bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative Predictive Features of Invasive Carcinoma Among Intraductal Papillary Mucinous Neoplasm of the Pancreas
Authors: Kazami Yusuke , Arita Junichi , Nishioka Yujiro , Kawaguchi Yoshikuni , Ichida Akihiko , Ishizawa Takeaki , Akamatsu Nobuhisa , Kaneko Junichi , Nakai Yousuke , Koike Kazuhiko , Hasegawa Kiyoshi
Published: July 2022

Objective

Noninvasive intraductal papillary mucinous neoplasms (IPMNs) theoretically do not metastasize. The purpose of this study is to preoperatively distinguish invasive carcinomas associated with IPMN from noninvasive IPMN.

Methods

A total of 131 patients who underwent surgical resection for IPMN were retrospectively analyzed to identify the predictors of invasive carcinoma, based on the International Association of Pancreatology Consensus Guidelines.

Results

Of the 131 patients, 29 (22%) had invasive carcinomas and 102 (78%) had noninvasive IPMN. An enhancing mural nodule (MN) greater than or equal to 5 mm, obstructive jaundice, an abrupt change in the caliber of the pancreatic duct (PD) with distal pancreatic atrophy, and lymphadenopathy were the significant predictors of invasive carcinoma in univariate analysis. The optimal cutoff value for the size of the enhancing MN to differentiate invasive carcinoma was 13 mm. In multivariate analysis, enhancing MN greater than or equal to 13 mm, obstructive jaundice, and an abrupt change in the PD caliber were the independent predictors. When all these factors were absent, only 17% were invasive carcinomas.

Conclusions

Enhancing MN greater than or equal to 13 mm, obstructive jaundice, and an abrupt change in the PD caliber were predictive factors for invasive carcinoma. Systematic lymph node dissection may be omitted when a high-risk patient has none of these factors.
Pediatric Critical Care Nursing Research Priorities in Asia: An eDelphi Study*
Authors: Poh Pei-Fen , Sng Qian Wen , Latour Jos M. , He Linxi , Fong Mei Fung , Muralidharah Jayashree , Abbas Qalab , Matsuishi Yujiro , Lee Jan Hau ,   on behalf of Pediatric Acute & Critical Care Medicine Asian Network (PACCMAN)
Published: July 2022

Objectives:

To identify nursing research priorities in pediatric critical care in Asia.

Design:

We conducted a modified three-round eDelphi survey with pediatric critical care nurses in Asia. The eDelphi technique has been extensively used within health research to achieve a common viewpoint from experts using questionnaires to gather research priorities. In round 1, participants were asked to list three to five research topics that they deemed important. These topics were thematically analyzed and categorized into a questionnaire. Participants rated the research topics in round 2 on a 6-point scale (1 = not important to 6 = extremely important). In round 3, the same questionnaire was used with addition of the calculated mean scores from round 2 for each topic. Research topics ranked among the top 10 were considered extremely important.

Settings:

Twenty-two PICUs in eight Asian countries.

SUBJECTS:

Clinical nurses, managers, educators, and researchers.

Interventions:

None.

Measurements and Main Results:

In round 1, 146 PICU nurses across eight countries provided 520 research topics. Topics from round 1 were categorized into seven domains with 52 research topics. Prioritized research topics included early recognition of patient deterioration (mean 5.58 ± 0.61), prevention of healthcare-associated infections (mean 5.47 ± 0.70), and interventions to reduce compassion fatigue (mean 5.45 ± 0.80). The top three research domains were end-of-life care (mean 5.34 ± 0.68), professionalism (mean 5.34 ± 0.69), and management of pain, sedation, and delirium (5.32 ± 0.72).

Conclusions:

This first PICU nursing research prioritization exercise within Asia identified key nursing research themes that should be prioritized and provide a framework for future collaborative studies.
Treatment Algorithm for Patients With von Willebrand Syndrome Type 2A and Congenital Heart Disease—A Treatment Algorithm May Reduce Perioperative Blood Loss in Children With Congenital Heart Disease
Authors: Wolf Julian , Brandenburger Christina , Dittrich Marcus , Flieder Tobias , Koster Andreas , Budde Ulrich , Knabbe Cornelius , Sandica Eugen , Laser Kai Thorsten , Birschmann Ingvild
Published: July 2022

Objectives:

In children with congenital heart disease (CHD), excessive perioperative bleeding is associated with increased morbidity and mortality, thus making adequate perioperative hemostasis crucial. We investigate the prevalence of acquired von Willebrand syndrome type 2A (aVWS) in CHD and develop a treatment algorithm for patients with aVWS and CHD (TAPAC) to reduce perioperative blood loss.

Design:

Retrospective cohort study.

Setting:

Single-center study.

Patients:

A total of 627 patients with CHD, undergoing corrective cardiac surgery between January 2008 and May 2017.

Interventions:

The evaluation of perioperative bleeding risk was based on the laboratory parameters von Willebrand factor (VWF) antigen, ristocetin cofactor activity, platelet function analyzer (PFA) closure time adenosine diphosphate, and PFA epinephrine. According to the bleeding risk, treatment was performed with desmopressin or VWF.

