bluuebunny/crossref_metadata_2025 huggingface dataset:
Heparan sulfate modified proteins affect cellular processes central to neurodegeneration and modulatepresenilinfunction
Authors: Schultheis Nicholas , Connell Alyssa , Kapral Alexander , Becker Robert J. , Mueller Richard , Shah Shalini , O’Donnell Mackenzie , Roseman Matthew , Wang Weihua , Yin Fei , Weiss Ryan , Selleck Scott B.
Published: January 2024

Mutations inpresenilin-1 (PSEN1)are the most common cause of familial, early-onset Alzheimer’s disease (AD), typically producing cognitive deficits in the fourth decade. A variant ofAPOE, APOE3 Christchurch (APOE3ch), was found associated with protection from both cognitive decline and Tau accumulation in a 70-year-old bearing the disease-causingPSEN1-E280Amutation. The amino acid change in ApoE3ch is within the heparan sulfate (HS) binding domain of APOE, and purified APOEch showed dramatically reduced affinity for heparin, a highly sulfated form of HS. The physiological significance ofApoE3chis supported by studies of a mouse bearing a knock-in of this human variant and its effects on microglia reactivity and Aβ-induced Tau deposition. The studies reported here examine the function of heparan sulfate-modified proteoglycans (HSPGs) in cellular and molecular pathways affecting AD-related cell pathology in human cell lines and mouse astrocytes. The mechanisms of HSPG influences onpresenilin-dependent cell loss and pathology were evaluated inDrosophilausing knockdown of the presenilin homolog,Psn, together with partial loss of function ofsulfateless (sfl), a homolog ofNDST1, a gene specifically affecting HS sulfation. HSPG modulation of autophagy, mitochondrial function, and lipid metabolism were shown to be conserved in cultured human cell lines,Drosophila, and mouse astrocytes. RNAi ofNdst1reduced intracellular lipid levels in wild-type mouse astrocytes or those expressing humanized variants ofAPOE, APOE3, andAPOE4. RNA-sequence analysis of human cells deficient in HS synthesis demonstrated effects on the transcriptome governing lipid metabolism, autophagy, and mitochondrial biogenesis and showed significant enrichment in AD susceptibility genes identified by GWAS. Neuron-directed knockdown ofPsninDrosophilaproduced cell loss in the brain and behavioral phenotypes, both suppressed by simultaneous reductions insflmRNA levels. Abnormalities in mitochondria, liposome morphology, and autophagosome-derived structures in animals withPsnknockdown were also rescued by simultaneous reduction ofsfl. sflknockdown reversedPsn-dependent transcript changes in genes affecting lipid transport, metabolism, and monocarboxylate carriers. These findings support the direct involvement of HSPGs in AD pathogenesis.
Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans
Authors: Huang Zirui , Mashour George A. , Hudetz Anthony G.
Published: January 2024

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. We observed a significant shift in this geometry during unconsciousness, marked by the dominance of unimodal over transmodal geometry. This alteration was closely linked to the spatial variations in the density of matrix cells within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core–matrix functional architecture in understanding the neural mechanisms of states of consciousness.
High-Resolution Laminar Identification in Macaque Primary Visual Cortex Using Neuropixels Probes
Authors: Zhang Li A. , Li Peichao , Callaway Edward M.
Published: January 2024

Laminar electrode arrays allow simultaneous recording of activity of many cortical neurons and assignment to layers using current source density (CSD) analyses. Electrode arrays with 100-micron contact spacing have been used to estimate borders between layer 4 versus superficial or deep layers, but in macaque primary visual cortex (V1) there are far more layers, such as 4A which is only 50-100 microns thick. Neuropixels electrode arrays have 20-micron spacing, and thus could potentially discern thinner layers and more precisely identify laminar borders. Here we show that laminar distributions of CSDs lack consistency and the spatial resolution required for thin layers and accurate layer boundaries. To take full advantage of high density Neuropixels arrays, we have developed approaches based on higher resolution electrical signals and analyses, including spike waveforms and spatial spread, unit density, high-frequency action potential (AP) power spectrum, temporal power change, and coherence spectrum, that afford far higher resolution of laminar distinctions, including the ability to precisely detect the borders of even the thinnest layers of V1.
SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)
Authors: Hill Joshua A. , Martens Michael J. , Young Jo-Anne H. , Bhavsar Kavita , Kou Jianqun , Chen Min , Lee Lik Wee , Baluch Aliyah , Dhodapkar Madhav V. , Nakamura Ryotaro , Peyton Kristin , Howard Dianna S. , Ibrahim Uroosa , Shahid Zainab , Armistead Paul , Westervelt Peter , McCarty John , McGuirk Joseph , Hamadani Mehdi , DeWolf Susan , Hosszu Kinga , Sharon Elad , Spahn Ashley , Toor Amir A. , Waldvogel Stephanie , Greenberger Lee M. , Auletta Jeffery J. , Horowitz Mary M. , Riches Marcie L. , Perales Miguel-Angel
Published: January 2024

Background

The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood.

