bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiochemical quality characteristics of sulgidduk
added with galangal (Alpinia officinarum Hance)
Authors: Kim Hyeyoung
Published: November 2024

This study was conducted to investigate the potential use of galangal, known for
its various efficacy, as a functional food ingredient. The quality
characteristics of sulgidduk added with galangal powder (GP)
were analyzed to determine the optimal GP loading. The moisture content of rice
flour is higher than that of GP. In sulgidduk with GP, the
lightness (L*) significantly decreased and the redness (a*) and yellowness (b*)
significantly increased with increasing amounts of added galangal, which may be
due to the color of GP. Texture analysis revealed no significant differences in
hardness or springiness between groups. Cohesiveness, gumminess, and chewiness
were significantly lower in the GP group than in the control group. Quantitative
descriptive analysis showed that the brown color, tenderness, moisture, specific
odor, and bitter taste significantly increased, and the sweet taste
significantly decreased with increasing amounts of GP. The consumer acceptance
results showed a negative effect with increasing amounts of added GP.
Appearance, flavor, texture, taste, and overall acceptability were all highest
in the control group and decreased with increasing amounts of added GP. The
total flavonoid content and 2,2-diphenyl-2-picrylhydrazyl (DPPH)
radical-scavenging activity increased significantly with the addition of GP. It
was found that up to 2% galangal addition had little effect on preference,
suggesting that this amount of added GP is optimal. Based on the results of this
study, it is recommended that galangal powder should be used at a concentration
of 2% or less, as it has high antioxidant activity but reduces sensory
properties when used in high concentrations.
Colorimetric gas indicators based on dye-doped natural polymers for
food freshness monitoring
Authors: Lim Junkyu , Ji Daeun , Lee Wonjin , Min Kyungtaek
Published: November 2024

In this study, we developed colorimetric gas indicators that respond to exposure
to ammonia gas, which may occur due to food spoilage. We prepared bio-compatible
and eco-friendly anthocyanin dye and cellulose acetate (CA) polymer to fabricate
the gas indicators. The color of anthocyanin-doped CA films changed depending on
the time of exposure to ammonia gas or the concentration of the gas, which can
be quantitatively analyzed by measuring the light absorption spectrum of the
indicators. As the color of the indicator changed from purple to blue when
exposed to ammonia gas, the absorption peak wavelength red-shifted from 535 nm
to 615 nm. By enclosing the colorimetric films in fresh food packaging, we could
monitor food spoilage in real-time. Additionally, we fabricated gas indicators
in the form of electrospun nanofibrous membranes, which are highly porous and
suitable for immediate gas detection. The nanofibrous gas indicators clearly
distinguished ammonia gas concentrations ranging from 150 to 10,000 ppm.
Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study
Authors: Ramaekers JG , Reckweg JT , Mason NL , Kuypers KPC , Toennes SW , Theunissen EL
Published: November 2024

3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N=14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. A battery of neurocognitive tests and questionnaires as well as measures of vital signs were repeatedly administered up to 5 hours after dosing. Overall, 3-MMC caused dose-dependent increases in heart rate and blood pressure, though not of clinical significance, and feelings of subjective high. Additionally, 3-MMC induced dose-related enhancement of task performance across several neurocognitive domains, including processing speed, cognitive flexibility, psychomotor function, attention and memory. Impulse control was not affected by 3-MMC. Participants also reported mild increases in dissociative and psychedelic effects, decreased appetite, and gave greater ratings of liking and wanting for 3-MMC that were transient over time. Overall, the cardiovascular, psychostimulant and psychotomimetic profile of 3-MMC appears consistent with that of compounds structurally related to amphetamine. It is concluded that low to moderate doses of 3-MMC were well tolerated and safe and that potential health risks might only occur at high or excessive doses of 3-MMC.
A roadmap for navigating partner engagement in community-based autopsy studies: Lessons from the field in rural KwaZulu-Natal, South Africa
Authors: Castle Alison , Shazi Gugu , Naidoo Threnesan , Govender Ashendree , Gqaleni Nceba , Wong Emily B. , Iwuji Collins , Herbst Kobus , Steyn Adrie JC , Siedner Mark J.
Published: November 2024

Background

The measurement of cause-specific mortality is critical for health system planning but remains a challenge in many low-resource settings due to societal, legal, and logistical barriers. We present a co-development process with community members for the design and implementation of an autopsy program to improve cause of death data in a historically underserved population.

Methods

We sought to develop an autopsy program at the Africa Health Research Institute (AHRI) Health and Demographic Surveillance Site (HDSS). The project proposes to obtain consent from families of deceased adults, to perform diagnostic autopsies by a trained pathologist, and to process samples to determine causes of death. Prior to launching the program, we engaged key partners in learning their perspectives about such a program and understanding the landscape of challenges needed for successful implementation. Herein, we describe lessons from interactions with these partners, including 1) the AHRI community advisory board (CAB), 2) the South Africa Department of Health (SA DoH), 3) local traditional authorities, 4) funeral home personnel, 5) traditional healers, and 6) healthcare providers. We also detail the development of community outreach efforts used to inform the public about the program.

