bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources of Resistance, Effect of Maturity Groups, and Marker-Trait Associations Associated with Fusarium graminearum Causing Root Rot of Soybean (Glycine max)
Authors: Okello Paul , Solanki Shyam , Rafi Nitha , Mathew Febina M.
Published: April 2023

Fusarium graminearum Schwabe is an important fungus causing root rot of soybean ( Glycine max L.) in the United States. In this study, 248 accessions (including the susceptible check ‘Williams 82’) from the United States Department of Agriculture germplasm collection (maturity group [MG] 0 to V) were screened with a single isolate of F. graminearum using the inoculum layer inoculation method in the greenhouse to identify resistant parental materials. Disease severity was evaluated 21 days postinoculation on a 1-to-5 rating scale and expressed as relative treatment effects (RTEs). Eight accessions (PI437949, PI438292, PI612761A, PI438094B, PI567301B, PI408309, PI361090, and P188788) had significantly lower RTEs when compared with Williams 82 based on 95% confidence intervals. Furthermore, the effect of MGs on disease severity was assessed, and accessions belonging to MG 0 or I had significantly greater RTEs than cultivars belonging to MGs II to V based on 95% confidence intervals. A genome-wide association study analysis was conducted using 42,079 single-nucleotide markers, and six marker-trait associations were identified that may be novel sources of F. graminearum resistance. The identification of new resistant parental materials and MTAs associated with resistance to F. graminearum will be useful in breeding programs for developing resistant cultivars.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Genome Sequencing of Strain Vm263, a Hypotoxic Strain of Valsa mali Causing Apple Valsa Canker
Authors: Li Dong-Shan , Guo Jia-Chen , Wang Ya-Nan , Hu Tong-Le , Cao Ke-Qiang , Wang Shu-Tong , Meng Xiang-Long
Published: April 2023

Apple valsa canker, caused by Valsa mali, has seriously endangered the sustainable development of the apple industry in China. Our previous study revealed that low-temperature induction increased the pathogenicity of strain Vm263, which is a hypotoxic strain of V. mali causing apple valsa canker. However, the regulatory mechanism of this phenomenon was still unclear. In this study, whole genome sequencing of strain Vm263 was performed using a combination of long-read single-molecule real-time sequencing technology (Pacific Biosciences) and MGISEQ sequencing. The genome size of strain Vm263 was 42.83 Mb and the assembly N50 was 5.09 Mb. The genome provides a valuable resource for facilitating our understanding of the response of V. mali to low temperature.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
How Consistent are International Rotations Between Plastic Surgery Training Programs?
Authors: Reddy Narainsai K. , Sasson Daniel C. , Wester James R. , Gosain Arun K.
Published: April 2023

Introduction:

Institutional partnerships between plastic surgery residency programs in the United States and providers in low- and middle-income countries can serve as bilateral and longitudinal capacity-building relationships. In the United States, obtaining approval for international rotations by a home institution and national review committee is highly encouraged but not required before resident international engagement. Acquiring approval at the institutional level is the first step to allow trainees to participate in international rotations on elective time rather than on vacation time. National approval through the American Council of Graduate Medical Education and American Board of Plastic Surgery allows cases to count toward the resident’s yearly case log.

Methods:

All 101 integrated and independent plastic surgery program directors/coordinators were asked to participate. The survey identified the requirements and details of existing international rotations.

Results:

In total, 57 programs responded (56% response rate) to the survey. An estimated 54% of all programs offered international rotations to their residents, and 94% of these programs obtained institutional approval. Additionally, 69% of these programs have received national approval.

Conclusions:

Institutional requirements for programs to provide international rotations vary significantly across institutions, which results in disparate experiences for residents and poses potential risks to international partners. This study will help promote transparency regarding international rotation requirements and better equip faculty to enhance international rotations that cater to the needs of the institution, residents, and most importantly, the host countries.
Acute effects of high-intensity resistance training on central blood pressure parameters of elderly hypertensive women: a crossover clinical trial
Authors: Galvão Luan , Póvoa Thaís Inácio Rolim , Jardim Paulo César Veiga , Lima Ana Luiza , Barroso Weimar Kunz Sebba , Seguro Camila Simões , Gentil Paulo , Jardim Thiago Veiga
Published: April 2023

Objective:

Assess the acute effects of a high-intensity resistance training session on central blood pressure (CBP) parameters of elderly hypertensive women.

Methods:

Forty physically active hypertensive women were included in resistance training and control protocols. Resistance training exercises were bench press, leg press and lat pull-down. The resistance training protocol consisted of three sets of 10 repetitions to volitional failure with 90 s of rest between sets. No exercise was performed in the control protocol. CBP parameters were measured in four moments: before (PRE), immediately after (T0), 30 min (T30) and 60 min (T60) following both protocols.

