bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Deep Learning to Determine Amyloid Deposition through PET and Clinical Data for Alzheimer’s Prognosis
Authors: Maddury Sucheer , Desai Krish 
Published: October 2022

AbstractAmyloid deposition is a vital biomarker in the process of Alzheimer’s diagnosis. Florbetapir PET scans can provide valuable imaging data to determine cortical amyloid quantities. However the process is labor and doctor intensive, requiring extremely specialized education and resources that may not be accessible to everyone, making the amyloid calculation process inefficient.Deep learning is a rising tool in Alzheimer’s research which could be used to determine amyloid deposition. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we identified 2980 patients with PET imaging, clinical, and genetic data. We tested various ResNet and EfficientNet convolutional neural networks and later combined them with Gradient Boosting Decision Tree algorithms to predict standardized uptake value ratio (SUVR) of amyloid in each patient session. We tried several configurations to find the best model tuning for regression-to-SUVR.We found that the EfficientNetV2-Small architecture combined with a grid search-tuned Gradient Boosting Decision Tree with 3 axial input slices and clinical and genetic data achieved the lowest loss. Using the mean-absolute-error metric, the loss converged to an MAE of 0.0466, equating to 96.11% accuracy across the 596 patient test set.We showed that this method is more consistent and accessible in comparison to human readers from previous studies, with lower margins of error and substantially faster calculation times. Deep learning algorithms could be used in hospitals and clinics with resource limitations for amyloid deposition, and shows promise for more imaging tasks as well.
Reversible restriction of electron flow across cytochrome b6f in dark acclimated cells limited for downstream electron sinks
Authors: Saroussi Shai , Karns Devin , Thomas Dylan C. , Redekop Petra , Wittkopp Tyler M. , Posewitz Matthew C. , Grossman Arthur R. 
Published: October 2022

ABSTRACTPhotosynthetic organisms frequently experience abiotic stresses that restrict their growth and development. Under such circumstances, most absorbed solar energy cannot be used for CO2 fixation and can cause the photoproduction of reactive oxygen species (ROS) that can damage the photosynthetic reaction centers, photosystems I and II (PSI and PSII), resulting in a decline in primary productivity. This work describes a biological ‘switch’ in the green alga Chlamydomonas reinhardtii that reversibly restricts photosynthetic electron transport (PET) at the cytochrome b6f complex when reductant and ATP generated by PET are in excess of the capacity of carbon metabolism to utilize these products; we specifically show a restriction at this switch when sta6 mutant cells, which cannot synthesize starch, are limited for nitrogen (growth inhibition) and subjected to a dark-to-light transition. This restriction, which may be a form of photosynthetic control, causes diminished electron flow to PSI, which prevents PSI photodamage. When electron flow is blocked the plastid alternative oxidase (PTOX) may also become activated, functioning as an electron valve that dissipates some of the excitation energy absorbed by PSII thereby lessening PSII photoinhibition. Furthermore, illumination of the cells following the dark acclimation gradually diminishes the restriction at cytochrome b6f complex. Elucidating this photoprotective mechanism and its modulating factors may offer new insights into mechanisms associated with photosynthetic control and offer new directions for optimizing photosynthesis.
Reconstruct a eukaryotic chromosome arm by de novo design and synthesis
Authors: Jiang Shuangying , Luo Zhouqing , Yu Kang , Zhao Shijun , Cai Zelin , Yu Wenfei , Wang Hui , Cheng Li , Liang Zhenzhen , Gao Hui , Monti Marco , Schindler Daniel , Huang Linsen , Zeng Cheng , Zhang Weimin , Zhou Chun , Tang Yuanwei , Li Tianyi , Ma Yingxin , Cai Yizhi , Boeke Jef D. , Dai Junbiao 
Published: October 2022

