bluuebunny/crossref_metadata_2025 huggingface dataset:
Fire traps in the wet subtropics: new perspectives from Hong Kong
Authors: Chan Aland H. Y. , Coomes David A.
Published: November 2023

Fires undermine efforts to restore degraded forests in the wet tropics and subtropics. Grasslands and shrublands established after fires are more fire-susceptible than forests and tend to be set alight more often, creating a positive feedback loop that curbs succession (i.e. create a fire trap). Understanding the factors that underpin the strength of these fire traps could transform restoration programmes by identifying the steps needed to escape them.

Fire traps are notoriously challenging to quantify because multiple factors influence fire occurrence and vegetation recovery. Here we used multi-decadal satellite imagery from Landsat to create a 34-year time series of burn areas and vegetation dynamics in wet subtropical Hong Kong. These dynamic maps were then used to characterise (1) the influence of successional stage on fire occurrence, having accounted for topographical and ignition source imbalances using neighbourhood analyses and entropy balancing (EBAL) weights, and (2) recovery time to the next successional stage by survival analysis with EBAL weights.

Our analyses revealed that fire regimes in the wet subtropics are defined by strong fire-vegetation feedbacks. Grasslands and shrublands were 20 and 9 times more susceptible to fires than forests in similar topographic positions. Human activities compounded these differences by disproportionally introducing more ignition sources to grasslands (2.3 times) and shrublands (2.0 times) than to forests.

Burnt shrublands recovered to forests faster (19 years) than grasslands (40 years). Proximity to forest patches had strong positive effects on recovery rates, highlighting the importance of seed sources. Post-fire recovery was faster on wetter northwest-facing sites and valleys. Overall, topography strongly influenced recovery processes but hardly affected fires occurrence.

Synthesis and applications. Our study provides the first quantification of fire-trap processes in the wet subtropics, which provides new opportunities for evidence-based fire suppression and post-fire restoration. Our results suggest that (1) fire traps could be mitigated by fire-suppression programmes as the traps are currently exacerbated by ignition source imbalance; (2) establishing green fire breaks represent an effective fire suppression measure in the wet subtropics; and (3) active restoration could target areas where models predict sluggish post-fire natural regeneration.
Aberrant hippocampal Ca2+micro-waves following synapsin-dependent adeno-associated viral expression of Ca2+indicators
Authors: Masala Nicola , Mittag Manuel , Ambrad Giovannetti Eleonora , O’Neil Darik A. , Distler Fabian , Rupprecht Peter , Helmchen Fritjof , Yuste Rafael , Fuhrmann Martin , Beck Heinz , Wenzel Michael , Kelly Tony
Published: November 2023

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca2+micro-waves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7 or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer, in a titre-dependent fashion. Ca2+micro-waves developed in hippocampal CA1 and CA3, but not dentate gyrus (DG) nor neocortex, were typically first observed at 4 weeks after viral transduction, and persisted up to at least 8 weeks. The phenomenon was robust, observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca2+micro-waves depend on the promoter and viral titre of the GECI, density of expression as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artifact. The results show that commonly used Ca2+-indicator AAV transduction procedures can produce artefactual Ca2+responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca2+micro-waves and we provide a potential solution.

Impact statement: Common AAV transduction procedures induce artefactual spatially confined Ca2+waves in the hippocampus.
FLASHQuant: a fast algorithm for proteoform quantification in top-down proteomics
Authors: Kim Jihyung , Jeong Kyowon , Kaulich Philipp T. , Winkels Konrad , Tholey Andreas , Kohlbacher Oliver
Published: November 2023

Liquid chromatography-mass spectrometry (LC-MS) based top-down proteomics (TDP) is an essential method for the analysis of intact proteoforms. The accurate quantification of individual proteoforms is a crucial step in identifying proteome-wide alterations in different biological conditions. Label-free quantification (LFQ) is the most common method for proteoform quantification as it requires no additional costly labeling. In TDP, due to frequent co-elution and complex signal structures, overlapping signals deriving from multiple proteoforms complicate accurate quantification. Here, we introduce FLASHQuant for MS1-level LFQ analysis in TDP, which is capable of automatically resolving and quantifying co-eluting proteoforms. FLASHQuant performs highly accurate and reproducible quantification in short runtimes of just a few minutes per LC-MS run. To validate the proteoforms reported by FLASHQuant, we evaluated them with identified proteoforms confirmed by tandem mass spectrometry, which showed high match rates. FLASHQuant is publicly available as platform-independent open-source software athttps://openms.org/flashquant/.
Protocol for 3D Virtual Histology of Unstained Human Brain Tissue using Synchrotron Radiation Phase-Contrast Microtomography
Authors: Lee Ju Young , Donato Sandro , Mack Andreas F. , Mattheus Ulrich , Tromba Giuliana , Longo Elena , D’Amico Lorenzo , Mueller Sebastian , Shiozawa Thomas , Bause Jonas , Scheffler Klaus , Longo Renata , Hagberg Gisela E.
Published: November 2023

