bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geobacter sulfurreducens’ unique metabolism results in cells with a high iron and lipid content
Authors: Howley Ethan , Ki Dongwon , Krajmalnik-Brown Rosa , Torres César I. 
Published: July 2022

AbstractGeobacter sulfurreducens is a ubiquitous iron reducing bacterium in soils, and in engineered systems it can respire an electrode to produce measurable electric current. Its unique metabolism, heavily dependent on an extensive network of cytochromes, requires a unique cell composition. In this work we used metallomics, cell fraction and elemental analyses, and transcriptomics to study and analyze the cell composition of G. sulfurreducens. Elemental composition studies (C,H,O,N, ash content) showed a high C:O and H:O ratios of approximately 1.7:1 and 0.25:1, indicative of more reduced cell composition that is consistent with a high lipid content. Our study shows that G. sulfurreducens cells have a large amount of iron (2 ± 0.2 μg/gdw) and lipids (32 ± 0.5% dw/dw) and that this composition does not change whether the cells are grown with a soluble or an insoluble electron acceptor. The high iron concentration, higher than similar microorganisms, is attributed to the production of cytochromes that are abundant in transcriptomic analyses in both solid and soluble electron acceptor growth. The unique cell composition of G. sulfurreducens must be considered when growing this microorganism for lab studies and commercial applications.ImportanceGeobacter sulfurreducens is an electroactive microorganism. In nature, it grows on metallic minerals by transferring electrons to them, effectively ‘breathing’ metals. In a manmade system, it respires an electrode to produce an electric current. It has become a model organism for the study of electroactive organisms. There are potential biotechnological applications of an organism that can bridge the gap between biology and electrical signal, and as a ubiquitous iron reducer in soils around the world, G. sulfurreducens and its relatives impact the global iron cycle. We measured the concentrations of metals, macromolecules, and basic elements in G. sulfurreducens to define this organism’s composition. We also used gene expression data to discuss which proteins those metals could be associated with. We found that G. sulfurreducens has a large amount of lipid and iron compared to other bacteria — these observations are important for future microbiologists and biotechnologists working with the organism.
Programmable acetylation modification of bacterial proteins by a Cas12a-guided acetyltransferase
Authors: Liu Yanqiang , Zuo Ni , Jiang Weihong , Gu Yang 
Published: July 2022

ABSTRACTProtein lysine acetylation (PLA) is a crucial post-translational modification in organisms that regulates a variety of metabolic and physiological activities. Many advances have been made in PLA-related research; however, the quick and accurate identification of causal relationships between specific protein acetylation events and phenotypic outcomes at the proteome level remains unattainable due to the lack of in situ targeted modification techniques. In this study, based on the characteristics of transcription-translation coupling in bacteria, we designed and constructed an in situ targeted protein acetylation (TPA) system fusing the dCas12a protein, guiding element crRNA, and bacterial acetylase At2. Rapid identification of multiple independent protein acetylation and cell phenotypic analyses in gram-negativeE. coliand gram-positiveC. ljungdahliidemonstrated that TPA is a specific and efficient targeting tool for protein modification studies and engineering.
No evidence for a common blood microbiome based on a population study of 9,770 healthy humans
Authors: Tan Cedric C.S. , Ko Karrie K.K. , Chen Hui , Liu Jianjun , Loh Marie ,   SG10K_Health Consortium, Chia Minghao , Nagarajan Niranjan 
Published: July 2022

AbstractHuman blood is conventionally considered sterile. Recent studies have challenged this, suggesting the presence of a blood microbiome in healthy humans. We present the largest investigation to date of microbes in blood, based on shotgun sequencing libraries from 9,770 healthy subjects. Leveraging the availability of data from multiple cohorts, we stringently filtered for laboratory contaminants to identify 117 microbial species detected in the blood of sampled individuals, some of which had signatures of DNA replication. These primarily comprise of commensals associated with human body sites such as the gut (n=40), mouth (n=32), and genitourinary tract (n=18), which are species that are distinct from common pathogens detected in clinical blood cultures based on more than a decade of records from a tertiary hospital. Contrary to the expectations of a shared blood microbiome, no species were detected in 84% of individuals, while only a median of one microbial species per individual was detected in the remaining 16%. Futhermore, microbes of the same species were detected in <5% of individuals, no co-occurrence patterns similar to microbiomes in other body sites was observed, and no associations between host phenotypes (e.g. demographics and blood parameters) and microbial species could be established. Overall, these results do not support the hypothesis of a consistent core microbiome endogenous to human blood. Rather, our findings support the transient and sporadic translocation of commensal microbes, or their DNA, from other body sites into the bloodstream.
The differing roles of flavins and quinones in extracellular electron transfer in Lactiplantibacillus plantarum
Authors: Tolar Joe G. , Li Siliang , Ajo-Franklin Caroline M. 
Published: July 2022

