bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilocus, Multiplex Detection of Ganoderma zonatum from Environmental Samples
Authors: Chakrabarti Seemanti , Loyd Andrew L. , Dhillon Braham
Published: July 2022

Ganoderma butt rot of palms is caused by a white rot basidiomycete fungus, Ganoderma zonatum. Typical symptoms include wilting of fronds that starts in the lower canopy and moves to the top. As wilting symptoms are also associated with other diseases and disorders, appearance of basidiomata on the trunks is necessary to confirm this disease. Basidiomata develop late in the disease cycle, making early diagnostics challenging. Here, we describe a DNA-based molecular diagnostic assay that could be used to confirm the presence of G. zonatum in palm trunks before conks are observed. Primers tailored to end on single-nucleotide polymorphisms (SNPs), that differentiate G. zonatum from 14 other Ganoderma taxa, were designed from multiple regions in four genes: internal transcribed spacer (ITS), RNA polymerase 1 (rpb1), rpb2, and translation elongation factor 1-α (tef1-α). A set of three primer pairs could successfully determine the incidence of G. zonatum with high specificity and sensitivity in different environmental samples such as sawdust collected from naturally infected palm trunks and soil samples containing G. zonatum basidiospores. This rapid PCR-based assay could potentially be used to detect inoculum sources of the fungus and track its movement and survival in different palm tissues and environments. Early detection of G. zonatum is a crucial step toward building and implementing better disease management strategies and mitigating potential risks from palm failures due to decay.
Role of circulating long non-coding RNA for the improvement of the predictive ability of the CHA2DS2–VASc score in patients with atrial fibrillation
Authors: Zhang Yuanbo , Wang Duan , Wu Na , Chen Xinghua , Yuan Zhiquan , Jia Xiaoyue , Li Chengying , Hu Qin , Chen Yanxiu , Zhang Zhihui , Zhong Li , Li Yafei
Published: July 2022

Background:

The CHA2DS2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA2DS2–VASc score in stroke and all-cause mortality.

Methods:

Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA2DS2–VASc score model.

Results:

Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA2DS2–VASc score significantly improved the discrimination and reclassification power of the CHA2DS2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA2DS2–VASc model for predicting all-cause mortality.

Conclusions:

Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA2DS2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.
Towards De-Implementation of low-value thyroid care in older adults
Authors: Perkins Jennifer M. , Papaleontiou Maria
Published: July 2022

Purpose of review

This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer.

Recent findings

Despite a shift to a “less is more” paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults.

Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.
Influences on Skeletal Health and Bone Mineralization in Children
Authors: Donohue Patricia , Kujath Amber S.
Published: July 2022

Bone is in its most active formation phase of mineralization in the pediatric and adolescent population. Peak bone mass is achieved around the late teens to early 20s. Deficient bone mineralization and decreased peak bone mass acquisition predispose an individual to childhood fractures or lifelong fracture risk. Adolescent fragility or stress fractures should prompt a secondary evaluation for the causes of a low bone mineral content, the root of a fracture. The purpose of this article is to review published literature that discusses the risk factors associated with a decreased bone mineral content in children from birth to the age of peak bone mass. The article also includes a public health planning model for pediatric osteoporosis.
COVID-19—A Qualitative Orthopaedic Nurse Perspective
Authors: Quinlan Patricia , Davis Jack , Jacobson Joy
Published: July 2022

In response to a March 2020, New York State mandate, our elective surgery center began a physical and operational transformation to provide inpatient care to COVID-19 patients. Research study aims included (1) a description of the orthopaedic nurses' experience during the pandemic, and (2) tactics used to cope with related stress. Researchers used a descriptive, qualitative design to achieve study aims. During April to December 2020, nine nurses responded to seven open-ended, study prompts asking them to journal their thoughts about the pandemic. The majority (66%) of participants were experienced nurses and all provided direct patient care. Nurses provided 51 journal entries that generated 12 themes, which encapsulated their experience living through the pandemic: (1) Whirlwind, (2) War, (3) Control, (4) Death and Dying, (5) Staying Safe, (6) Loss, (7) Looking for Meaning, (8) Whatever It Takes, (9) Adaptability and Resilience, (10) What I Have Learned, (11) The New Normal, and (12) When Will This Be Over? Orthopaedic nurses in this study pivoted to the needs of patients requiring them to draw on all their training and resources. Nurses described the enormity and taxing nature of the viral threat and their ability to manage their well-being while caring for patients and loved ones, amidst social distancing and need for aggressive infection control. Support from peers and leadership were paramount factors in nurse coping. Positive thinking and personal resilience were considered essential. Most participants described personal growth; however, decreased participation in journal responses overtime, suggested emotional strain. Future studies should examine nurses' observations about the impact of changes to their practice brought on by the pandemic, and reliance on technology.
Low-Vision Evaluations and Interventions Used in Practice
Authors: Nastasi Julie Ann , Blasland Rachel , Desseyn Danielle , Gaynor Samantha , Grieco Alexa , Kelly Emily , McMullen Brigid , Rice Lauren , Strassle Brianna
Published: July 2022