Results:

Resistance training significantly increased central SBP (cSBP) 107.4 ± 16.3 vs. 117.5 ± 16.7), augmentation index ((24.9 ± 12.7 vs. 33.1 ± 12.0), pulse wave velocity (PWV 9.7 ± 1.0 vs. 10.3 ± 1.1), peripheral pulse pressure (pPP 48.5 ± 11.7 vs. 58.9 ± 13.1), central pulse pressure (cPP 38.3 ± 11.6 vs. 46.5 ± 13.1) and amplified pulse pressure (ampPP 10.2 ± 4.2 vs. 12.4 ± 5.6) immediately after exercises. The comparison between groups showed higher values of cSBP (117.5 ± 16.7 vs. 106.3 ± 14.6), augmentation index (20.9 ± 11.0 vs. 33.1 ± 12.0), pPP (46.6 ± 11.0 vs. 58.9 ± 13.1) and cPP (36 ± 10.2 vs. 46.5 ± 13.1) at T0. After 30 min, all variables returned to the baseline values.

Conclusion:

High-intensity resistance training session increased CBP parameters immediately after exercises, but those changes were not sustained after 30 min.
Impaired β2-adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019
Authors: Faconti Luca , Farukh Bushra , McNally Ryan J. , Brett Sally , Chowienczyk Phil J.
Published: April 2023

Aim:

The pulse wave response to salbutamol (PWRS) – change in augmentation index (AIx) – provides a means to assess endothelial vasodilator function in vivo. Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown.

Methods:

Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample.

Results:

One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls (n = 34) and those recovered from mild symptoms of COVID-19 (n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] −2.85 [−5.52, −0.188] %, −2.32 [−5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively (P = 0.001). In a sub-sample (n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [−2.15,2.24] vs. −3.96 [−7.01. −2.18], P = 0.006) with no significant difference between hospitalized (n = 12) and nonhospitalized participants (n = 10).

Conclusions:

In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Graphical abstract:

http://links.lww.com/HJH/C164
How Physician Self-Perceptions Affect the Impact of Peer Comparison Feedback on Opioid Prescribing
Authors: Liao Joshua M. , Sun Chuxuan , Yan Xiaowei S , Patel Mitesh S. , Small Dylan S. , Isenberg William M. , Landa Howard M. , Bond Barbara L. , Rareshide Charles A.L. , Volpp Kevin G. , Delgado M. Kit , Lei Victor J. , Shen Zijun , Navathe Amol S.
Published: April 2023

Peer comparison feedback is a promising strategy for reducing opioid prescribing and opioid-related harms. Such comparisons may be particularly impactful among underestimating clinicians who do not perceive themselves as high prescribers relative to their peers. But peer comparisons could also unintentionally increase prescribing among overestimating clinicians who do not perceive themselves as lower prescribers than peers. The objective of this study was to assess if the impact of peer comparisons varied by clinicians’ preexisting opioid prescribing self-perceptions. Subgroup analysis of a randomized trial of peer comparison interventions among emergency department and urgent care clinicians was used. Generalized mixed-effects models were used to assess whether the impact of peer comparisons, alone or combined with individual feedback, varied by underestimating or overestimating prescriber status. Underestimating and overestimating prescribers were defined as those who self-reported relative prescribing amounts that were lower and higher, respectively, than actual relative baseline amounts. The primary outcome was pills per opioid prescription. Among 438 clinicians, 54% (n = 236) provided baseline prescribing self-perceptions and were included in this analysis. Overall, 17% (n = 40) were underestimating prescribers whereas 5% (n = 11) were overestimating prescribers. Underestimating prescribers exhibited a differentially greater decrease in pills per prescription compared to nonunderestimating clinicians when receiving peer comparison feedback (1.7 pills, 95% CI, −3.2 to −0.2 pills) or combined peer and individual feedback (2.8 pills, 95% CI, −4.8 to −0.8 pills). In contrast, there were no differential changes in pills per prescription for overestimating versus nonoverestimating prescribers after receiving peer comparison (1.5 pills, 95% CI, −0.9 to 3.9 pills) or combined peer and individual feedback (3.0 pills, 95% CI, −0.3 to 6.2 pills). Peer comparisons were more impactful among clinicians who underestimated their prescribing compared to peers. By correcting inaccurate self-perceptions, peer comparison feedback can be an effective strategy for influencing opioid prescribing.
Definition and measurement of alcohol-associated insight in early liver transplantation for acute alcohol-associated hepatitis: A systematic review
Authors: Winder Gerald Scott , Clifton Erin G. , Fernandez Anne C. , MacEachern Mark , Andrews Sarah , Perumalswami Ponni , DiMartini Andrea F. , Mellinger Jessica L.
Published: April 2023

Background:

Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are challenging because they rely on detailed psychosocial assessments and interpretations of psychiatric and substance use disorder data, which often must occur rapidly according to the acuity of end-stage liver disease. Such difficulties commonly occur during the process of candidate selection and liver allocation, particularly during early LT (eLT) in patients with acute alcohol-associated hepatitis (AAH). Patients with AAH commonly have very recent or active substance use, high short-term mortality, psychiatric comorbidities, and compressed evaluation and treatment timetables. LT clinicians report that patients’ alcohol-associated insight (AAI) is among the most relevant psychosocial data in this population, yet no studies exist examining how LT teams define and use AAI in eLT or its effect on clinical outcomes. In April 2022, we searched Ovid MEDLINE, Elsevier Embase, EBSCOhost PsycInfo and CINAHL, and Wiley Cochrane Central Register of Controlled Trials for reports describing AAH populations who underwent eLT, which also described psychosocial evaluation parameters. The searches retrieved 1603 unique reports. After eligibility screening, 8 were included in the qualitative analysis. This systematic review reveals that AAI is a poorly defined construct that is not measured in a standardized way. Yet it is a commonly cited parameter in articles that describe the psychosocial evaluation and decision-making of patients undergoing eLT for AAH. This article also discusses the general challenges of assessing AAI during eLT for AAH, existing AAI definitions and rating scales, how AAI has been used to date in the broader hepatology and LT literature, and future areas for clinical and research progress.
Venous Invasion in Pancreatic Neuroendocrine Tumors Is Independently Associated With Disease-free Survival and Overall Survival
Authors: Shi Chanjuan , Chen Wei , Davis Richard , Morse Michael A.
Published: April 2023

In this study, we evaluated venous invasion and its association with survival in patients with resected pancreatic neuroendocrine tumor (PanNET). Surgical Pathology Archives were searched for pancreatectomies performed for PanNET between October 1, 2005, and December 31, 2019. Hematoxylin and eosin (H&E)-stained slides were evaluated for venous invasion, and Movat’s stain was performed in all cases with no venous invasion detected on H&E stains. Pathology reports and electronic medical records were also reviewed. Venous invasion was identified in 23 of 145 (15.9%) cases on H&E stains, and Movat’s stain identified additional 34 cases with venous invasion (39.3% overall). Orphan arteries with adjacent well-defined tumor nodules or subtle hyalinizing nodules in hyalinizing tumors are highly specific for venous invasion. In stage I-III cases (n=122), venous invasion was associated with larger tumor size, higher World Health Organization (WHO) tumor grade, perineural invasion, extrapancreatic extension, lymph node metastasis, and liver metastasis (P<0.05). In univariate analyses, tumor size, WHO grade, venous invasion, perineural invasion, T stage, and lymph node metastasis all correlated with disease-free survival; however, only venous invasion was associated with worse disease-free survival in multivariate analyses (P<0.01). In all-stage cases, venous invasion was the only attributor associated with worse overall survival in multivariate analyses (P=0.03). In summary, venous invasion in PanNET can be histologically subtle, and Movat’s stain can greatly increase the detection rate. More importantly, enhanced venous invasion by Movat’s stain correlates independently with disease-free survival in patients with stage I-III tumors and overall survival in all-stage patients.
Recent Advancements in Computed Tomography Assessment of Fibrotic Interstitial Lung Diseases
Authors: Suman Garima , Koo Chi Wan
Published: April 2023

Interstitial lung disease (ILD) is a heterogeneous group of disorders with complex and varied imaging manifestations and prognosis. High-resolution computed tomography (HRCT) is the current standard-of-care imaging tool for ILD assessment. However, visual evaluation of HRCT is limited by interobserver variation and poor sensitivity for subtle changes. Such challenges have led to tremendous recent research interest in objective and reproducible methods to examine ILDs. Computer-aided CT analysis to include texture analysis and machine learning methods have recently been shown to be viable supplements to traditional visual assessment through improved characterization and quantification of ILDs. These quantitative tools have not only been shown to correlate well with pulmonary function tests and patient outcomes but are also useful in disease diagnosis, surveillance and management. In this review, we provide an overview of recent computer-aided tools in diagnosis, prognosis, and longitudinal evaluation of fibrotic ILDs, while outlining some of the pitfalls and challenges that have precluded further advancement of these tools as well as potential solutions and further endeavors.
Bycatch mitigation in the West Greenland lumpfish (
Cyclopterus lumpus
) fishery using modified gillnets
Authors: Post Søren , Merkel Flemming , Bak-Jensen Zita , Koch Christoffer , Hedeholm Rasmus Berg
Published: April 2023

Bycatch in gillnets is a global issue and mitigation measures that balance target species catch rates, bycatch reduction and fisher support are scarce. In the North Atlantic lumpfish fisheries, bycatch includes marine mammals and seabirds, and there are no permanent technical initiatives to reduce the bycatch. In the West Greenland fishery, common eider bycatch is several thousand individuals annually. We explored if bycatch in this fishery could be reduced by modifying standard lumpfish gillnets by adding a 45 cm high small-meshed net panel to the bottom part of the net. We tested the nets in combination with standard nets and estimated catch rates in a controlled setting in 2021 and in the commercial fishery in 2022. The modified nets had a 71% reduced bycatch rate for common eider and a 25% reduced catch rate for female lumpfish. A combination of the panel and increased seaweed entanglement was the most likely explanation for the effect. In addition to the effect of the net modification, the common eider bycatch decreased significantly during the season, and we recommend studying the net effect further and exploring the option of postponing the fishing season as a simpler way of reducing bycatch.
Cell polarity linked to gravity sensing is generated by protein translocation from statoliths to the plasma membrane
Authors: Nishimura Takeshi , Mori Shogo , Shikata Hiromasa , Nakamura Moritaka , Hashiguchi Yasuko , Abe Yoshinori , Hagihara Takuma , Yoshikawa Hiroshi Y. , Toyota Masatsugu , Higaki Takumi , Morita Miyo Terao
Published: April 2023