Results

The partners provided valuable feedback on the study design and informed us of issues that needed to be addressed: community concerns about organ retention and sale (CAB), implications of how autopsy findings could spur litigation and erode trust in healthcare providers who determined alternate causes of death (SA DoH), a cultural practice that conflicts with the autopsy procedure (traditional healers), the need to educate families before they engage with funeral businesses (funeral homes), and enhancing our death referral network through healthcare providers. This led to protocol changes and an adapted community engagement strategy, which included educating healthcare providers, hosting community dialogs, broadcasting radio advertisements, and developing a film to describe autopsy procedures to families considering participation.

Conclusions

We present a comprehensive model of partner engagement for a community-based autopsy program in South Africa, leading to the co-development of a program that incorporates local customs around death while promoting buy-in and support from the government, civil society, and medical partners.
Postglacial recolonization of the Southern Ocean by elephant seals occurred from multiple glacial refugia
Authors: Berg Andrew A. , Askew Megan , Seersholm Frederik V. , Verry Alexander J. F. , Hoelzel A. Rus , Welch Andreanna , Greig Karen , Walter Richard , Knapp Michael , Barlow Axel , Paijmans Johanna L.A. , Waters Jonathan M. , Bunce Michael , McDonald Kate , O’Connor Sue , Hall Brenda , Koch Paul , Baroni Carlo , Salvatore Maria Cristina , Faulkner Patrick , Ho Simon Y. W. , Rawlence Nicolas J. , de Bruyn Mark
Published: November 2024

The Southern Ocean is warming more rapidly than other parts of our planet. How this region’s endemic biodiversity will respond to such changes can be illuminated by studying past events, through genetic analyses of time-series data sets including historic and fossil remains. Archaeological and subfossil remains show that the southern elephant seal (Mirounga leonina) was common along the coasts of Australia and New Zealand in the recent past. This species is now mostly confined to sub-Antarctic islands and the southern tip of South America. We analysed ancient seal samples from Australia (Tasmania), New Zealand, and the Antarctic mainland to examine how southern elephant seals have responded to a changing climate and anthropogenic pressures during the Holocene. Our analyses show that these seals formed part of a broader Australasian lineage, comprising seals from all sampled locations from the south Pacific sector of the Southern Ocean. Our study demonstrates that southern elephant seal populations have dynamically altered both range and population sizes under climatic and human pressures, over surprisingly short evolutionary timeframes for such a large, long-lived mammal.

Significance Statement

Genetic data, alongside historic, archaeological, and subfossil remains show that Australasian populations of the southern elephant seal have been shaped by range expansions and contractions following the Last Glacial Maximum, with subsequent contractions during the late Holocene. These expansion and contraction events are likely to have been a direct result of climate change-induced habitat expansion and contraction, along with Indigenous and European sealing. Prehistoric climate change and more recent human pressures have substantially altered the geographic distribution and population size of southern elephant seals over short evolutionary timescales.
Cold-inducible GOT1 activates the malate-aspartate shuttle in brown adipose tissue to support fuel preference for fatty acids
Authors: Park Chul-Hong , Park Minsung , Kelly Miranda E. , Cheng Helia , Lee Sang Ryeul , Jang Cholsoon , Chang Ji Suk
Published: November 2024

Brown adipose tissue (BAT) simultaneously metabolizes fatty acids (FA) and glucose under cold stress but favors FA as the primary fuel for heat production. It remains unclear how BAT steer fuel preference toward FA over glucose. Here we show that the malate-aspartate shuttle (MAS) is activated by cold in BAT and plays a crucial role in promoting mitochondrial FA utilization. Mechanistically, cold stress selectively induces glutamic-oxaloacetic transaminase (GOT1), a key MAS enzyme, via the β-adrenergic receptor-PKA-PGC-1α axis. The increase in GOT1 activates MAS, transferring reducing equivalents from the cytosol to mitochondria. This process enhances FA oxidation in mitochondria while limiting glucose oxidation. In contrast, loss of MAS activity by GOT1 deficiency reduces FA oxidation, leading to increased glucose oxidation. Together, our work uncovers a unique regulatory mechanism and role for MAS in mitochondrial fuel selection and advances our understanding of how BAT maintains fuel preference for FA under cold conditions.

Highlights

Got1is markedly induced by cold in BAT via a β-adrenergic receptor-PKA-PGC-1α axis

The increase in cytosolic GOT1 activates the malate-aspartate shuttle (MAS)

MAS activation promotes fatty acid oxidation while reducing glucose oxidation

Loss of MAS activity in BAT byGot1deletion shifts the fuel preference to glucose
Exploration of the Roles of HLAs When Predicting Infection Status by T Cell Receptors
Authors: Ding Feng , Liu Si , Sun Wei
Published: November 2024