X-ray phase-contrast micro computed tomography using synchrotron radiation (SR PhC-µCT) offers unique 3D imaging capabilities for visualizing microstructure of the human brain. Its applicability for unstained soft tissue is an area of active research. Acquiring images from a tissue block without needing to section it into thin slices, as required in routine histology, allows for investigating the microstructure in its natural 3D space. This paper presents a detailed step-by-step guideline for imaging unstained human brain tissue at resolutions of a few micrometers with SR PhC-µCT implemented at SYRMEP, the hard X-ray imaging beamline of Elettra, the Italian synchrotron facility. We present examples of how blood vessels and neurons appear in the images acquired with isotropic 5 µm and 1 µm voxel sizes. Furthermore, the proposed protocol can be used to investigate important biological substrates such as neuromelanin or corpora amylacea. Their spatial distribution can be studied using specifically tailored segmentation tools that are validated by classical histology methods. In conclusion, SR PhC-µCT using the proposed protocols, including data acquisition and image processing, offers viable means of obtaining information about the anatomy of the human brain at the cellular level in 3D.
Metabolic Regulation of Single Synaptic Vesicle Exo- and Endocytosis in Hippocampal Synapses
Authors: Myeong Jongyun , Stunault Marion I , Klyachko Vitaly A , Ashrafi Ghazaleh
Published: November 2023

Glucose has long been considered a primary source of energy for synaptic function. However, it remains unclear under what conditions alternative fuels, such as lactate/pyruvate, contribute to powering synaptic transmission. By detecting individual release events in cultured hippocampal synapses, we found that mitochondrial ATP production from oxidation of lactate/pyruvate regulates basal vesicle release probability and release location within the active zone (AZ) evoked by single action potentials (APs). Mitochondrial inhibition shifted vesicle release closer to the AZ center, suggesting that the energetic barrier for vesicle release is lower in the AZ center that the periphery. Mitochondrial inhibition also altered the efficiency of single AP evoked vesicle retrieval by increasing occurrence of ultrafast endocytosis, while inhibition of glycolysis had no effect. Mitochondria are sparsely distributed along hippocampal axons and we found that nerve terminals containing mitochondria displayed enhanced vesicle release and reuptake during high-frequency trains, irrespective of whether neurons were supplied with glucose or lactate. Thus, synaptic terminals can entirely bypass glycolysis to robustly maintain the vesicle cycle using oxidative fuels in the absence of glucose. These observations further suggest that mitochondrial metabolic function not only regulates several fundamental features of synaptic transmission but may also contribute to modulation of short-term synaptic plasticity.

Highlights

Synapses can sustain neurotransmission across various activity levels by bypassing glycolysis and utilizing oxidative fuels.

Mitochondria, but not glycolysis, regulate release probability and nanoscale organization of vesicle release within the active zone.

Mitochondrial inhibition increases the occurrence of vesicle retrieval via ultra-fast endocytosis.

Mitochondrial localization in nerve terminals enhances vesicle release and retrieval in the absence of glucose, representing a form of synaptic plasticity.
Improving Hi-C contact matrices using genome graphs
Authors: Shen Yihang , Yu Lingge , Qiu Yutong , Zhang Tianyu , Kingsford Carl
Published: November 2023

Three-dimensional chromosome structure plays an important role in fundamental genomic functions. Hi-C, a high-throughput, sequencing-based technique, has drastically expanded our comprehension of 3D chromosome structures. The first step of Hi-C analysis pipeline involves mapping sequencing reads from Hi-C to linear reference genomes. However, the linear reference genome does not incorporate genetic variation information, which can lead to incorrect read alignments, especially when analyzing samples with substantial genomic differences from the reference such as cancer samples. Using genome graphs as the reference facilitates more accurate mapping of reads, however, new algorithms are required for inferring linear genomes from Hi-C reads mapped on genome graphs and constructing corresponding Hi-C contact matrices, which is a prerequisite for the subsequent steps of the Hi-C analysis such as identifying topologically associated domains and calling chromatin loops. We introduce the problem of genome sequence inference from Hi-C data mediated by genome graphs. We formalize this problem, show the hardness of solving this problem, and introduce a novel heuristic algorithm specifically tailored to this problem. We provide a theoretical analysis to evaluate the efficacy of our algorithm. Finally, our empirical experiments indicate that the linear genomes inferred from our method lead to the creation of improved Hi-C contact matrices. These enhanced matrices show a reduction in erroneous patterns caused by structural variations and are more effective in accurately capturing the structures of topologically associated domains.
Unraveling Shared Pathways: A Comprehensive Systematic Review of Common Fiber Tracts in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia using Diffusion Tensor Imaging
Authors: Alruwaili Ashwag Rafea S , Devine Matthew , Mccombe Pamela
Published: November 2023