Low vision creates challenges in completing vision-dependent tasks and activities. The purpose of this 3-round e-Delphi study was to determine a consensus for the evaluations and interventions commonly used in low-vision rehabilitation for older adults with low vision. Ten occupational therapists with at least 3 years of practice in low-vision rehabilitation participated in the study. The results of the study identified the most frequently used evaluations and interventions for older adults with low vision. Findings of this study coincided with the literature and can be integrated into current practice with this population.
Achieving Digital Competence for Adults With Low Vision
Authors: Budash Deborah Elgin
Published: July 2022

Today many occupations are done using technology. This not only provides opportunities for continued occupational engagement for many but can also hinder participation for those with low vision. This article reviews the literature on digital literacy for individuals with low vision and found that it is in its infancy. Currently, occupational therapy practice is informed by core principles, relies on education research on students with low vision, and the basic low-vision principles related to occupational performance. This article assembles practical recommendations to enable occupational therapy practitioners to advance in this area and build a body of evidence. This article also provides recommendations for the interdisciplinary team to support digital literacy for patients with low vision.
Physical Activity in Older Adults With Visual Impairment
Authors: Nastasi Julie Ann , Kenyon Kaitlin , Tirney Devon
Published: July 2022

Visual impairment presents challenges for older adults to participate in physical activity or exercise. The purpose of this collective case study is to explore how older adults with visual impairment participate in physical activity. Four older adults with visual impairment were recruited to participate in the study. Three out of the 4 participants were able to complete all rounds of the study prior to COVID-19 pandemic halting the study. Five themes emerged from the study: exercise to enhance health and well-being, occupations as activity, loss of participation, adaptation to vision loss, and motivation to stay healthy. The findings support the use physical activity to enhance overall health and well-being.
Dual Sensory Impairment and Ways to Enhance Therapy Services
Authors: Chang Kristen Marie-Weber
Published: July 2022

Dual sensory impairment is a concomitant change to hearing and vision and is increasingly common due to the aging population. Although seemingly separate, these sensory systems enhance each other and when both are impaired, patients experience increased comorbidities and disability as compared with individuals with a single sensory impairment. Occupational therapy practitioners can support function and quality of life when working with an individual with dual sensory impairment by promoting independence with hearing aid management, incorporating sensory redundancy into assistive devices, and optimizing the environment to enhance auditory and visual cues.
Impact of the COVID-19 Pandemic on Individuals With Low Vision
Authors: Hsu Yu-Pin , Pingale Vidya
Published: July 2022

This qualitative case study explored the impact of lockdown and social distancing measures used during COVID-19 on the lives of individuals with low vision. A purposive sample of 6 participants with low vision was recruited. Data were collected using in-depth semistructured interviews consisting of 10 open-ended questions. A thematic analysis was conducted to understand the unified subjective experiences of the participants. The analysis revealed 4 themes: (1) Changes, a lot of them; (2) Emotional roller coaster; (3) Life goes on; and (4) Technology as the catalyst. Participants demonstrated ongoing adaptation to meet the changing demands imposed by the pandemic.
Prevention and management of behavioural and psychological symptoms in patients with dementia in acute care: a best practice implementation project
Authors: Akrour Rachid , Courret-Gilgen Catherine , Perrenoud Beatrice
Published: July 2022

Introduction:

Behavioural and psychological symptoms of dementia are very common in acute care. Agitation and aggressive behaviours are the most common symptoms and are challenging to manage. Early detection and a nonpharmacological approach are recommended.

Objectives:

To implement evidence-based recommendations for the prevention and management of aggression/agitation in patients with dementia in an acute geriatric care unit.

Methods:

The project used the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback tool. A baseline audit was conducted with seven audit criteria based on evidence summaries. It was followed by the implementation of an action plan and a follow-up audit.

Results:

Results showed moderate improvements in compliance with best practice recommendations. The second audit indicated an improvement up to 46% with the identification of factors/triggers that precipitate aggression/agitation and completion of a risk assessment. The highest improvement was the training of the nursing team (79%). Compliance with the involvement of patients and their families in the care planning improved slightly (14%). The lowest improvement was for the development and implementation of individualized care plans (10%).