Measurements and Main Results:

aVWS was confirmed in 63.3 %, with a prevalence of 45.5% in the moderate and 66.3 % in the high-risk group. In addition, prevalence increased with ascending peak velocity above the stenosis (vmax) from 40.0% at less than or equal to 3 m/s to 83.3% at greater than 5 m/s. TAPAC reduced mean blood loss by 36.3% in comparison with a historical control cohort (p < 0.001), without increasing the number of thrombotic or thromboembolic events during the hospital stay. With ascending vmax, there was an increase in perioperative blood loss in the historical cohort (p < 0.001), which was not evident in the TAPAC cohort (p = 0.230).

Conclusions:

The prevalence of aVWS in CHD seems to be higher than assumed and leads to significantly higher perioperative blood loss, especially at high vmax. Identifying these patients through appropriate laboratory analytics and adequate treatment could reduce blood loss effectively.
Trends in Percentages of the US Population Covered by State-Issued COVID-19 Nonpharmaceutical Interventions, March 1, 2020-August 15, 2021
Authors: Joo Heesoo , Howard-Williams Mara , McCord Russell F. , Sunshine Gregory , Fuller James A. , Maskery Brian A.
Published: July 2022

Trends in the percentages of the US population covered by state-issued nonpharmaceutical interventions (NPIs), including restaurant and bar restrictions, stay-at-home orders, gathering limits, and mask mandates, were examined by using county-specific data sets on state-issued orders for NPIs from March 1, 2020, to August 15, 2021. Most of the population was covered by multiple NPIs early in the pandemic. Most state-issued orders were lifted or relaxed as COVID-19 cases decreased during summer 2020. Few states reimplemented strict NPIs during later surges in US COVID-19 cases over the winter of 2020-2021. The exceptions were mask mandates, which covered about 80% of the population between August 2020 and February 2021, and the most restrictive gathering limits, which covered a maximum of 66% of the population in early 2020 and 68% of the population in winter 2020-2021. Most NPIs were lifted by the end of the analysis period.
“That's frustrating”: Perceptions of ankle foot orthosis provision, use, and needs among people with cerebral palsy and caregivers
Authors: Zaino Nicole L. , Yamagami Momona , Gaebler-Spira Deborah J , Steele Katherine M. , Bjornson Kristie F. , Feldner Heather A.
Published: July 2022

Background:

Cerebral palsy (CP) affects roughly 3 per 1000 births in the United States and is the most common pediatric developmental motor disability. Ankle foot orthoses (AFOs) are commonly prescribed to provide support and improve function for individuals with CP.

Objectives:

The study objective was to evaluate the lived experiences of individuals with CP and their caregivers regarding AFO access, use, and priorities. We examined experiences around the perceived purpose of AFOs, provision process, current barriers to use, and ideas for future AFO design.

Study design:

Secondary qualitative data analysis.

Methods:

Secondary data analysis was performed on semistructured focus groups that included 68 individuals with CP and 74 caregivers. Of the focus group participants, 66 mentioned AFOs (16 individuals with CP and 50 caregivers). Deidentified transcripts were analyzed using inductive coding, and the codes were consolidated into themes.

Results:

Four themes emerged: 1) AFO provision is a confusing and lengthy process, 2) participants want more information during AFO provision, 3) AFOs are uncomfortable and difficult to use, and 4) AFOs can benefit mobility and independence. Caregivers and individuals with CP recommended ideas such as 3D printing orthoses and education for caregivers on design choices to improve AFO design and provision.

Conclusions:

Individuals with CP and their caregivers found the AFO provision process frustrating but highlight that AFOs support mobility and participation. Further opportunities exist to support function and participation of people with CP by streamlining AFO provision processes, creating educational materials, and improving AFO design for comfort and ease of use.
Decay of coronavirus disease 2019 mRNA vaccine-induced immunity in people with HIV
Authors: Woldemeskel Bezawit A. , Karaba Andrew H. , Garliss Caroline C. , Beck Evan J. , Aytenfisu Tihitina Y. , Johnston Trevor S. , Laeyendecker Oliver , Cox Andrea L. , Blankson Joel N.
Published: July 2022

Current coronavirus disease 2019 (COVID-19) mRNA vaccines induce robust SARS-CoV-2-specific humoral and cellular responses in people with HIV (PWH). However, the rate of decay of effector immune responses has not been studied in these individuals. Here, we report a significant waning of antibody responses but persistent T-cell responses 6 months post vaccination in virally suppressed PWH with high CD4+ T-cell counts. These responses are comparable with those seen in healthy donors.
Synchronous Metastatic Medullary Thyroid Carcinoma and Paraesophageal Parathyroid Adenoma Detected on 18F-Ethylcholine PET/US Fusion Imaging
Authors: Freesmeyer Martin , Müller Ulrich A. , Männel Matthias , Mtuka-Pardon Gabriele , Seifert Philipp
Published: July 2022