This systematic review evaluated MRI studies of fibre tract abnormalities in patients with amyotrophic lateral sclerosis (ALS) and/or fronto-temporal dementia (FTD). After searching 5 databases, 63 papers met inclusion criteria reporting 1674 patients and 1411 healthy controls. The papers studied a range of fibre tracts. Techniques used included overall comparisons and regions of interest. All papers reported results of fractional anisotropy (FA) and some also reported other DTI metrics. In ALS, the hallmark feature of cortico-spinal tracts (CST) involvement is consistently found, while in FTD the only part of the motor tracts that was found to show changes is the corona radiata (CR). The review also highlighted overlapping abnormalities between ALS and FTD, suggesting that these conditions exist on a spectrum. Both ALS and FTD exhibited CST abnormalities, with extra-motor involvement in the cingulum and the CC. Many tracts including the corpus callosum (CC) and cingulum (Cg), the superior longitudinal fasciculus (SLF) and inferior fronto-occiptal fasciculus (IFOF), were abnormal in both ALS and FTD. The integrity of specific white matter tracts, such as the uncinated fasciculus (uncF), forceps minor, and callosal radiation, appeared critical for cognitive functions related to Theory of Mind, cognitive control, and emotion recognition.There was, however, extramotor involvement in ALS.
Glial ferritin maintains neural stem cells via transporting iron required for self-renewal inDrosophila
Authors: Ma Zhixin , Wang Wenshu , Yang Xiaojing , Rui Menglong , Wang Su
Published: November 2023

Stem cell niche is critical for regulating the behavior of stem cells. Drosophila neural stem cells (Neuroblasts, NBs) are encased by glial niche cells closely, but it still remains unclear whether glial niche cells can regulate the self-renewal and differentiation of NBs. Here we show that ferritin produced by glia, cooperates with Zip13 to transport iron into NBs for the energy production, which is essential to the self-renewal and proliferation of NBs. The knockdown of glial ferritin encoding genes causes energy shortage in NBs via downregulating aconitase activity and NAD+level, which leads to the low proliferation and premature differentiation of NBs mediated by Prospero entering nuclei. More importantly, ferritin is a potential target for tumor suppression. In addition, the level of glial ferritin production is affected by the status of NBs, establishing a bicellular iron homeostasis. In this study, we demonstrate that glial cells are indispensable to maintain the self-renewal of NBs, unveiling a novel role of the NB glial niche during brain development.
The Determinants of Malnutrition Among Adolescent Girls: A Systematic Review
Authors: Hameed Abdul Rahman , Ghaffari Mohtasham , Fung Teresa T. , Daneshzad Elnaz , Ghaffari Mohtasham , Mousavi Sayed Hamid , Azadbakht Leila
Published: November 2023

Background

Malnutrition, encompassing deficiencies, excesses, or imbalances in energy and nutrient intake, continues to be a critical global issue. Adolescent girls, with their pivotal role as potential future mothers, are particularly susceptible to the challenges of malnutrition. The vulnerability of this group emanates from factors including inadequate nutritional intake and a lack of essential nutritional knowledge. This comprehensive systematic review strives to meticulously scrutinize the impact of environmental and behavioral determinants on malnutrition among adolescent girls in educational settings.

Methods

Adhering rigorously to the guidelines stipulated by the Preferred Reporting Items for Systematic Review and Meta-Analysis, an exhaustive literature search was conducted up to April 9th, 2023, across esteemed databases such as PubMed, Web of Science, and Google Scholar. Employing a refined search strategy incorporating Boolean operators, the search query (“Malnutrition” [Major]) AND “Adolescent” [MeSH] was deployed. Inclusivity criteria comprised original cross-sectional and case-control studies that comprehensively investigated the determinants of malnutrition among adolescent girls. This review places notable emphasis on studies published between 2013 and 2023, ensuring a contemporary and nuanced analysis of this critical subject matter.

Results

The initial search resulted in 2438 articles. Twenty studies fully met the inclusion criteria. Most studies found that socioeconomic status, dietary patterns and their role, cultural and social norms, education and knowledge, early marriage and pregnancy, access to healthcare, and food security are the main key determinants of malnutrition among adolescent girls.

Conclusion

The complex issue of malnutrition among adolescent girls, identifies various factors contributing to it, including social, economic, cultural, and individual factors. To combat malnutrition effectively, a holistic approach is needed, focusing on education, gender equality, and improved healthcare access, rather than just providing more food. This requires collaboration among policymakers, healthcare professionals, and local communities to raise awareness, empower economically, and remove healthcare barriers. By uniting these efforts, we can loosen the grip of malnutrition on adolescent girls and pave the way for their robust development and a brighter future.
Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function
Authors: Rosner Grace M. , Goswami Himanshu B. , Sessions Katherine , Mendyka Lindsay K. , Kerin Brenna , Vlasac Irma , Mellinger Diane , Gwilt Lorraine , Hampton Thomas H. , Graber Martha , Ashare Alix , Harris William T. , Christensen Brock , Stanton Bruce A. , Swiatecka-Urban Agnieszka , Skopelja-Gardner Sladjana
Published: November 2023

Background

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF.

