bluuebunny/crossref_metadata_2025 huggingface dataset:
Contaminated fungi in dried salted fishes: Isolation, identification, and their inhibition by chitooligosaccharide‐gallic acid conjugate
Authors: Buatong Jirayu , Preedanon Sita , Mittal Ajay , Palamae Suriya , Benjakul Soottawat
Published: October 2023

Contaminated fungi on dried salted fish of three species including Talang queenfish (TQF, Scomberroides commersonianus), Hamilton's thryssa fish (HTF, Thryssa hamiltonii), and Cobia fish (CF, Rachycentron canadum) were isolated and identified. One hundred and sixty‐nine isolates were obtained from TQF and HTF, respectively, while no fungi were detected in CF. The dominant genera were Aspergillus spp. (n = 79), Penicillium spp. (n = 60), and non‐sporulating fungi (n = 30). The representative groups of Aspergillus spp. (n = 6) and Penicillium spp. (n = 3) based on different morphological characteristics were selected for species identification by molecular methods involving ITS1‐5.8s‐ITS2 region and Matrix‐Assisted Laser Desorption/Ionization Time‐of Flight Mass Spectrometer (MALDI‐TOF MS) analysis. The nine isolates were identified to be Aspergillus versicolor (n = 2), Aspergillus montevidensis (n = 3), Penicillium citrinum (n = 3), and Aspergillus sp. (n = 1). The antifungal activity of chitooligosaccharide‐gallic acid (COS‐GAL) conjugate against A. versicolor F1/10M9, A. montevidensis F1/30M20, and P. citrinum F1/23M14 was examined. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were in the range of 0.625–2.5 mg/mL and 1.25–10 mg/mL, respectively. COS‐GAL conjugate at the concentration of 5 mg/mL completely inhibited the spore germination of A. versicolor F1/10M9 and P. citrinum F1/23M14 after 72 h of treatment. COS‐GAL conjugate at 4 × MIC mainly affected the mycelium of A. versicolor F1/10M9 and P. citrinum F1/23M14 after treatment with COS‐GAL conjugate for 3 days by coating mycelium surface and reducing the size of mycelium. Therefore, COS‐GAL conjugate could be used as a food additive to inhibit or prevent the growth of fungi contaminated in dried salted fish or other relevant products.

Practical Application

During processing, dried salted fish can be contaminated with fungi, which may cause food poisoning and food spoilage. The contaminated fungi are capable of producing mycotoxin that is harmful to consumers. Synthetic food preservatives have long been used to inhibit fungal growth, but the side effects to consumers are of concern. Chitooligosaccharide is a nontoxic chitosan derivative produced from shrimp shell and its conjugate namely chitooligosaccharide‐gallic acid conjugate showed high efficacy in inhibiting the growth of fungi including Aspergillus spp. and Penicillium spp. Therefore, it can serve as a natural alternative preservative for the prevention of fungal growth in dried salted fish.
Multiresolution Categorical Regression for Interpretable Cell-Type Annotation
Authors: Molstad Aaron J. , Motwani Keshav
Published: October 2023

In many categorical response regression applications, the response categories admit a multiresolution structure. That is, subsets of the response categories may naturally be combined into coarser response categories. In such applications, practitioners are often interested in estimating the resolution at which a predictor affects the response category probabilities. In this paper, we propose a method for fitting the multinomial logistic regression model in high dimensions that addresses this problem in a unified and data-driven way. Our method allows practitioners to identify which predictors distinguish between coarse categories but not fine categories, which predictors distinguish between fine categories, and which predictors are irrelevant. For model fitting, we propose a scalable algorithm that can be applied when the coarse categories are defined by either overlapping or nonoverlapping sets of fine categories. Statistical properties of our method reveal that it can take advantage of this multiresolution structure in a way existing estimators cannot. We use our method to model cell-type probabilities as a function of a cell's gene expression profile (i.e., cell-type annotation). Our fitted model provides novel biological insights which may be useful for future automated and manual cell-type annotation methodology.
Genotype–phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis
Authors: Shimamoto Yusaku , Takeuchi Yoji , Ishiguro Shingo , Nakatsuka Shin‐ichi , Yunokizaki Hiroshi , Ezoe Yasumasa , Nakajima Takeshi , Tanaka Kumiko , Ishihara Ryu , Takayama Tetsuji , Yoshida Teruhiko , Sugano Kokichi , Mutoh Michihiro , Ishikawa Hideki
Published: October 2023

Familial adenomatous polyposis (FAP) patients develop various life‐threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype–phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high‐grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398–1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.
Unraveling brain fog in post‐COVID syndrome: Relationship between subjective cognitive complaints and cognitive function, fatigue, and neuropsychiatric symptoms
Authors: Delgado‐Alonso Cristina , Díez‐Cirarda María , Pagán Josué , Pérez‐Izquierdo Carlos , Oliver‐Mas Silvia , Fernández‐Romero Lucía , Martínez‐Petit Álvaro , Valles‐Salgado María , Gil‐Moreno María José , Yus Miguel , Matías‐Guiu Jorge , Ayala José Luis , Matias‐Guiu Jordi A.
Published: October 2023

Background and purpose

“Brain fog” is a frequent and disabling symptom that can occur after SARS‐CoV‐2 infection. However, its clinical characteristics and the relationships among brain fog and objective cognitive function, fatigue, and neuropsychiatric symptoms (depression, anxiety) are still unclear. In this study, we aimed to examine the characteristics of brain fog and to understand how fatigue, cognitive performance, and neuropsychiatric symptoms and the mutual relationships among these variables influence subjective cognitive complaints.