An 80-year-old woman with osteoporosis without fractures was referred with asymptomatic primary hyperparathyroidism and elevated calcitonin level. Ultrasound, 99mTc-pertechnetate scintigraphy, 99mTc-MIBI scintigraphy, and CT revealed a suspicious thyroid nodule and enlarged submandibular lymph nodes. However, no parathyroid adenoma was depictable. 18F-choline PET/CT showed increased uptake of the proximal esophagus, but neither CT nor US revealed a parathyroid lesion, and only 18F-choline PET/US fusion imaging confirmed a paraesophageal parathyroid adenoma. Resection of both medullary thyroid carcinoma and ectopic parathyroid adenoma through a single cervicotomy was conducted (thyroidectomy, neck dissection, extirpation of parathyroid adenoma); parathyroid hormone and calcitonin dropped to normal. Multiple endocrine neoplasia IIa syndrome was suspected.
AL-Type Amyloidosis Involving Stomach and Lungs in 99mTc-DPD Bone Scan
Authors: Lee Yeongjoo , Yoo Ie Ryung , O Joo Hyun
Published: July 2022

Systemic AL (amyloid light-chain) amyloidosis is a relatively rare disease. 99mTc-DPD (3,3-diphosphono-1,2-pyrophosphate) bone scan is a highly sensitive diagnostic tool for cardiac amyloidosis of ATTR (transthyretin) type. In AL amyloidosis, there have been some previous reports of extracardiac DPD uptake in liver, kidney, and spleen, but not in stomach. We present 99mTc-DPD bone scan images of AL-type amyloidosis involving stomach and lung.
Transanal Irrigation for People With Neurogenic Bowel Dysfunction
Authors: Boman Erika , Nylander Malin , Oja Josefine , Olofsson Birgitta
Published: July 2022

Transanal irrigation has been introduced as a complement to standard bowel care for people with neurogenic bowel dysfunction. There is no contemporary integrative review of the effectiveness and feasibility of transanal irrigation from a holistic nursing perspective, only fragments of evidence to date. The aim was to investigate the effectiveness and feasibility of transanal irrigation for people with neurogenic bowel dysfunction. An integrative literature review was conducted. Nineteen studies were included. According to the results, transanal irrigation can reduce difficulties associated with defecation, episodes of incontinence, and the time needed for evacuation and bowel care. Transanal irrigation can increase general satisfaction with bowel habits and quality of life and decrease level of dependency. However, there are practical problems to overcome and adverse effects to manage. Discontinuation is relatively common. The results support the effectiveness of transanal irrigation, but feasibility is inconclusive. Users, including caregivers, report practical problems, and compliance was not always easy to achieve. It is important that users, including caregivers, are well informed and supported during transanal irrigation treatment, especially during introduction. The quality of the studies found was generally weak; therefore, high-quality quantitative and qualitative studies are needed on the topic.
Inflammatory Bowel Disease Self-Management
Authors: Malloy Caeli , Rawl Susan M. , Miller Wendy R.
Published: July 2022

The purpose of this qualitative study was to explore the challenges adolescents with inflammatory bowel disease (IBD) experience with disease self-management as expressed in an online Instagram social support community. Public Instagram posts between January and December 2019 were manually collected from an online IBD support community. To focus on adolescent self-management needs, only posts from Instagram users who (1) indicated they had inflammatory bowel disease, (2) were 13–24 years old, or were in middle school, high school, or college were collected. Using thematic analysis, authors independently coded and identified emerging themes about self-management. Of 2,700 Instagram posts assessed for eligibility, 83 posts met inclusion criteria. Six major themes about inflammatory bowel disease self-management emerged: Desire for Normalcy, Dietary Changes, Education and Career, Healthcare System, Relationships With Others, and Symptoms and Complications. As the first thematic analysis of Instagram posts in an online inflammatory bowel disease community, results provide a crucial perspective of the concerns of adolescents with inflammatory bowel disease. Self-management challenges were wide-ranging and complex, underscoring the importance of IBD self-management in the adolescent population. Nurses should take a holistic approach to assess self-management challenges and tailor care to the specific needs of adolescents living with inflammatory bowel disease.
Trends, Social Context, and Transplant Implications of Obesity Among Incident Dialysis Patients in the United States
Authors: Lavenburg Linda-Marie U. , Kim Yuna , Weinhandl Eric D. , Johansen Kirsten L. , Harhay Meera N.
Published: July 2022

Background.

Kidney transplant programs have variable thresholds to accept obese candidates. This study aimed to examine trends and the social context of obesity among United States dialysis patients and implications for kidney transplant access.

Methods.

We performed a retrospective cohort study of 1 084 816 adults who initiated dialysis between January 2007 and December 2016 using the United States Renal Data System data. We estimated national body mass index (BMI) trends and 1-y cumulative incidence of waitlisting and death without waitlisting by BMI category (<18.5 kg/m2, ≥18.5 and <25 kg/m2 [normal weight], ≥25 and <30 kg/m2 [overweight], ≥30 and <35 kg/m2 [class 1 obesity], ≥35 and <40 kg/m2 [class 2 obesity], and ≥40 kg/m2 [class 3 obesity]). We then used Fine-Gray subdistribution hazard regression models to examine associations between BMI category and 1-y waitlisting with death as a competing risk and tested for effect modification by End Stage Renal Disease (ESRD) network, patient characteristics, and neighborhood social deprivation index.