AbstractLactiplantibacillus plantarum is a lactic acid bacteria that is commonly found in the human gut and fermented food products. Despite its overwhelmingly fermentative metabolism, this microbe can perform extracellular electron transfer (EET) when provided with an exogenous quinone, 1,4-dihydroxy-2-naphthoic acid (DHNA) and riboflavin. However, the separate roles of DHNA and riboflavin in EET in L. plantarum has remained unclear. Here we seek to understand the role of quinones and flavins for EET by monitoring iron and anode reduction in the presence and absence of these small molecules. We found that either addition of DHNA or riboflavin can support robust iron reduction, indicating electron transfer to extracellular iron occurs through both flavin-dependent and DHNA-dependent routes. Using genetic mutants of L. plantarum, we found that flavin-dependent iron reduction requires Ndh2 and EetA, while DHNA-dependent iron reduction largely relies on Ndh2 and PplA. In contrast to iron reduction, DHNA-containing media supported more robust anode reduction than riboflavin-containing media, suggesting electron transfer to an anode proceeds most efficiently through the DHNA-dependent pathway. Furthermore, we found that flavin-dependent anode reduction requires EetA, Ndh2, and PplA, while DHNA-dependent anode reduction requires Ndh2 and PplA. Taken together, we identify multiple EET routes utilized by L. plantarum and show that the EET route depends on access to environmental biomolecules and on the extracellular electron acceptor. This work expands our molecular-level understanding of EET in Gram-positive microbes and provides additional opportunities to manipulate EET for biotechnology.ImportanceLactic acid bacteria are named because of their nearly exclusive fermentative metabolism. Thus, the recent observation of EET activity - typically associated with anaerobic respiration - in this class of organisms has forced researchers to rethink the rules governing microbial metabolic strategies. Our identification of multiple routes for EET in L. plantarum that depend on two separate redox active small molecules expands our understanding of how microbes metabolically adapt to different environments to gain an energetic edge and how these processes can be manipulated for biotechnological uses. Understanding the role of EET in lactic acid bacteria is of great importance due to the significance of lactic acid bacteria in agriculture, bioremediation, food production, and gut health. Furthermore, the maintenance of multiple EET routes speak to the importance of this process to function in a variety of environmental conditions.
Higher Perceived Stress during the COVID-19 pandemic increased Menstrual Dysregulation and Menopause Symptoms
Authors: de leon Romina Garcia , Baaske Alexandra , Albert Arianne Y , Booth Amy , Racey C. Sarai , Gordon Shanlea , Smith Laurie W. , Gottschlich Anna , Sadarangani Manish , Kaida Angela , Ogilvie Gina S. , Brotto Lori A. , Galea Liisa A.M. 
Published: July 2022