Conclusion:

The project implementation achieved some positive changes. A formalized process for preventing aggression/agitation is in place. The interprofessional collaboration, the support given to the nursing team and the basket of nonpharmacological interventions were strengthened. The electronic documentation and a limited collaboration of the nursing team were challenging. As further strategies were implemented, further audit would be required to assess achievement in change and/or demonstration of improved care provided for this vulnerable population.
A linear DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain elicits protective immunity in domestic cats
Authors: Conforti Antonella , Sanchez Elisa , Salvatori Erika , Lione Lucia , Compagnone Mirco , Pinto Eleonora , Palombo Fabio , Sun Yuhua , Viscount Brian , Hayward James , Shorrock Clay , Diel Diego G. , Impellizeri Joseph A. , Aurisicchio Luigi
Published: July 2022

Since its first detection in China in late 2019, SARS-CoV-2, the etiologic agent of COVID-19 pandemic, has infected a wide range of animal species, especially mammals, all over the world. Indeed, as reported by the American Veterinary Medical Association, besides human-to-human transmission, human-to-animal transmission has been observed in some wild animals and pets, especially in cats. With animal models as an invaluable tool in the study of infectious diseases combined with the fact that the intermediate animal source of SARS-CoV-2 is still unknown, researchers have demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a randomized Phase I/II clinical study conducted in domestic cats to assess safety and immunogenicity of a linear DNA (“linDNA”) vaccine encoding the RBD domain of SARS-CoV-2. No significant adverse events occurred and both RBD-specific binding/neutralizing antibodies and T cells were detected. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans.
The ‘Candidatus Phytoplasma mali’ effector protein SAP11CaPm interacts with MdTCP16, a class II CYC/TB1 transcription factor that is highly expressed during phytoplasma infection
Authors: Mittelberger Cecilia , Hause Bettina , Janik Katrin
Published: July 2022

‘Candidatus Phytoplasma mali’, is a bacterial pathogen associated with the so-called apple proliferation disease in Malus × domestica. The pathogen manipulates its host with a set of effector proteins, among them SAP11CaPm, which shares similarity to SAP11AYWB from ‘Candidatus Phytoplasma asteris’. SAP11AYWB interacts and destabilizes the class II CIN transcription factors of Arabidopsis thaliana, namely AtTCP4 and AtTCP13 as well as the class II CYC/TB1 transcription factor AtTCP18, also known as BRANCHED1 being an important factor for shoot branching. It has been shown that SAP11CaPm interacts with the Malus × domestica orthologues of AtTCP4 (MdTCP25) and AtTCP13 (MdTCP24), but an interaction with MdTCP16, the orthologue of AtTCP18, has never been proven. The aim of this study was to investigate this potential interaction and close a knowledge gap regarding the function of SAP11CaPm. A Yeast two-hybrid test and Bimolecular Fluorescence Complementation in planta revealed that SAP11CaPm interacts with MdTCP16. MdTCP16 is known to play a role in the control of the seasonal growth of perennial plants and an increase of MdTCP16 gene expression has been detected in apple leaves in autumn. In addition to this, MdTCP16 is highly expressed during phytoplasma infection. Binding of MdTCP16 by SAP11CaPm might lead to the induction of shoot proliferation and early bud break, both of which are characteristic symptoms of apple proliferation disease.
Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021- January 2022
Authors: de Gier Brechje , van Asten Liselotte , Boere Tjarda M. , van Roon Annika , van Roekel Caren , Pijpers Joyce , van Werkhoven C.H. (Henri) , van den Ende Caroline , Hahné Susan J.M. , de Melker Hester E. , Knol Mirjam J. , van den Hof Susan
Published: July 2022

Background

We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose.

Methods

National registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin.

Results

VE against COVID-19 mortality was >90% for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80% at 7-8 months post-primary series for most groups, and around 60% for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to >85% in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups.

Conclusion

At the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.
Prevalence and predictors of Motoric Cognitive Risk syndrome in a community-dwelling older Scottish population: a longitudinal observational study
Authors: Mullin Donncha S. , Stirland Lucy E , Welstead Miles , Russ Tom C. , Luciano Michelle , Muniz-Terrera Graciela
Published: July 2022

Objectives

This study aimed to determine the prevalence of Motoric Cognitive Risk (MCR), describe associated risk factors for this syndrome, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults.

Methods

A longitudinal prospective study using data from the Lothian Birth Cohort 1936 (LBC1936) and follow-up data from six, nine, and 12 years later. A total of 690 participants (mean [SD] age 76.3 [0.8] years) free from dementia were classified into non-MCR or MCR groups and baseline characteristics (age 69.5 [0.8] years) between the groups were compared.