Objective

To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy.

Design

Multicenter prospective observational study.

Setting

34 centers in the United States.

Participants

466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022.

Interventions

SARS-CoV-2 vaccination as part of routine care.

Measurements

We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup.

Results

Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels.

Limitations

The majority of participants were adults and received mRNA vaccines.

Conclusions

These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy.

Funding

National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health
Mosquito and human characteristics influence natural Anopheline biting behavior andPlasmodium falciparumtransmission
Authors: Markwalter Christine F , Lapp Zena , Abel Lucy , Kimachas Emmah , Omollo Evans , Freedman Elizabeth , Chepkwony Tabitha , Amunga Mark , McCormick Tyler , Bérubé Sophie , Mangeni Judith N , Wesolowski Amy , Obala Andrew A , Taylor Steve M , O’Meara Wendy P
Published: January 2024

The human infectious reservoir ofPlasmodium falciparummalaria parasites is governed by the efficiency of parasite transmission during vector human contact as well as mosquito biting preferences. Understanding mosquito biting bias in a natural setting can help inform precise targeting of interventions to efficiently interrupt transmission. In a 15-month longitudinal cohort study in a high transmission setting in western Kenya, we investigated human and mosquito factors associated with differential mosquito biting by matching human DNA in single- and multi-sourceAnophelesbloodmeals to the individuals they bit. We employed risk factor analyses and econometric models of probabilistic choice to assess mosquito biting behavior with respect to both human-to-mosquito transmission and mosquito-to-human transmission. We observed thatP. falciparum-infected school-age boys accounted for 50% of bites potentially leading to onward transmission to mosquitoes and had an entomological inoculation rate 6.4x higher than any other group, that infectious mosquitoes were 2.8x more likely to bite cohort members harboringP. falciparumparasites compared to noninfectious mosquitoes, and that this preference to feed on infected people was enhanced by the presence of higher sporozoite loads in the mosquito head-thorax. Taken together, these results suggest that school-age boys disproportionately contribute to theP. falciparumtransmission cycle and thatP. falciparumsporozoites modify mosquito biting preferences to favor feeding on infected people.

Significance

The malaria parasite transmission cycle is doubly-dependent on mosquito-human contact rates. To efficiently deploy transmission-reducing interventions, it is important to understand how mosquito biting preferences shape the human infectious reservoir. Here, we match human DNA in mosquito bloodmeals to the people they bit to quantify mosquito biting preferences and understand how mosquito characteristics shape these preferences. We observed that school-age boys were bitten the most and contributed most to onward transmission to mosquitoes. We also observed that, compared to non-infectious mosquitoes, mosquitoes harboring infectiousPlasmodium falciparumwere more likely to biteP. falciparum-infected people. These observations increase our understanding of malaria parasite transmission and evolution and provide a foundation for developing effective transmission-reducing interventions.
Associations of age at diagnosis of breast cancer with incident myocardial infarction and heart failure: a prospective cohort study
Authors: Liang Jie , Pan Yang , Zhang Wenya , Gao Darui , Wang Yongqian , Xie Wuxiang , Zheng Fanfan
Published: January 2024

Background

The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer.

Methods

Data were from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF were collected at baseline and follow-ups (median=12.8 years). The propensity score matching method and Cox proportional hazards models were employed.

Results

A total of 251 277 female participants (mean age: 56.8±8.0 years), of whom 16 241 had breast cancer, were included. Among participants with breast cancer, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (HR=1.36, 95%CI: 1.19 to 1.56,P<0.001) and HF (HR=1.31, 95% CI: 1.18 to 1.46,P<0.001). After propensity score matching, breast cancer patients with younger diagnosis ages had significantly higher risks of MI and HF than healthy controls.

Conclusion

Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger ages to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases.
Effects of Preanalytical Sample Collection and Handling on Comprehensive Metabolite Measurements in Human Urine Biospecimens
Authors: Braisted John , Henderson Theresa , Newman John W. , Moore Steven C. , Sampson Joshua , McClain Kathleen , Ross Sharon , Baer David J. , Mathé Ewy A. , Zanetti Krista A.
Published: January 2024