Organisms have evolved under the gravitational force and sense the direction of gravity via statoliths in specialized cells. In the gravitropism of flowering plants, the starch-accumulating plastids, amyloplasts, in gravity sensing cells act as statoliths. The gravity sensing mechanism has long been considered a mechanosensing process by which amyloplasts transmit forces to intracellular structures, but the molecular support has not been reported. This study revealed that LAZY1-LIKE family proteins involved in gravity signaling in statocytes are localized to the amyloplast periphery and its proximal plasma membrane, resulting in polar localization according to the direction of gravity. We propose a gravity sensing mechanism by which LZY transmits the positional information of amyloplasts, i.e., the direction of gravity, by translocating to the plasma membrane.
Evaluation of Xpert®MTB/XDR test for susceptibility testing ofMycobacterium tuberculosisto first and second-line drugs in Uganda
Authors: Katamba Achilles , Ssengooba Willy , Sserubiri James , Semugenze Derrick , William Kasule George , Abdunoor Nyombi , Byaruhanga Raymond , Turyahabwe Stavia , Joloba Moses L
Published: April 2023

Background

Drug-Resistant Tuberculosis (DR-TB) is one of the key challenges toward TB control. There is an urgent need for rapid and accurate drug susceptibility tests (DST) for the most commonly used 1stand 2ndline TB drugs.

Design and Methods

In a blinded, laboratory-based cross-sectional study, we set out to validate the performance of the Xpert®MTB/XDR test for DST ofM. tuberculosis. Sputum samples or culture isolates collected between January 2020 and December 2021 from patients with rifampicin resistance –TB and/or with higher suspicion index for isoniazid (INH) resistance and/or 2ndline fluoroquinolones (FQ) and injectable agents (IAs) were tested using the Xpert®MTB/XDR test from 11/September 2021 to 26/May /2022. Diagnostic accuracy and factors for laboratory uptake of Xpert®MTB/XDR test were compared to MGIT960 and the Hain Genotype® MTBDRplusand MDRsl assays (LPA) as reference DST methods.

Results

A total of 100 stored sputum samples were included in this study. Of the samples tested using MGIT960, 65/99 (65.6%) were resistant to INH, 5/100 (5.0%) resistant to FQ and none were resistant to IAs. The sensitivity and specificity, n (%; 95%Confidence Interval, CI) of Xpert®MTB/XDR test for; INH were 58 (89.2; 79.1-95.5) and 30 (88.2; 72.5-96.6), FQ; 4 (80.0; 28.3-99.4) and 95 (100; 96.2-100), respectively. The specificity for AIs was 100 (100; 96.3-100).

Using LPA as a reference standard, a total of 52/98 (53.1%) were resistant to INH, 3/100 (3.0%) to FQ, and none to IA. The sensitivity and specificity, n (%; 95%CI) of Xpert®MTB/XDR test compared to LPA for; INH was 50 (96.1; 86.7-99.5) and 34 (74.0; 58.8-85.7) and FQ 3 (100; 29.2-100) and 96 (99.0; 94.3-99.9) respectively. The specificity of IAs was 96 (100; 96.2-100).

The factors for laboratory uptake and roll-out included; no training needed for technicians with previous Xpert-ultra experience and one day for those without, recording and reporting needs were not different from those of Xpert ultra, the error rate was 4/100 (4%), no uninterpretable results reported, test turn-around-time was 1hr/45 minutes and workflow similar to that of the Xpert-ultra test.

Conclusion

There is high sensitivity and specificity of Xpert®MTB/XDR test for isoniazid, fluoroquinolones, and Injectable agents. There are acceptable Xpert®MTB/XDR test attributes for test uptake and roll-out.
Stricturing Crohn’s disease single-cell RNA sequencing reveals fibroblast heterogeneity and intercellular interactions
Authors: Mukherjee Pranab K. , Nguyen Quang Tam , Li Jiannan , Zhao Shuai , Christensen Stephen M. , West Gail A. , Chandra Jyotsna , Gordon Ilyssa O. , Lin Sinan , Wang Jie , Mao Ren , Czarnecki Douglas , Rayan Carla , Kotak Prerna , Plesec Thomas , Lal Samir , Fabre Thomas , Asano Shoh , Bound Kathryn , Hart Kevin , Park Chanyoung , Martinez Robert , Dower Ken , Wynn Thomas A. , Hu Shaomin , Naydenov Nayden , Decaris Martin , Turner Scott , Holubar Stefan D. , Steele Scott R. , Fiocchi Claudio , Ivanov Andrei I. , Kravarik Kellie M. , Rieder Florian
Published: April 2023

Background

Fibroblasts play a key role in stricture formation in Crohn’s disease (CD) but understanding it’s pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation.