T cells are critical components of human immune system. When a cell is infected by a virus, it presents viral peptides on its surface using human leukocyte antigen (HLA) proteins. These peptide-HLA complexes are recognized by T cells through interactions with T cell receptors (TCRs). A human blood sample can contain millions of unique TCRs, which is a sample from the TCR repertoire of the individual. TCR repertoire-wide association studies (TReWAS) aim to evaluate the association between individual TCRs and disease or exposure status. Previous studies have demonstrated that TCRs associated with viral infections can be identified through TReWAS, and such TCRs can be used to predict current or past infection with high accuracy. Notably, many TCRs are strongly associated with specific HLA alleles, suggesting that incorporating HLA information could enhance the accuracy of TReWAS analyses and TCR-based predictions. In our study, we evaluated TCR-based predictions by conditioning on individual HLA alleles or their k-nearest neighbors. We observed improved prediction accuracy for certain HLA alleles. Furthermore, these HLA-specific predictions provide insights into the role of specific HLAs in the infection or disease of interest, offering potential applications in personalized medicine.
Fate mapping of peripherally derived macrophages reveals a long-lasting engrafted population that maintains a distinct transcriptomic profile for up to 8 months after Traumatic Brain Injury
Authors: Paladini Maria Serena , Yang Benjamin A. , Feng Xi , Frias Elma S. , Krukowski Karen , Sit Rene , Morri Maurizio , Lam Wendy , Pedoia Valentina , Tyanova Stefka , Rosi Susanna
Published: November 2024

Traumatic Brain Injury (TBI) is one of the most established environmental risk factors for the development of dementia and long term neurological deficits representing a critical health problem for our society. It is well-established that TBI-induced neuroinflammation contributes to the long-lasting cognitive deficits and engages brain-resident macrophages (microglia) as well as monocytes-derived macrophages (MDMs) recruited from the periphery. While numerous studies have characterized microglia response to TBI, and the critical role of early infiltrated MDMs in the development of cognitive dysfunctions, the fate of MDMs in TBI remains unknown. Microglia and MDMs have distinct embryological origins and it is unclear if MDMs can fully transition to microglia after infiltrating the brain. This gap in knowledge is due to the fact that after brain engraftment, MDMs stop expressing their signature markers, thus making discrimination from resident microglia cells elusive. Here, for the first time, we longitudinally trace the fate of MDMs by taking advantage of two complementary yet distinct fate mapping mouse lines, CCR2-creERT2and Ms4a3-cre, where inflammatory monocytes are permanently labeled even afterin situreprogramming. We demonstrated that early infiltrated MDMs persist in the brain for up to 8 months after TBI in adult female and male mice. Notably, MDMs retain their phagocytic activity while remaining transcriptomically distinct from microglia, and show a signature associated with aging and disease. Our data significantly advance the understanding of long-lasting MDMs and provide critical knowledge for developing more targeted therapeutic interventions for myeloid cells.
The role of histone modifications and transposable elements in the epigenetic regulation of gene dosage after gene duplication
Authors: Wolfe Thomas D , Chain Frederic J.J.
Published: November 2024

The duplication of genes has long been recognized as a substrate for evolutionary novelty and adaptation, but the factors that govern fixation of paralogs soon after duplication are only partially understood. Duplication often leads to an increase in gene dosage, or the amount of functional gene product. For genes with which an increased dosage is harmful (i.e., triplosensitive genes), a dosage balancing mechanism needs to be present immediately after duplication if it is to evade negative selection. Previous research in vertebrates has demonstrated a potential role for epigenetic factors in allowing triplosensitive genes to increase in copy number by regulating their expression post-duplication. Here we expand this research by investigating the epigenetic landscape of duplicate genes inD. discoideum, a basal lineage separated from humans by over a billion years. We found that activating histone modifications are quickly lost in duplicate genes before gradually increasing in enrichment as paralogs age. For the repressive modification H3K9me3, we found it was enriched in the youngest paralogs, and that this enrichment was likely mediated by heterochromatin spread from transposable elements. We similarly found enrichment of H3K9me3 in young human duplicates, and again found transposable elements as a potential mediator. Finally, we leveraged recent genome-wide estimates of triplosensitivity in human genes to directly examine the relationship between this kind of dosage sensitivity and enrichment for repressive histone modifications. Interestingly, while we found no significant link between enrichment for the repressive mark H3K9me3 and triplosensitivity in human paralogs, we did find a significant association between triplosensitivity and transposon proximity. Our findings suggest that transposons may contribute to the epigenetic regulatory environment associated with dosage balancing of young duplicates in both protists and humans.
Expanded chromosomal microarray comprising screening for spinal muscular atrophy and monogenic diseases3
Authors: Luan Xiaorui , Xu Naixin , Xie Yaojun , Shi Weihui , Cao Xianling , Zhou Xuanyou , Chen Songchang , Xu Chenming
Published: November 2024

Background

Copy number variants platforms, as critical supports for genetic diagnosis, have been well implemented in prenatal diagnosis. However, numerous severe conditions with underlying single-gene defects are not included in current invasive prenatal screening. To bridge this gap, an expanded chromosomal microarray analysis was developed, employing a meticulous designed single nucleotide polymorphism chip. This chip incorporated additional probes to augment its efficacy in screening for spinal muscular atrophy and diagnosing monogenic disorders.