Results

MCR prevalence rate ranged from 5.3-5.7% across the three waves. The presence of MCR was significantly associated with older age (six and nine years later), lower occupational socioeconomic status (six years later), and a range of tests of executive function (six, nine and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment and almost all the MCR group had either Prefrailty or Frailty.

Conclusions

The prevalence of MCR in this Scottish cohort is lower than the pooled global average but higher than the prevalence in neighbouring countries. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status. This study can serve as a foundation for future studies to improve dementia risk assessments and potentially develop new interventions to reduce incident dementia.

Key points

Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is quick, inexpensive, and practical to assess and diagnose, and it can identify individuals at high risk of developing dementia

The prevalence of MCR in this older Scottish cohort ranged from 5.3-5.7% over three follow-up waves

Factors associated with MCR in this cohort include age, socioeconomic status and tests of executive function

There is partial overlap between individuals with MCR and Mild Cognitive Impairment (MCI), but almost all individuals with MCR also had either Prefrailty or Frailty.
Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol
Authors: Truong Lisa , Chen Yen-Wei , Barrere-Cain Rio , Shuck Karissa , Xiao Wen , Levenson Max T. , da Veiga Beltrame Eduardo , Panter Blake , Reich Ella , Sternberg Paul W. , Yang Xia , Allard Patrick
Published: July 2022

Single-cell RNA transcriptomic platforms have significantly contributed to our understanding of tissue heterogeneity as well as of developmental and cellular differentiation trajectories. They also provide an opportunity to map an organism’s response to environmental cues with high resolution and unbiasedly identify the cell types that are the most transcriptionally sensitive to exposures. Here, we applied single nucleus RNA-seq experimental and computational approaches to C. elegans to establish the transcriptome of the adult nematode and comprehensively characterize the transcriptional impact of ethanol as a model environmental exposure on the entire organism at cell type-resolution over several generations. Clustering, tissue and phenotype enrichment, and gene ontology analyses identified 31 clusters representing a diverse number of adult cell types, including those from syncytial and multi-nucleated tissues which are difficult to assess by single cell RNA-seq, such as the mitotic and meiotic germline, hypodermal cells, and the intestine. We applied this method to identify the impact of inter- and trans-generational exposure to two human-relevant doses of alcohol. Cell type proportions were not significantly altered by ethanol. However, Euclidean distance analysis identified several germline, striated muscle, and neuronal clusters as being major transcriptional targets of ethanol at both the F1 and F3 generations although the relative order of clusters changed between generations. The impact on germline clusters was further confirmed by phenotypic enrichment analysis as well as functional validation, namely a remarkable inter- and trans-generational increase in germline apoptosis, aneuploidy, and embryonic lethality. Together, snRNA-seq of the adult C. elegans represents a powerful approach for the detailed examination of an adult organism’s response to environmental cues.
Development of a first-in-class unimolecular dual GIP/GLP-2 analogue, GL-0001, for the treatment of bone fragility
Authors: Gobron Benoit , Couchot Malory , Irwin Nigel , Legrand Erick , Bouvard Béatrice , Mabilleau Guillaume
Published: July 2022

Due to ageing of the population, bone frailty is dramatically increasing worldwide. Although some therapeutic options exist, they do not fully protect or prevent against the occurrence of new fractures. All current drugs approved for the treatment of bone fragility target bone mass. However, bone resistance to fracture is not solely due to bone mass but relies also on bone ECM material properties, i.e. the quality of the bone matrix component. Here, we introduce the first-in-class unimolecular dual GIP/GLP-2 analogues, GL-0001, that activate simultaneously the glucose-dependent insulinotropic polypeptide receptor (GIPr) and the glucagon-like peptide-2 receptor (GLP-2r). GL-0001 acts synergistically through a cAMP-LOX pathway to enhance collagen maturity. Furthermore, in mice with ovariectomy-induced bone fragility, GL-0001 prevented excess trabecular bone degradation at the appendicular skeleton and also enhanced bone ECM material properties through reduction of the degree of mineralization and augmentation in enzymatic collagen crosslinking. These results demonstrate that targeting bone ECM material properties is a viable option to enhance bone strength and opens an innovative pathway for the treatment of patients suffering of bone fragility.
Contribution of Signaling Partner Association to Strigolactone Receptor Selectivity
Authors: Chen Jiming , Shukla Diwakar
Published: July 2022