SUMMARYThe genome of an organism is inherited from its ancestor and keeps evolving over time, however, how much the current version could be altered remains unknown. Here, we use the left arm of chromosome XII (chrXIIL) as an example to probe the genome plasticity in Saccharomyces cerevisiae. A neochromosome was designed to harbor originally dispersed genes. The essentiality of sequences in chrXIIL was dissected by targeted DNA removal, chromosome truncation and random deletion. Notably, 12 genes were sufficient for survival, while 25 genes are required to retain robust fitness. Next, we demonstrated these genes could be reconstructed using synthetic regulatory sequences and recoded open-reading frames with “one-amino-acid-one-codon” strategy. Finally, we built a neochromsome, which could substitute for chrXIIL for cell viability, with these reconstructed genes. Our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional chromosomes with completely artificial sequences.HIGHLIGHTSA neochromosome was designed to facilitate the assembly of exogenous DNA for stable expression in yeastThe left arm of chrXII could be minimized to just 12 genes to maintain viability, but additional genes were required to retain robust fitnessComprehensive recoding and transcriptional refactoring using artificial regulatory sequences produced a functional chromosome armA completely reconstructed neochromosome could replace the chrXIIL to maintain comparable fitness
Modelling the effectiveness of targeting Rift Valley fever virus vaccination using imperfect network information
Authors: Sulaimon Tijani A. , Chaters Gemma L. , Nyasebwa Obed M. , Swai Emanuel S. , Cleaveland Sarah , Enright Jessica , Kao Rowland R. , Johnson Paul C. D. 
Published: October 2022

ABSTRACTLivestock movements contribute to the spread of several infectious diseases. Data on livestock movements can therefore be harnessed to guide policy on targeted interventions for controlling infectious livestock diseases, including Rift Valley fever (RVF) — a vaccine-preventable arboviral fever. While detailed livestock movement data are available in many countries, such data are generally lacking in others, including many in East Africa, where multiple RVF outbreaks have been reported in recent years. Available movement data are imperfect, and the impact of imperfect movement data on targeted vaccination is not fully understood. Here, we used a network simulation model to describe the spread of RVF within and between 398 wards in northern Tanzania connected by cattle movements, on which we evaluated the impact of targeting vaccination using imperfect movement data. We show that pre-emptive vaccination guided by only market movement permit data could prevent large outbreaks. Targeted control (either by the risk of RVF introduction or onward transmission) at any level of imperfect movement information is preferred over random vaccination, and any improvement in information reliability is advantageous to their effectiveness. Our modelling approach demonstrates how targeted interventions can be carefully applied to inform animal and public health policies on disease control planning in settings where detailed data on livestock movements are unavailable or imperfect due to a lack of data-gathering resources.
Mechanosensitive channel-based optical membrane tension biosensor
Authors: Hsu Yen-Yu , Irizarry Agnes M. Resto , Fu Jianping , Liu Allen P. 
Published: October 2022

ABSTRACTPlasma membrane tension functions as a global physical organizer of cellular activities. Technical limitations of current membrane tension measurement techniques have hampered in-depth investigation of cellular membrane biophysics and the role of plasma membrane tension in regulating cellular processes. Here, we develop an optical membrane tension biosensor by repurposing anE. colimechanosensitive channel via insertion of circularly permuted GFP (cpGFP), which undergoes a large conformational rearrangement associated with channel activation and thus fluorescence intensity changes under increased membrane tension.
Effects of high temperature and heavy precipitation on drinking water quality and child hand contamination levels in rural kenya
Authors: Powers Julie E. , Mureithi Maryanne , Mboya John , Campolo Jake , Swarthout Jenna M. , Pajka Joseph , Null Clair , Pickering Amy J. 
Published: October 2022

