hirt Myriam R. , Brose Ulrich , Evans Darren M. , Gaston Kevin J. , Gauzens Benoit , Ryser Remo
Published: October 2023

Artificial light at night (ALAN) is eroding natural light cycles and thereby changing species distributions and activity patterns. Yet little is known about how ecological interaction networks respond to this global change driver. Here, we assess the scientific basis of the current understanding of community-wide ALAN impacts. Based on current knowledge, we conceptualize and review four major pathways by which ALAN may affect ecological interaction networks by (i) impacting primary production, (ii) acting as an environmental filter affecting species survival, (iii) driving the movement and distribution of species, and (iv) changing functional roles and niches by affecting activity patterns. Using an allometric–trophic network model, we then test how a shift in temporal activity patterns for diurnal, nocturnal and crepuscular species impacts food web stability. The results indicate that diel niche shifts can severely impact community persistence by altering the temporal overlap between species, which leads to changes in interaction strengths and rewiring of networks. ALAN can thereby lead to biodiversity loss through the homogenization of temporal niches. This integrative framework aims to advance a predictive understanding of community-level and ecological-network consequences of ALAN and their cascading effects on ecosystem functioning.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Scaling artificial light at night and disease vector interactions into socio-ecological systems: a conceptual appraisal
Authors: Coetzee Bernard W. T. , Burke Ashley M. , Koekemoer Lizette L. , Robertson Mark P. , Smit Izak P. J.
Published: October 2023

There is burgeoning interest in how artificial light at night (ALAN) interacts with disease vectors, particularly mosquitoes. ALAN can alter mosquito behaviour and biting propensity, and so must alter disease transfer rates. However, most studies to date have been laboratory-based, and it remains unclear how ALAN modulates disease vector risk. Here, we identify five priorities to assess how artificial light can influence disease vectors in socio-ecological systems. These are to (i) clarify the mechanistic role of artificial light on mosquitoes, (ii) determine how ALAN interacts with other drivers of global change to influence vector disease dynamics across species, (iii) determine how ALAN interacts with other vector suppression strategies, (iv) measure and quantify the impact of ALAN at scales relevant for vectors, and (v) overcome the political and social barriers in implementing it as a novel vector suppression strategy. These priorities must be addressed to evaluate the costs and benefits of employing appropriate ALAN regimes in complex socio-ecological systems if it is to reduce disease burdens, especially in the developing world.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Forest tree extracts induce resistance toPseudomonas syringaepv.tomatoin Arabidopsis
Authors: Soltaniband Veedaa , Barrada Adam , Delisle-Houde Maxime , Dorais Martine , Tweddell Russell J. , Michaud Dominique
Published: October 2023

Background

The widespread use of conventional pesticides to control plant fungal and bacterial pathogens poses significant risks to human health and the environment, and there is an urgent need for safer and more sustainable alternatives in agricultural management. Studies have shown that plant extracts can be effective in controlling plant diseases either by directly targeting the pathogens or by reinforcing the host plant’s own defenses. Here, we examined the potential of ethanolic extracts from forest tree species eastern hemlock, English oak, eastern red cedar and red pine for their antibacterial activity againstPseudomonas syringaepv.tomato(Pst) strain DC3000 and the ability of these forestry by-products to trigger effective defense responses in the model plantArabidopsis thaliana.

Results

The four tree extracts exhibited direct toxic effects againstPstDC3000, as notably observed for the English oak extract inhibiting bacterial growth and showing bactericidal activity at relatively low concentrations. Using an Arabidopsis line expressing reporter protein ß-glucuronidase under the control of a salicylic acid-inducible pathogenesis-related protein gene promoter, the extracts were shown also to induce defense-related genes expression in leaf tissue. RT-qPCR assays with DNA primers for different gene markers further confirmed this conclusion and highlighted gene-inducing effects for the tree extracts triggering, at different rates, the expression of salicylic acid- and oxidative stress-responsive genes. The extracts direct antibacterial effects, combined with their defense gene-inducing effectsin planta, resulted in a strong host plant-protecting effect againstPstDC3000 associated with bacterial growth rates reduced by ∼75 to 98% seven days post-infection, depending on the extract.