Results.

The median age was 65 (interquartile range 54–75) y, 43% were female, and 27% were non-Hispanic Black. From 2007 to 2016, the adjusted prevalence of class 1 obesity or higher increased from 31.9% to 38.2%. Class 2 and 3 obesity but not class 1 obesity were associated with lower waitlisting rates relative to normal BMI, especially for younger individuals, women, those of Asian race, or those living in less disadvantaged neighborhoods (p
interaction < 0.001 for all).

Conclusions.

Obesity prevalence is rising among US incident dialysis patients. Relative to normal BMI, waitlisting rates with class 2 and 3 obesity were lower and varied substantially by region, patient characteristics, and socioeconomic context.
Biomechanical Investigation of Ancient Maya Warfare at Mayapan, Yucatan, Mexico
Authors: Dorranian Darius , Serafin Stanley , Lope Carlos Peraza , González Eunice Uc , Russell Bradley W. , Murphy Ellen , Wilson Laura A. B.
Published: July 2022

Despite significant advancements in the reconstruction of activity patterns from skeletal remains and growing scholarly interest in ancient warfare, few biomechanical studies have investigated weaponry use. We adopt a biomechanical approach to investigate who participated in ancient Maya warfare and the types of weaponry used at the Late Postclassic (ca. 1200-1450 A.D.) regional political capital of Mayapán located in northwestern Yucatán, Mexico. This has implications for the nature and scale of Maya warfare and the size of territories that could be controlled by Maya polities. Comparative Finite Element Analysis is a powerful, non-destructive method that can be applied to skeletal remains to model strain, stress and deformation of structures in response to a defined loading regime. Here, biomechanical data extracted using cross-sectional geometry were combined with Finite Element Analysis models of three ancient Maya humeri from Mayapán: one elite male, one elite female, and one commoner female. Models were created with loading conditions of archery and spear use to assess evidence for skeletal adaptation to habitual weapon use. Following suggestions by some Mayanists that elite status males were the principal participants in warfare, we hypothesized that the elite male humerus would exhibit lower strains than the two female humeri in all the loading conditions. This was supported by the Finite Element model results, with the exception of spear throwing. The elite female humerus showed similar trends to the elite male humerus, suggesting the possibility of elite female participation in warfare.
Triterpenoid production with a minimally engineered Saccharomyces cerevisiae chassis
Authors: Guo Hao , Jacobsen Simo Abdessamad Baallal , Walter Kerstin , Lewandowski Anna , Czarnotta Eik , Knuf Christoph , Polakowski Thomas , Maury Jérôme , Lang Christine , Förster Jochen , Blank Lars M. , Ebert Birgitta E.
Published: July 2022

Triterpenoids, one of the most diverse classes of natural products, have been used for centuries as active ingredients in essential oils and Chinese medicines and are of interest for many industrial applications ranging from low-calorie sweeteners to cosmetic ingredients and vaccine adjuvants. However, not only can the extraction from plant material be cumbersome due to low concentrations of the specific triterpenoid, but concerns are also increasing regarding the sustainability of wild plant harvest while meeting market demands. The alternative is to produce triterpenoids with engineered microbes. Here, we present a generally applicable strategy for triterpenoid production in the yeast Saccharomyces cerevisiae based on a modified oxidosqualene cyclase Erg7. The modification reduces the flux into the sterol pathway while increasing the precursor supply for triterpenoid production. The minimally engineered strain was exploited for the exemplary production of the lupane triterpenoids betulin, betulin aldehyde, and betulinic acid at a total titer above 6 g/L, the highest reported so far. To further highlight the chassis concept, squalene, oleanane- and dammarane-type triterpenoids were synthesized to titers at a similar gram scale. We propose the developed baker’s yeast as a host for the thousands of triterpenoid synthesis pathways from plants, reducing the pressure on the natural resources.
Mid-summer snow-free albedo across the Arctic tundra was mostly stable or increased over the past two decades
Authors: Plekhanova Elena , Kim Jin-Soo , Oehri Jacqueline , Erb Angela , Schaaf Crystal , Schaepman-Strub Gabriela
Published: July 2022

Arctic vegetation changes, such as increasing shrub-cover, are expected to accelerate climate warming through increased absorption of incoming radiation and corresponding decrease in summer shortwave albedo. Here we analyze mid-summer shortwave land-surface albedo and its change across the pan-Arctic region based on MODIS satellite observations over the past two decades (2000-2021). In contrast to expectations, we show that terrestrial mid-summer shortwave albedo has not significantly changed in 82% of the pan-Arctic region, while 14% show an increase and 4% a decrease. By analyzing the visible and near-/shortwave-infrared range separately, we demonstrate that the slight increase arises from an albedo increase in the near-/shortwave-infrared range domain while being partly compensated by a decrease in visible albedo. A similar response was found across different tundra vegetation types. We argue that this increase in reflectance is typical with increasing biomass as a result of increased multiple reflection in the canopy. However, CMIP6 global climate model albedo predictions showed the opposite sign and different spatial patterns of snow-free summer albedo change compared to satellite-derived results. We suggest that a more sophisticated vegetation parametrization can reduce this discrepancy, and provide albedo estimates per vegetation type.
Detergent-Free Decellularization Preserves the Structural and Biological Integrity of Murine Tendon
Authors: Marvin Jason C. , Mochida Ai , Paredes Juan , Vaughn Brenna , Andarawis-Puri Nelly
Published: July 2022