Methods

We performed scRNAseq of 13 fresh full thickness CD resections containing non-involved, inflamed non-strictured, and strictured segments as well as 7 normal non-CD bowel segments. Each segment was separated into mucosa/submucosa or muscularis propria and analyzed separately for a total of 99 tissue samples and 409,001 cells. We validated cadherin-11 (CDH11) as a potential therapeutic target by using whole tissues, isolated intestinal cells, NanoString nCounter, next generation sequencing, proteomics and animal models.

Results

Our integrated dataset revealed fibroblast heterogeneity in strictured CD with the majority of stricture-selective changes detected in the mucosa/submucosa, but not the muscle layer. Cell-cell interaction modeling revealed CXCL14+ as well as MMP/WNT5A+ fibroblasts displaying a central signaling role in CD strictures. CDH11, a fibroblast cell-cell adhesion molecule, was broadly expressed and upregulated, and its pro-fibrotic function was validated by NanoString nCounter, RNA sequencing, tissue target expression,in vitrogain- and loss-of-function experiments, proteomics, and two animal models of experimental colitis.

Conclusion

A full-thickness bowel scRNAseq atlas revealed previously unrecognized fibroblast heterogeneity and interactions in CD strictures and CDH11 was validated as a potential therapeutic target. These results provide a new resource for a better understanding of CD stricture formation and opens potential therapeutic developments.
Genetic contributions of noncognitive skills to academic development
Authors: Malanchini Margherita , Allegrini Andrea G. , Nivard Michel G. , Biroli Pietro , Rimfeld Kaili , Cheesman Rosa , Stumm Sophie von , Demange Perline A. , Bergen Elsje van , Grotzinger Andrew D. , Raffington Laurel , Fuente Javier De la , Pingault Jean-Baptiste , Harden K. Paige , Tucker-Drob Elliot M. , Plomin Robert
Published: April 2023

Noncognitive skills such as motivation and self-regulation, are partly heritable and predict academic achievement beyond cognitive skills. However, how the relationship between noncognitive skills and academic achievement changes over development is unclear. The current study examined how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of over 10,000 children from England and Wales. Noncognitive skills were increasingly predictive of academic achievement across development. Twin and polygenic scores analyses found that the contribution of noncognitive genetics to academic achievement became stronger over the school years. Results from within-family analyses indicated that associations with noncognitive genetics could not simply be attributed to confounding by environmental differences between nuclear families and are consistent with a possible role for evocative/active gene-environment correlations. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.
Functional genomics identifies extension of complex N-glycans as a mechanism to evade lysis by natural killer cells
Authors: Zhuang Xiaoxuan , Woods James , Ji Yanlong , Scheich Sebastian , Mo Fei , Voss Matthias , Urlaub Henning , Pan Kuan-Ting , Long Eric O.
Published: April 2023

Somatic mutations can lead to the transformation of healthy cells into malignant cells and allow their evasion from immune surveillance. To uncover genes that play a role in the detection and lysis of tumor cells by natural killer (NK) cells, a B lymphoblastoid cell line was subjected to a genome-wide CRISPR screen. Among the top hits that facilitated NK evasion wasSPPL3, which encodes an intramembrane protease that cleaves transmembrane glycosyltransferases in the Golgi apparatus.SPPL3-deficient cells accumulated glycosyltransferases, such as acetylglucosaminyltransferase 5 (MGAT5), and displayed increased N-glycosylation. Binding of NK receptors NKG2D and CD2 to their corresponding ligands MICB and CD58, and binding of rituximab to CD20, was disrupted bySPPL3-deletion. Inhibition of N-glycan maturation restored receptor binding and sensitivity to NK cells. To elucidate the mechanism of this resistant phenotype, a secondary CRISPR screen was performed inSPPL3-deficient cells. This screen identified glycosyltransferases that catalyze the formation of highly branched N-glycans and N-acetyl-lactosamine (LacNAc) extensions as key regulators that prevent killing. A significant enrichment of poly-LacNAc-containing tetra-antennary species was confirmed by glycoproteomic analysis. These findings provide mechanistic insight into howSPPL3deletions have been linked to cancer.
Structural and neurophysiological alterations in Parkinson’s disease are aligned with cortical neurochemical systems
Authors: Wiesman Alex I. , Silva Castanheira Jason da , Fon Edward A. , Baillet Sylvain ,   PREVENT-AD Research Group,   Quebec Parkinson Network
Published: April 2023