Conclusions

These findings show the effectiveness of tree extracts as eventual plant protectants against the plant bacterial pathogenPst. In a broader perspective, they suggest the potential of these forestry by-products as a source of bioactive compounds useful in plant protection and as a sustainable, eco-friendly alternative to conventional synthetic pesticides for the management of economically important plant pathogens.
Gut microbiota promotes pain in fibromyalgia
Authors: Cai Weihua , Haddad May , Haddad Rana , Kesten Inbar , Hoffman Tseela , Laan Reut , Wong Calvin , Brown Nicole , Tansley Shannon , Lister Kevin C. , Hooshmandi Mehdi , Wang Feng , Sharif Behrang , Westfall Susan , Sahar Tali , Clayton Charlotte , Wu Neil , Zhang Ji , Bar-Yoseph Haggai , Pitashny Milena , Mogil Jeffrey S. , Prager-Khoutorsky Masha , Séguéla Philippe , King Irah L. , De Koninck Yves , Brereton Nicholas J.B , Gonzalez Emmanuel , Shir Yoram , Minerbi Amir , Khoutorsky Arkady
Published: October 2023

Fibromyalgia is a chronic syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. Despite affecting 2–4% of the population, primarily women1, the cause and underlying mechanisms of fibromyalgia remain elusive, and effective targeted treatments are currently unavailable. The gut microbiota of women with fibromyalgia differs from healthy controls2,3. However, it is unknown whether changes in gut microbiota have a causal role in mediating pain and other symptoms of fibromyalgia. Here, we show that fecal microbiota transplantation (FMT) from individuals with fibromyalgia, but not from healthy controls, into germ-free mice induces persistent pain hypersensitivity. FMT from fibromyalgia patients led to a reduction in intraepidermal nerve fiber density and alterations in the peripheral immune profile, and induced activation of spinal microglia, which contributed to the development of pain in mice. Notably, the pain hypersensitivity in mice that were administered microbiota from fibromyalgia patients resolved after FMT from healthy controls. Consistent with these findings, an open-label pilot study showed that transplanting microbiota from healthy individuals to humans with fibromyalgia alleviated pain and reduced overall symptom severity. Thus, altered gut microbiota has a causal role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.
APOE4poses opposite effects of plasma LDL on white matter integrity in older adults
Authors: Ye Zhenyao , Pan Yezhi , McCoy Rozalina G. , Bi Chuan , Chen Mo , Feng Li , Yu Jiaao , Lu Tong , Liu Song , Gao Si , Hatch Kathryn S. , Ma Yizhou , Chen Chixiang , Mitchell Braxton D. , Thompson Paul M. , Hong L. Elliot , Kochunov Peter , Ma Tianzhou , Chen Shuo
Published: October 2023

INTRODUCTION

APOE4 is a strong genetic risk factor of Alzheimer’s disease and is associated with changes in metabolism. However, the interactive relationship between APOE4 and plasma metabolites on the brain remains largely unknown.

MEHODS

In the UK Biobank, we investigated the moderation effects of APOE4 on the relationship between 249 plasma metabolites derived from nuclear magnetic resonance spectroscopy on whole-brain white matter integrity, measured by fractional anisotropy using diffusion magnetic resonance imaging.

RESULTS

The increase in the concentration of metabolites, mainly LDL and VLDL, is associated with a decrease in white matter integrity (b= -0.12, CI= [-0.14, -0.10]) among olderAPOE4carriers, whereas an increase (b= 0.05, CI= [0.04, 0.07]) among non-carriers, implying a significant moderation effect ofAPOE4(b= -0.18, CI= [-0.20,-0.15]).

DISCUSSION

The results suggest that lipid metabolism functions differently inAPOE4carriers compared to non-carriers, which may inform the development of targeted interventions forAPOE4carriers to mitigate cognitive decline.
Early- but not late-adolescent Western diet consumption programs for long-lasting memory impairments in male but not female rats
Authors: Hayes Anna M. R. , Kao Alicia E. , Ahuja Arun , Subramanian Keshav S. , Klug Molly E. , Rea Jessica J. , Nourbash Anna C. , Tsan Linda , Kanoski Scott E.
Published: October 2023