The parasitic plant witchweed, or Striga hermonthica, results in agricultural losses of billions of dollars per year. It perceives its host via plant hormones called strigolactones, which acts as a germination stimulant for witchweed. Strigolactone signaling involves substrate binding to the strigolactone receptor followed by substrate hydrolysis and a conformational change from an inactive, or open state, to an active, or closed state. While in the active state, the receptor associates with a signaling partner, MAX2. Recently, it was shown that this MAX2 association process acts as a strong contributor to the uniquely high signaling activity observed in ShHTL7, however, it is unknown why ShHTL7 has enhanced MAX2 association affinity. Using an umbrella sampling molecular dynamics approach, we characterized the association processes of At D14, ShHTL7, a mutant of ShHTL7, and ShHTL6 with MAX2 homolog OsD3. From these results, we show that ShHTL7 has an enhanced standard binding free energy of OsD3 compared to the other receptors. Additionally, our results suggest that the overall topology of the T2-T3 helix region is likely an important modulator of MAX2 binding. Thus, differences in MAX2 association, modulated by differences in the T2-T3 helix region, are a contributor to differences in signaling activity between different strigolactone receptors.
Pressure-driven perfusion system to control, multiplex and recirculate cell culture medium for Organs-on-Chips
Authors: de Graaf Mees N. S. , Vivas Aisen , van der Meer Andries D. , Mummery Christine L. , Orlova Valeria V.
Published: July 2022

Organ-on-Chip (OoC) devices are increasingly used to mimic the tissue microenvironment of cells in intact organs. This includes microchannels to mimic, for example, fluidic flow through vessels. Present methods for controlling microfluidic flow in these systems rely on gravity, rocker systems or external pressure pumps. For many purposes, pressure pumps give the most consistent flow profiles but they are not well-suited for high throughput as might be required for testing drug responses. Here, we describe a method which allows multiplexing of microfluidic channels in OoC devices plus the accompanying custom software necessary to run the system. Moreover, we show the approach is also suited to for recirculation of culture medium, an essential cost consideration when expensive culture reagents are used that are not “spent” through uptake by the cells during transient unidirectional flow.
Diffusion MRI Head Motion Correction Methods are Highly Accurate but Impacted by Denoising and Sampling Scheme
Authors: Cieslak Matthew , Cook Philip A. , Tapera Tinashe M. , Radhakrishnan Hamsanandini , Elliott Mark , Roalf David R. , Oathes Desmond J. , Bassett Dani S. , Tisdall M. Dylan , Rokem Ariel , Grafton Scott T. , Satterthwaite Theodore D.
Published: July 2022

Correcting head motion artifacts in diffusion-weighted MRI (dMRI) scans is particularly challenging due to the dramatic changes in image contrast at different gradient strengths and directions. Head motion correction is typically performed using a Gaussian Process model implemented in FSL’s Eddy. Recently, the 3dSHORE-based SHORELine method was introduced to correct any dMRI sequence that has more than one shell. Here we perform a comprehensive evaluation of both methods on realistic simulations of a software fiber phantom that provides known ground-truth head motion. We demonstrate that both methods perform remarkably well, but that performance can be impacted by sampling scheme, the pervasiveness of head motion, and the denoising strategy applied before head motion correction. Our study also provides an open and fully-reproducible workflow that could be used to accelerate evaluation studies of other dMRI processing methods in the future.

HIGHLIGHTS

Both Eddy and SHORELine head motion correction methods performed quite well on a large variety of simulated data

Denoising with MP-PCA can improve head motion correction performance when Eddy is used

SHORELine effectively corrects motion in non-shelled acquisitions
The APE2 nuclease is essential for DNA double strand break repair by microhomology-mediated end-joining
Authors: Fleury Hubert , MacEachern Myles K. , Stiefel Clara M. , Anand Roopesh , Sempeck Colin , Nebenfuehr Benjamin , Dodd Benjamin , Taylor Erin , Dansoko Djelika , Ortega Raquel , Leung Justin W. , Boulton Simon J. , Arnoult Nausica
Published: July 2022

Microhomology-mediated end-joining (MMEJ) is an intrinsically mutagenic pathway of DNA double strand break repair essential for proliferation of homologous recombination (HR) deficient tumors. While targeting MMEJ has emerged as a powerful strategy to eliminate HR-deficient (HRD) cancers, this is limited by an incomplete understanding of the mechanism and factors required for MMEJ repair. Here, we identify the APE2 nuclease as a novel MMEJ effector. We show that loss of APE2 blocks the fusion of deprotected telomeres by MMEJ and inhibits MMEJ in DNA repair reporter assays to levels comparable to Pol Theta suppression. Mechanistically, we demonstrate that APE2 possesses intrinsic flap-cleaving activity, that its MMEJ function in cells depends on its nuclease domain and further identify uncharacterized domains required for recruitment to damaged DNA. We conclude that HR-deficient cells are addicted to APE2 due to a previously unappreciated role in MMEJ, which could be exploited in the treatment of cancer.
High-resolutionde novostructure prediction from primary sequence
Authors: Wu Ruidong , Ding Fan , Wang Rui , Shen Rui , Zhang Xiwen , Luo Shitong , Su Chenpeng , Wu Zuofan , Xie Qi , Berger Bonnie , Ma Jianzhu , Peng Jian
Published: July 2022