Tissue decellularization has demonstrated widespread applications across numerous organ systems for tissue engineering and regenerative medicine applications. Decellularized tissues are expected to retain structural and/or compositional features of the natural extracellular matrix (ECM), enabling investigation of biochemical factors and cell-ECM interactions that drive tissue homeostasis, healing, and disease. However, the dense collagenous tendon matrix has limited the efficacy of traditional decellularization strategies without the aid of harsh chemical detergents and/or physical agitation that disrupt tissue integrity and denature proteins involved in regulating cell behavior. Here, we adapted and established the advantages of a detergent-free decellularization method that relies on Latrunculin B actin destabilization, alternating hypertonic-hypotonic salt and water incubations, nuclease-assisted elimination of cellular material, and protease inhibitor supplementation under aseptic conditions. Compared with previous tendon decellularization studies, our method minimized collagen denaturation while adequately removing cells and preserving bulk tissue alignment and mechanical properties. Furthermore, we demonstrated that decellularized tendon ECM-derived coatings isolated from different mouse strains, injury states (i.e., naïve and acutely injured/’provisional’), and anatomical sites harness distinct biochemical cues and robustly maintain tendon cell viability in vitro. Together, our work provides a simple and scalable decellularization method to facilitate mechanistic studies that will expand our fundamental understanding of tendon ECM and cell biology.

Impact Statement

In this study, we present a decellularization method for tendon that does not rely on any detergents or physical processing techniques. We assessed the impact of detergent-free decellularization using tissue, cellular, and molecular level analyses and validated the preservation of tendon structural organization, collagen molecular integrity, and ECM-associated biological cues that are essential for studying physiological cell-ECM interactions. Lastly, we demonstrated the success of this method on healthy and injured tendon environments, across mouse strains, and for different types of tendons, illustrating the utility of this approach for isolating the contributions of biochemical cues within unique tendon ECM microenvironments.
Phosphorylation and ubiquitination independent endocytosis of BRI1
Authors: Alves Neubus Claus Lucas , Liu Derui , Hohmann Ulrich , Vukašinović Nemanja , Pleskot Roman , Liu Jing , Schiffner Alexei , Jaillais Yvon , Wu Guang , Wolf Sebastian , Van Damme Daniël , Hothorn Michael , Russinova Eugenia
Published: July 2022

The brassinosteroid (BR) hormone and its plasma membrane receptor BR INSENSITIVE1 (BRI1) is one of the best-studied receptor-ligand pairs for understanding the interplay between receptor endocytosis and signaling in plants. BR signaling is mainly determined by the plasma membrane pool of BRI1, whereas BRI1 endocytosis ensures signal attenuation. Since BRs are ubiquitously distributed in the plant, the tools available to study BRI1 function without interference from endogenous BRs are limited. Here, we designed a BR-binding-deficient mutant based on protein sequence-structure analysis and homology modeling of BRI1 and its close homologues. This new tool allowed us to re-examine the BRI1 endocytosis and signal attenuation model. We show that despite decreased phosphorylation and ubiquitination, the BR-binding-deficient BRI1 was internalized similar to the wild type form. These results reinforce the hypothesis that BRI1 is internalized via parallel endocytic routes and machineries. In addition, BR-binding-deficient mutant provides opportunities to study non-canonical ligand-independent BRI1 functions.
Quinolinate Promotes Immune Tolerance through Macrophage Polarization in Glioblastoma
Authors: Kesarwani Pravin , Kant Shiva , Zhao Yi , Chinnaiyan Prakash
Published: July 2022

There has been considerable scientific effort dedicated to understanding the biologic consequence and therapeutic implications of aberrant tryptophan metabolism in brain tumors and neurodegenerative diseases. An overwhelming majority of this work has focused on the upstream metabolism of tryptophan; however, this has not resulted in clinical application. Using global metabolomic profiling of patient-derived brain tumors, we identify the downstream metabolism of tryptophan and accumulation of quinolinate (QA) as a metabolic node in glioblastoma and went on to demonstrate its critical role in promoting immune tolerance. QA acts as a “metabolic checkpoint” in glioblastoma by inducing NMDA receptor activation and Foxo1/PPARγ signaling, resulting in amplification of immune suppressive macrophages. Using a genetically-engineered mouse model designed to inhibit production of QA, we identify kynureninase as a promising therapeutic target to revert the potent immune suppressive microenvironment in glioblastoma. These findings offer the scientific community an opportunity to revisit the biologic consequence of this pathway as it relates to oncogenesis and neurodegenerative disease and a framework for developing new immune modulatory agents to further clinical gains in these otherwise incurable diseases.
A branching model of cell fate decisions in the enteric nervous system
Authors: Laddach Anna , Chng Song Hui , Lasrado Reena , Progatzky Fränze , Shapiro Michael , Artemov Artem , Castaneda Marisol Sampedro , Erickson Alek , Bon-Frauches Ana Carina , Kleinjung Jens , Boeing Stefan , Ultanir Sila , Adameyko Igor , Pachnis Vassilis
Published: July 2022