Methods

Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies.

Results

PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronicPseudomonas aeruginosainfection.

Conclusions

Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and highPseudomonas aeruginosaburden suggests that pulmonary disease may contribute to renal injury in CF.
The cross-sectional correlation between the oxidative balance score and cardiometabolic risk factors and its potential correlation with longitudinal mortality in patients with cardiometabolic risk factors
Authors: Lai Qiancheng , Ye Liu , Luo Jun , Zhang Cheng , Shao Yue
Published: November 2023

Background

This study sought to analyze the correlation between oxidative balance score (OBS) and cardiometabolic risk factors (CMRFs) and mortality in individuals with CMRFs.

Methods

Data were chosen from the National Health and Nutrition Examination Survey. The survey-weighted multivariable logistic regression models were implemented to explore the relationship between OBS and the risk of CMRFs. Then, Cox proportional hazard models were employed to estimate the impact of OBS on mortality in individuals with CMRFs.

Results

Following multivariate adjustment, the subjects in the highest quartile exhibited a 46% reduction in the risk of CMRFs, a 33% reduction in the risk of diabetes, a 31% reduction in the risk of hypertension, and a 36% reduction in the risk of hyperlipidemia, compared with those in the lowest quartile. Furthermore, each 1-unit increase in OBS was remarkably negatively correlated with the prevalence of CMRFs, diabetes, hypertension, and hyperlipidemia. The correlation between OBS and CMFRs was found to be mediated by serum γ-glutamyltransferase (GGT) and white blood cells (WBC), and the mediation effect of GGT levels and WBC, accounting for 6.90% and 11.51%, respectively. Lastly, the multivariate Cox regression model revealed that elevated OBS, irrespective of whether it was treated as a categorical or continuous variable, exhibited a significant association with decreased mortality from all causes, cardiovascular disease, and cancer.

Conclusions

An increased OBS might reflect a lower risk of CMRFs and a favorable prognosis for individuals with CMRFs. Moreover, WBC and GGT may play a potential mediating role between OBS and CMRFs.

What is new?

An elevated OBS was correlated with a reduced risk of developing CMRFs. Furthermore, WBC and GGT could act as mediators in this association.

An increased OBS might indicate a positive prognosis for individuals with CMRFs.

What are the clinical implications?

OBS might serve as a valuable tool to guide the general population toward adopting healthy diets and positive lifestyle patterns in order to mitigate the risk of CMRFs and enhance the prognosis of CMRFs individuals with CMRFs.
Prognostic Implications of Right Ventricular Dysfunction in Degenerative Mitral Regurgitation
Authors: Bohbot Yohann , Essayagh Benjamin , Benfari Giovanni , Bax Jeroen J. , Le Tourneau Thierry , Topilsky Yan , Antoine Clemence , Rusinaru Dan , Grigioni Francesco , Ajmone Marsan Nina , van Wijngaarden Aniek , Hochstadt Aviram , Roussel Jean Christian , Thapa Prabin , Michelena Hector I , Enriquez-Sarano Maurice , Tribouilloy Christophe
Published: November 2023

Background

The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with survival in patients with DMR.

Methods

We used data from the Mitral Regurgitation International DAtabase-Quantitative (MIDA-Q) which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 4,379 (mean age: 67 years, 64.6% males, follow-up:5.3[3.3-8.2]years) consecutive patients with significant (≥moderate) DMR was included and long-term survival was analyzed.

Results

RVD, identified in 584(13.3%) patients, was associated with reduced 10-year survival (49±3%vs.67±1%;p<0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures and surgery (adjusted HR[95%CI]=1.55[1.31-1.84];p<0.001). This excess mortality was observed under medical management (adjusted HR[95%CI]=1.39[1.12-1.72];p=0.003) and after surgical correction of mitral regurgitation (adjusted HR[95%CI]=1.56[1.08-2.27];p=0.019). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 10-year survival (73±4% vs. 38±4%;p<0.001), even after adjustment (adjusted HR[95%CI]=0.53[0.35-0.81];p=0.003)despite an increase of 1-month post-operative mortality (5% vs 2.2% for patients without RVD;p<0.001).