Early life Western diet (WD) consumption leads to impaired memory function, particularly for processes mediated by the hippocampus. However, the precise critical developmental window(s) during which WD exposure negatively impacts hippocampal function are unknown. Here, we exposed male and female rats to a WD model involving free access to a variety of high-fat and/or high-sugar food and drink items during either the early-adolescent period (postnatal days [PN] 26-41; WD-EA) or late-adolescent period (PN 41-56; WD-LA). Control (CTL) rats were given healthy standard chow throughout both periods. To evaluate long-lasting memory capacity well beyond the early life WD exposure periods, we performed behavioral assessments after both a short (4 weeks for WD-EA, 2 weeks for WD-LA) and long (12 weeks for WD-EA, 10 weeks for WD-LA) period of healthy diet intervention. Results revealed no differences in body weight or body composition between diet groups, regardless of sex. Following the shorter period of healthy diet intervention, both male and female WD-EA and WD-LA rats showed deficits in hippocampal-dependent memory compared to CTL rats. Following the longer healthy diet intervention period, memory impairments persisted in male WD-EA but not WD-LA rats. In contrast, in female rats the longer healthy diet intervention reversed the initial memory impairments in both WD-EA and WD-LA rats. Collectively, these findings reveal that early-adolescence is a critical period of long-lasting hippocampal vulnerability to dietary insults in male but not female rats, thus highlighting developmental- and sex-specific effects mediating the relationship between the early life nutritional environment and long-term cognitive health.
Complement C1q-dependent engulfment of alpha-synuclein induces ENS-resident macrophage exhaustion and accelerates Parkinson’s-like gut pathology
Authors: Mackie PM , Koshy J , Bhogade M , Hammoor T , Hachmeister W , Lloyd GM , Paterno G , Bolen M , Tansey MG , Giasson BI , Khoshbouei H
Published: October 2023

Deposition of misfolded α-synuclein (αsyn) in the enteric nervous system (ENS) is found in multiple neurodegenerative diseases. It is hypothesized that ENS synucleinopathy contributes to both the pathogenesis and non-motor morbidity in Parkinson’s Disease (PD), but the cellular and molecular mechanisms that shape enteric histopathology and dysfunction are poorly understood. Here, we demonstrate that ENS-resident macrophages, which play a critical role in maintaining ENS homeostasis, initially respond to enteric neuronal αsyn pathology by upregulating machinery for complement-mediated engulfment. Pharmacologic depletion of ENS-macrophages or genetic deletion of C1q enhanced enteric neuropathology. Conversely, C1q deletion ameliorated gut dysfunction, indicating that complement partially mediates αsyn-induced gut dysfunction. Internalization of αsyn led to increased endo-lysosomal stress that resulted in macrophage exhaustion and temporally correlated with the progression of ENS pathology. These novel findings highlight the importance of enteric neuron-macrophage interactions in removing toxic protein aggregates that putatively shape the earliest stages of PD in the periphery.
Enabling brain-wide mapping of layer-specific functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression
Authors: Chang Wei-Tang , Lin Weili , Giovanello Kelly S.
Published: October 2023

Layer-dependent functional magnetic resonance imaging (fMRI) is a promising yet challenging approach for investigating layer-specific functional connectivity (FC). Achieving a brain-wide mapping of layer-specific FC requires several technical advancements, including sub-millimeter spatial resolution, sufficient temporal resolution, functional sensitivity, global brain coverage, and high spatial specificity. Although gradient echo (GE)–based echo planar imaging (EPI) is commonly used for rapid fMRI acquisition, it faces significant challenges due to the draining-vein contamination. In this study, we addressed these limitations by integrating velocity-nulling (VN) gradients into a GE-BOLD fMRI sequence to suppress vascular signals from the vessels with fast-flowing velocity. The extravascular contamination from pial veins was mitigated using a GE-EPI sequence at 3T rather than 7T, combined with phase regression methods. Additionally, we incorporated advanced techniques, including simultaneous multi-slice (SMS) acceleration and NOise Reduction with DIstribution Corrected principal component analysis (NORDIC PCA) denoising, to improve temporal resolution, spatial coverage, and signal sensitivity. This resulted in a VN fMRI sequence with 0.9-mm isotropic spatial resolution, a repetition time (TR) of 4 seconds, and brain-wide coverage. The VN gradient strength was determined based on results from a button-pressing task. Using resting-state data, we validated layer-specific FC through seed-based analyses, identifying distinct connectivity patterns in the superficial and deep layers of the primary motor cortex (M1), with significant inter-layer differences. Further analyses with a seed in the primary sensory cortex (S1) demonstrated the reliability of the method. Brain-wide layer-dependent FC analyses yielded results consistent with prior literature, reinforcing the efficacy of VN fMRI in resolving layer-specific functional connectivity. Given the widespread availability of 3T scanners, this technical advancement has the potential for significant impact across multiple domains of neuroscience research.
Environmental change drives multi-generational shifts in the gut microbiome that mirror changing animal fitness
Authors: Williams Candace L. , Williams Claire E. , King Shauna N. D. , Shier Debra M.
Published: October 2023