Objective(s)

This study aimed to evaluate the accuracy, efficacy, and incremental yield of expanded chromosomal microarray, compared with karyotype analysis and low-depth genome sequencing for routine prenatal diagnosis.

Study Design

In this prospective study, total of 512 fetuses were included in this study. In this study three distinct diagnostic techniques-karyotype analysis, low-depth genome sequencing, and expanded chromosomal microarray-were processed to evaluate each sample. Aneuploidies and multigene copy number variations were detected and analyzed in a blinded fashion.SMN1exonic copy number variations were confirmed by multiplex ligation-dependent probe amplification and single nucleotide variations were confirmed by sanger sequencing.

Results

Overall, expanded chromosomal microarray identified genetic abnormalities in 91 out of 512 cases (17.6%). The encountered rate was significantly higher than the rates observed with low-depth genome sequencing (66 out of 512 cases, 12.9%) and conventional chromosome karyotyping (42 out of 512 cases, 8.2%). Expanded chromosomal microarray not only detected all these non-mosaic aneuploidies and copy number variations in 62(12.1%) diagnosed cases identified by low-depth genome sequencing (low-depth genome sequencing), but also detected 9 cases with regions of homozygosity, 10(2.0%) cases with exonic deletions (SMN1andDMD), and 13(2.5%) cases with single nucleotide variations.

Conclusions

Compared with low-depth GS, expanded chromosomal microarray increased the additional detection rate by 4.7% (24/512). Compared with traditional chromosomal microarray, expanded chromosomal microarray increased the additional detection rate by 3.9% (20/512) in 512 fetuses. Although the expanded chromosomal microarray (ECMA) has limited accuracy for detecting single nucleotide variations, its screening capacity is significantly enhanced when complemented with Sanger sequencing validation. Using expanded chromosomal microarray, we detected not only copy number variations, but also exonic deletions, regions of homozygosity with high accuracy in an acceptable turnaround time (2-3 weeks). Our results suggest that expanded chromosomal microarray has the potential to be a promising prenatal diagnostic tool with incremental yield of screening exonic copy number variations inSMN1.
Densely Populated Cell and Organelles Segmentation with U-Net Ensembles
Authors: Fulton Samuel J. , Baenen Cameron M. , Storrie Brian , Yang Zijie , Leapman Richard D. , Aronova Maria A.
Published: November 2024

The complex and highly intertwined morphology of activated platelets within thrombi poses significant challenges for segmentation. In this work, we present a robust dual-network pipeline for cell and organelle segmentation. This multi-network approach enables the detection of fine details near the membrane while simultaneously facilitating long-range smoothing in regions distal to the membrane, drastically improving the performance of the watershed clustering algorithm compared to single-network approaches. We further enhance segmentation performance by collecting neural network predictions along multiple axes, capturing 3D correlations using only 2D neural networks. We segment and analyze hundreds of platelets and report quantitative morphological measurements, showing volumes consistent with hand-segmented results. We apply our segmentation pipeline to the CREMI neuron segmentation challenge data and provide state-of-the-art results.
Modulatory effect of plasma-activated water on arbuscular mycorrhizal symbiosis inLotus japonicus
Authors: Cortese Enrico , Binci Filippo , Nouri Erfan , Capparotto Arianna , Settimi Alessio G. , Dabalà Manuele , Antoni Vanni , Squartini Andrea , Giovannetti Marco , Navazio Lorella
Published: November 2024

Plasma-activated water (PAW) is a recently developed cutting-edge technology that is increasingly gaining interest for its applications in medicine, food industry and agriculture. In plant biology, PAW has been shown to promote seed germination, plant growth, and plant resistance to biotic and abiotic stresses. Despite increasing knowledge of the beneficial effects exerted by PAW on plants, little information is currently available about how this emerging technology may affect the mutualistic plant-microbe interactions in the rhizosphere. In this work we have investigated the impact of irrigation with PAW, generated by a plasma torch, on arbuscular mycorrhizal (AM) symbiosis between the model legumeLotus japonicusand the AM fungusRhizophagus irregularis.Since PAW sensing by plants has recently been demonstrated to occur through calcium-mediated signalling, we monitored early cellular responses to different doses of PAW inL. japonicusroots expressing the Ca2+-sensitive photoprotein aequorin targeted to either the cytosol or nucleus. Quantitative analyses of AM fungal accommodation in host roots along with phosphate accumulation in leaves, as well as chemical analysis of N, C, S in shoots, showed that treatments with PAW play a modulatory role on plant AM symbiotic performance, in a manner dependent on the time interval of water exposure to the plasma and on the duration of plant irrigation treatment with PAW. Establishing a solid scientific ground for plasma-related technology may provide key elements to develop tools and treatments aimed to increase crop plant yield in a sustainable manner.
Expectation Violations as an Effective Alternative to Complex Mentalizing in Novel Communication
Authors: Buidze Tatia , Yao Yuan-Wei , Gläscher Jan
Published: November 2024