How neurogenesis and gliogenesis are coordinated during development and why mature glial cells often share properties with neuroectodermal progenitors remains unclear. Here, we have used single cell RNA sequencing to map the regulatory landscape of neuronal and glial differentiation in the mammalian enteric nervous system (ENS). Our analysis indicates that neurogenic trajectories branch directly from a linear gliogenic axis defined by autonomic neural crest cells adopting sequential states as they progressively lose their strong neurogenic bias and acquire properties of adult enteric glia. We identify gene modules associated with transcriptional programs driving enteric neurogenesis and cell state transitions along the gliogenic axis. By comparing the chromatin accessibility profile of autonomic neural crest and adult enteric glia we provide evidence that the latter maintain an epigenetic memory of their neurogenic past. Finally, we demonstrate that adult enteric glia maintain neurogenic potential and are capable of generating enteric neurons in certain contexts by activating transcriptional programs employed by early ENS progenitors. Our studies uncover a novel configuration of enteric neurogenesis and gliogenesis that enables the coordinate development of ENS lineages and provides a mechanistic explanation for the ability of enteric glia to be functionally integrated into the adult intestine and simultaneously maintain attributes of early ENS progenitors.
Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
Authors: Luppi Andrea I. , Hansen Justine Y. , Adapa Ram , Carhart-Harris Robin L. , Roseman Leor , Timmermann Christopher , Golkowski Daniel , Ranft Andreas , Ilg Rüdiger , Jordan Denis , Bonhomme Vincent , Vanhaudenhuyse Audrey , Demertzi Athena , Jaquet Oceane , Bahri Mohamed Ali , Alnagger Naji L.N. , Cardone Paolo , Peattie Alexander R. D. , Manktelow Anne E. , de Araujo Draulio B. , Sensi Stefano L. , Owen Adrian M. , Naci Lorina , Menon David K. , Misic Bratislav , Stamatakis Emmanuel A.
Published: July 2022

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.
OptoPi: An open source flexible platform for the analysis of small animal behaviour
Authors: Cano-Ferrer Xavier , Roberts Ruairí J.V. , French Alice S. , de Folter Joost , Gong Hui , Nightingale Luke , Strange Amy , Imbert Albane , Prieto-Godino Lucia L.
Published: July 2022

Behaviour is the ultimate output of neural circuit computations, and therefore its analysis is a cornerstone of neuroscience research. However, every animal and experimental paradigm requires different illumination conditions to capture and, in some cases, manipulate specific behavioural features. This means that researchers often develop, from scratch, their own solutions and experimental set-ups. Here, we present OptoPi, an open source, affordable (∼ £600), behavioural arena with accompanying multi-animal tracking software. The system features highly customisable and reproducible visible and infrared illumination and allows for temporally precise optogenetic stimulation. OptoPi acquires images using a Raspberry Pi camera, features motorised LED-based illumination, Arduino control, as well as spectrum and irradiance monitoring to fine-tune illumination conditions with real time feedback. Our open-source software (BIO) can be used to simultaneously track multiple animals while accurately keeping individual animal’s identity both in on-line and off-line modes. We demonstrate the functionality of OptoPi by recording and tracking under different illumination conditions the spontaneous behaviour of larval zebrafish as well as adult Drosophila flies and their first instar larvae, an experimental animal that due to its small size and transparency has classically been hard to track. Further, we showcase OptoPi’s optogenetic capabilities through a series of experiments using transgenic Drosophila larvae.
The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein
Authors: Piacentini Sara , Riccio Anna , Santopolo Silvia , Pauciullo Silvia , Frazia Simone La , Rossi Antonio , Rossignol Jean-Francois , Santoro M. Gabriella
Published: July 2022

Coronaviridaeis recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15-30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections, as well as enteric and neurological diseases. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50ranging between 0.05 and 0.15 μg/ml and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.
Comparative analyses of the N-glycoproteomes in HCT116 cancer cells and their non-tumorigenic DNMT1/3b double knockout (DKO1) cells and insight into the Mannose-6-phosphate pathway
Authors: Chen Minyong , Assis Diego M. , Benet Matthieu , McClung Colleen M. , Gordon Elizabeth , Ghose Shourjo , Dupard Steven J. , Willetts Matthew , Taron Christopher H. , Samuelson James C.
Published: July 2022