Epidemiology studies evaluate associations between the metabolome and disease risk. Urine is a common biospecimen used for such studies due to its wide availability and non-invasive collection. Evaluating the robustness of urinary metabolomic profiles under varying preanalytical conditions is thus of interest. Here we evaluate the impact of sample handling conditions on urine metabolome profiles relative to the gold standard condition (no preservative, no refrigeration storage, single freeze thaw). Conditions tested included the use of borate or chlorhexidine preservatives, various storage and freeze/thaw cycles. We demonstrate that sample handling conditions impact metabolite levels, with borate showing the largest impact with 125 of 1,048 altered metabolites (adjusted P < 0.05). When simulating a case-control study with expected inconsistencies in sample handling, we predicted the occurrence of false positive altered metabolites to be low (< 11). Predicted false positives increased substantially (≥63) when cases were simulated to undergo alternate handling. Finally, we demonstrate that sample handling impacts on the urinary metabolome were markedly smaller than those in serum. While changes in urine metabolites incurred by sample handling are generally small, we recommend implementing consistent handling conditions and evaluating robustness of metabolite measurements for those showing significant associations with disease outcomes.
Controlling biomedical devices using pneumatic logic
Authors: Hoang Shane , Shehada Mabel , Karydis Konstantinos , Brisk Philip , Grover William H.
Published: January 2024

Many biomedical devices are powered and controlled by electrical components. These electronics add to the cost of a device (possibly making the device too expensive for use in resource-limited or point-of-care settings) and can also render the device unsuitable for use in some environments (for example, high-humidity areas like incubators where condensation could cause electrical short circuits, ovens where electronic components may overheat, or explosive or flammable environments where electric sparks could cause serious accidents). In this work, we show that pneumatic logic can be used to power and control biomedical devices without the need for electricity or electric components. Originally developed for controlling microfluidic “lab-on-a-chip” devices, these circuits use microfluidic valves like transistors in air-powered logic “circuits.” We show that a modification to the basic valve design—adding additional air channels in parallel through the valve—creates a “high-flow” valve that is suitable for controlling a broad range of bioinstruments, not just microfluidics. As a proof-of-concept, we developed a high-flow pneumatic oscillator that uses five high-flow Boolean NOT gates arranged in a loop. Powered by a single constant vacuum source, the oscillator provides five out-of-phase pneumatic outputs that switch between vacuum and atmospheric pressure every 1.3 seconds. Additionally, a user can adjust the frequency of the oscillator by squeezing a bellows attached to one of the pneumatic outputs. We then used the pneumatic oscillator to power a low-cost 3D-printed laboratory rocker/shaker commonly used to keep blood products, cell cultures, and other heterogenous samples in suspension. Our air-powered rocker costs around $5 USD to build and performs as well as conventional electronic rockers that cost $1000 USD or more. This is the first of many biomedical devices that can be made cheaper and safer using pneumatic logic.
Prescribing pre-exposure prophylaxis (PrEP) for HIV prevention: A cross-sectional survey of General Practitioners in Australia
Authors: Wu Jason , Fairley Christopher K. , Grace Daniel , Bavinton Benjamin R. , Fraser Doug , Chan Curtis , Chow Eric P.F. , Ong Jason J.
Published: January 2024

Background

Pre-exposure prophylaxis (PrEP) is a safe and effective medication for preventing HIV acquisition. We examined Australian general practitioners’ (GP) knowledge of PrEP efficacy, characteristics associated with ever prescribing PrEP, and barriers to prescribing.

Methods

We conducted an online cross-sectional survey of GPs working in Australia between April and October 2022. We performed univariable and multivariable logistic regression analyses to identify factors associated with: 1) the belief that PrEP was at least 80% efficacious; and 2) ever prescribed PrEP. We asked participants to rate the extent to which barriers affected their prescribing of PrEP.

Results

407 participants with a median age of 38 years (interquartile range 33-44). Half of the participants (50%, 205/407) identified how to correctly take PrEP, 63% (258/407) had ever prescribed PrEP, and 45% (184/407) felt confident with prescribing PrEP. Ever prescribing PrEP was associated with younger age (AOR 0.97, 95%CI: 0.94-0.99), extra training in sexual health (AOR 2.57, 95%CI: 1.54-4.29), and being a S100 Prescriber (OR 2.95, 95%CI: 1.47-5.90). The main barriers to prescribing PrEP included: ‘Difficulty identifying clients who require PrEP/relying on clients to ask for PrEP’ (76%, 310/407), ‘Lack of knowledge about PrEP’ (70%, 286/407), and ‘Lack of time’ (69%, 281/407).

Conclusion

Less than half of our GP respondents were confident in prescribing PrEP, and most had difficulty identifying who would require PrEP. Specific training on PrEP, which focuses on PrEP knowledge, identifying suitable clients, and making it time efficient is recommended, with GPs being remunerated for their time.
Plasticity in inhibitory networks improves pattern separation in early olfactory processing
Authors: Joshi Shruti , Haney Seth , Wang Zhenyu , Locatelli Fernando , Lei Hong , Cao Yu , Smith Brian , Bazhenov Maxim
Published: January 2024