Methods

A total of 170 patients with cognitive complaints in the context of post‐COVID syndrome were evaluated using a comprehensive neuropsychological protocol. The FLEI scale was used to characterize subjective cognitive complaints. Correlation analysis, regression machine‐learning algorithms, and mediation analysis were calculated.

Results

Cognitive complaints were mainly attention and episodic memory symptoms, while executive functions (planning) issues were less often reported. The FLEI scale, a mental ability questionnaire, showed high correlations with a fatigue scale and moderate correlations with the Stroop test, and anxiety and depressive symptoms. Random forest algorithms showed an R2 value of 0.409 for the prediction of FLEI score, with several cognitive tests, fatigue and depression being the best variables used in the prediction. Mediation analysis showed that fatigue was the main mediator between objective and subjective cognition, while the effect of depression was indirect and mediated through fatigue.

Conclusions

Brain fog associated with COVID‐19 is mainly characterized by attention and episodic memory, and fatigue, which is the main mediator between objective and subjective cognition. Our findings contribute to understanding the pathophysiology of brain fog and emphasize the need to unravel the main mechanisms underlying brain fog, considering several aspects.
The adverse consequences of not using sunscreens
Authors: Young Antony R.
Published: October 2023

The adverse effects of solar ultraviolet radiation (UVR) on normal skin are well established, especially in those with poorly melanized skin. Clinically, these effects may be classified as acute, such as erythema or chronic such as keratinocyte and melanocyte skin cancers. Apart from skin type genetics, clinical responses to solar UVR are dependent on geophysical (e.g., solar intensity) and behavioural factors. The latter are especially important because they may result in ‘solar overload’ with unwanted clinical consequences and ever greater burdens to healthcare systems. Correctly used, sunscreens can mitigate the acute and chronic effects of solar UVR exposure. Laboratory studies also show that sunscreens can inhibit the initial molecular and cellular events that are responsible for clinical outcomes. Despite public health campaigns, global trends continue to show increasing incidence of all types of skin cancer. Large‐scale epidemiological studies have shown the benefits of sunscreen use in preventing skin cancer, though it is likely that sunscreen use has not been optimal in such studies. It is evident that without substantial changes in sun‐seeking behaviour, sunscreen use is a very important part of the defence against the acute and chronic effects of solar exposure. Ideally, sunscreens should be able to provide the level of protection that reduces the risk of skin cancer in susceptible skin types to that observed in heavily melanized skin.
Intergenerational transmission or local labour market context? A comparative analysis of the formation of work value patterns in 65 European regions
Authors: Hörisch Felix , Weiss Julia
Published: October 2023

This article analyses the driving factors behind the formation of individual work values in European welfare states. By comparing relative preferences for extrinsic and intrinsic work values, we shed light on the discussion of the effects of intergenerational transmission and the structuring effects of labour market policies and regional opportunity structures on the formation of work values. Therefore, a multilevel analysis is applied using the innovative CUPESSE data set, which provides data on young adults and their parents in 65 NUTS‐1‐regions from 11 European countries. The results show that individual work values of young Europeans are most substantively shaped by the respective values of their parents. Furthermore, we demonstrate that individual characteristics such as sex, education and personal unemployment experiences determine preferences for work values. Finally, the paper shows that the local labour market context and welfare state arrangements also play a decisive role in the formation of individual work values.
Engeletin alleviates depression‐like phenotype by increasing synaptic plasticity via the BDNF‐TrkB‐mTORC1 signalling pathway
Authors: Xu Yangyang , Zhang Jie , Yu Linyao , Zhang Wei , Zhang Yingtian , Shi Yaoqin , Zhang Shuping , Li Chunmei , Tian Jingwei
Published: October 2023

Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first‐line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side‐effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Engeletin, a natural Smilax glabra rhizomilax derivative, is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The effects of engeletin were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Engeletin was also investigated in the chronic restraint stress (CRS) mouse model of depression with fluoxetine (FLX) as the positive control. Changes in prefrontal cortex (PFC) spine density, synaptic plasticity‐linked protein expressions and the brain‐derived neurotrophic factor (BDNF)‐tyrosine kinase B (TrkB)‐ mammalian target of rapamycin complex 1 (mTORC1) signalling pathway after chronic stress and engeletin treatment were then investigated. The TrkB and mTORC1 selective inhibitors, ANA‐12 and rapamycin, respectively, were utilized to assess the engeletin's antidepressive mechanisms. Our data shows that engeletin exhibited antidepressant‐like activity in the FST and TST in mice without affecting locomotor activity. Furthermore, it exhibited efficiency against the depression of CRS model. Moreover, it enhanced the BDNF‐TrkB‐mTORC1 pathway in the PFC during CRS and altered the reduction in dendritic spine density and levels of synaptic plasticity‐linked protein induced by CRS. In conclusion, engeletin has antidepressant activity via activation of the BDNF‐TrkB‐mTORC1 signalling pathway and upregulation of PFC synaptic plasticity.
Effect of ultrasound‐assisted thin bed drying for retaining the quality of red bell pepper and compare the predictive ability of the mathematical model with artificial neural network
Authors: Sasikumar Raju , Mangang Irengbam Barun , Vivek Kambhampati , Jaiswal Amit K.
Published: October 2023

Red bell peppers (Capsicum annuum L.) are low in calories and high in nutrients, including vitamins A and C. Various factors such as weight loss, senescence, and microbial influence affect their quality during storage. To address this, the present study aims to preserve and retain the quality of red bell peppers using ultrasound‐assisted thin‐bed drying. The results were analyzed using an Artificial Neural Network (ANN) for more accurate prediction of variables involved in the process. Variations in moisture ratio and moisture content during drying were calculated and predicted. The Midilli model provided satisfactory curve fitting at an air velocity of 1.5 m/s, with R2 = 0.9993, χ2 = 0.0002, and RMSE = 0.0134. The two‐term and modified page models fit better with drying curves at air velocities of 2 and 2.5 m/s, with R2 = 0.9995, χ2 = 0.002, RMSE = 0.0016 and R2 = 0.9996, χ2 = 0.00003, RMSE = 0.00003, respectively. However, the trained standard backpropagation ANN algorithm demonstrated excellent predictive ability, outperforming the mathematical models with R2 = 0.9989 (training), MSE = 0.0001 (training), and R2 = 0.9996 (testing), MSE = 0.0002 (testing). Most importantly, the ultrasound‐assisted drying process retains the essential nutrients in red bell peppers, including vitamin C, carotenoids, polyphenols, and flavonoids, across various conditions. The antioxidant potential, as measured by DPPH and FRAP assays, remains largely unchanged compared to untreated samples. However, ABTS activity shows a significant difference at an air velocity of 1.5 m/s and temperatures of 60 and 70°C compared to the control sample.

Practical applications

In terms of vitamins and antioxidants, red bell peppers are a great provider. Interestingly, capsaicin, the substance responsible for spiciness, is found in very little to no quantity in red bell peppers making it appealable to consumers. To achieve a certain level of processing, the quality of the dried product needs to be monitored while fulfilling the needs of consumers. Particularly, the quality‐determining parameters were vitamin C, total carotenoids, total polyphenols, total flavonoid content, DPPH, ABTS, and FRAP activity. These qualities were retained after drying with the potential novel combination of ultrasound with thin bed drying at low temperatures and air velocity. This means that the bioactive compounds responsible for improving the health of humans are readily available in dried form all year round. The drying kinetics were modeled, predicted, and compared with mathematical and ANN models.
Pedagogy of the great pandemic of the 21st century: Epistemic implications for individual psychology, family science, and psychotherapies
Authors: Medina Centeno Raúl
Published: October 2023

As an effect of the severe health crisis caused by COVID‐19, lockdown constituted a psychosocial laboratory that represented an experiment on a global scale. The lessons from the research findings in the pandemic environment have been of enormous importance to the disciplines of human behavior. This paper explores two themes evidenced in this context: people's psychological well‐being is underpinned by a socio‐emotional network, and the most frequent psychological symptoms experienced in the pandemic are a socio‐political problem; in particular it was observed that women reported greater discomfort than men in that period, showing with it that gender inequality remains a structural malaise. The conclusion points to two issues. First, an individualistic psychology is impossible without social content, especially in the collective affectivity, where the person participates. Second, psychotherapists should contemplate, in diagnosis and intervention, the socio‐emotional and political context in which the symptomatology appears. The focus of this article is based on systemic third‐order thinking, from where the socio‐economic and cultural structural order is closely linked to identity, well‐being, or personal discomfort.
The transcription factor FgStuA regulates virulence and mycotoxin biosynthesis via recruiting the SAGA complex in Fusarium graminearum
Authors: Xu Chaoyun , Wang Jing , Zhang Yueqi , Luo Yuming , Zhao Youfu , Chen Yun , Ma Zhonghua
Published: October 2023

The conserved Spt‐Ada‐Gcn5‐Acetyltransferase (SAGA) complex controls eukaryotic transcription by modifying acetylation of histones. However, the mechanisms for this complex in regulating the transcription of target‐specific genes remain largely unknown in phytopathogenic fungi.

A filamentous fungal‐specific transcription factor FgStuA was identified to interact with the SAGA complex physically. The coordinative mechanisms of FgStuA with the SAGA complex in regulating secondary metabolism and virulence were investigated in Fusarium graminearum with genetic, biochemical and molecular techniques.