Recent breakthroughs have used deep learning to exploit evolutionary information in multiple sequence alignments (MSAs) to accurately predict protein structures. However, MSAs of homologous proteins are not always available, such as with orphan proteins or fast-evolving proteins like antibodies, and a protein typically folds in a natural setting from its primary amino acid sequence into its three-dimensional structure, suggesting that evolutionary information and MSAs should not be necessary to predict a protein’s folded form. Here, we introduce OmegaFold, the first computational method to successfully predict high-resolution protein structure from a single primary sequence alone. Using a new combination of a protein language model that allows us to make predictions from single sequences and a geometry-inspired transformer model trained on protein structures, OmegaFold outperforms RoseTTAFold and achieves similar prediction accuracy to AlphaFold2 on recently released structures. OmegaFold enables accurate predictions on orphan proteins that do not belong to any functionally characterized protein family and antibodies that tend to have noisy MSAs due to fast evolution. Our study fills a much-encountered gap in structure prediction and brings us a step closer to understanding protein folding in nature.
ZAXINONE SYNTHASE 2 regulates growth and arbuscular mycorrhizal symbiosis in rice
Authors: Ablazov Abdugaffor , Votta Cristina , Fiorilli Valentina , Wang Jian You , Aljedaani Fatimah , Jamil Muhammad , Balakrishna Aparna , Balestrini Raffaella , Liew Kit Xi , Rajan Chakravarthy , Berqdar Lamis , Blilou Ikram , Lanfranco Luisa , Al-Babili Salim
Published: July 2022

Carotenoid cleavage, catalyzed by CAROTENOID CLEAVAGE DIOXYGENASES (CCDs), provides signaling molecules and precursors of plant hormones. Recently, we showed that zaxinone, a novel apocarotenoid metabolite formed by the CCD Zaxinone Synthase (ZAS), is a growth regulator required for normal rice growth and development. The rice genome encodes three OsZAS homologs, called here OsZAS1b, OsZAS1c, and OsZAS2, with unknown functions. Here, we investigated the enzymatic activity, expression pattern, and subcellular localization of OsZAS2, and generated and characterized loss-of-function CRISPR/Cas9-Oszas2 mutants. We show that OsZAS2 formed zaxinone in vitro. OsZAS2 is a plastid-localized enzyme mainly expressed in the root cortex under phosphate starvation. Moreover, OsZAS2 expression increased during mycorrhization, specifically in arbuscule-containing cells. Oszas2 mutants contained lower zaxinone content in roots and exhibited reduced root and shoot biomass, less productive tiller, and higher strigolactone (SL) levels. Exogenous zaxinone application repressed SL biosynthesis and partially rescued the growth retardation of Oszas2 mutant. Consistent with the OsZAS2 expression pattern, Oszas2 mutants displayed a lower frequency of AM colonization. In conclusion, OsZAS2 encodes a further zaxinone-forming enzyme that determines rice growth and architecture and strigolactone content and is required for optimal mycorrhization.
Population genomics ofXenopus laevisin southern Africa
Authors: Premachandra Tharindu , Cauret Caroline M. S. , Conradie Werner , Measey John , Evans Ben J.
Published: July 2022

Allotetraploid genomes have two distinct genomic compartments called subgenomes that are derived from separate diploid ancestral species. Many genomic characteristics such as gene function, expression, recombination, and transposable element mobility may differ significantly between subgenomes. To explore the possibility that subgenome population structure and gene flow may differ as well, we examined genetic variation in an allotetraploid frog – the African clawed frog (Xenopus laevis) – over the dynamic and varied habitat of its native range in southern Africa. Using reduced representation genome sequences from 91 samples from 12 localities, we found no strong evidence that population structure and gene flow differed substantially by subgenome. We then compared patterns of population structure in the nuclear genome to the mitochondrial genome using Sanger sequences from 455 samples from 183 localities. Our results provide further resolution to the geographic distribution of mitochondrial and nuclear diversity in this species and illustrate that population structure in both genomes corresponds roughly with variation in seasonal rainfall and with the topography of the southern Africa.
Durability of the Neutralizing Antibody Response to mRNA Booster Vaccination Against SARS-CoV-2 BA.2.12.1 and BA.4/5 Variants
Authors: Qu Panke , Faraone Julia N. , Evans John P. , Zheng Yi-Min , Carlin Claire , Lozanski Gerard , Saif Linda J. , Oltz Eugene M. , Gumina Richard J. , Liu Shan-Lu
Published: July 2022