Distinguishing between nectar and non-nectar odors is challenging for animals due to shared compounds and varying ratios in complex mixtures. Changes in nectar production throughout the day - and potentially many times within a forager’s lifetime - add to the complexity. The honeybee olfactory system, containing fewer than 1,000 principal neurons in the early olfactory relay, the antennal lobe (AL), must learn to associate diverse volatile blends with rewards. Previous studies identified plasticity in the AL circuits, but its role in odor learning remains poorly understood. Using a biophysical computational network model, tuned by in vivo electrophysiological data, and live imaging of the honeybee’s AL, we explored the neural mechanisms and functions of plasticity in the early olfactory system. Our findings revealed that when trained with a set of rewarded and unrewarded odors, the AL inhibitory network suppresses shared chemical compounds while enhancing responses to distinct compounds. This results in improved pattern separation and a more concise neural code. Our calcium imaging data support these predictions. Analysis of a graph convolutional neural network performing an odor categorization task revealed a similar mechanism for contrast enhancement. Our study provides insights into how inhibitory plasticity in the early olfactory network reshapes the coding for efficient learning of complex odors.

Significance Statement

By combining biophysical modeling, machine learning, electrophysiology and analysis of calcium imaging data, we demonstrate that associative and nonassociative plasticity in the honeybee antennal lobe (AL) the first relay of the insect olfactory system - work together to enhance the contrast between rewarded and unrewarded odors. Training the AL’s inhibitory network within specific odor environments enables the suppression of neural responses to common odor components while amplifying responses to distinctive ones. This study sheds light on the olfactory system’s ability to adapt and efficiently learn new odor-reward associations across varying environments, and it proposes innovative, energy-efficient principles applicable to artificial intelligence.
Mechanistic basis of gene-specific transcription regulation by the Integrator complex
Authors: Sabath Kevin , Nabih Amena , Arnold Christian , Moussa Rim , Domjan David , Zaugg Judith B. , Jonas Stefanie
Published: January 2024

The Integrator complex (INT) regulates gene expression via premature transcription termination of RNA polymerase II (RNAP2) at promoter-proximal pausing sites. This attenuation of transcription is required for cellular response to external stimuli, cell differentiation and neurodevelopment. How gene-specific regulation is achieved by INT in an inducible manner remains unclear. Here, we identify two sites on INT subunits 13/14 that serve as direct binding hubs for diverse sets of sequence-specific transcription factors (TFs) and other transcription effector complexes. The TFs co-localize with INT genome-wide, increase INT abundance on target genes and co-regulate inducible transcriptional programs. Consistently, disruption of INT-TF contacts impairs sensory cilia formation in response to glucose starvation. Structural analysis places INT’s TF binding hubs upstream of the transcription bubble when attached to paused RNAP2, consistent with simultaneous TF-promoter association. Our data establish TF-mediated recruitment of INT to promoters as a widespread mechanism for targeted and inducible transcription attenuation.
Rat anterior cingulate neurons responsive to rule or strategy changes are modulated by the hippocampal theta rhythm and sharp-wave ripples
Authors: Khamassi M , Peyrache A , Benchenane K , Hopkins DA , Lebas N , Douchamps V , Droulez J , Battaglia FP , Wiener SI
Published: January 2024

To better understand neural processing during adaptive learning of stimulus-response-reward contingencies, we recorded synchrony of neuronal activity in anterior cingulate cortex (ACC) with hippocampal rhythms in male rats acquiring and switching between spatial and visual discrimination tasks in a Y-maze. ACC population and single unit activity responded shortly after task rule changes, or just before the rats adopted different task strategies. Hippocampal theta oscillations (associated with memory encoding) modulated an elevated proportion of rule-change responsive neurons (70%), but other neurons that were correlated with strategy-change, strategy value, and reward-rate were not. However, hippocampal sharp wave-ripples modulated significantly higher proportions of rule-change, strategy-change and reward-rate responsive cells during post-session sleep but not pre-session sleep. This suggests an underestimated mechanism for hippocampal mismatch and contextual signals to facilitate ACC detection of contingency changes for cognitive flexibility, a function that is attenuated after it is damaged.
Pinpointing the microbiota of tardigrades: what is really there?
Authors: Surmacz Bartłomiej , Stec Daniel , Prus-Frankowska Monika , Buczek Mateusz , Michalczyk Łukasz , Łukasik Piotr
Published: January 2024

Microbiota have been proposed as an important aspect of tardigrade biology, but little is known about their diversity and distribution. Here, we attempted to characterize the microbiota of 44 cultured species of tardigrades using 16S rRNA amplicon sequencing, using different specimen pooling strategies, various DNA extraction kits, and multiple types of controls. We also estimated the number of microbes in samples using synthetic DNA spike-ins. Additionally, we reanalyzed data from previous studies.