The transcription factor FgStuA binds to a 7‐bp cis‐element (BVTGCAK) of its target gene promoter. Under mycotoxin deoxynivalenol (DON) induction conditions, FgStuA recruits the SAGA complex into the promoter of TRI6, a core regulator of the DON biosynthesis gene cluster, leading to enhanced transcription of TRI6. During this process, we found that FgStuA is subject to acetylation by the SAGA complex, and acetylation of FgStuA plays a critical role for its enrichment in the TRI6 promoter. In addition, FgStuA together with the SAGA complex modulates fungal virulence.

This study uncovers a novel regulatory mechanism of a transcription factor, which recruits and interacts with the SAGA complex to activate specific gene expression in pathogenic fungi.
A pilot study for a practical screening tool for dementia: validation of 5‐minute cognitive test in a geriatric population
Authors: Hafızoğlu Merve , Okyar Baş Arzu , Şahiner Zeynep , Oytun Merve Güner , Atbaş Cansu , Karaduman Didem , İleri İbrahim , Balcı Cafer , Halil Meltem Gülhan , Cankurtaran Mustafa , Doğu Burcu Balam
Published: October 2023

Background

The aim of this study is to validate the Turkish version of the 5‐minute cognitive test (FCT) in a geriatric population.

Materials and Method

In total, 61 participants aged ≥65 years with normal cognitive functions, mild cognitive impairment (MCI), and early stage dementia were included. The FCT was compared to the standardised Mini Mental State Examination (MMSE) and the Qmci‐TR (quick mild cognitive impairment) test.

Results

Test reliability for the FCT was strong (Cronbach's α = 0.747). We demonstrated a strong correlation of FCT scores with MMSE and Qmci‐TR scores (respectively, r = 0.730, P < 0.001, r = 0.723, P < 0.001). The fact that the scores obtained in the dementia group were significantly lower also showed that the test can be used reliably in the differentiation of MCI and early dementia (P < 0.001).

Conclusions

The FCT is a brief, reliable, and valid cognitive screening test for screening dementia at early stages in a Turkish geriatric population.
A single nitrogen application maintains wheat yield and quality in dryland Mediterranean Vertisol
Authors: Fernandez‐Garcia Purificacion , Lopez‐Bellido Luis , Lopez‐Bellido Francisco J. , Lopez‐Bellido Rafael J.
Published: October 2023

In dryland Mediterranean Vertisols, split nitrogen (N) application is usual in wheat crops. Because of the high clay content of these soils and the low rainfall, a single application might offer ecological and economic benefits without yield loss. We conducted a 5‐year study as part of a long‐term experiment and compared the split application of N (50% at tillering, 50% at stem elongation phase) with a single application (tillering) in 10 cropping systems resulting from the combination of type of cultivation (no‐till and conventional tillage) and 2‐year crop rotations (wheat–wheat, wheat–fallow, wheat–chickpea, wheat–faba bean and wheat–sunflower). Depending on the system × crop rotation interaction, a single application of 100 or 150 kg N ha−1 maintained grain yield, protein content and apparent N recovery, with no effect on nitrate content compared with a traditional split application. The average grain yield did not differ between split and single application of N (3.27 and 3.23 Mg ha−1, respectively, for single and split application of 100 kg N ha−1 rate; 3.46 and 3.40 Mg ha−1, respectively, for single and split application of 150 kg N ha−1 rate). The soil nitrate concentration at pre‐seeding in the 0–0.3 m layer showed similar results, except in the case of the wheat–faba rotation, with lower nitrate concentration in the sub‐subplots of single application and no‐till. This work shows that adopting the single N application strategy in rotations on Mediterranean dryland Vertisols will reduce economic and environmental costs.
Genome sequences and population genomics provide insights into the demographic history, inbreeding, and mutation load of two ‘living fossil’ tree species of Dipteronia
Authors: Feng Yu , Comes Hans Peter , Chen Jun , Zhu Shanshan , Lu Ruisen , Zhang Xinyi , Li Pan , Qiu Jie , Olsen Kenneth M. , Qiu Yingxiong
Published: October 2023

‘Living fossils’, that is, ancient lineages of low taxonomic diversity, represent an exceptional evolutionary heritage, yet we know little about how demographic history and deleterious mutation load have affected their long‐term survival and extinction risk. We performed whole‐genome sequencing and population genomic analyses on Dipteronia sinensis and D. dyeriana, two East Asian Tertiary relict trees. We found large‐scale genome reorganizations and identified species‐specific genes under positive selection that are likely involved in adaptation. Our demographic analyses suggest that the wider‐ranged D. sinensis repeatedly recovered from population bottlenecks over late Tertiary/Quaternary periods of adverse climate conditions, while the population size of the narrow‐ranged D. dyeriana steadily decreased since the late Miocene, especially after the Last Glacial Maximum (LGM). We conclude that the efficient purging of deleterious mutations in D. sinensis facilitated its survival and repeated demographic recovery. By contrast, in D. dyeriana, increased genetic drift and reduced selection efficacy, due to recent severe population bottlenecks and a likely preponderance of vegetative propagation, resulted in fixation of strongly deleterious mutations, reduced fitness, and continuous population decline, with likely detrimental consequences for the species' future viability and adaptive potential. Overall, our findings highlight the significant impact of demographic history on levels of accumulation and purging of putatively deleterious mutations that likely determine the long‐term survival and extinction risk of Tertiary relict trees.
Characteristics of breastfeeding newborns in the first month of life with in-utero selective serotonin reuptake inhibitor medication exposure: a scoping review protocol
Authors: Cantin Christina , Snelgrove-Clarke Erna , Gaudet Laura , Ross-White Amanda
Published: October 2023