Conclusions

RVD is observed in 13.3% of significant DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision-making process.
Structural alterations in a rumination-related network in patients with major depressive disorder
Authors: Cheng Paul Z. , Lee Hsin-Chien , Lane Timothy J. , Hsu Tzu-Yu , Duncan Niall W.
Published: November 2023

Rumination is a common symptom in major depressive disorder (MDD) and has been linked to risk for that disorder, its prognosis, and relapse likelihood. Previous work has linked individual differences in rumination to structural properties in a variety of brain regions. Some of these regions, such as the dorsolateral prefrontal cortex (dlPFC), have also been highlighted as being altered in MDD, suggesting a connection between structural changes and ruminative symptoms. Although informative, such localised relations have some limitations in the context of a network view of the brain. To further investigate rumination-related structural changes in depression and to situate these within potential functional networks, we acquired structural data from patients with MDD (n = 32) and controls (n = 69). Analysis of cortical grey-matter identified group differences in the dlPFC that were, however, not related to rumination. Instead, rumination was correlated with grey-matter properties in the right precuneus. Using normative functional connectivity analysis on a large independent sample, we show that these two regions are interconnected. It was further shown that the rumination-related precuneus region is highly connected with networks associated with processes such as executive function, autobiographical memory, and visual perception. Notably, each of these processes has been connected to rumination. These results suggest that rumination in depression may be linked to focal structural changes that disrupt a distributed functional network.
Distinct expression patterns of Hedgehog signaling components In mouse gustatory system during postnatal tongue development and adult homeostasis
Authors: Kumari Archana , Franks Nicole E. , Li Libo , Audu Gabrielle , Liskowicz Sarah , Johnson John D. , Mistretta Charlotte M. , Allen Benjamin L.
Published: November 2023

It is well established that the Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae, and taste organ maintenance and regeneration in adults. However, there are knowledge gaps in determining HH signaling regulation in postnatal taste organ differentiation and maturation. Importantly, the HH transcription factors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; and, the receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, remain unexplored. UsinglacZreporter mouse models, we mapped expression of the HH ligand SHH, receptors, and transcription factors in FP, CVP and FOP in early and late postnatal and adult stages. In adults we also studied the soft palate, and the geniculate and trigeminal ganglia which extend afferent fibers to the anterior tongue.ShhandGas1are the only components that were consistently expressed within taste buds of all three papillae and the soft palate. In the first postnatal week, we observed a broad expression of HH signaling components in FP and adjacent, non-taste filiform (FILIF) papillae in epithelium or stroma and tongue muscles. Remarkably, we observed elimination ofGli1in FILIF andGas1in muscles, and downregulation ofPtch1in lingual epithelium and ofCdon,Gas1andHhipin stroma from late postnatal stage. Further, HH receptor expression patterns in CVP and FOP epithelium differed from anterior FP. Among all the components, only known positive regulators of HH signaling, SHH,Ptch1,Gli1andGli2, were expressed in the ganglia. Our studies emphasize differential regulation of HH signaling in distinct postnatal developmental periods and in anterior versus posterior taste organs, and lay the foundation for functional studies to understand the roles of numerous HH signaling components in postnatal tongue development.
Herbicidal Quassinoids Isolated fromAilanthus altissimaLeaves
Authors: Kim Young Sook , Moon Surk-Sik , Choi Jung Sup
Published: November 2023

Bioassay-guided fractionation of the methanolic extract ofAilanthus altissimaleaves led to the isolation of one new quassinoid, named 6-α-tigloyloxyailanthone (3), and three known quassinoids, ailanthone (1), 13, 18-dehydroglaucarubinone (2), and 6-α-tigloyloxychaparrinone (4) by a series of chromatographic methods. The structures of the isolates were established by one-dimensional (1D) and 2D-nuclear magnetic resonance (NMR) analysis along with high-resolution time-of-flight mass spectrometry (HRTOFMS) and chemical methods. In addition, herbicidal activity against five grassy weeds and five broad-leaf weeds was evaluated.
Frommeccassette tordhA: a keyDehalobactergenomic neighborhood in a chloroform and dichloromethane–transforming microbial consortium
Authors: Bulka Olivia , Picott Katherine , Mahadevan Radhakrishnan , Edwards Elizabeth A.
Published: November 2023

Chloroform (CF) and dichloromethane (DCM) are groundwater contaminants of concern due to their high toxicity and inhibition of important biogeochemical processes such as methanogenesis. Anaerobic biotransformation of CF and DCM has been well documented but typically independently of one another. CF is the electron acceptor for certain organohalide-respiring bacteria that use reductive dehalogenases (RDases) to dechlorinate CF to DCM. In contrast, known DCM-degraders use DCM as their electron donor, which is oxidized using a series of methyltransferases and associated proteins encoded by themeccassette to facilitate the entry of DCM to the Wood-Ljungdahl pathway. The SC05 culture is an enrichment culture sold commercially for bioaugmentation, that transforms CF via DCM to CO2. This culture has the unique ability to dechlorinate CF to DCM using electron equivalents provided by the oxidation of DCM to CO2. Here we use metagenomic and metaproteomic analysis to identify the functional genes involved in each of these transformations. Though 91 metagenome-assembled genomes were assembled, the genes for an RDase—namedacdA—and a completemeccassette were found to be encoded on a single contig belonging toDehalobacter. AcdA and critical Mec proteins were also highly expressed by the culture. Heterologously-expressed AcdA dechlorinated CF and other chloroalkanes but had 100-fold lower activity on DCM. Overall, the high expression of Mec proteins and the activity of AcdA suggest aDehalobactercapable of dechlorination of CF to DCM, and subsequent mineralization of DCM using themeccassette.