Effective communication in the absence of a shared language is a fundamental challenge, often addressed through complex cognitive mechanisms such as Theory of Mind, which allows individuals to infer others’ intentions and beliefs. However, this process is cognitively demanding and may not always be necessary. In this study, we propose that a more parsimonious cognitive mechanism—expectancy violations—can serve as an efficient alternative for communication in novel interactions. We tested this in the Tacit Communication Game, where we simulated Sender behavior using four computational models: the Surprise model based on expectancy violations and three levels of Theory of mind. After human Receivers interacted with these simulated Senders, we assessed the effectiveness of communication by analyzing accuracy and reaction times. Our results revealed that Receivers paired with the Surprise model achieved accuracy rates comparable to those interacting with the most complex Theory of mind model and exhibited more human-like message patterns. Additionally, models associated with higher accuracies also resulted in faster reaction times, indicating a reduced cognitive load. These findings challenge the necessity of complex mentalizing strategies in novel human interactions and suggest that an intuitive mechanism of expectancy violation may be a more plausible cognitive mechanism, while also providing quick responses.
Model-Driven Elucidation of Lactose and Galactose Metabolism via Oxidoreductive Pathway inSungouiella intermediafor Cell Factory Applications
Authors: Peri Kameshwara. V. R. , Domenzain Ivan , Alalam Hanna D , Valverde Rascon Abril , Nielsen Jens , Geijer Cecilia
Published: November 2024

Converting industrial side streams into value-added chemicals using microbial cell factories is of increasing interest, as such processes offer solutions to reduce waste and production costs. However, developing new, efficient cell factories for precision fermentation remains challenging due to limited knowledge about their metabolic capabilities. Here, we investigate the lactose and galactose metabolism of the non-conventional yeastSungouiella intermedia(formerlyCandida intermedia), using knowledge-matching of high-quality genome-scale metabolic model (GEM) with extensive experimental analysis and determine its potential as a future cell factory on lactose-rich industrial side-streams. We show that this yeast possesses the conserved Leloir pathway as well as an oxidoreductive galactose catabolic route. Contextualization of RNAseq data intoSint-GEMhighlights the regulatory mechanisms on the oxidoreductive pathway and how this pathway can enable adaptation to diverse environments. Model simulations, together with experimental data from continuous and batch bioreactors, indicate thatS. intermediauses upstream enzymes of the oxidoreductive pathway, in a condition-dependent manner, and produce the sugar alcohol galactitol as a carbon overflow metabolite, coupled to redox co-factor balancing during both lactose and galactose growth. Furthermore, the new metabolic insights facilitated the development of an improved bioprocess design, where an engineeredS. intermediastrain could achieve galactitol yields of >90% of the theoretical maximum at improved production rates using the industrial side-stream cheese whey permeate as feedstock. Additional strain engineering resulted in galactitol-to-tagatose conversion, proving the versatility of the future production host. Overall, this work sheds new light on the intrinsic interplay between parallel metabolic pathways that shape the lactose and galactose catabolism inS. intermedia. It also demonstrates how a GEM combined with experimental analysis can work in synergy to fast-forward metabolic characterization and development of new, non-conventional yeast cell factories.

Highlights

An oxidoreductive pathway functions in concert with the Leloir pathway for galactose catabolism.

GEM predicts that galactitol secretion enables efficient carbon overflow metabolism and maintains redox balance.

Knowledge-matching of GEM with experimental results highlights cell factory potential.

High galactitol yields and proof-of-concept tagatose production using whey permeate as feedstock.
Building a robust backbone forAstragalus(Fabaceae) using a clade-specific target enrichment bait set
Authors: Buono Daniele , Kadereit Gudrun , Liston Aaron , Zarre Shahin , Morales-Briones Diego F.
Published: November 2024

Premise of the study

With over 3100 species,Astragalus(Fabaceae) has long fascinated botanists as the largest genus of flowering plants. With an origin in the Middle Miocene,Astragalushas one of the highest diversification rates known in flowering plants. Comprehensive taxonomic treatments exist, and the genus is currently subdivided into 136 sections in the Old World and 93 sections in the New World based on morphological characters. Despite considerable efforts, a comprehensive and well-resolved phylogeny of the genus is still lacking.

Methods

Here, we reconstruct the backbone phylogeny ofAstragalususing a custom bait set capturing 819 loci specifically designed for a target enrichment approach in the Astragalean clade. We carefully selected a set of 107 taxa representing all major clades currently recognized inAstragalus. Of those, 80 newly sequenced taxa were obtained from herbarium specimens as old as 110 years.

Key results

We retrieved all the targeted loci and additional off-target plastome sequences for all samples, including the 80 herbarium specimens. Our phylogenetic analysis reinforced the currently accepted backbone phylogeny ofAstragaluswith high support and unprecedented details, additionally providing insights into cytonuclear phylogenetic conflicts in the genus. Evidence for potential reticulate evolution was found, providing a possible explanation for the conflicts observed.