Objective:

The objective of this scoping review is to understand the extent and type of evidence in relation to the characteristics of breastfeeding newborns in the first month of life who have been exposed in-utero to selective serotonin reuptake inhibitor (SSRI) medications.

Introduction:

SSRIs are the most prescribed antidepressant medication in pregnancy. Up to 30% of newborns who are prenatally exposed to SSRIs demonstrate withdrawal signs. Poor neonatal adaptation syndrome represents a constellation of signs observed in these newborns. Little information has been studied regarding breastfeeding, as it relates to the impact of in-utero SSRI exposure on the newborn. Parents have many questions regarding the safety of taking medications during pregnancy and breastfeeding. It is important for health care providers to collate evidence-based information and facilitate shared-decision making. We aim to identify the approaches researchers have used to investigate in-utero SSRI exposure among breastfed newborns to determine knowledge gaps.

Inclusion criteria:

Primary peer-reviewed studies will be considered for inclusion according to the following criteria: newborns, 31 days of age or less, with in-utero SSRI exposure in any trimester of pregnancy, who were breastfed or received breast-milk feedings.

Methods:

MEDLINE, CINAHL, EMBASE, LactMed, the Maternity and Infant Care Database, and Clinical Trials databases will be searched. JBI methodology will be used. Abstracts will be assessed for eligibility and full texts will be retrieved if they meet the inclusion criteria. Two reviewers will independently extract the data from identified studies using a data extraction form and the results will be summarized descriptively and in tabular format.

Review registration:

Open Science Framework (osf.io/2bt39)
LixCoyOz thin-films deposition through thermal atomic layer deposition
Authors: Peisert Antoine , Adjeroud Noureddine , Lenoble Damien , Lamblin Guillaume
Published: October 2023

3D-Li ion batteries are identified as one of the most promising technologies for improving portable and safe energy storage devices. One of the main remaining challenges to be tackled in that regard is the manufacture of efficient nanostructured electrode materials. In this paper, we report on the first realization of an electrochemically active cathodic LixCoyOz material grown via a thermal atomic layer deposition process based on the combination of Co(thd)2 and Li(thd) organometallic ligands and O3 as an oxidizing agent. Comprehensive characterizations comprising XPS, Raman, HIM (helium ion microscopy)-SIMS, and the first ever SEM images of a thermal-atomic layer deposition (ALD) deposited LixCoyOz material are shown and discussed as well and the very first electrochemical results to attest the electrochemical activity of the deposited material. Those results act as the first demonstration that lithiated materials and more precisely, LixCoyOz, can be grown via an advanced thermal ALD.
Multifunctional fibers enable modulation of cortical and deep brain activity during cognitive behavior in macaques
Authors: Garwood Indie C. , Major Alex J. , Antonini Marc-Joseph , Correa Josefina , Lee Youngbin , Sahasrabudhe Atharva , Mahnke Meredith K. , Miller Earl K. , Brown Emery N. , Anikeeva Polina
Published: October 2023

Recording and modulating neural activity in vivo enables investigations of the neurophysiology underlying behavior and disease. However, there is a dearth of translational tools for simultaneous recording and localized receptor-specific modulation. We address this limitation by translating multifunctional fiber neurotechnology previously only available for rodent studies to enable cortical and subcortical neural recording and modulation in macaques. We record single-neuron and broader oscillatory activity during intracranial GABA infusions in the premotor cortex and putamen. By applying state-space models to characterize changes in electrophysiology, we uncover that neural activity evoked by a working memory task is reshaped by even a modest local inhibition. The recordings provide detailed insight into the electrophysiological effect of neurotransmitter receptor modulation in both cortical and subcortical structures in an awake macaque. Our results demonstrate a first-time application of multifunctional fibers for causal studies of neuronal activity in behaving nonhuman primates and pave the way for clinical translation of fiber-based neurotechnology.
Tree diversity increases productivity through enhancing structural complexity across mycorrhizal types
Authors: Ray Tama , Delory Benjamin M. , Beugnon Rémy , Bruelheide Helge , Cesarz Simone , Eisenhauer Nico , Ferlian Olga , Quosh Julius , von Oheimb Goddert , Fichtner Andreas
Published: October 2023