Our results suggest that the microbial community profiles of cultured tardigrades are dominated by bacterial OTUs and genotypes originating from food, medium, or laboratory reagents. We found microbial strains consistently enriched in certain tardigrades (relative to the culture media and controls), which indicates likely symbiotic associations, but the reads representing putative true tardigrade-associated microbes rarely exceeded 20% of the datasets. Some of the identified tardigrade-associated microbes matched symbionts identified by other studies. However, we also identified serious contamination issues with previous studies of tardigrade microbiome, making some of their conclusions questionable. We conclude that tardigrades are not universally dependent on specialized microbes and highlight the necessary safeguards in future studies of the microbiota of microscopic organisms.
Thiosulfinate tolerance gene clusters are common features ofBurkholderiaonion pathogens
Authors: Paudel Sujan , Zhao Mei , Stice Shaun P. , Dutta Bhabesh , Kvitko Brian H.
Published: January 2024

Burkholderia gladiolipv.alliicola, B.cepacia, andB. orbicolaare common bacterial pathogens of onion. Onions produce organosulfur thiosulfinate defensive compounds after cellular decompartmentalization. Using whole genome sequencing andin silicoanalysis, we identified putative thiosulfinate tolerance gene (TTG) clusters in multiple onion-associatedBurkholderiaspecies similar to those characterized in otherAllium-associated bacterial endophytes and pathogens. Sequence analysis revealed the presence of threeBurkholderiaTTG cluster types with both Type A and Type B being broadly distributed inB. gladioli,B. cepacia, andB. orbicolain both the chromosome and plasmids. Based on isolate natural variation and generation of isogenic strains, we determined thein vitroandin vivocontribution of TTG clusters inB. gladioli,B. cepacia, andB. orbicola. TheBurkholderiaTTG clusters contributed to enhanced allicin tolerance and improved growth in filtered onion extract by all three species. TTG clusters also made clear contributions toB gladiolifoliar necrosis symptoms and bacterial populations. Surprisingly, the TTG cluster did not contribute to bacterial populations in onion bulb scales by these three species. Based on our findings, we hypothesize onion-associatedBurkholderiamay evade or inhibit the production of thiosulfinates in onion bulb tissues.
Extracellular ATP is an environmental cue in bacteria
Authors: Tronnet Sophie , Pandey Vikash , Lloret-Berrocal Miriam , Pérez-del-Pozo Mario , Söderholm Niklas , Hernández-Ortego Carlos , Billker Oliver , Nordström Anders , Puhar Andrea
Published: January 2024

In animals and plants extracellular ATP (eATP) functions as signal and regulates the immune response. During inflammation intestinal bacteria are exposed to elevated eATP originating from the mucosa. However, whether bacteria respond to eATP is unclear. Here we show that non-pathogenicEscherichia coliresponds to eATP by modifying its transcriptional and metabolic landscapes. A genome-scale promoter library showed that the response is time-, concentration-, and medium-dependent and ATP-specific. The second messenger cAMP and genes related to metabolism, quorum sensing, and envelope stress were regulated downstream of eATP. Metabolomics confirmed that eATP triggers enrichment of compounds with bioactive properties on the host or bacteria. Combined genome-scale modelling revealed global metabolic and biomass building blocks modifications. Consequently, eATP altered the sensitivity to antibiotics and antimicrobial peptides. Finally, in pathogens eATP controlled virulence factor expression. Our results indicate that eATP is an environmental cue in prokaryotes which broadly regulates physiology, antimicrobial resistance, and virulence.
Development of a qPCR assay and a LAMP assay forVerticillium longisporumdetection and a triplex qPCR assay for simultaneous detection ofV. longisporum,Leptosphaeria biglobosaandL. maculansfrom canola samples
Authors: Fu Heting , Yang Yalong , Jiang Junye , Daniels Greg C. , Hill Blake , Xue Shiming , Zahr Kher , Stellar L. , Harding Michael W. , Feindel David , Bvindi Carol , Fernando Dilantha , Wang Lipu , Feng Jie
Published: January 2024

Verticillium wilt, Verticillium stem striping, and Verticillium stripe, are common disease names that all denote infection caused byVerticillium longisporum, on canola, or other Brassica crops. In this study, a quantitative PCR (qPCR) assay and a loop-mediated isothermal amplification (LAMP) assay were developed for the detection ofV. longisporumfrom canola stem samples. Both assays are specific toV. longisporumat the species level and ubiquitous at the strain level. The low limit for positive detection of the two assays is 1 pg fungal DNA in a 20-µ L reaction or 1,400 fungal cells in 100-mg plant tissue. The qPCR assay was combined with the duplex qPCR assay for the two blackleg pathogens,Leptosphaeria biglobosaandL. maculansto constitute a triplex qPCR system for simultaneous detection of all three pathogens. The usefulness of this triplex qPCR system was verified on canola samples collected from various locations in Alberta, Canada. Using this triplex qPCR system,V. longisporumwas detected from one sample, while the two blackleg pathogens were detected at higher frequencies. Since it is sometimes difficult to differentiate Verticillium stripe and blackleg on Alberta canola samples based on visual symptoms, the triplex qPCR system is an important tool for the detection ofV. longisporum, especially when its presence is masked or obscured by symptoms of blackleg.
Measuring excitation-inhibition balance through spectral components of local field potentials
Authors: Diehl Geoffrey W , Redish A David
Published: January 2024