Gut microbiomes can dramatically affect host health and fitness and can also be highly dynamic in response to changing environmental conditions. This intricate interplay between gut microbiota, environmental pressures, and host health necessitates accounting for all these variables when predicting the response of animals to a changing environment. These predictions are of broad concern but are highly relevant to conservation biology, and more specifically to populations transitioning from the wild to human care for the purposes ofex situbreeding programs. Captivity can dramatically alter both host-associated microbial communities and host health, but the dynamics of how the host and microbiome transition between the wild and captive state—within and across generations—are not well described. Here, we evaluate the microbiome and host fitness metrics for Pacific pocket mice (Perognathus longimembris pacificus) during the establishment of anex situconservation breeding program to characterize how pocket mice and their microbiomes respond to the environmental pressures of captivity across five generations. We found that the microbiome assumes a novel, stable conformation after two to three generations in captivity and that the patterns observed in the transitioning microbiota mirror the patterns of transitioning hosts’ weight and reproductive metrics. Moreover, we identify several microbial taxa which are correlated with successful reproduction. Our results provide insight not only into the effects of captivity but can be broadly applicable for understanding the effects of environmental change on organisms and their gut microbiota, which we propose may require multiple generations to reach an alternative stable state.
Nationally endorsed learning objectives to improve course design in introductory biology
Authors: Hennessey Kelly M , Freeman Scott
Published: October 2023

Introductory biology for majors is one of the most consequential courses in STEM, with annual enrollments of several hundred thousand students in the United States alone. To support increased student success and meet current and projected needs for qualified STEM professionals, it will be crucial to redesign majors biology by using explicit learning objectives (LOs) that can be aligned with assessments and active learning exercises. When a course is designed in this way, students have opportunities for the practice and support they need to learn, and instructors can collect the evidence they need to evaluate whether students have mastered key concepts and skills. Following an iterative process of review, revision, and evaluation, which included input from over 800 biology instructors around the country, we produced a nationally endorsed set of lesson-level LOs for a year-long introductory biology for major’s course. These LOs are granular enough to support individual class sessions and provide instructors with a framework for course design that is directly connected to the broad themes inVision and Changeand the general statements in the BioCore and BioSkills Guides. Instructors can implement backward course design by aligning these community endorsed LOs with daily and weekly learning activities and with formative and summative assessments.
NeoHeadHunter: an algorithm for the detection, ranking and probabilistic classification of neoepitope candidates
Authors: Zhao Xiaofei
Published: October 2023

Background

The manufacturing of personalized cancer vaccine requires the accurate identification of neoepitopes, abnormal peptides presented by cancer cells and recognized by the host immune system of the cancer patient.

Results

We designed and developed NeoHeadHunter, a computational algorithm and pipeline to detect and rank neoepitope candidates. Unlike other algorithms, NeoHeadHunter can estimate the probability that each predicted neoepitope candidate is true positive. To evaluate NeoHeadHunter, we used the Tumor neoantigEn SeLection Alliance (TESLA) data-set derived from the sequencing of nine patients and characterized by 44 experimentally validated positive neoepitopes, a data-set derived from the sequencing of three cancer patients and characterized by eight experimentally validated positive neoepitopes and a manually curated data-set consisting of 64 experimentally validated positive neoepitopes. Our evaluation shows that NeoHeadHunter performs the best compared with other algorithms for both detecting and ranking neoepitope candidates and that NeoHeadHunter can accurately predict such probabilities.