Conclusions

This work represents an important milestone in obtaining a comprehensive, herbarium-based phylogeny ofAstragalus, which will constitute the base to study a wealth of relevant biological questions, for example, the still unanswered question of what drove the rapid diversification ofAstragalus, with important repercussions on our understanding of diversification in natural contexts.
The effects of running shoe stack height on running style and stability during level running at different running speeds
Authors: Kettner Cagla , Stetter Bernd , Stein Thorsten
Published: November 2024

The footwear market contains a wide variety of running shoe solutions aiming at optimizing performance and minimizing injuries. Stack height is one of the most highly discussed design features of running shoes, but its effects are not yet well understood. This study investigated the effects of different shoes differing mainly in their stack heights (High: 50 mm, Medium: 35 mm & Low: 27 mm) on running style and stability during treadmill running at 10 and 15 km/h. A total of 17 healthy experienced runners participated in this study. The kinematic data were recorded with a 3D motion capturing system. The running style was investigated by a dual-axis framework with duty factor (DF) and leg length normalized to step frequency (SFnorm). Additionally, the ratio of landing to take-off duration, the lower body joint angle time series in the sagittal and frontal planes, the vertical center of mass oscillation (COMosc), and the stiffness parameters (kver & kleg) were compared for different conditions. The stability was analyzed using linear (i.e. discrete frontal ankle parameters) and nonlinear methods (i.e. Maximum Lyapunov Exponent for local dynamic stability of head, trunk, hip, and foot, and detrended fluctuation analysis of stride time). High resulted in longer ground contact relative to stride time (DF) compared to Low. The higher the stack height, the higher was the COMosc. Furthermore, High led to a longer foot eversion during stance compared to Medium. In addition, the local dynamic stability of the hip decreased with High in comparison with Low. The higher stack heights (≥ 35 mm) led to a lower SFnorm at 15 km/h but not at 10 km/h. The remaining shoe effects were independent of the running speed. Findings showed that changes in stack height can affect running style. Furthermore, the highest stack height resulted in changes related with instabilities (i.e., longer foot eversion and lower hip dynamic stability) which may be a critical issue in terms of injuries and performance. However, this study did not include joint load analysis or running performance measures such as VO2. Future studies may benefit from the combination of analysis approaches to better understand stack height effects on running injuries and performance.
Molecular determinant of sterol recognition by sterol cleavage activatory protein
Authors: Khiewdee Charal , Ounjai Puey , Pipatpolkai Tanadet
Published: November 2024

Intracellular cholesterol homeostasis is regulated by the sterol response element-binding protein (SREBP) pathway through the SREBP cleavage-activating protein (SCAP) and the insulin-induced gene protein (INSIG). Previous studies highlighted that high concentrations of cholesterol mediated the dimerisation between INSIG and SCAP, which led to an inhibition of cholesterol uptake and biogenesis. However, the molecular understanding of SCAP-INSIG and cholesterol interactions remains elusive. Here, we used coarse-grained (CG) and atomistic (AT) molecular dynamics (MD) simulation to determine interactions between INSIG, SCAP and cholesterol. Our work highlighted the novel binding pocket in the luminal domain at the atomistic resolution. Using a combination of the AlphaFold3 model and Gō-martini forcefield, we showed that loop 7 dynamics are crucial for cholesterol binding and are able to highlight conserved residues, which lead to INSIG-SCAP dimerisation. Together, our work highlights novel mechanisms of cholesterol sensor pathways and will benefit the development of novel therapeutic strategies for diseases, such as neuroinflammatory disease, caused by irregular cholesterol homeostasis.
The ALS- and FTD-associated proteins Annexin A11 and CHMP2B act sequentially in membrane repair
Authors: Heffner Catherine M , Starling Georgina P , Isaacs Adrian , Carlton Jeremy G
Published: November 2024

Maintenance of plasma membrane and organellar integrity is essential for cell viability. Cells must recognise damaged membranes and orchestrate repair programmes to preserve compartmentalisation. A variety of cellular factors including ESCRTs, Annexins, stress granules, lipids and proteins allowing vesicle and organelle fusion with damaged membranes have been reported to contribute to membrane repair. However, whether these factors operate independently or together to repair membranes is unclear. Here, we expose temporal differences and interdependencies in the recruitment of ESCRT-III and Annexin proteins to sites of membrane damage. We show that while Annexins are recruited immediately to sites of damage, ESCRT-III assembles only after membrane sealing. We show that ESCRT-III acts to shed damaged membranes from the cell and that FTD-and ALS-associated mutations in CHMP2B and ANXA11 compromise the repair process. These data present an integrated "sealing and healing" model of events allowing membrane repair and restoration of membrane integrity.
The sequence and structural integrity of the SARS-CoV-2 Spike protein transmembrane domain is crucial for viral entry
Authors: Ortiz-Mateu J , Belda D , Avilés-Alía AI , Alonso-Romero J , García-Murria MJ , Mingarro I , Geller R , Martinez-Gil L
Published: November 2024