AbstractObjectiveThe increased stress the globe has experienced with the COVID-19 pandemic has affected mental health, disproportionately affecting women. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated.MethodsResidents in British Columbia, Canada, were surveyed online as part of the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE). A subgroup (n=4171) who were assigned female sex at birth (age 25-69) and were surveyed within the first 6-12 months of the pandemic (August 2020-February 2021), prior to the widespread rollout of vaccines, were retrospectively asked if they noticed changes in their menstrual or menopausal symptoms, as well as completing validated measures of stress, depression, and anxiety.ResultsWe found that 27.8% reported menstrual cycle disturbances and 6.7% reported increased menopause symptoms. Those who scored higher on perceived stress, depression, and anxiety scales were more likely to have reproductive cycle disturbances. Free text responses revealed that reasons for disturbances were perceived to be related to the pandemic.ConclusionsThe COVID-19 pandemic has highlighted the need to research women’s health issues, such as menstruation. Our data indicates that in the first year of the pandemic, almost a third of the menstruating population reported disturbances in their cycle, which is approximately two times higher than in non-pandemic situations and four times higher than any reported changes in menopausal symptoms across that first year of the pandemic.Summary SentencesWomen+ with higher anxiety, depression or perceived stress scores during the first year of the pandemic were more likely to have experienced menstrual cycle phase disturbance or menopausal status disruption. Younger women were particularly prone to disturbances in their reproductive cycles.
Detecting salivary host-microbiome RNA signature for aiding diagnosis of oral and throat cancer
Authors: Banavar Guruduth , Ogundijo Oyetunji , Julian Cristina , Toma Ryan , Camacho Francine , Torres Pedro J. , Hu Lan , Kenny Liz , Vasani Sarju , Batstone Martin , Dimitrova Nevenka , Vuyisich Momchilo , Amar Salomon , Punyadeera Chamindie 
Published: July 2022

AbstractObjectivesOral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the two major subtypes of head and neck cancer (HNC) that can go undetected resulting in late detection and poor outcomes. We describe the development and validation of a convenient and easy-to-use test, called CancerDetect for Oral & Throat cancer™ (CDOT), to detect markers of OSCC and/or OPSCC within a high-risk population using salivary metatranscriptomics.Materials and MethodsWe collected saliva samples from 1,175 unique individuals who were 50 years or older, or adults who had a history of tobacco use. All saliva samples were processed through a metatranscriptomic method to isolate microbial organisms and functions, as well as human transcripts. Of the 1175 samples, 945 were used to train a classifier using machine learning methods, resulting in a salivary RNA metatranscriptomic signature. The classifier was then independently validated on the 230 remaining samples unseen by the classifier, consisting of 20 OSCC (all stages), 76 OPSCC (all stages), and 134 negatives (including 14 pre-malignant).ResultsOn the validation cohort, the specificity of the CDOT test was 94%, sensitivity was 90% for participants with a histopathological diagnosis of OSCC, and 84.2% for participants with a diagnosis of OPSCC. Similar classification results were observed among people in early stage (stages I & II) vs late stage (stages III & IV) of OSCC and OPSCC.ConclusionsCDOT is a non-invasive test that can be easily administered in dentist offices, primary care centers and specialized cancer clinics for early detection of OPSCC and OSCC. This test, having received breakthrough designation by the US Food and Drug Administration (FDA), will broadly enable early diagnosis of OSCC and OPSCC, saving lives and significantly reducing healthcare expenditure.
A single dose of intravenous human amniotic membrane-derived mesenchymal stem cells limits transmural infarction, reduces fibrosis size, and improves left ventricular systolic function in the myocardial ischemic/reperfusion model of rats
Authors: Sung Jia-Wei , Yeh Yen-Ting , Peng Fu-Shiang , Chen Yi-Chen , Li Ai-Hsien , Wu Shinn-Chih 
Published: July 2022

AbstractDespite the advances in coronary reperfusion in acute myocardial infarction (MI), post-MI heart failure is still a large burden of public health. Transmural infarction and extended fibrosis contribute largely to post-MI systolic dysfunction and heart failure, and thus cardioprotective strategies are crucial. Human amniotic membrane-derived mesenchymal stem cells (hAMSCs) have been shown with properties of immunomodulation, anti-inflammation, and low immunogenicity, which make them good candidates for cell therapies. In this study, a myocardial ischemia/reperfusion (I/R) model was established in rats, and hAMSCs were administered via the tail vein during coronary reperfusion. Compared to the control group, the rats receiving hAMSCs during the I/R procedure (hAMSC group) exhibited significantly better left ventricular ejection fractions after MI. Histological examinations of the hearts in hAMSC group showed minimal transmural infarction 4 weeks after the I/R procedure. Compared to the control group, hAMSC group had reduced size of cardiac fibrosis and less thinning of myocardial wall. In conclusion, intravenous hAMSCs limit transmural infarction, reduce fibrosis size, and improve left ventricular systolic function after MI in the animal model.
KAP is the neuronal organelle adaptor for Kinesin-2 KIF3AB and KIF3AC
Authors: Garbouchian Alex , Montgomery Andrew , Gilbert Susan P. , Bentley Marvin 
Published: July 2022