ABSTRACTClimate change may impact human health through the influence of weather on environmental transmission of diarrhea. Previous studies have found that high temperatures and heavy precipitation are associated with increased diarrhea prevalence, but the underlying causal mechanisms are not clear. We linked measurements of Escherichia coli in source water (n=1,673), stored drinking water (n=8,924), and hand rinses from children <2 years old (n=2,660) with publicly available gridded temperature and precipitation data (at ≤0.2 degree spatial resolution and daily temporal resolution) by the GPS coordinates and date of sample collection. Measurements were collected over a 3-year period across a 2500 km2 area in rural Kenya. In drinking water sources, high 7-day temperature was associated with a 0.16 increase in log10E. coli levels (p<0.001), while heavy 7-day total precipitation was associated with a 0.29 increase in log10E. coli levels (p<0.001). In household stored drinking water, heavy 7-day precipitation was associated with a 0.079 increase in log10E. coli levels (p=0.042). On child hands, high 7-day temperature was associated with a 0.39 decrease in log10E. coli levels (p<0.001). Our findings provide insight on how climate change could impact environmental transmission of bacterial pathogens in Kenya, and suggest water treatment could be a mitigation strategy.
Structure of mycobacterial respiratory Complex I
Authors: Liang Yingke , Plourde Alicia , Bueler Stephanie A. , Liu Jun , Brzezinski Peter , Vahidi Siavash , Rubinstein John L. 
Published: October 2022

AbstractOxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by Mycobacterium tuberculosis and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found at low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of Mycobacterium smegmatis in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the “orphan” two-component response regulator protein MSMEG_2064 as a subunit of the assembly. MSMEG_2064 in the complex occupies a site similar to the proposed redox sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel and suggests that menaquinone interacts more extensively than ubiquinone with a key catalytic histidine residue in the enzyme.
Microbial mat compositions and localization patterns explain the virulence of black band disease in corals
Authors: Wada Naohisa , Iguchi Akira , Urabe Yuta , Yoshioka Yuki , Abe Natsumi , Takase Kazuki , Hayashi Shuji , Kawanabe Sakiko , Sato Yui , Tang Sen-Lin , Mano Nobuhiro 
Published: October 2022

AbstractBlack band disease (BBD) in corals is characterized by a distinctive, band-like microbial mat, which spreads across the tissues and often kills infected colonies. The microbial mat is dominated by cyanobacteria but also commonly contains sulfide-oxidizing bacteria (SOB), sulfate-reducing bacteria (SRB), and other microbes. The migration rate in BBD varies across different environmental conditions including temperature, light, and pH. However, whether variations in the migration rates reflect differences in the microbial consortium within the BBD mat remains unknown. Here, we show that the micro-scale surface structure, bacterial composition, and spatial distribution differed across BBD lesions with different migration rates. The migration rate was positively correlated with the relative abundance of potential SOBs belonging toArcobacteraceaelocalized in the middle layer within the mat and negatively correlated with the relative abundance of other potential SOBs belonging toRhodobacteraceae. Our study highlights the microbial composition in BBD as an important determinant of virulence.
Structural transition of the ground-state structure to steady-state structures by sequential binding of ATP to V/A-ATPase
Authors: Nakanishi Atsuko , Kishikawa Jun-ichi , Mitsuoka Kaoru , Yokoyama Ken 
Published: October 2022

AbstractV/A-ATPase is a rotary ATPase that shares a common rotary catalytic mechanism with FoF1 ATP synthase. Structural images of V/A-ATPase obtained by single-particle cryo-electron microscopy (cryo-EM) during ATP hydrolysis identified several intermediates, revealing the rotary mechanism under steady-state conditions. Here, we identified the cryo-EM structures of V/A-ATPase corresponding to short-lived initial intermediates during the activation of the ground state structure by time-resolving snapshot analysis. These intermediate structures provide insights into how the ground-state structure changes to the active, steady state through the sequential binding of ATP to its three catalytic sites. All the intermediate structures of V/A-ATPase adopt the same asymmetric structure, whereas the three catalytic dimers adopt different conformations. This is significantly different from the initial activation process of FoF1, where the overall structure of the F1 domain changes during the transition from a pseudo-symmetric to a canonical asymmetric structure. Our findings will enhance the future prospects for the initial activation processes of the enzymes with dynamical information, which contains unknown intermediate structures in their functional pathway.
Host Phylogeny Shapes Viral Transmission Networks in an Island Ecosystem
Authors: French Rebecca K. , Anderson Sandra H. , Cain Kristal E. , Greene Terry C. , Minor Maria , Miskelly Colin M. , Montoya Jose M. , Muller Chris G. , Taylor Michael W. ,   Kākāpō Recovery Team, Holmes Edward C. 
Published: October 2022