Importance

Chloroform (CF) and dichloromethane (DCM) are regulated groundwater contaminants. A cost-effective approach to remove these pollutants from contaminated groundwater is to employ microbes that transform CF and DCM as part of their metabolism, thus depleting the contamination as the microbes continue to grow. In this work, we investigate bioaugmentation culture SC05, a mixed microbial consortium that effectively and simultaneously degrades both CF and DCM coupled to the growth ofDehalobacter. We identified the functional genes responsible for the transformation of CF and DCM in SC05. These genetic biomarkers provide a means to monitor the remediation process in the field.
Modeling the effect of spatial structure on solid tumor evolution and ctDNA composition
Authors: Rachman Thomas , Bartlett David , Laframboise William , Wagner Patrick , Schwartz Russell , Carja Oana
Published: November 2023

Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform on cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones end up over-represented in ctDNA, clonal diversity can appear elevated in the blood, and spatial bias in shedding can inflate subclonal variant allele frequencies (VAFs). Additionally, we find that tumors that are mostly quiescent can display similar biases, but are far less detectable, and the extent of perceptible spatial bias strongly depends on sequence detection limits. Overall, we show that spatially structured shedding might cause liquid biopsies to provide highly biased profiles of tumor state. While this may enable more sensitive detection of expanding clones, it could also increase the risk of targeting a subclonal variant for treatment. Our results indicate that the effects and clinical consequences of spatially variable cell death on ctDNA composition present an important area for future work.
flowVI: Flow Cytometry Variational Inference
Authors: Inecik Kemal , Meric Adil , König Lars , Theis Fabian J.
Published: November 2023

Single-cell flow cytometry stands as a pivotal instrument in both biomedical research and clinical practice, not only offering invaluable insights into cellular phenotypes and functions but also significantly advancing our understanding of various patient states. However, its potential is often constrained by factors such as technical limitations, noise interference, and batch effects, which complicate comparison between flow cytometry experiments and compromise its overall impact. Recent advances in deep representation learning have demonstrated promise in overcoming similar challenges in related fields, particularly in the context of single-cell transcriptomic sequencing data analysis. Here, we proposeflowVI, a multimodal deep generative model, tailored for integrative analysis of multiple massively parallel cytometry datasets from diverse sources. By effectively modeling noise variances, technical biases, and batch-specific heterogeneity using probabilistic data representation, we demonstrate that flowVI not only excels in the imputation of missing protein markers but also seamlessly integrates data from distinct cytometry panels. FlowVI thus emerges as a potent tool for constructing comprehensive flow cytometry atlases and enhancing the precision of flow cytometry data analyses. The source code for replicating these findings is hosted onGitHub, ‘theislab/flowVI’
Human trophoblast stem cells can be used to model placental susceptibility toToxoplasma gondiiand highlight the critical importance of the trophoblast cell surface in pathogen resistance
Authors: da Silva Rafaela J. , Cabo Leah F. , George Jada L. , Cahoon Laty A. , Yang Liheng , Coyne Carolyn B. , Boyle Jon P.
Published: November 2023

The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance to understand these mechanisms and challenges in replicating trophoblast-pathogeninteractions usingin vitromodels, we tested an existing stem-cell derived model of trophoblast development for its relevance to infection withToxoplasma gondii. We grew human trophoblast stem cells (TSCT) under conditions leading to either syncytiotrophoblast (TSSYN) or cytotrophoblast (TSCYT) and infected them withT. gondii. We evaluatedT. gondiiproliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TSSYNscells showed similar ultrastructure compared to primary cells and villous explants when analyzed by TEM and SEM, a resistance toT. gondiiadhesion could be visualized on the SEM level. Furthermore, TSSYNswere highly refractory to parasite adhesion and replication, while TSCYTwere not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded toT. gondiiinfection. We also evaluated if TSSC-derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen,Listeria monocytogenes. We demonstrate that TSSYNsare highly resistant toL. monocytogenes, while TSCYTsare not. LikeT. gondii, TSSYNresistance toL. monocytogeneswas at the level of bacterial adhesion. Altogether, our data indicate that stem-cell derived trophoblasts recapitulate resistance profiles of primary cells toT. gondiiand highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.
Modifications in the T arm of tRNA globally determine tRNA maturation, function and cellular fitness
Authors: Schultz Sarah K. , Katanski Christopher D. , Halucha Mateusz , Pena Noah , Fahlman Richard P. , Pan Tao , Kothe Ute
Published: November 2023