ABSTRACTKinesin-driven organelle transport is crucial for neuron development and maintenance, yet the mechanisms by which kinesins specifically bind their organelle cargoes remain undefined. In contrast to other transport kinesins, the neuronal function and specific organelle adaptors of heterodimeric Kinesin-2 family members KIF3AB and KIF3AC remain unknown. We developed a novel microscopy-based assay to define protein–protein interactions in intact neurons. The experiments found that KIF3AB and KIF3AC both bind KAP. These interactions are mediated by the distal C-terminal tail regions and not the coiled-coil domain. We used live-cell imaging in cultured hippocampal neurons to define the localization and trafficking parameters of KIF3AB and KIF3AC organelle populations. We discovered that KIF3AB/KAP and KIF3AC/KAP bind the same organelle populations and defined their transport parameters in axons and dendrites. The results also show that ∼12% of KIF3 organelles contain the RNA binding protein, adenomatous polyposis coli. These data point towards a model in which KIF3AB and KIF3AC use KAP as their neuronal organelle adaptor and that these kinesins mediate transport of a range of organelles.
Enhanced production of natural shiga toxin by overexpressing A subunit of Stx2e in Stx2e-producing Escherichia coli isolated in South Korea
Authors: Seo Byoung Joo , Yu Jeong Hee , Kim Seung Chai , Yu Yeong Ju , Park Byung Yong , Park Jung Hee , Kim Won Il , Hur Jin 
Published: July 2022

AbstractThis study explored the optimal culture conditions for maximizing shiga toxin production in Stx2e-producing Escherichia coli (STEC) 150229, isolated from porcine edema disease (ED), with the goal of preparing a Stx2e toxoid vaccine candidate. High cytotoxicity was observed for this strain [tissue culture cytotoxic dose 50% (104 TCCD50/100 µl)] from 48 h after incubation. Stx2e was overexpressed by transforming pStx2e A into STEC 150229, resulting in the production of recombinant Stx2e A/B complex combined with intrinsic Stx2e B. The enhanced production of Stx2e was evaluated based on the level of cytotoxicity against Vero cells. The highest cytotoxicity (105 TCCD50/100 µl) was observed with the samples of recombinant Stx2e A/B complex eluted with 500 mM imidazole at 48 h of incubation. In conclusion, the recombinant Stx2e A protein forms an active protein complex with the intrinsic Stx2e B component from STEC 150229, producing high levels of shiga toxin.
An ERAD-independent role for rhomboid pseudoprotease Dfm1 in mediating sphingolipid homeostasis
Authors: Bhaduri Satarupa , Aguayo Analine , Ohno Yusuke , Proietto Marco , Jung Jasmine , Wang Isabel , Kandel Rachel , Singh Narinderbir , Ibrahim Ikran , Fulzele Amit , Bennett Eric , Kihara Akio , Neal Sonya E. 
Published: July 2022

SUMMARYNearly one-third of nascent proteins are initially targeted to the endoplasmic reticulum (ER) where they are correctly folded and assembled before being delivered to their final cellular destinations. To prevent the accumulation of misfolded membrane proteins, ER-associated-degradation (ERAD) removes these clients from the ER membrane to the cytosol in a process known as retrotranslocation. Our recent work demonstrates that rhomboid pseudoprotease, Dfm1, is involved in the retrotranslocation of ubiquitinated integral membrane ERAD substrates. To survey for potential interaction partners of Dfm1, we performed protein-proximity labeling by BioID (proximity-dependent biotin identification) followed by mass spectrometry and identified several interacting proteins known to play a role in the sphingolipid biosynthesis pathway. Specifically, we found that Dfm1 physically interacts with the SPOTS complex, which is composed of serine palmitoyltransferase (SPT) enzymes and accessory components and is critical for catalyzing the first rate-limiting step of the sphingolipid biosynthesis pathway. We demonstrate for the first time that Dfm1 has a role in ER export, a function that is independent of Dfm1’s canonical ERAD retrotranslocation function. Specifically, we show that loss of Dfm1 results in the accumulation of phosphorylated Orm2 at the ER, suggesting a novel role for Dfm1 in controlling Orm2 export from the ER and its subsequent degradation by EGAD. Moreover, recruitment of Cdc48 by Dfm1, which is critical for its role in ERAD retrotranslocation, is dispensable for Dfm1’s role in ER export. Given that the accumulation of human Orm2 homologs, ORMDLs, are associated with many maladies, our study serves as a molecular foothold for understanding how dysregulation of sphingolipid metabolism leads to various diseases.
A genome-wide association study of Chinese and English language abilities in Hong Kong Chinese children
Authors: Lin Yu-Ping , Shi Yujia , Zhang Ruoyu , Xue Xiao , Rao Shitao , Lui Kevin Fai-Hong , Pan Dora Jue , Maurer Urs , Choy Richard Kwong-Wai , Paracchini Silvia , McBride Catherine , So Hon-Cheong 
Published: August 2022