Tree species diversity and mycorrhizal associations play a central role for forest productivity, but factors driving positive biodiversity-productivity relationships remain poorly understood. In a biodiversity experiment manipulating tree diversity and mycorrhizal associations, we examined the roles of above- and belowground processes in modulating wood productivity in young temperate tree communities and potential underlying mechanisms. We found that tree species richness, but not mycorrhizal associations, increased forest productivity by enhancing aboveground structural complexity within communities. Structurally complex communities were almost twice as productive as structurally simple stands, particularly when light interception was high. We further demonstrate that overyielding was largely explained by positive net biodiversity effects on structural complexity with functional variation in shade tolerance and taxonomic diversity being key drivers of structural complexity in mixtures. Consideration of stand structural complexity appears to be a crucial element in predicting carbon sequestration in the early successional stages of mixed-species forests.
The maternal microbiome promotes placental development in mice
Authors: Pronovost Geoffrey N. , Yu Kristie B. , Coley-O’Rourke Elena J. L. , Telang Sahil S. , Chen Angela S. , Vuong Helen E. , Williams Drake W. , Chandra Anisha , Rendon Tomiko K. , Paramo Jorge , Kim Reuben H. , Hsiao Elaine Y.
Published: October 2023

The maternal microbiome is an important regulator of gestational health, but how it affects the placenta as the interface between mother and fetus remains unexplored. Here, we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate cultured endothelial cell tube formation and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.
TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma
Authors: Yakou Marina H. , Ghilas Sonia , Tran Kelly , Liao Yang , Afshar-Sterle Shoukat , Kumari Anita , Schmid Kevin , Dijkstra Christine , Inguanti Chantelle , Ostrouska Simone , Wilcox Jordan , Smith Maxine , Parathan Pavitha , Allam Amr , Xue Hai-Hui , Belz Gabrielle T. , Mariadason John M. , Behren Andreas , Drummond Grant R. , Ruscher Roland , Williams David S. , Pal Bhupinder , Shi Wei , Ernst Matthias , Raghu Dinesh , Mielke Lisa A.
Published: October 2023

Intraepithelial lymphocytes (IELs), including αβ and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/
TCF7
and a reduced effector and cytotoxic profile, including low expression of granzymes. Targeted deletion of TCF-1 in γδ T-IELs induced a distinct effector profile and reduced colon tumor formation in mice. In addition, TCF-1 expression was significantly reduced in γδ T-IELs present in human colorectal cancers (CRCs) compared with normal healthy colon, which strongly correlated with an enhanced γδ T-IEL effector phenotype and improved patient survival. Our work identifies TCF-1 as a colon-specific T-IEL transcriptional regulator that could inform new immunotherapy strategies to treat CRC.
From drab to Fab; PLP1’s fit is redressed for MS
Authors: Bayer Alexandra C. , O’Connor Kevin C.
Published: October 2023

Curated expression of proteolipid protein 1 (PLP1) is essential for multiple sclerosis–derived autoantibody recognition.
In vitro
potency of xeruborbactam in combination with multiple β-lactam antibiotics in comparison with other β-lactam/β-lactamase inhibitor (BLI) combinations against carbapenem-resistant and extended-spectrum β-lactamase-producing
Enterobacterales
Authors: Lomovskaya Olga , Castanheira Mariana , Lindley Jill , Rubio-Aparicio Debora , Nelson Kirk , Tsivkovski Ruslan , Sun Dongxu , Totrov Maxim , Loutit Jeffery , Dudley Michael
Published: October 2023

Recently, several β-lactam (BL)/β-lactamase inhibitor (BLI) combinations have entered clinical testing or have been marketed for use, but limited direct comparative studies of their
in vitro
activity exist. Xeruborbactam (XER, also known as QPX7728), which is undergoing clinical development, is a cyclic boronate BLI with potent inhibitory activity against serine (serine β-lactamase) and metallo-β-lactamases (MBLs). The objectives of this study were (i) to compare the potency and spectrum of β-lactamase inhibition by various BLIs in biochemical assays using purified β-lactamases and in microbiological assays using the panel of laboratory strains expressing diverse serine and metallo-β-lactamases and (ii) to compare the
in vitro
potency of XER in combination with multiple β-lactam antibiotics to that of other BL/BLI combinations in head-to-head testing against recent isolates of carbapenem-resistant
Enterobacterales
(CRE). Minimal inhibitory concentrations (MICs) of XER combinations were tested with XER at fixed 4 or 8 µg/mL, and MIC testing was conducted in a blinded fashion using Clinical and Laboratory Standards Institute reference methods. Xeruborbactam and taniborbactam (TAN) were the only BLIs that inhibited clinically important MBLs. The spectrum of activity of xeruborbactam included several MBLs identified in
Enterobacterales,
e.g., and various IMP enzymes and NDM-9 that were not inhibited by taniborbactam. Xeruborbactam potency against the majority of purified β-lactamases was the highest in comparison with other BLIs. Meropenem-xeruborbactam (MEM-XER, fixed 8 µg/mL) was the most potent combination against MBL-negative CRE with MIC
90
values of 0.125 µg/mL. MEM-XER and cefepime-taniborbactam (FEP-TAN) were the only BL/BLIs with activity against MBL-producing CREs; with MEM-XER (MIC
90
of 1 µg/mL) being at least 16-fold more potent than FEP-TAN (MIC
90
of 16 µg/mL). MEM-XER MIC values were ≤8 µg/mL for >90% of CRE, including both MBL-negative and MBL-positive isolates, with FEP-TAN MIC of >8 µg/mL. Xeruborbactam also significantly enhanced potency of other β-lactam antibiotics, including cefepime, ceftolozane, ceftriaxone, aztreonam, piperacillin, and ertapenem, against clinical isolates of
Enterobacterales
that carried various class A, class C, and class D extended-spectrum β-lactamases and carbapenem-resistant
Enterobacterales
, including metallo-β-lactamase-producing isolates. These results strongly support further clinical development of xeruborbactam combinations.
Evaluation of
in vitro
antiviral activity of SARS-CoV-2 M
pro
inhibitor pomotrelvir and cross-resistance to nirmatrelvir resistance substitutions
Authors: Tong Xiao , Keung Walter , Arnold Lee D. , Stevens Laura J. , Pruijssers Andrea J. , Kook Seunghyi , Lopatin Uri , Denison Mark , Kwong Ann D.
Published: October 2023