The recent emergence of the SARS-CoV-2 BA.4/5 and BA.2.12.1 variants has led to rising COVID-19 case numbers and concerns over the continued efficacy of mRNA booster vaccination. Here we examine the durability of neutralizing antibody (nAb) responses against these SARS-CoV-2 Omicron subvariants in a cohort of health care workers 1-40 weeks after mRNA booster dose administration. Neutralizing antibody titers fell by ∼1.5-fold 4-6 months and by ∼2.5-fold 7-9 months after booster dose, with average nAb titers falling by 11-15% every 30 days, far more stable than two dose induced immunity. Notably, nAb titers from booster recipients against SARS-CoV-2 BA.1, BA.2.12.1, and BA.4/5 variants were ∼4.7-, 7.6-, and 13.4-fold lower than against the ancestral D614G spike. However, the rate of waning of booster dose immunity was comparable across variants. Importantly, individuals reporting prior infection with SARS-CoV-2 exhibited significantly higher nAb titers compared to those without breakthrough infection. Collectively, these results highlight the broad and stable neutralizing antibody response induced by mRNA booster dose administration, implicating a significant role of virus evolution to evade nAb specificity, versus waning humoral immunity, in increasing rates of breakthrough infection.
Human Brain Development: a cross-sectional and longitudinal study integrating multiple neuromorphological features
Authors: Kalantar-Hormozi Hadis , Patel Raihaan , Dai Alyssa , Ziolkowski Justine , Dong Hao-Ming , Holmes Avram , Raznahan Armin , Devenyi Gabriel A. , Chakravarty M. Mallar
Published: July 2022

Brain maturation studies typically examine relationships linking a single morphometric feature with aspects of cognition, behavior, age, or other demographic characteristics. However, the coordinated spatiotemporal arrangement of morphological features across development and their associations with behavior are unclear. Here, we examine covariation across multiple cortical features (cortical thickness [CT], surface area [SA], local gyrification index [GI], and mean curvature [MC]) using magnetic resonance images from the long-running National Institute of Mental Health developmental cohort (ages 5-25). Neuroanatomical covariance was examined using non-negative matrix factorization (NMF), which decomposes covariance resulting in a parts-based representation. Cross-sectionally, we identified six components of covariation which demonstrate differential contributions of CT, GI, and SA in hetero- vs. unimodal areas. We sought to use this technique longitudinally to examine covariance in rates of change, which highlighted a preserved SA in unimodal areas and changes in CT and GI in heteromodal areas. Using behavioral partial least squares (PLS), we identified a single latent variable (LV; 96 % covariance explained) that recapitulated patterns of reduced CT, GI, and SA that are generally related to older age, with limited contributions of IQ and SES. Longitudinally, PLS revealed three LVs that demonstrated a nuanced developmental pattern that highlighted a higher rate of maturational change in SA and CT in higher IQ and SES females. This novel characterization of brain maturation provides an important understanding of the interdependencies between morphological measures, their coordinated development, and their relationship to biological sex, cognitive ability, and the resources of the local environment.

Significance

The complex anatomy of the cortical sheet is best characterized using multiple morphometric characteristics. We expanded on recent developments in matrix factorization to identify spatial patterns of covariance across the cortical sheet. Using a large, well-characterized dataset, we examined the differential contributions of neuroanatomical features to cortical covariation in a single analytical framework using both cross-sectional and longitudinal data. We identified dominant modes of covariance between cortical morphometric features and their coordinated pattern of change, demonstrating sexually differentiated patterns and a strong association with variability in age, socioeconomic status, and cognitive ability. This novel characterization of cortical morphometry provides an important understanding of the interdependencies between neuroanatomical measures in the brain and behavioral development context.
IMC-Denoise: a content aware denoising pipeline to enhance Imaging Mass Cytometry
Authors: Lu Peng , Oetjen Karolyn A. , Bender Diane E. , Ruzinova Marianna B. , Fisher Daniel A.C. , Shim Kevin G. , Pachynski Russell K. , Brennen W. Nathaniel , Oh Stephen T. , Link Daniel C. , Thorek Daniel L.J.
Published: July 2022