N-glycoproteomic analyses provide valuable resources for investigation of cancer mechanisms, biomarkers, and therapeutic targets. Here, we mapped and compared the site-specific N-glycoproteomes of colon cancer HCT116 cells and isogenic non-tumorigenic DNMT1/3b double knockout (DKO1) cells using Fbs1-GYR N-glycopeptide enrichment technology and trapped ion mobility spectrometry. Many significant changes in site-specific N-glycosylation were revealed, providing a molecular basis for further elucidation of the role of N-glycosylation in protein function. HCT116 cells display hypersialylation especially in cell surface membrane proteins. Both HCT116 and DKO1 show an abundance of paucimannose and 80% of paucimannose-rich proteins are annotated to reside in exosomes. The most striking N-glycosylation alteration was the degree of mannose-6-phosphate (M6P) modification. N-glycoproteomic analyses revealed that HCT116 display hyper-M6P modification, which was orthogonally validated by M6P immunodetection. Significant observed differences in N-glycosylation patterns of the major M6P receptor, CI-MPR in HCT116 and DKO1 may contribute to the hyper-M6P phenotype of HCT116 cells.
Genetic and physiological insights into the diazotrophic activity of a non-cyanobacterial marine diazotroph
Authors: Joublin-Delavat Aurélie , Touahri Katia , Crétin Pauline , Morot Amandine , Rodrigues Sophie , Jesus Bruno , Trigodet Florian , Delavat François
Published: July 2022

Nitrogen (N2) fixation, or diazotrophy, supports a large part of primary production in oceans. Culture-independent approaches highlighted the presence in abundance of marine non-cyanobacterial diazotrophs (NCD) but their ecophysiology remains elusive, mostly because of the low number of isolated NCD and because of the lack of available genetic tools for these isolates. Here, a dual genetic and functional approach allowed unveiling the ecophysiology of a marine NCD affiliated to the speciesVibrio diazotrophicus. Physiological characterization of the first marine NCD mutant obtained so far was performed using a soft-gellan assay, demonstrating that a ΔnifHmutant in not able to grow in nitrogen-deprived media. Furthermore, we demonstrated thatV. diazotrophicusproduces a thick biofilm under diazotrophic conditions, suggesting biofilm production as an adaptive response of this NCD to cope with the inhibition of nitrogen-fixation by molecular oxygen. Finally, the genomic signature ofV. diazotrophicusis essentially absent from metagenomic data ofTara Oceanexpeditions, despite having been isolated from various marine environments. We think that the genetically tractableV. diazotrophicusstrain used in this study may serve as an ideal model to study the ecophysiology of these overlooked procaryotic group.
Ionic control of porin permeability in bacteria
Authors: Caño Muñiz Santiago E. , Hagting Anja , Evans Ieuan E. , Alsulami Ali F , Summers David , Blundell Tom L , Floto R. Andres
Published: July 2022

Bacterial porins permit permeation of hydrophilic nutrients and antibiotics across the outer membrane but also contribute to proton leak from the periplasmic space, suggesting that their activity might be dynamically regulated. Here we show, in Escherichia coli, that porin permeability is controlled by changes in periplasmic ions, inhibited by periplasmic acidification, thereby limiting proton loss during electron transport chain activity, and enhanced during starvation, promoting nutrient uptake. Growth in glucose increases periplasmic potassium through activating the voltage-gated channel Kch, triggering enhanced porin permeation and membrane action potentials. This metabolic control of porin permeability explains the recognized decrease in antibiotic susceptibility when bacteria are grown in lipid media and the impact of mutations in central metabolism genes on drug resistance, identifying Kch as a therapeutic target to improve bacterial killing by antibiotics.

One sentence summary

The permeability of bacterial porin is dynamically regulated by periplasmic pH and potassium levels, altering antibiotic resistance.
Sugar sensation and mechanosensation in the egg-laying preference shift of Drosophila suzukii
Authors: Wang Wanyue , Dweck Hany K M , Talross Gaëlle J S , Zaidi Ali , Gendron Joshua M. , Carlson John R
Published: July 2022

The agricultural pest Drosophila suzukii differs from most other Drosophila species in that it lays eggs in ripe, rather than overripe, fruit. Previously we showed that changes in bitter taste sensation accompanied this adaptation (Dweck et al., 2021). Here we show that D. suzukii has also undergone a variety of changes in sweet taste sensation. D. suzukii has a weaker preference than D. melanogaster for laying eggs on substrates containing all three primary fruit sugars: sucrose, fructose, and glucose. Major subsets of D. suzukii taste sensilla have lost electrophysiological responses to sugars. Expression of several key sugar receptor genes is reduced in the taste organs of D. suzukii. By contrast, certain mechanosensory channel genes, including nompC, are expressed at higher levels in the taste organs of D. suzukii, which has a higher preference for stiff substrates. Finally, we find that D. suzukii responds differently from D. melanogaster to combinations of sweet and mechanosensory cues. Thus, the two species differ in sweet sensation, mechanosensation, and their integration, which are all likely to contribute to the differences in their egg-laying preferences in nature.
Cryopreservation of mosquito microbiota for use in microcosm experiments
Authors: Zhao Serena Y. , Hughes Grant L. , Coon Kerri L.
Published: July 2022