The Spike protein of SARS-CoV-2 is a type I membrane protein that mediates target cell recognition and membrane fusion. Its transmembrane domain (TMD) is usually considered a passive physical anchor that attaches the protein to the viral envelope. However, current knowledge of the dynamics and biogenesis of integral membrane proteins indicates that TMDs generally play key functions beyond membrane anchoring. Here, we explored the role of the SARS-CoV-2 Spike protein TMD during viral entry. To do so, we generated a series of amino acid substitutions and insertions within the hydrophobic core of the TMD and analyzed their impact on protein function. Our results indicate that the SARS-CoV-2 Spike protein is highly susceptible to changes in its TMD. Furthermore, the TMD sequence and structural parameters relevant for viral entry are distributed across the entire segment, albeit with a stronger implication of the N-terminal portion. The relative orientation of the regions before and after the TMD was also found to be relevant for particle entry. Finally, our results suggest that the SARS-CoV-2 Spike protein TMD can form homo-oligomers through a motif in which small residues are necessary.
Microbial dysbiosis is evident in oral squamous cell carcinoma (OSCC) tissues of a group of Sri Lankan male patients with oral risk habits
Authors: Perera Manosha Lakmali , Perera Irosha Rukmali
Published: November 2024

Background

Metagenomic investigations into components of the oral microbiome in a single study remain scarce.

Objective

To ascertain the microbiome profile of oral squamous cell carcinoma (OSCC) tissues in a group of Sri Lankan male patients.

Methods

From the main sample of an unmatched case-control study, a sub-sample consisting of 29 OSCC cases and 25 Fibroepithelial polyp (FEP) controls were selected. OSCC incisional and FEP excisional biopsies were collected and stored at -800C. DNA was extracted from frozen specimens using Gentra Puregene Tissue kit (Qiagen, Germany), solid tissue protocol. The DNA extracts were stored at -800C. Extracted DNA samples were sequenced by Illumina’s 2×300 bp chemistry. High quality non-chimeric merged reads were classified to the species level by prioritized BLASTN-algorithm for bacteriome and BLASTN-algorithm with UNITE’s named species sequences as reference for mycobiome.

Results

Our study identifies several potential periodontal pathogens, includingCampylobacter concisus, Prevotella salivae, Prevotella loeschii, andFusobacterium oral taxon 204. Additionally,Candida albicansis frequently associated with oral potentially malignant disorders (OPMDs) and oral cancers. Notably, we found a significant association betweenCandida etchelliiand oral cancer for the first time. Furthermore, Capnocytophaga, Atopobium, and Candida were the most abundant microbial genera present in oral squamous cell carcinoma (OSCC) tissues.

Conclusions

A dysbiotic microbiome was discovered in the tumor microenvironment of a group of OSCC male patients with oral risk habits. Validation of these biomarkers indifferent cohorts to supplement inadequacy in the diagnosis of epithelial dysplasia histologically is much warranted in the golden era ofmicrobiome-first-medicine
Long-lasting, subtype-specific regulation of somatostatin interneurons during sensory learning
Authors: Zhu Mo , Mosso Matthew B. , Ma Xiaoyang , Park Eunsol , Barth Alison L.
Published: November 2024

Somatostatin (SST)-expressing inhibitory neurons are a major class of neocortical γ-amino butyric acid (GABA) neurons, where morphological, electrophysiological, and transcriptomic analyses indicate more than a dozen different subtypes. However, whether this diversity is related to specific roles in cortical computations and plasticity remains unclear. Here we identify learning-dependent, subtype-specific plasticity in layer 2/3 SST neurons of the mouse somatosensory cortex. Martinotti-type, SST neurons expressing calbindin-2 show a selective decrease in excitatory synaptic input and stimulus-evoked calcium responses as mice learn a stimulus-reward association. Using these insights, we develop a label-free classifier using basal activity fromin vivoimaging that accurately predicts learning-associated response plasticity. Our data indicate that molecularly-defined SST neuron subtypes play specific and highly-regulated roles in sensory information processing and learning.
Cross-species Comparison of Ultramafic Rock Bio-accelerated Weathering Performance
Authors: Plante Luke , Klug Jacob D. , Lee Joseph , Hornby Adrian , Adair James , Marecos Sabrina , Reid Matthew C. , Gazel Esteban , Barstow Buz
Published: November 2024