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments that has the ability to detect the spatial distribution of at least 40 cell markers. However, this new modality has unique image data processing requirements, particularly when applying this technology to patient tissue specimens. In these cases, signal-to-noise ratio for particular markers can be low despite optimization of staining conditions, and the presence of pixel intensity artifacts can deteriorate image quality and the subsequent performance of downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images. Specifically, we deploy a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for filtering shot noise (DeepSNF). IMC-Denoise outperforms existing methods for adaptive hot pixel removal, and delivers significant image quality improvement and background noise removal to a diverse set of IMC channels and datasets. This includes a unique, technically challenging, human bone marrow IMC dataset; in which we achieve noise level reduction of 87% for a 5.6-fold higher contrast-to-noise ratio, and more accurate background noise removal with approximately two-fold improved F1 score. Our approach remarkably enhances both manual gating and automated phenotyping with cell-scale down-stream analysis on these complex data. We anticipate that IMC-Denoise will provide similar benefits in mass cytometry imaging domains to more deeply characterize the complex and diverse tissue microenvironment.
Encoding of hunger by the neuronal epigenome slows aging in Drosophila
Authors: Weaver KJ , Holt RA , Henry E , Pletcher SD
Published: July 2022

Hunger is, by necessity, an ancient motivational drive, yet the molecular nature of homeostatic pressures of this sort and how they modulate health and physiology are largely unknown. Here we show that the molecular encoding of hunger slows aging in Drosophila. We identify the branched-chain amino acids (BCAAs) as dietary hunger signals that extend lifespan despite increasing food intake when reduced, and in parallel show that optogenetic activation of a subset of hunger-promoting neurons is sufficient to recapitulate these effects. We find that remodeling of the neuronal histone acetylome is associated with dietary BCAA reduction, and that this requires BCAA metabolism in specific subsets of neurons. Preventing the histone acetylome from being molded by dietary BCAAs abrogates both increased feeding and extended lifespan. However, the mechanisms that promote feeding and modulate aging downstream of alterations in histone acetylation occur through spatially and temporally distinct responses; differential usage of the histone variant H3.3A in the brain is an acute response to hunger that promotes increased feeding without modulating lifespan, while a prolonged experience of hunger may slow aging by promoting a beneficial decrease of a set-point around which hunger levels are regulated. Identification of a molecular basis for the encoding of hunger and demonstration of its sufficiency in extending lifespan reveals that motivational states alone are deterministic drivers of aging and behavior.
TLR4 regulates proinflammatory intestinal immune responses mediated by an atopic gut microbiota
Authors: Campbell Evelyn , Maccio-Maretto Lisa , Hesser Lauren A. , Kemter Andrea M. , Canani Roberto Berni , Nocerino Rita , Paparo Lorella , Patry Robert T. , Nagler Cathryn R.
Published: July 2022

The increasing prevalence of food allergies has been causally associated with the depletion of allergy protective intestinal bacteria. However, few studies have investigated the role of the gut microbiota in promoting allergic responses. In a cohort of infants affected by cow’s milk allergy (CMA), we have identified a patient with a proinflammatory and atopic microbiota. In comparison to a healthy microbiota, this CMA-associated gut microbiota has increased abundance of Bacteroidetes, a Gram-negative phylum of bacteria that has been associated with increased incidence of allergy. Using this microbiota, we investigated the host-microbe interactions that mediate these intestinal inflammatory responses. To examine these interactions, we used mice with global and conditional abrogation in TLR4 signaling, since Gram- negative bacteria signal through this receptor via membrane-derived lipopolysaccharide (LPS). We show that this donor’s microbiota induces expression of serum amyloid A1 (Saa1) and other Th17-, B cell-, and Th2-associated genes in the ileal epithelium. Accordingly, this microbiota also induces Th17 cells, as well as regulatory T cell populations and fecal IgA. Importantly, we used both antibiotic treated SPF and rederived germ-free mice with a conditional mutation of TLR4 in the CD11c+compartment to demonstrate that the induction of proinflammatory genes, fecal IgA, and Th17 cells is dependent on TLR4 signaling. Furthermore, metagenomic sequencing revealed that the CMA-associated gut microbiota also has increased abundance of LPS biosynthesis genes. Lastly, upon sensitization with β-lactoglobulin, this CMA microbiota induces a TLR4-dependent mixed type 2/type 3 response in innate lymphoid cells (ILCs) during the early phases of allergic sensitization. Taken together, our results show that a Bacteroidetes-enriched microbiota with increased abundance of LPS genes promotes proinflammatory gene expression and a mixed type 2/type 3 response in a subset of infants with cow’s milk allergy.

Paper Highlights

A cow’s milk allergy (CMA)-associated gut microbiota has an enrichment of Bacteroidetes, which is associated with atopy

The CMA-associated gut microbiota promotes intestinal inflammation, which includes inflammatory gene expression, induction of Th17 cells, and production of IgA

Proinflammatory responses induced by the CMA-associated gut microbiota are dependent on TLR4 signaling in various cellular compartments

Upon sensitization, the CMA-associated gut microbiota induces an innate mixed type 2/type 3 inflammatory response