The balance between excitation and inhibition is critical to brain functioning, and dysregulation of this balance is a hallmark of numerous psychiatric conditions. Measuring this excitation-inhibition (E:I) balancein vivohas remained difficult, but theoretical models have proposed that characteristics of local field potentials (LFP) may provide an accurate proxy. To establish a conclusive link between LFP and E:I balance, we recorded single units and LFP from the prefrontal cortex (mPFC) of rats during decision making. Dynamic measures of synaptic coupling strength facilitated direct quantification of E:I balance and revealed a strong inverse relationship to broadband spectral power of LFP. These results provide a critical link between LFP and underlying network properties, opening the door for non-invasive recordings to measure E:I balance in clinical settings.
Harnessing the diversity ofBurkholderiaspp. prophages for therapeutic potential
Authors: Nordstrom Hayley R. , Griffith Marissa P. , Srinivasa Vatsala Rangachar , Wallace Nathan R. , Li Anna , Cooper Vaughn S. , Shields Ryan K. , Van Tyne Daria
Published: January 2024

Burkholderiaspp. are often resistant to antibiotics, and infections with these organisms are difficult to treat. A potential alternative treatment forBurkholderiaspp. infections is bacteriophage (phage) therapy; however, it can be difficult to locate phages that target these bacteria. Prophages incorporated into the bacterial genome have been identified withinBurkholderiaspp. and may represent a source of useful phages for therapy. Here we investigate whether prophages withinBurkholderiaspp. clinical isolates can kill conspecific and heterospecific isolates. Thirty-twoBurkholderiaspp. isolates were induced for prophage release, and harvested prophages were tested for lytic activity against the same 32 isolates. Lytic phages were passaged and their host ranges were determined, resulting in four unique phages of prophage origin that showed different ranges of lytic activity. We also analyzed the prophage content of 35Burkholderiaspp. clinical isolate genomes, and identified several prophages present in the genomes of multiple isolates of the same species. Finally, we observed thatB. cenocepaciaisolates were more phage-susceptible thanBurkholderia multivoransisolates. Overall, our findings suggest that prophages present withinBurkholderiaspp. genomes are a potentially useful starting point for the isolation and development of novel phages for use in phage therapy.
Metagenomic analysis of colonic tissue and stool microbiome in patients with colorectal cancer in a South Asian population
Authors: Gamage Bawantha Dilshan , Ranasinghe Diyanath , Sahankumari AGP , Malavige Gathsaurie Neelika
Published: January 2024

Objective

The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population.

Design

The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n=112) and colonic tissue (n=36) in 112 individuals. Of these had CRC (n=24), premalignant lesions (n=10), healthy individuals (n=50) and in those with diabetes (n=28).

Results

Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium, were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p< 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes.

Conclusion

Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, withPrevotellaspecies, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population.
Limitations of probabilistic error cancellation for open dynamics beyond sampling overhead
Authors: Ma Yue , Kim M. S.
Published: January 2024

Quantum simulation of dynamics is an important goal in the noisy intermediate-scale quantum era, within which quantum error mitigation may be a viable path towards modifying or eliminating the effects of noise. Most studies on quantum error mitigation have focused on the resource cost due to its exponential scaling in the circuit depth. Methods such as probabilistic error cancellation rely on discretizing the evolution into finite time steps and applying the mitigation layer after each time step, modifying only the noise part without any Hamiltonian dependence. This may lead to Trotter-like errors in the simulation results even if the error mitigation is implemented ideally, which means that the number of samples is taken as infinite. Here we analyze the aforementioned errors which have been largely neglected before. We show that they are determined by the commutating relations between the superoperators of the unitary part, the device noise part, and the noise part of the open dynamics to be simulated. We include both digital quantum simulation and analog quantum simulation setups and consider defining the ideal error mitigation map both by exactly inverting the noise channel and by approximating it to first order in the time step. We use single-qubit toy models to numerically demonstrate our findings. Our results illustrate fundamental limitations of applying probabilistic error cancellation in a stepwise manner to continuous dynamics, thus motivating the investigations of truly time-continuous error cancellation methods.