Carbon mineralization is a natural process that sequesters atmospheric CO2by reacting it with cations (e.g., Mg2+, Ca2+) released by weathering of rocks to form solid carbonates. However, this process is too slow to capture the excess CO2resulting from anthropogenic emissions in time to prevent significant warming of the atmosphere1–3. Additionally, accelerating carbon mineralization process by chemical or mechanical methods has proven prohibitively expensive to date4. Microbial rock-dissolution processes, including acidolysis, redoxolysis, and complexolysis, have the potential to accelerate weathering with low energy input5. However, there is no industrially useful microbe capable of dissolving ultramafic (rich in ferromagnesian minerals) rocks, suggesting that one will need to be discovered or built with synthetic biology. While microbes are known to dissolve ultramafic minerals6,7, the performance envelopes for these processes remain uncharacterized, and significant gaps exist in our knowledge of microbe-mineral interaction processes. Here, we make a normalized performance comparison of the dissolution of the ultramafic rock dunite (> 90% olivine ((Mg, Fe)2SiO4)) by three well-known mineral-dissolving microbes:Gluconobacter oxydans7–9,Sphingomonas desiccabilis10,11, andPenicillium simplicissimum12–14. We show thatG. oxydansoutperformedP. simplicissimumandS. desiccabilis, producing the most acidic biolixiviant (pH 2.15 when leaching 1% pulp density), and extracting the most magnesium (3,130 mg/L when leaching at 3% pulp density). Additionally,G. oxydansco-dissolves nine other metals, eight of which are critical for energy technologies (Cr, Mn, Co, Ni, Cu, and Zn)15,16with a maximum dissolved concentration of 33 mg/L for Ni. While increasing the pulp density of the dunite (solid to liquid ratio) resulted in higher metal dissolution byG. oxydansandS. desiccabilis, notably pulp densities above 2% inhibited mineral dissolution byP. simplicissimum. Our results provide evidence that the gap in performance betweenG. oxydansand the other two microbes increases with pulp density, and thus,G. oxydansis best suited for process and genetic engineering to maximize performance and minimize costs and environmental impacts of bio-accelerated weathering. Finally, we propose thatG. oxydansandP. simplicissimumcan use cellulosic hydrolysate as a cost-effective substitute for glucose for biolixiviant production.
The effects of chronic neuropathic pain on the self-administration of highly potent MOR agonist, fentanyl
Authors: Burgess Gwendolyn E. , Traynor John R. , Jutkiewicz Emily M.
Published: November 2024

There is significant overlap between chronic pain and opioid use disorder (OUD) patient populations such that approximately 50-65% of chronic pain patients have OUD. However, we understand relatively little about how chronic, long-lasting pain states alter ongoing self-administration of opioid analgesics. Thus, the goal of this study was to determine if chronic neuropathic pain altered the ongoing self-administration of fentanyl, or a non-opioid drug of abuse, cocaine. Animals were trained to self-administer fentanyl or cocaine in a multi-dose self-administration procedure composed of five 25-min components, exposing animals to multiple doses of drug per day. Operant behavior was established prior to induction of chronic pain via the spared nerve injury (SNI). Animals were allowed 72 hours of post-operative recovery and resumed self-administration on post-operative day 4. All animals dose-dependently self-administered fentanyl prior to surgery. On post-operative day 4, both sham and SNI groups showed a significant decrease in fentanyl self-administration. By post-operative day 9, fentanyl intake was no longer significantly different from pre-surgical intake. Over the course of 4 weeks of self-administration, there was an increase in intake of specifically the 10 ug/kg/inf dose of fentanyl. Cocaine self-administration was not altered at any point following either surgery. Collectively, these results suggest that SNI-induced hypersensitivity failed to alter the reinforcing effects of fentanyl, or non-opioid drug of abuse, cocaine. Future studies should evaluate the abuse potential of lower efficacy MOR agonists such as nalbuphine or buprenorphine, as small changes were observed in fentanyl-maintained behavior over time in both SNI and sham groups.

Significance statement

MOR agonists are excellent analgesics; however, they are not first-line treatments for chronic pain, in part due to abuse potential. This study demonstrates that small, significant rightward shifts in the fentanyl dose response curve were observed following induction ofbothsham and spared nerve injury (SNI) (chronic neuropathic pain-like) states, suggesting these changes were observed independent of pain state. These data indicate that SNI-induced neuropathic pain failed to alter the ongoing self-administration of highly potent MOR agonist, fentanyl.
Detection ofDeltacoronavirusin Environmental Fecal Samples from Seabirds in the Saint Peter and Saint Paul Archipelago, central equatorial Atlantic Ocean
Authors: Gomes Fernanda , da Silva Alexandre Freitas , Prado Tatiana , Bueno Marina Galvão , Appolinario Luciana , Flores Patrícia Soares , Resende Paola Cristina , Siqueira Marilda , Corrêa Leonardo , Brandão Martha , Reck Jose , da Luz Wallau Gabriel , Ogrzewalska Maria
Published: November 2024

This study investigates the presence of avian coronaviruses (CoVs), influenza A viruses (IAVs), and Avian rotaviruses (RVs) group A in seabird populations inhabiting the Saint Peter and Saint Paul Archipelago (SPSPA), an isolated and remote oceanic island situated in the equatorial region of the Atlantic Ocean. In July 2022, 95 environmental fecal samples were collected from seabird colonies and screened for the viruses by quantitative one-step real-time RT-PCR (IAVs and RVs), by the conventional pancoronavirus RT-PCR protocols and metatranscriptomics of a positive sample. Four environmental feces samples tested positive for CoVs. Avian IAVs and RVs were not detected. Phylogenetic analysis revealed CoVs closely related to avian deltacoronaviruses previously identified in waterbirds from Asia and Australia. We could not recover the CoV by metatranscriptomics but we recovered a single viral contig of an avian enterovirus. The findings contribute valuable insights into virus dynamics among seabird populations, laying the groundwork for future investigations in this field.