All elongator tRNAs harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, which are generated by the enzymes TrmA and TruB, respectively.Escherichia coliTrmA and TruB both act as tRNA chaperones, and strains lackingtrmAortruBare outcompeted by wildtype. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion oftrmAandtruBinE. colicauses a global decrease in aminoacylation and alters other tRNA modification such as acp3U47. Whereas overall protein synthesis is not affected in ΔtrmAand ΔtruBstrains, the translation of a specific subset of codons is significantly impaired, and the expression of many specific proteins is translationally changed. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness and explainingtrmAandtruBconservation.
Sterility-Independent Enhancement of Proteasome Function via Floxuridine-Triggered Detoxification inC. elegans
Authors: Dubey Abhishek Anil , Szulc Natalia A. , Piechota Małgorzata , Serwa Remigiusz A. , Pokrzywa Wojciech
Published: November 2023

The ubiquitin-proteasome system (UPS) functionality is vital for proteostasis, contributing to stress resilience, lifespan, and thermal adaptability. InCaenorhabditis elegans, proteasome constituents such as the RPN-6 and PBS-6 subunits or the PSME-3 activator are respectively linked to heat resistance, survival at low temperatures (4°C), and longevity at moderate cold (15°C). Since the inhibition of germline stem cells proliferation is associated with robust proteostasis in worms, we utilized floxuridine (FUdR), a compound known for inducing sterility, to examine whether it could reinforce UPS under proteasome dysfunction, particularly to foster cold survival. We demonstrate that FUdR promotes proteasome resilience during its inhibition or subunit deficits, supporting normal lifespan and facilitating adaptation to cold. FUdR’s elevation of the UPS activity occurs independently of main proteostasis regulators and is partly driven by SKN-1-regulated transcription, especially under reduced proteasome function. Additionally, we uncover a FUdR-stimulated detoxification pathway, distinct from both SKN-1 and the germline, with GST-24 emerging as a critical mediator of the UPS buffering. This research underscores FUdR’s role in the UPS modulation and its contribution to survival of worms in low-temperature conditions.

HIGHLIGHTS

Floxuridine (FUdR) enhances ubiquitin-proteasome system activity inC. elegans, independent of primary proteostasis regulators.

FUdR permits worms to maintain a normal lifespan and facilitates their adaptation to cold in the context of proteasome deficits.

Acting independently of the germline and SKN-1, FUdR triggers a detoxification pathway, with GST-24 as a pivotal component in modulating the ubiquitin-proteasome system.
The perceived problem‐solving potential of deliberative minipublics: Evidence from a survey of Belgian citizens
Authors: VAN DIJK LISA , WERNER HANNAH , MARIEN SOFIE
Published: November 2023

Concerns about widespread democratic dissatisfaction have prompted a search for remedies, such as increasing citizens’ role in politics. While the public seems supportive, it remains unclear whether such newly introduced procedures can effectively tackle citizens’ dissatisfaction with present‐day politics. This paper develops a problem‐solving approach to studying this question. It proposes that combining insights on what ‘pushes’ and ‘pulls’ people to support procedural reform is crucial: Only then can we uncover if and how people consider procedural reform as addressing the problem(s) they see in the representative system today. Using the example of deliberative minipublics and original, pre‐registered survey data from Belgium (n = 1,579), we find that respondents generally think of minipublics as problem‐solvers rather than problem‐creators, albeit to different degrees. For instance, this perceived problem‐solving potential is more pronounced among discontent citizens. This study sheds new light on the importance of studying citizens’ reasoning about the roots and remedies for political dissatisfaction.
Does encouraging mastery goals benefit performance in a scoring exercise? It may depend on chronic self‐adopted achievement goals
Authors: Winkens Jim , Hamstra Melvyn R. W.
Published: November 2023

Introduction

Mastery goals (aims to learn or attain skill) have traditionally been portrayed in achievement‐motivation literature as the optimal goal for ensuring objective performance and well‐being outcomes (relative to performance goals – aims to outperform others). This portrayal often yielded the recommendation that those in applied settings, such as coaches, managers, and teachers, should encourage those whom they lead to pursue mastery goals. We put this assertion to a test by examining whether the effect of situationally induced goals depends on the goals that individuals personally self‐adopt.

Methods

We hypothesized that inducing mastery goals would be beneficial for individuals who self‐adopt performance goals (Hypothesis 1), while inducing performance goals would be beneficial for individuals who self‐adopt mastery goals (Hypothesis 2). We conducted an experiment among amateur field hockey players to test these hypotheses in a scoring exercise.

Results

We found that encouraging a mastery goal (compared with a performance goal) led to higher scoring accuracy among players high in self‐adopted performance goals (supporting Hypothesis 1) but also unexpectedly for individuals low in self‐adopted mastery goals. We did not find support for Hypothesis 2.