AbstractBackgroundReading and language skills are important and known to be heritable, and dyslexia and developmental language disorder are commonly recognized learning difficulties worldwide. However, the genetic basis underlying these skills remains poorly understood. In particular, most previous genetic studies were performed on Westerners. To our knowledge, few or no previous genome-wide association studies (GWAS) have been conducted on literacy skills in Chinese as a native language or English as a second language (ESL) in a Chinese population.MethodsWe conducted GWAS and related bioinformatics analyses on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; N=1046). We performed association tests at the single-variant, gene, pathway levels, and transcriptome-wide association studies (TWAS) to explore how imputed expression changes might affect the phenotypes. In addition, we tested genetic overlap of these cognitive traits with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis.ResultsTotally 9 independent loci (LD-clumped at r2=0.01) reached genome-wide significance (p<5e-08) (filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs(r2>0.5) with p<1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, dictation and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with intelligence, EA other neuropsychiatric phenotypes, such as MANEA, TNR, PLXNC1 and SHTN1. We also revealed significantly enriched genes and pathways based on SNP-based analysis. In PRS analysis, EA and CP showed significant polygenic overlap with a variety of language traits, especially English literacy skills. ADHD PRS showed a significant association with English vocabulary score.ConclusionsThis study revealed numerous genetic loci that may be associated with Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings and elucidate the mechanisms involved.
Accuracy of sensor-based classification of clinically relevant motor activities in daily life of children with mobility impairments
Authors: Rast Fabian Marcel , Jucker Florence , Labruyère Rob 
Published: August 2022

AbstractBackgroundWearable inertial sensors enable objective, long-term monitoring of motor activities in the children’s habitual environment after rehabilitation. However, sophisticated algorithms are needed to derive clinically relevant outcome measures. Therefore, we developed three independent algorithms based on the needs of pediatric rehabilitation. The first algorithm estimates the duration of lying, sitting, and standing positions and the number of sit-to-stand transitions with data of a trunk and a thigh sensor. The second algorithm detects active wheeling periods and distinguishes it from passive wheeling with data of a wrist and a wheelchair sensor. The third algorithm detects walking periods, discriminates between free and assisted walking, and estimates the covered altitude change during stair climbing with data of a single ankle sensor and a sensor placed on walking aids.Research questionThis study aimed to determine the accuracy of each algorithm in children undergoing rehabilitation.MethodsThirty-one children and adolescents with various medical diagnoses and levels of mobility impairments performed a semi-structured activity circuit. They wore inertial sensors on both wrists, the sternum, and the thigh and shank of the less-affected side. Video recordings, which were labeled by two independent researchers, served as reference criteria to determine the algorithms’ performance.ResultsThe activity classification accuracy was 97% for the posture detection algorithm, 96% for the wheeling detection algorithm, and 93% for the walking detection algorithm.SignificanceThis study presents three novel algorithms that provide a comprehensive and clinically relevant view of the children’s motor activities. These algorithms are described reproducibly and can be applied to other inertial sensor technologies. Moreover, they were validated in children with mobility impairments and can be used in clinical practice and clinical trials to determine the children’s motor performance in their habitual environment. To enable the evaluation of future algorithms, we published the labeled dataset.