Published by the American Physical Society
2024
Quantized conductance in hybrid split-gate arrays of superconducting quantum point contacts with semiconducting two-dimensional electron systems
Authors: Delfanazari Kaveh , Li Jiahui , Xiong Yusheng , Ma Pengcheng , Puddy Reuben K. , Yi Teng , Farrer Ian , Komori Sachio , Robinson Jason W.A. , Serra Llorenc , Ritchie David A. , Kelly Michael J. , Joyce Hannah J. , Smith Charles G.
Published: January 2024

A quantum point contact (QPC)—a constriction in a semiconducting two-dimensional electron system with a quantized conductance—is a building block of novel spintronic and topological electronic circuits. QPCs can also be used as readout electronics, charge sensors, or switches in quantum nanocircuits. A short and impurity-free constriction with superconducting contacts is a Cooper-pair QPC analogue known as a superconducting quantum point contact (SQPC). The technological development of such quantum devices has been prolonged due to the challenges of maintaining their geometrical requirement and near-unity superconductor-semiconductor interface transparency. Here, we develop advanced nanofabrication, material and device engineering techniques and report on an innovative realization of nanoscale hybrid SQPC arrays with split gate technology in semiconducting 2D electron systems. We exploit the special gate tunability of the quantum wells, and demonstrate the first experimental observation of conductance quantization in hybrid InGaAs-Nb SQPCs. We observe reproducible quantized conductance at zero magnetic fields in multiple quantum nanodevices fabricated in a single chip and systematically investigate the quantum transport of SQPCs at low and high magnetic fields for their potential applications in quantum metrology, for extremely accurate voltage standards, and fault-tolerant quantum technologies.

Published by the American Physical Society
2024
Searching for high-frequency axion in quantum electromagnetodynamics through interface haloscopes
Authors: Li Tong , Dai Chang-Jie , Zhang Rui-Jia
Published: January 2024

The so-called Witten effect implies a close relationship between the axion and magnetic monopole. A sound quantization in the presence of magnetic monopoles, called quantum electromagnetodynamics (QEMD), was utilized to construct a more generic axion-photon Lagrangian in the low-energy axion effective field theory. This generic axion-photon Lagrangian introduces the interactions between axion and two four-potentials, and leads to new axion-modified Maxwell equations. The interface haloscopes place an interface between two electromagnetic media with different properties and are desirable to search for high-mass axions ma≳O(10)  μeV. In this work, for the generic axion-photon couplings built under QEMD, we perform comprehensive calculations of the axion-induced propagating waves and energy flux densities in different interface setups. We also obtain the sensitivity to new axion-photon couplings for high-mass axions.

Published by the American Physical Society
2024
Classical Larmor formula through the Unruh effect for uniformly accelerated electrons
Authors: Vacalis Georgios , Higuchi Atsushi , Bingham Robert , Gregori Gianluca
Published: January 2024

We investigate the connection between the classical Larmor formula and the quantum Unruh effect by computing the emitted power by a uniformly accelerated charged particle and its angular distribution in the coaccelerated frame. We consider a classical particle accelerated with nonzero charge only for a finite period and then take the infinite-time limit after removing the effects due to the initial charging and final discharging processes. We show that the result found for the interaction rates agrees with previous studies in which the period of acceleration with nonzero charge was taken to be infinite from the beginning. We also show that the power and angular distribution of emission, which is attributed either to the emission or absorption of a Rindler photon in the coaccelerated frame, is given by the Larmor formula, confirming that, at tree level, it is necessary to take into account the Unruh effect in order to reproduce the classical Larmor radiation formula in the coaccelerated frame.

Published by the American Physical Society
2024
Self-organization of ecosystems to exclude half of all potential invaders
Authors: Cockrell Cillian , O'Sullivan Jacob D. , Terry J. Christopher D. , Nwankwo Emmanuel C. , Trachenko Kostya , Rossberg Axel G.
Published: January 2024

Species-rich Lotka-Volterra competition models of ecosystem dynamics transition with increasing species pool size from a phase with well-defined stable equilibrium to a dynamic phase that remains incompletely understood. We analytically describe the statistical mechanics of the steady state deep inside this dynamic phase, characterized by incessant turnover in species composition, and extract the distribution of invasion fitness of random invaders. We find that steady state invasion probability universally equals 1/2. This striking result agrees well with observations in plants and animals.

Published by the American Physical Society
2024
Promoting
p
-based Hall effects by
p−d−f
hybridization in Gd-based dichalcogenides
Authors: Zeer Mahmoud , Go Dongwook , Schmitz Peter , Saunderson Tom G. , Wang Hao , Ghabboun Jamal , Blügel Stefan , Wulfhekel Wulf , Mokrousov Yuriy
Published: January 2024

We conduct a first-principles study of Hall effects in rare-earth dichalcogenides, focusing on monolayers of the H-phase EuX2 and GdX2, where X=S, Se, and Te. Our predictions reveal that all EuX2 and GdX2 systems exhibit high magnetic moments and wide band gaps. We observe that while in the case of EuX2 the p and f states hybridize directly below the Fermi energy, the absence of f and d states of Gd at the Fermi energy results in the p-like spin-polarized electronic structure of GdX2, which mediates p-based magnetotransport. Notably, these systems display significant anomalous, spin, and orbital Hall conductivities. We find that in GdX2, the strength of correlations controls the relative position of the

p

,

 

d

, and f states and their hybridization, which has a crucial impact on p-state polarization and the anomalous Hall effect, but not the spin and orbital Hall effects. Moreover, we find that the application of strain can significantly modify the electronic structure of the monolayers, resulting in quantized charge, spin, and orbital transport in GdTe2 via a strain-mediated orbital inversion mechanism taking place at the Fermi energy. Our findings suggest that rare-earth dichalcogenides hold promise as a platform for topological spintronics and orbitronics.