Conclusions

NeoHeadHunter can increase the effectiveness of personalized cancer vaccine by sensitively detect, accurately rank and probabilistically classify neoepitope candidates. NeoHeadHunter is released under the APACHE-II license athttps://github.com/XuegongLab/neoheadhunterfor academic use.
Semi-automated seizure detection using interpretable machine learning models
Authors: Antonoudiou Pantelis , Basu Trina , Maguire Jamie
Published: October 2023

Numerous methods have been proposed for seizure detection automation, yet the tools to harness these methods and apply them in practice are limited. Here we compare four interpretable and widely-used machine learning models (decision tree, gaussian naïve bayes, passive aggressive classifier, stochastic gradient descent classifier) on an extensive electrographic seizure dataset collected from chronically epileptic mice. We find that the gaussian naïve bayes model achieved the highest precision and f1 score, while also detecting all seizures in our dataset and only requires a small amount of data to train the model and achieve good performance. We use this model to create an open-source python application SeizyML that couples model performance with manual curation allowing for efficient and accurate detection of electrographic seizures.

Author Summary

Seizure detection based on electrographic recordings is critical for epilepsy diagnosis and research. However, the current gold standard for seizure detection is manual curation, which is biased, costly, incredibly laborious, and requires extensive training and expertise, prohibiting advances in epilepsy diagnosis and research. Here we demonstrate that fast, simple, and interpretable machine learning (ML) models are sufficient to detect all seizures in an extensive dataset collected from a well-established mouse model of epilepsy. Importantly, we created an open-source python application, SeizyML, that integrates the most precise model tested here with human curation of the detected events. This semi-automated approach greatly enhances efficiency and precision of seizure detection while also being transparent. We believe that the adoption of semi-automated and transparent technologies is indispensable for understanding ML model predictions, improving their reliability, and fostering trust between ML models and neurodiagnostic professionals.
Involvement of TRPV4 in temperature-dependent perspiration in mice
Authors: Kashio Makiko , Derouiche Sandra , Yoshimoto Reiko U. , Sano Kenji , Lei Jing , Kido Mizuho A. , Tominaga Makoto
Published: October 2023

Reports indicate that an interaction between TRPV4 and anoctamin 1 could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, anoctamin 1 (ANO1) and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca2+increases that was inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice, and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deleted mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with AIGA (acquired idiopathic generalized anhidrosis) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targets to develop agents that regulate perspiration.
Metabolic similarity and the predictability of microbial community assembly
Authors: Vila Jean C.C. , Goldford Joshua , Estrela Sylvie , Bajic Djordje , Sanchez-Gorostiaga Alicia , Damian-Serrano Alejandro , Lu Nanxi , Marsland Robert , Rebolleda-Gomez Maria , Mehta Pankaj , Sanchez Alvaro
Published: October 2023

Abstract

When microbial communities form, their composition is shaped by selective pressures imposed by the environment. Can we predict which communities will assemble under different environmental conditions? Here, we hypothesize that quantitative similarities in metabolic traits across metabolically similar environments lead to predictable similarities in community composition. To that end, we measured the growth rate and by-product profile of a library of proteobacterial strains in a large number of single nutrient environments. We found that growth rates and secretion profiles were positively correlated across environments when the supplied substrate was metabolically similar. By analyzing hundreds of in-vitro communities experimentally assembled in an array of different synthetic environments, we then show that metabolically similar substrates select for taxonomically similar communities. These findings lead us to propose and then validate a comparative approach for quantitatively predicting the effects of novel substrates on the composition of complex microbial consortia.
Development of a genome scale metabolic model for the lager hybrid yeastS. pastorianusto understand evolution of metabolic pathways in industrial settings
Authors: Timouma Soukaina , Balarezo-Cisneros Laura Natalia , Schwartz Jean-Marc , Delneri Daniela
Published: October 2023