Conclusion

The findings indicate that situationally inducing a mastery goal may be beneficial for individuals who do not already self‐adopt mastery goals strongly.
Production of recombinant humanized monoclonal anti‐human neutrophil antigen (HNA) antibodies with potential applicability as standard antibodies
Authors: Ishimoto Yuko , Taniguchi Kikuyo , Bayat Behnaz , Tobita Ryutaro , Miyazaki Toru , Onodera Rie , Kurita Emi , Kobayashi Masao , Muroi Kazuo , Tsuno Nelson Hirokazu
Published: November 2023

Background

Antibodies against human neutrophil antigen (HNA) are involved in the pathogenesis of neonatal alloimmune neutropenia, autoimmune neutropenia, and transfusion‐related acute lung injury. The present methods for anti‐HNA antibody identification strongly depend on the presence of standard antisera with known allo/isospecificities. Here, we aimed to produce recombinant humanized antibodies to HNA from available mouse monoclonal antibodies (MoAbs).

Study Design and Methods

RNAs were extracted from available hybridoma cells producing mouse anti‐HNA antibodies recognizing HNA‐1a (TAG‐1), ‐1b (TAG‐2), ‐2 (TAG‐4), and FcγRIIIb, and the cDNA was synthesized. Recombinant fragments consisting of the variable regions of the H and L chains of the mouse MoAb ligated to the constant region of human IgG were incorporated into an expression vector and transfected into CHO cells. Antibody specificity of the selected humanized monoclonal antibodies was confirmed, and tested by the participants of the ISBT Granulocyte Immunobiology Working Party (GIWP) workshop 2020.

Results

GIFT results confirmed the specific reactivity of TAGH‐1 to ‐4, except for a cross‐reactivity of TAGH‐2 with HNA‐1a/a neutrophils, only in flow‐cytometry. MAIGA results showed clear specificity of all humanized antibodies, but the selection of the appropriate capture monoclonal antibody was essential for the test. The results of the ISBT GIWP showed high concordance among the labs.

Conclusions

These are the first humanized monoclonal antibodies to HNA‐1 and HNA‐2 antigens produced and they will be important standard reagents for laboratories testing for neutrophil antibodies. We plan to have these humanized MoAbs available through WHO.
A decoupling interpretation of an old argument for Vinogradov's Mean Value Theorem
Authors: Cook Brian , Hughes Kevin , Li Zane Kun , Mudgal Akshat , Robert Olivier , Yung Po‐Lam
Published: November 2023

We interpret into decoupling language a refinement of a 1973 argument due to Karatsuba on Vinogradov's mean value theorem. The main goal of our argument is to answer what precisely solution counting in older partial progress on Vinogradov's mean value theorem corresponds to in Fourier decoupling theory.
An updated checklist of recent non-marine Ostracoda (Crustacea) from Venezuela
Authors: SCOTT-FRÍAS JOXMER , GONZÁLEZ ERNESTO , PARDO MARÍA JOSÉ , TORRES RUBÉN , HIGUTI JANET , COHUO SERGIO , LÓPEZ CARLOS
Published: November 2023

Information on the known species diversity of the non-marine ostracods in Venezuela is compiled from the available literature. The review resulted in 34 species and two varieties, belonging to the superfamilies Cypridoidea and Cytheroidea. Of these, the presence of one species should be confirmed for the country. Furthermore, eight taxonomic entities classified with open nomenclature are mentioned. As additional contributions to the annotated list, georeferences of the records are included, as well as amendments in names and information for some localities. Finally, information about the distribution of some species, which were erroneously assigned to other biogeographic areas, is clarified, which is essential to optimizing the accuracy of subsequent analyses.
Notes on Indian wolf spiders: III. Genera Acantholycosa Dahl, 1908, Evippomma Roewer, 1959, Hippasosa Roewer, 1960 and Trochosa C.L. Koch, 1847 (Araneae: Lycosidae)
Authors: SANKARAN PRADEEP M. , CALEB JOHN T.D.
Published: November 2023

The species of the genera Acantholycosa Dahl, 1908, Evippomma Roewer, 1959, Hippasosa Roewer, 1960 and Trochosa C.L. Koch, 1847 described/recorded from India, are reviewed. The following new combinations are recognized: Arctosa dhikala comb. et nom. nov. (ex. Trochosa), Arctosa kalpiensis (Gajbe, 2004) comb. nov. (ex. Hippasosa), Evippa baltoroi (Caporiacco, 1935) comb. nov. (ex. Acantholycosa), Pardosa evippiformis Caporiacco, 1935 comb. rest. (ex. Evippomma), and Pirata punctipes (Gravely, 1924) comb. nov. (ex. Trochosa). Photographs of all the examined type material and supplementary descriptions for A. dhikala comb. et nom. nov., E. baltoroi comb. nov., P. evippiformis comb. rest., and P. punctipes comb. nov. are provided. Lectotypes have been designated for E. baltoroi comb. nov., P. evippiformis comb. rest. and P. punctipes comb. nov. With the new combination for T. punctipes, the genus Pirata Sundevall, 1833 is recorded for the first time in India, and that for A. baltoroi and E. evippiforme show the record of the genera Acantholycosa and Evippomma from India is incorrect.