The unprecedented scale of the COVID-19 pandemic and the rapid evolution of SARS-CoV-2 variants underscore the need for broadly active inhibitors with a high barrier to resistance. The coronavirus main protease (M
pro
) is an essential cysteine protease required for viral polyprotein processing and is highly conserved across human coronaviruses. Pomotrelvir is a novel M
pro
inhibitor that has recently completed a phase 2 clinical trial. In this report, we demonstrated that pomotrelvir is a potent competitive inhibitor of SARS-CoV-2 M
pro
with high selectivity against human proteases. In the enzyme assay, pomotrelvir is also active against M
pro
proteins derived from human coronaviruses CoV-229E, CoV-OC43, CoV-HKU1, CoV-NL63, MERS, and SARS-CoV. In cell-based SARS-CoV-2 replicon and SARS-CoV-2 infection assays, pomotrelvir has shown potent inhibitory activity and is broadly active against SARS-CoV-2 clinical isolates including Omicron variants. Many resistance substitutions of the M
pro
inhibitor nirmatrelvir confer cross-resistance to pomotrelvir, consistent with the finding from our enzymatic analysis that pomotrelvir and nirmatrelvir compete for the same binding site. In a SARS-CoV-2 infection assay, pomotrelvir is additive when combined with remdesivir or molnupiravir, two nucleoside analogs targeting viral RNA synthesis. In conclusion, our results from the
in vitro
characterization of pomotrelvir antiviral activity support its further clinical development as an alternative COVID-19 therapeutic option.
The newest Oxford Nanopore R10.4.1 full-length 16S rRNA sequencing enables the accurate resolution of species-level microbial community profiling
Authors: Zhang Tianyuan , Li Hanzhou , Ma Silin , Cao Jian , Liao Hao , Huang Qiaoyun , Chen Wenli
Published: October 2023

The long-read amplicon provides a species-level solution for the community. With the improvement of nanopore flowcells, the accuracy of Oxford Nanopore Technologies (ONT) R10.4.1 has been substantially enhanced, with an average of approximately 99%. To evaluate its effectiveness on amplicons, three types of microbiomes were analyzed by 16S ribosomal RNA (hereinafter referred to as “16S”) amplicon sequencing using Novaseq, Pacbio sequel II, and Nanopore PromethION platforms (R9.4.1 and R10.4.1) in the current study. We showed the error rate, recall, precision, and bias index in the mock sample. The error rate of ONT R10.4.1 was greatly reduced, with a better recall in the case of the synthetic community. Meanwhile, in different types of environmental samples, ONT R10.4.1 analysis resulted in a composition similar to Pacbio data. We found that classification tools and databases influence ONT data. Based on these results, we conclude that the ONT R10.4.1 16S amplicon can also be used for application in environmental samples.

IMPORTANCE

The long-read amplicon supplies the community with a species-level solution. Due to the high error rate of nanopore sequencing early on, it has not been frequently used in 16S studies. Oxford Nanopore Technologies (ONT) introduced the R10.4.1 flowcell with Q20+ reagent to achieve more than 99% accuracy as sequencing technology advanced. However, there has been no published study on the performance of commercial PromethION sequencers with R10.4.1 flowcells on 16S sequencing or on the impact of accuracy improvement on taxonomy (R9.4.1 to R10.4.1) using 16S ONT data. In this study, three types of microbiomes were investigated by 16S ribosomal RNA (rRNA) amplicon sequencing using Novaseq, Pacbio sequel II, and Nanopore PromethION platforms (R9.4.1 and R10.4.1). In the mock sample, we displayed the error rate, recall, precision, and bias index. We observed that the error rate in ONT R10.4.1 is significantly lower, especially when deletions are involved. First and foremost, R10.4.1 and Pacific Bioscience platforms reveal a similar microbiome in environmental samples. This study shows that the R10.4.1 full-length 16S rRNA sequences allow for species identification of environmental microbiota.
Rumen
Lachnospiraceae
isolate NK3A20 exhibits metabolic flexibility in response to substrate and coculture with a methanogen
Authors: Kaminsky Rachel A. , Reid Peter M. , Altermann Eric , Kenters Nikki , Kelly William J. , Noel Samantha J. , Attwood Graeme T. , Janssen Peter H.
Published: October 2023