In silicotools such as genome-scale metabolic models (GSMM) have shown to be powerful for metabolic engineering of microorganisms. Here, we created the iSP_1513 GSMM for the aneuploid hybridS. pastorianusCBS1513 to allow top-down computational approaches to predict the evolution of metabolic pathways and to aid strain optimisation and media engineering in production processes. The iSP_1513 comprises 4062 reactions, 1808 alleles and 2747 metabolites, and takes into account the functional redundancy in the gene-protein-reaction rule caused by the presence of orthologous genes. Moreover, a universal algorithm to constrain GSMM reactions using transcriptome data was developed as a python library and enabled the integration of temperature as parameter. Essentiality datasets, growth data on various carbohydrates and volatile metabolites secretion were used to validate the model. Overall, the iSP_1513 GSMM represent an important step towards understanding the metabolic capabilities, evolutionary trajectories and adaptation potential ofS. pastorianusin different industrial settings.
Transcriptomic network analysis of brain and bone reveals shared molecular mechanisms underlying Alzheimer’s Disease and related dementias (ADRD) and Osteoporosis
Authors: Nagarajan Archana , Laird Jason , Ugochukwu Obiadada , Reppe Sjur , Gautvik Kaare , Ross Ryan D. , Bennett David A. , Rosen Clifford , Kiel Douglas P. , Higginbotham Lenora A. , Seyfried Nicholas , Lary Christine W.
Published: October 2023

Alzheimer’s disease and related dementias (ADRD) and Osteoporosis (OP) are two prevalent diseases of aging with numerous epidemiological associations, but the underlying molecular mechanisms contributing to this association are unknown. We used WGCNA (weighted gene co-expression network analysis) to develop transcriptomic networks in bone and brain tissue using two different studies to discover common molecular mechanisms. We used RNA-sequencing data from the dorsolateral prefrontal cortex tissue of autopsied brains in 629 participants from ROSMAP (Religious Orders Study and the Memory and Aging Project), including a subset of 298 meeting criteria for inclusion in five ADRD categories and the full set in a secondary analysis, and RNA array data from transiliac bone in 84 participants from the Oslo study of postmenopausal women. After developing each network, we analyzed associations between modules (groups of co-expressed genes) with multiple bone and neurological traits, examined overlap in modules between networks, and performed pathway enrichment analysis to discover conserved mechanisms. We discovered three modules in ROSMAP that showed significant associations with ADRD and bone related traits and four modules in Oslo that showed significant associations with multiple bone outcomes. We found significant module overlap between the two networks, most notably among those modules linked to canonical Wnt signaling and skeletal tissue homeostasis and development. These results were preserved with a network from the full ROSMAP cohort (n=629), which included a broader spectrum of participants. Our results require validation in experimental studies but show support for Wnt signaling as an important driver of pathology in OP and ADRD. We additionally show a strong link between Dementia with Lewy bodies and bone outcomes. These results have translational significance in the development of novel treatments and biomarkers for both ADRD and OP.
Intermittent Nicotine Access is as Effective as Continuous Access in Promoting Nicotine Seeking and Taking in Rats
Authors: Algallal Hajer E , Jacquemet Vincent , Samaha Anne-Noël
Published: October 2023

Nicotine is a principal psychoactive agent in tobacco, contributing to tobacco’s addictive potential. Preclinical studies on the effects of voluntary nicotine intake typically use self-administration procedures that provide continuous nicotine access during each self-administration session. However, many smokers consume cigarettes intermittently rather than continuously throughout each day. For drugs including cocaine and opioids, research in laboratory rats shows that intermittent intake can be more effective than continuous intake in producing patterns of drug use relevant to addiction. We asked, therefore, how intermittent versus continuous nicotine self-administration influences nicotine seeking and taking behaviours. Female and male rats had continuous (i.e., Long Access; LgA, 6 h/day) or intermittent (IntA; 12 min ON, 60 min OFF, for 6 h/day) access to intravenous nicotine (15 µg/kg/infusion), for 12 daily sessions. We then assessed intake, responding for nicotine under a progressive ratio schedule of drug reinforcement and cue- and nicotine-induced reinstatement of drug seeking. We also estimated nicotine pharmacokinetic parameters during LgA and IntA self-administration. Overall, LgA rats took twice more nicotine than did IntA rats, yielding more sustained increases in estimated brain concentrations of the drug. However, the two groups showed similar motivation to seek and take nicotine, as measured using reinstatement and progressive ratio procedures, respectively. Thus, intermittent nicotine use is just as effective as continuous use in producing addiction-relevant behaviours, despite significantly less nicotine exposure. This has implications for modeling nicotine self-administration patterns in human smokers and resulting effects on brain and behaviour.
Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation
Authors: Zhu Wenliang , Du Wan , Rameshbabu Arun Prabhu , Armstrong Ariel Miura , Silver Stewart , Kim Yehree , Wei Wei , Shu Yilai , Liu Xuezhong , Lewis Morag A , Steel Karen P. , Chen Zheng-Yi
Published: October 2023