AbstractViral transmission between host species underpins disease emergence. Both host phylogenetic relatedness and aspects of their ecology, such as species interactions and predator-prey relationships, may govern cross-species virus transmission and zoonotic risk, although their relative impact is unknown. By characterising the virome of a relatively isolated island ecological community linked through a food web we show that phylogenetic barriers result in distantly related host species sharing fewer viruses. Host ecology had a much smaller influence on overall virome composition. Network analysis revealed that hosts with a high diversity of viruses were more likely to gain new viruses, and that generalist viruses were more likely to infect new hosts. Such a highly connected ecological community heightens the risk of disease emergence, particularly among closely related species.One-Sentence SummarySequencing of an entire island virome reveals that closely related hosts have highly connected virus communities, increasing emergence risk.
DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage
Authors: Liu Hon Wing , Roisné-Hamelin Florian , Beckert Bertrand , Myasnikov Alexander , Li Yan , Gruber Stephan 
Published: October 2022

SummaryStructural maintenance of chromosomes (SMC) complexes fold DNA by loop extrusion to support chromosome segregation, genome maintenance, and gene expression. Wadjet systems (JetABCD/MksBEFG/EptABCD) are derivative SMC complexes with proposed roles in bacterial immunity against selfish DNA elements. Here, we show that JetABCD systems restrict extrachromosomal circular DNA with an upper size limit of about 100 kb, while a linear plasmid evades restriction. Recombinant preparations of a JetABCD complex cleave circular DNA regardless of its helical topology but not linear DNA; cleavage occurs at random positions and depends on ATP as well as the SMC ATPase. We solve a structure of the JetABCD core by cryo-EM revealing an alternative dimer-of-dimers configuration. The two SMC DNA motor units face in opposite orientations—rather than the same as observed with MukBEF—possibly representing a restriction-specific state of JetABCD. We hypothesize that JetABCD is a DNA-shape-specific endonuclease and present a model for the activation of DNA cleavage exclusively when extrusion of an entire plasmid has been completed by a single JetABCD complex. The self-stalling of two opposing DNA motor units may serve as signal to trigger DNA cleavage. Complete extrusion by a single complex cannot be achieved on the much larger chromosome, explaining how self-DNA may evade cleavage.
Context matters: environmental microbiota of ice cream processing facilities affects the inhibitory performance of two lactic acid bacteria against Listeria monocytogenes
Authors: Rolon M. Laura , Chandross-Cohen Tyler , Kaylegian Kerry E. , Roberts Robert F , Kovac Jasna 
Published: October 2022