Hydrogen (H
2
) is the primary electron donor for methane formation in ruminants, but the H
2
-producing organisms involved are largely uncharacterized. This work integrated studies of microbial physiology and genomics to characterize rumen bacterial isolate NK3A20 of the family
Lachnospiraceae
. Isolate NK3A20 was the first recognized isolate of the NK3A20 group, which is among the ten most abundant bacterial genera in 16S rRNA gene surveys of rumen microbiota. NK3A20 produced acetate, butyrate, H
2
, and formate from glucose. The end product ratios varied when grown with different substrates and at different H
2
partial pressures. NK3A20 produced butyrate as a major product using glucose or under high H
2
partial pressures and switched to mainly acetate in the presence of galacturonic acid (an oxidized sugar) or in coculture with a methanogen. Growth with galacturonic acid was faster at elevated H
2
concentrations, while elevated H
2
slowed growth with glucose. Genome analyses revealed the presence of multiple hydrogenases including a membrane-bound Ech hydrogenase, an electron bifurcating butyryl-CoA dehydrogenase (Bcd-Etf), and an Rnf complex that may be involved in modulating the observed metabolic pathway changes, providing insight into H
2
formation in the rumen.

IMPORTANCE

The genus-level NK3A20 group is one of the ten most abundant genera of rumen bacteria. Like most of the rumen bacteria that produce the hydrogen that is converted to methane in the rumen, it is understudied, without any previously characterized isolates. We investigated isolate NK3A20, a cultured member of this genus, and showed that it modulates hydrogen production in response to its growth substrates and the hydrogen concentration in its environment. Low-hydrogen concentrations stimulated hydrogen formation, while high concentrations inhibited its formation and shifted the fermentation to more reduced organic acid products. We found that growth on uronic acids, components of certain plant polymers, resulted in low hydrogen yields compared to glucose, which could aid in the selection of low-methane feeds. A better understanding of the major genera that produce hydrogen in the rumen is part of developing strategies to mitigate biogenic methane emitted by livestock agriculture.
Selection of mutant
Listeria
phages under food-relevant conditions can enhance application potential
Authors: Schamp Claire N. , Dhowlaghar Nitin , Hudson Lauren K. , Bryan Daniel W. , Zhong Qixin , Fozo Elizabeth M. , Gaballa Ahmed , Wiedmann Martin , Denes Thomas G.
Published: October 2023

Bacteriophages are viruses that infect and kill bacteria. Currently, phage products are available for the control of the pathogen
Listeria monocytogenes
in food products in the United States. In this study, we explore whether experimental evolution can be used to generate phages with improved abilities to function under specific food-relevant conditions. Ultra-pasteurized oat and whole milk were chosen as test matrices as they represent different food groups, yet have similar physical traits and macronutrient composition. We showed that (i) wild-type phage LP-125 infection kinetics are different in the two matrices and (ii) LP-125 has a significantly higher burst size in oat milk. From this, we attempted to evolve LP-125 to have improved infection kinetics in whole milk. Ancestral LP-125 was passaged through 10 rounds of amplification in milk conditions. Plaque-purified DNA samples from milk-selected phages were isolated and sequenced, and mutations present in the isolated phages were identified. We found two nonsynonymous substitutions in
LP125_108
and
LP125_112
genes, which encode putative baseplate-associated glycerophosphoryl diester phosphodiesterase and baseplate protein, respectively. Protein structural modeling showed that the substituted amino acids in the mutant phages are predicted to localize to surface-exposed helices on the corresponding structures, which might affect the surface charge of proteins and their interaction with the bacterial cell. The phage containing the
LP125_112
mutation adsorbed significantly faster than the ancestral phage in both oat and whole milk. Follow-up experiments suggest that fat content may be a key factor for the expression of the phenotype of this mutation.

IMPORTANCE

Bacteriophages are one of the tools available to control the foodborne pathogen,
Listeria monocytogenes
. Phage products must work under a broad range of food conditions to be an effective control for
L. monocytogenes
. Here, we show that the experimental evolution of phages can be used to generate new phages with phenotypes useful under specific conditions. We used this approach to select for a mutant phage that more efficiently binds to
L. monocytogenes
that is grown in whole milk and oat milk. We show that the fat content of these milks is necessary for the expression of this phenotype. Our findings show that experimental evolution can be used to select for improved phages with better performance under specific conditions. This approach has the potential to support the development of condition-specific phage-based biocontrols in the food industry.