Published by the American Physical Society
2024
Two levels of topology in skyrmion lattice dynamics
Authors: Schick Daniel , Weißenhofer Markus , Rózsa Levente , Rothörl Jan , Virnau Peter , Nowak Ulrich
Published: January 2024

Skyrmions are localized, topological spin structures that can be described as quasiparticles. Skyrmions in thin films are an ideal model system to study Brownian motion and lattice formation in two dimensions. They follow an equation of motion, the Thiele equation, which includes a topology-dependent chiral term, linear in velocity, causing a skyrmion Hall effect and a drastic reduction of the diffusion coefficient for individual skyrmions, as compared to normal Brownian particles. Using Brownian dynamics simulations, we show that this topological suppression of the diffusion can be partially lifted in two-dimensional lattices of skyrmions. Counterintuitively, this causes enhanced diffusive properties with increasing particle density, similar to odd-diffusive Brownian particles. We show how the topological charge of the skyrmions influences the dynamics of topological lattice defects, which also affects the dynamics of the phase formation.

Published by the American Physical Society
2024
Momentum-space signatures of the Anderson transition in a symplectic, two-dimensional, disordered ultracold gas
Authors: Arabahmadi Ehsan , Schumayer Daniel , Grémaud Benoît , Miniatura Christian , Hutchinson David A. W.
Published: January 2024

We study Anderson localization in two-dimensional, disordered, spin-orbit systems belonging to the symplectic symmetry class using momentum-space signatures such as the coherent backscattering antipeak and the coherent forward-scattering peak. Significantly, these momentum-space features are readily accessible in ultracold atom experiments through absorption imaging after time-of-flight expansion. Here, the critical exponent and mobility edge of the metal-insulator transition are successfully obtained through a finite-time analysis of the coherent backscattering width. An anomalous residual diffusion, unique to two dimensions, is identified at the transition point where the system changes from a metal to an insulator. A spin localization phenomenon is also observed in the deep localized regime.

Published by the American Physical Society
2024
Impact of Isotopic Exchange on Hydrated Protein Dynamics Revealed by Polarized Neutron Scattering
Authors: Nidriche Agathe , Moulin Martine , Oger Philippe , Stewart J. Ross , Mangin-Thro Lucile , Schmidt Wolfgang , Kneller Gerald , Peters Judith
Published: January 2024

Within the last decades, it was often assumed that in hydrogen-rich disordered samples, such as proteins in solution or hydrated powder form, incoherent neutron scattering from hydrogen nuclei dominated the scattering signal to an extent that allowed all other contributions to be neglected. As incoherent scattering arises solely from self-correlations, it further justified such a choice. Consequently, heavy water was often used as a contrast tool to highlight molecular motions in live samples. Coherent scattering, which implies the scattering from many nuclei and therefore collective processes, is another non-negligible contribution to neutron scattering where cross sections of other nuclei than hydrogen are significant. The recent advent of instrumentation based on polarization of neutron beams and the analysis of their polarization state after scattering for dynamical studies allows us to separate and shed light on the two contributions. In the present study we reveal that, unexpectedly, the isotopic exchange of water in the hydration shell of proteins arises on a much faster timescale than assumed so far. Moreover, the collective and local D-bond network relaxation of hydration water contributes to a high extent to the coherent scattering signal, at odds with usual “static” approaches used to estimate the relative impacts of dynamics in the sample. Hence, hydration water necessarily contaminates nonpolarized standard experiments. The findings are of paramount importance for all neutron scattering experiments where partial or full deuteration is used.

Published by the American Physical Society
2024
Parameterized absorptive electron scattering factors
Authors: Thomas M. , Cleverley A. , Beanland R.
Published: January 2024

In electron diffraction, thermal atomic motion produces incoherent scattering over a relatively wide angular range, which appears as a diffuse background that is usually subtracted from measurements of Bragg spot intensities in structure solution methods. The transfer of electron flux from Bragg spots to diffuse scatter is modelled using complex scattering factors f + if′ in the Bloch wave methodology. In a two-beam Einstein model the imaginary `absorptive' scattering factor f′ can be obtained by the evaluation of an integral containing f over all possible scattering angles. While more sophisticated models of diffuse scatter are widely used in the electron microscopy community, it is argued in this paper that this simple model is appropriate for current structure solution and refinement methods. The two-beam model is a straightforward numerical calculation, but even this simplistic approach can become time consuming for simulations of materials with large numbers of atoms in the unit cell and/or many incident beam orientations. Here, a parameterized form of f′ is provided for 103 elements as neutral, spherical atoms that reduces calculation time considerably.