ABSTRACTPathogenic L. monocytogenes may inhabit dairy processing environments, increasing the risk for cross-contamination of foods. Using biocontrol microorganisms that inhibit or outcompete L. monocytogenes to complement sanitation of dairy processing facilities may enhance the control of L. monocytogenes. However, it remains unknown whether the resident microbiota of dairy processing facilities affects the antilisterial activity of biocontrol strains. Here, two lactic acid bacteria (LAB) strains (Enterococcus PS01155 and PS01156) were tested for their biocontrol potential in the context of microbiomes collected from three ice cream processing facilities (A, B, and C). Antilisterial ability was assessed by co-culturing LABs with 8-L. monocytogenes strains in the presence of microbiota for 3 days at 15°C, followed by quantification of the most probable number of attached L. monocytogenes. L. monocytogenes concentration increased by 0.38±0.77 log10 MPN/sample in treatments containing microbiota from facility A, while it decreased by 0.99±1.13 and 2.54±0.84 log10 MPN/sample in treatments with microbiota from facilities B and C, respectively. The attachment of LAB to an abiotic surface was assessed by co-culturing LABs in with the microbiomes at 15°C for 3 days, followed by characterization of attached microbiota composition using amplicon sequencing. All samples containing microbiomes from facilities A and B had high relative abundance of Pseudomonas, while samples with facility C microbiome had high relative abundance of Enterococcus. Overall, we show that microbiota composition of ice cream processing facilities affected the antilisterial ability of LABs.IMPORTANCEAntilisterial lactic acid bacteria strains had been proposed as biological pathogen control agents for application in food processing environments. However, the effect of resident food processing environment microbiota on the performance on antilisterial lactic acid bacteria strains is poorly understood. Our study shows that the composition of the microbiota collected from ice cream processing facilities’ environmental surfaces can affect the attachment and inhibitory effect of lactic acid bacteria strains against L. monocytogenes. Further studies are therefore needed to evaluate whether individual microbial taxa affect antilisterial properties of lactic acid bacteria strains and to characterize the underlying mechanisms.
Kinetics of naturally induced binding and neutralizing anti-SARS-CoV-2 antibody levels and potencies among Kenyan patients with diverse grades of COVID-19 severity
Authors: Kimotho John , Sein Yiakon , Sayed Shahin , Shah Reena , Mwai Kennedy , Saleh Mansoor , Wanjiku Perpetual , Mwacharo Jedidah , Nyagwange James , Karanja Henry , Kutima Bernadette , Gitonga John , Mugo Daisy , Karanu Ann , Moranga Linda , Oluoch Vivian , Shah Jasmit , Mutiso Julius , Mburu Alfred , Nneka Zaitun , Betti Peter , Mutinda Wanzila Usyu , Abdi Abdirahman Issak , Bejon Philip , Ochola-Oyier Lynette Isabella , Warimwe George M. , Nduati Eunice , Ndungu Francis M. 
Published: October 2022

AbstractBackgroundGiven the low levels of COVID-19 vaccine coverage in Sub-Saharan Africa, despite high levels of natural SARS-CoV-2 exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of natural immunity.MethodsWe used ELISA to measure whole-spike IgG and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody neutralizing potency against the wild-type (Wuhan) SARS-CoV-2 pseudo-virus in a subset of 51 patients over three successive time points. Binding and neutralizing antibody levels and potencies were then tested for correlations with COVID-19 severities, graded according to the National Institute of Health (NIH), USA criteria.ResultsRates of sero-conversion increased from Day 0 (day of PCR testing) to Day 180 (six months) (63.6% to 100 %) and (69.3 % to 97%) for anti-spike IgG and anti-spike-RBD binding Igs, respectively. Levels of these binding antibodies peaked at Day 28 (P<0.0001) and were subsequently maintained for six months without significant decay (p>0.99). Similarly, antibody neutralizing potencies peaked at Day 28 (p<0.0001) but had decreased by three-folds, six months after COVID-19 diagnosis (p<0.0001). Binding antibodies levels were highly correlated with neutralizing antibody potencies at all the time points analyzed (r>0.6, P<0.0001). Levels and potencies of binding and neutralizing antibodies increased with disease severity.ConclusionMost COVID-19 patients from Sub-Saharan Africa generate SARS-CoV-2 specific binding antibodies that remain stable during the first six months of infection. Although antibody binding levels and neutralizing potencies were directly correlated, the respective neutralizing antibodies decayed three-fold by the sixth month of COVID-19 diagnosis suggesting that they are short-lived, consistent with what has been observed elsewhere. Thus, just like for other populations, regular vaccination boosters will be required to broaden and sustain the high levels of predominantly naturally acquired anti-SARS-CoV-2 neutralizing antibodies.