Parkinson’s disease (PD) affects cortical structures and neurophysiology. How these deviations from normative variants relate to the neurochemical systems of the cortex in a manner corresponding to motor and cognitive symptoms is unknown. We measured cortical thickness and spectral neurophysiological alterations from structural magnetic resonance imaging and task-free magnetoencephalography in patients with idiopathic PD (NMEG= 79; NMRI= 65), contrasted with similar data from matched healthy controls (NMEG= 65; NMRI= 37). Using linear mixed-effects models and cortical atlases of 19 neurochemical systems, we found that the structural and neurophysiological alterations of PD align with several receptor and transporter systems (acetylcholine, serotonin, glutamate, and noradrenaline) albeit with different implications for motor and non-motor symptoms. Some neurophysiological alignments are protective of cognitive functions: the alignment of broadband power increases with acetylcholinergic systems is related to better attention function. However, neurochemical alignment with structural and other neurophysiological alterations is associated with motor and psychiatric impairments, respectively. Collectively, the present data advance understanding of the association between the nature of neurophysiological and structural cortical alterations in PD and the symptoms that are characteristic of the disease. They also demonstrate the value of a new nested atlas modeling approach to advance research on neurological and neuropsychiatric diseases.
Impact of Cardiac Troponin Release and Fluid Resuscitation on Outcomes of Patients with Sepsis
Authors: Ma Zhiyuan , Krishnamurthy Mahesh , Modi Vivek , Allen David , Shirani Jamshid
Published: April 2023

Background

Septic patients are predisposed to myocardial injury manifested as cardiac troponin release (TnR). Prognostic significance and management implications of TnR and its relationship to fluid resuscitation and outcomes in the intensive care unit (ICU) setting has not been fully elucidated.

Methods

A total of 24,778 patients with sepsis from eICU-CRD (n=11,992), MIMIC-III (n=6,638) and MIMIC-IV (n=6,148) databases were included in this retrospective study. In-hospital mortality and survival at 1 year were examined using multivariable logistic, Cox regression analysis, or Kaplan-Meier survival analysis with overlap weighting adjustment, as well as generalized additive models for fluid resuscitation.

Results

TnR on admission was associated with higher in-hospital mortality [adjusted odds ratios (OR)=1.33; 95% confidence interval (CI)=1.23-1.43; p<0.001 in unweighted analysis and adjusted OR=1.39; 95% CI=1.29-1.50; p< 0.001 with overlap weighting]. One-year survival was lower in patients with admission TnR (Kaplan-Meier survival analysis; p=0.002). A trend was noted for association between admission TnR and 1-year mortality [adjusted OR=1.16; 95% CI=0.99-1.37; p=0.067 in unweighted analysis] while the association was statistically significant after overlap weighting (adjusted OR=1.25; 95% CI=1.06-1.47; p=0.008). We also found that patients with admission TnR were less likely to benefit from more liberal fluid resuscitation. Adequate fluid resuscitation within a range of 70 to 90 ml/kg in the first 24 hours of ICU stay was associated with lower in-hospital mortality in septic patients without TnR but not in those with admission TnR.

Conclusions

Admission TnR was significantly associated with higher in-hospital mortality and worse 1-year survival among septic patients. Adequate fluid resuscitation improved in-hospital mortality in septic patients without but not with admission TnR.
A novel tablet-based software for the acquisition and analysis of gaze and eye movement parameters: a preliminary validation study in Parkinson’s disease
Authors: de Villers-Sidani Étienne , Voss Patrice , Guitton Daniel , Cisneros-Franco J. Miguel , Ducharme Simon
Published: April 2023

The idea that eye movements can reflect certain aspects of brain function and inform on the presence of neurodegeneration is not a new one. Indeed, a growing body of research has shown that several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s Disease, present characteristic eye movement anomalies and that specific gaze and eye movement parameters correlate with disease severity. The use of detailed eye movement recordings in research and clinical settings, however, has been limited due to the expensive nature and limited scalability of the required equipment. Here we test a novel technology that can track and measure eye movement parameters using the embedded camera of a mobile tablet. We show that using this technology can replicate several well-known findings regarding oculomotor anomalies in Parkinson’s disease, and furthermore show that several parameters significantly correlate with disease severity as assessed with the MDS-UPDRS motor subscale. This tablet-based tool has the potential to accelerate eye movement research via affordable and scalable eye-tracking and aid with the identification of disease status and monitoring of disease progression in clinical settings.
Tristetraprolin promotes survival of mammary progenitor cells by restraining TNFα levels
Authors: Micaela Stedile , Angela Lara Montero , Emilio García Solá Martín , Victoria Goddio María , Inés Beckerman , Emilia Bogni , Marina Ayre , Zaira Naguila , Omar Coso , Kordon Edith C.
Published: April 2023