Mosquitoes develop in a wide range of aquatic habitats containing highly diverse and variable bacterial communities that shape both larval and adult traits, including the capacity of adult females of some mosquito species to vector disease-causing organisms to humans. However, while most mosquito studies control for host genotype and environmental conditions, the impact of microbiota variation on phenotypic outcomes of mosquitoes is often unaccounted for. The inability to conduct reproducible intra- and inter-laboratory studies of mosquito-microbiota interactions has also greatly limited our ability to identify microbial targets for mosquito-borne disease control. Here, we developed an approach to isolate and cryopreserve microbial communities derived from mosquito larval rearing environments in the lab and field. We then validated the use of our approach to generate experimental microcosms colonized by standardized lab- and field-derived microbial communities. Our results overall reveal minimal effects of cryopreservation on the recovery of bacteria when directly compared with isolation from non-cryopreserved fresh material. Our results also reveal improved reproducibility of microbial communities in replicate microcosms generated using cryopreserved stocks over fresh material. Altogether, these results provide a critical next step toward the standardization of mosquito studies to include larval rearing environments colonized by defined microbial communities. They also lay the foundation for long-term studies of mosquito-microbe interactions and the identification and manipulation of taxa with potential to reduce mosquito vectorial capacity.
ProteinSGM: Score-based generative modeling forde novoprotein design
Authors: Lee Jin Sub , Kim Jisun , Kim Philip M.
Published: July 2022

The generation ofde novoprotein structures with predefined function and properties remains a challenging problem in protein design. Diffusion models, a novel state-of-the-art class of generative models, have recently shown astounding empirical performance in image synthesis. Here we use image-based representations of protein structure to develop ProteinSGM, a score-based diffusion model that produces realisticde novoproteins and can inpaint plausible backbones and domains into structures of predefined length. Withunconditional generation, we show that ProteinSGM can generate native-like protein structures, surpassing the performance of previously reported generative models. We experimentally validate somede novodesigns and observe strong structural consistency with generated backbones. Finally, we applyconditional generationtode novoprotein design by formulating it as an image inpainting problem, allowing precise and modular design of protein structure.
Hippocampal microstructure, but not macrostructure, mediates age differences in episodic memory
Authors: Ibrahim Kirolos , Bennett Ilana J.
Published: July 2022

Separate unimodal magnetic resonance imaging (MRI) literatures have shown that hippocampal gray matter macrostructure (volume) and microstructure (diffusion) decline in aging and relate to episodic memory performance, with multimodal MRI studies reporting that episodic memory may be better explained by a combination of these metrics. However, these effects are often assessed independent of age or only within older adults and therefore do not address whether these distinct modalities mediate the effect of age on episodic memory. Here, we simultaneously examined the unique and joint contribution of hippocampal volume and diffusion to age-related differences in episodic memory in 83 younger and 61 older adults who underwent a T1-and diffusion-weighted MRI and completed the Rey Auditory Verbal Learning Test. As expected, older age was significantly related to smaller volume and higher diffusion (intracellular, dispersion, and free) in bilateral hippocampus and to worse episodic memory performance (immediate and delayed free recall, recognition). Structural equation modelling revealed that the age-memory relationship was significantly mediated by hippocampal diffusion, but not volume. A non-significant influential indirect effect further revealed that the structural metrics did not jointly mediate the age-memory relationship. Together, these findings indicate that hippocampal microstructure uniquely contributes to age-related differences in episodic memory and suggest that volume and diffusion capture distinct neurobiological properties of hippocampal gray matter.
Novel Viral and Microbial Species in a Translocated Toutouwai (Petroica longipes) Population from Aotearoa/New Zealand
Authors: French Rebecca K. , Stone Zoë L. , Parker Kevin A. , Holmes Edward C.
Published: July 2022

Background

Translocation is a common tool in wildlife management and been responsible for many conservation successes. During translocations, any associated infectious agents are moved with their wildlife hosts. Accordingly, translocations can present a risk of infectious disease emergence, although they also provide an opportunity to restore natural infectious communities (‘infectome’) and mitigate the long-term risks of reduced natural resistance.

Methods

We used metatranscriptomic sequencing to characterise the infectome of 41 toutouwai (North Island robin, Petroica longipes) that were translocated to establish a new population within the North Island of New Zealand. We also screened for pathogenic bacteria, fungi and parasites.

Results

Although we did not detect any known avian diseases, which is a positive outcome for the translocated toutouwai population, we identified a number of novel viruses of interest, including a novel avian hepatovirus, as well as a divergent calici-like virus and four hepe-like viruses of which the host species is unknown. We also revealed a novel spirochete bacterium and a coccidian eukaryotic parasite.

Conclusions

The presumably non-pathogenic viruses and microbial species identified here support the idea that the majority of microorganisms likely do not cause disease in their hosts, and that translocations could serve to help restore and maintain native infectious communities. We advise greater surveillance of infectious communities of both native and non-native wildlife before and after translocations to better understand the impact, positive or negative, that such movements may have on both host and infectome ecology.