Mutations inmicroRNA-96(MIR96) cause dominant delayed onset hearing loss DFNA50 without treatment. Genome editing has shown efficacy in hearing recovery by intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications. Here, we developed an editing therapy for a C>A point mutation in the seed region of theMir96gene,Mir9614C>Aassociated with hearing loss by screening gRNAs for genome editors and optimizing Cas9 and sgRNA scaffold for efficient and specific mutation editing in vitro. By AAV delivery in pre-symptomatic (3-week-old) and symptomatic (6-week-old) adultMir9614C>Amutant mice, hair cell on-target editing significantly improved hearing long-term, with an efficacy inversely correlated with injection age. We achieved transient Cas9 expression without the evidence of AAV genomic integration to significantly reduce the safety concerns associated with editing. We developed an AAV-sgmiR96-master system capable of targeting all known humanMIR96mutations. As mouse and humanMIR96sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lays the foundation for future treatment of DFNA50 caused byMIR96mutations.
Biophysical constraints on avian adaptation and diversification
Authors: Sayol Ferran , Reijenga Bouwe , Tobias Joseph A. , Pigot Alex L.
Published: October 2023

The capacity of organisms to adapt to vacant niches or changing environments is limited by physical constraints on morphological evolution. Substantial progress has been made in identifying how these constraints shape the form and function of producers (plants), but our understanding of evolutionary limits in consumers (animals) remains highly limited, in part because the requisite data have not been available at sufficient scale. Using morphometric measurements for all birds, we demonstrate that observed variation is highly restricted—both for beak shape and overall body shape—to triangular regions of morphospace with clearly defined boundaries and vertices. By combining morphometric data with new information on physical functions of measured traits, we provide evidence that the extent of avian morphospace is constrained by biophysical trade-offs between three functional objectives (strength, reach and engulfment capacity) that characterize resource acquisition and processing by the beak, and three locomotory modalities (aerial, aquatic and terrestrial) that characterize avian lifestyles. Our results suggest that over avian evolutionary history, trajectories of morphological change trend towards the vertices, with birds evolving from a core of biophysical generalists to biophysical specialists, associated with faster macroevolutionary turnover of lineages at the periphery or morphospace. Our analyses reveal that the structure of avian morphological diversity follows relatively simple rules defined by biophysical constraints and trade-offs, shedding light on the process shaping modern animal diversity and responses to environmental change.
Quality control ofBradyrhizobiuminoculant strains: Detection ofnosZand correlation of symbiotic efficiency with soybean leaf chlorophyll levels
Authors: Brignoli Damián , Frickel-Critto Emilia , Sandobal Tamara J. , Balda Rocío S. , Castells Cecilia B. , Mongiardini Elías J. , Pérez-Giménez Julieta , Lodeiro Aníbal R.
Published: October 2023

Greenhouse gas emissions, such as N2O from excessive N-fertilizer use, are of concern. Symbiotic N2-fixation by pulses as soybean might mitigate this issue, for which inoculants carrying locally adaptedBradyrhizobiumstrains are recommended. In the frame of this goal, enhancing the quality control of these inoculants is required on two key aspects: determining the presence ofnosZ, for the strains being able to reduce N2O, and assessing N2-fixation potential. Yet, simple and non- destructive methods to assess N2-fixation are lacking. Here we aimed to leverage the correlation between N and chlorophyll levels by cultivating soybeans in vermiculite with N-free nutrient solution, inoculating them with variousBradyrhizobiumfield isolates, and subsequently measuring chlorophyll with a portable chlorophyllometer, correlating it to symbiotic parameters. We observed significant correlations between chlorophyll and shoot nitrogen levels as well as with nodule dry mass. TwoB. diazoefficiensstrains stood out and possessednosZ. In contrast,B. elkaniiandB. japonicumisolates displayed lower chlorophyll and symbiotic performance, and lackednosZ. Our findings highlight the potential of measuring chlorophyll contents and testing for the presence ofnosZas two straightforward techniques that may enhance quality control, enabling selection of superior and safe locally isolated strains for soybean inoculants.