Tristetraprolin (TTP) is a RNA binding protein that destabilizes mRNA of factors that up-regulate proliferation, invasiveness and inflammation. Here we show that TTP expression is higher in mammary progenitor cells than in other cell populations, and that reducing its levels impairs mammary gland morphogenesisin vivoand mammosphere formation in culture. Knocking down TTP in stem-like HC11 mouse mammary cell line increased inflammatory cytokine mRNAs and signaling cascades involving NFκB, STAT3 and MAPK p38 activation, which led to apoptosis. Importantly, TNFα overexpression and the consequent p38 phosphorylation would be the leading cause of progenitor cell death upon TTP expression restriction. Taken together, our results reveal the relevance of negative posttranscriptional regulation on TNFα, exerted by TTP, for the maintenance of the progenitor cell compartment in the mammary gland.
Spatial and temporal metagenomics of river compartments reveals viral community dynamics in an urban impacted stream
Authors: Rodríguez-Ramos Josué , Oliverio Angela , Borton Mikayla A. , Danczak Robert , Mueller Birgit M. , Schulz Hanna , Ellenbogen Jared , Flynn Rory M. , Daly Rebecca A. , Schopflin LeAundra , Shaffer Michael , Goldman Amy , Lewandowski Joerg , Stegen James C. , Wrighton Kelly C.
Published: April 2023

Although river ecosystems comprise less than 1% of Earth’s total non-glaciated area, they are critical modulators of microbially and virally orchestrated global biogeochemical cycles. However, most studies either use data that is not spatially resolved or is collected at timepoints that do not reflect the short life cycles of microorganisms. As a result, the relevance of microbiome interactions and the impacts they have over time on biogeochemical cycles are poorly understood. To assess how viral and microbial communities change over time, we sampled surface water and pore water compartments of the wastewater-impacted River Erpe in Germany every 3 hours over a 48-hour period resulting in 32 metagenomes paired to geochemical and metabolite measurements. We reconstructed 6,500 viral and 1,033 microbial genomes and found distinct communities associated with each river compartment. We show that 17% of our vMAGs clustered to viruses from other ecosystems like wastewater treatment plants and rivers. Our results also indicated that 70% of the viral community was persistent in surface waters, whereas only 13% were persistent in the pore waters taken from the hyporheic zone. Finally, we predicted linkages between 73 viral genomes and 38 microbial genomes. These putatively linked hosts included members of theCompetibacteraceae,which we suggest are potential contributors to carbon and nitrogen cycling. Together, these findings demonstrate that microbial and viral communities in surface waters of this urban river can exist as stable communities along a flowing river; and raise important considerations for ecosystem models attempting to constrain dynamics of river biogeochemical cycles.
Linking the evolution of two prefrontal brain regions to social and foraging challenges in primates
Authors: Bouret Sebastien , Paradis Emmanuel , Prat Sandrine , Castro Laurie , Perez Pauline , Gilissen Emmanuel , Garcia Cecile
Published: April 2023

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily travelled distance (an index of ecological constraints) and population density (an index of social constraint). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data clarifies the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.
Approach-avoidance reinforcement learning as a translational and computational model of anxiety-related avoidance
Authors: Yamamori Yumeya , Robinson Oliver J , Roiser Jonathan P
Published: April 2023

Although avoidance is a prevalent feature of anxiety-related psychopathology, differences in the measurement of avoidance between humans and non-human animals hinder our progress in its theoretical understanding and treatment. To address this, we developed a novel translational measure of anxiety-related avoidance in the form of an approach-avoidance reinforcement learning task, by adapting a paradigm from the non-human animal literature to study the same cognitive processes in human participants. We used computational modelling to probe the putative cognitive mechanisms underlying approach-avoidance behaviour in this task and investigated how they relate to subjective task-induced anxiety. In a large online study (n = 372), participants who experienced greater task-induced anxiety avoided choices associated with punishment, even when this resulted in lower overall reward. Computational modelling revealed that this effect was explained by greater individual sensitivities to punishment relative to rewards. We replicated these findings in an independent sample (n = 627) and we also found fair-to-excellent reliability of measures of task performance in a sub-sample retested one week later (n = 57). Our findings demonstrate the potential of approach-avoidance reinforcement learning tasks as translational and computational models of anxiety-related avoidance. Future studies should assess the predictive validity of this approach in clinical samples and experimental manipulations of anxiety.
Harmonized diffusion MRI data and white matter measures from the Adolescent Brain Cognitive Development Study
Authors: Cetin-Karayumak Suheyla , Zhang Fan , Billah Tashrif , Zekelman Leo , Makris Nikos , Pieper Steve , O’Donnell Lauren J. , Rathi Yogesh
Published: April 2023

The Adolescent Brain Cognitive Development (ABCD) study has collected data from over 10,000 children across 21 sites, providing valuable insights into adolescent brain development. However, site-specific scanner variability has made it challenging to use diffusion MRI (dMRI) data from this study. To address this, a database of harmonized and processed ABCD dMRI data has been created, comprising quality-controlled imaging data from 9345 subjects. This resource required significant computational effort, taking ∼50,000 CPU hours to harmonize the data, perform white matter parcellation, and run whole brain tractography. The database includes harmonized dMRI data, 800 white matter clusters, 73 anatomically labeled white matter tracts both in full-resolution (for analysis) and low-resolution (for visualization), and 804 different dMRI-derived measures per subject. It is available via the NIMH Data Archive and offers tremendous potential for scientific discoveries in structural connectivity studies of neurodevelopment in children and adolescents. Additionally, several post-harmonization experiments were conducted to demonstrate the success of the harmonization process on the ABCD dataset.
NG2 glia protect against prion neurotoxicity by inhibiting prostaglandin E2 signaling
Authors: Liu Yingjun , Guo Jingjing , Matoga Maja , Korotkova Marina , Jakobsson Per-Johan , Aguzzi Adriano
Published: April 2023

Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. This raises the question of how myelinating cells interact with neurodegenerative processes. Here, we found that NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia unleashed a microglial reaction promoting the biosynthesis of prostaglandin E2 (PGE2), which augmented prion neurotoxicity in the HovS cell line, primary neurons and COCS through binding to the EP4 receptor. Single-cell RNA sequencing revealed molecular signatures of inflammatory, disease-associated and MHC+microglia but not of interferon-responsiveness in PGE2-producing microglia of prion-inoculated mice. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.
Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1
Authors: Potter Bastiaan de , Raas Maximilian W. D. , Seidl Michael F. , Verrijzer C. Peter , Snel Berend
Published: April 2023

Polycomb group (PcG) proteins modulate chromatin states to silence gene transcription in plants and animals. Most PcG proteins function as part of distinct multi-subunit Polycomb repressive complexes (PRCs). Gene repression by the Polycomb system involves chromatin compaction by canonical PRC1 (cPRC1), mono-ubiquitylation of histone H2A (H2Aub1) by non-canonical PRC1 (ncPRC1) and tri-methylation of histone H3K27 (H3K27me3) by PRC2. Prevalent models for Polycomb repression emphasize a tight functional coupling between PRC1 and PRC2. However, whether this paradigm indeed reflects the evolution and functioning of the Polycomb system remains unclear. Here, we examined the relationship between cPRC1, ncPRC1 and PRC2 through a comprehensive analysis of their presence and evolution across the entire eukaryotic tree of life. We show that both PRC1 and PRC2 were present in the Last Eukaryotic Common Ancestor (LECA), but that their subsequent evolution is uncoupled. The identification of orthologs for ncPRC1-defining subunits in unicellular relatives of animals and of fungi suggests that the origin of ncPRC1 predates that of cPRC1, and we develop a scenario for the evolution of cPRC1 from ncPRC1. Our results demonstrate the independent evolution and function of PRC1 and PRC2 and show that crosstalk between these complexes is a secondary development in evolution.
Juvenile and adult expression of polyglutamine expandedhuntingtinproduce distinct aggregate distributions inDrosophilamuscle
Authors: Barwell Taylor , Raina Sehaj , Page Austin , MacCharles Hayley , Seroude Laurent
Published: April 2023

While Huntington’s disease (HD) is widely recognized as a disease affecting the nervous system, much evidence has accumulated to suggest peripheral or non-neuronal tissues are affected as well. Here, we utilize the UAS/GAL4 system to express a pathogenic HD construct in the muscle of the fly, and characterize the effects. We observe detrimental phenotypes such as reduced lifespan, decreased locomotion, and accumulation of protein aggregates. Strikingly, depending on the GAL4 driver used to express the construct we saw different aggregate distributions and severity of phenotypes. These different aggregate distributions were found to be dependent on expression level and the timing of expression. Hsp70, a well-documented suppressor of polyglutamine aggregates, was found to strongly reduce the accumulation of aggregates in the eye, but in the muscle it did not prevent the reduction of the lifespan. Therefore, the molecular mechanisms underlying the detrimental effects of aggregates in the muscle are distinct from the nervous system.
Phables: from fragmented assemblies to high-quality bacteriophage genomes
Authors: Mallawaarachchi Vijini , Roach Michael J. , Decewicz Przemyslaw , Papudeshi Bhavya , Giles Sarah K. , Grigson Susanna R. , Bouras George , Hesse Ryan D. , Inglis Laura K. , Hutton Abbey L. K. , Dinsdale Elizabeth A. , Edwards Robert A.
Published: April 2023

Motivation

Microbial communities influence both human health and different environments. Viruses infecting bacteria, known as bacteriophages or phages, play a key role in modulating bacterial communities within environments. High-quality phage genome sequences are essential for advancing our understanding of phage biology, enabling comparative genomics studies, and developing phage-based diagnostic tools. Most available viral identification tools consider individual sequences to determine whether they are of viral origin. As a result of the challenges in viral assembly, fragmentation of genomes can occur, leading to the need for new approaches in viral identification. Therefore, the identification and characterisation of novel phages remain a challenge.

Results

We introduce Phables, a new computational method to resolve phage genomes from fragmented viral metagenome assemblies. Phables identifies phage-like components in the assembly graph, models each component as a flow network, and uses graph algorithms and flow decomposition techniques to identify genomic paths. Experimental results of viral metagenomic samples obtained from different environments show that Phables recovers on average over 49% more high-quality phage genomes compared to existing viral identification tools. Furthermore, Phables can resolve variant phage genomes with over 99% average nucleotide identity, a distinction that existing tools are unable to make.

Availability and Implementation

Phables is available on GitHub athttps://github.com/Vini2/phables.

Contact

vijini.mallawaarachchi@flinders.edu.au