bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Total Antioxidant Capacity Value Improves Survival of Fat Grafts in Rat Model
Authors: Cinar Fatih , Yalcin Can Ege , Ayas Gorkem , Celik Ugur , Okyay Mehmet Fatih , Demiröz Anil , Bağhaki Semih , Cetinkale Oguz
Published: June 2023

Background:

Although studies aiming to increase fat graft survival continue, in this study, the authors aimed to investigate the effects of different antioxidants on total antioxidant capacity (TAC) and their effect on graft survival.

Methods:

Thirty-two male Wistar rats were divided into four equally sized groups, including a control group and three antioxidant groups receiving either melatonin (10 mg/kg), zinc (2 mg/kg), or vitamins E and C (100 mg/kg). Autologous fat grafts (1.7 ± 0.4 g) were transferred to the dorsal subcutaneous region, and total antioxidant capacity was measured on days 0 and 1, week 1, and monthly until the third month. Transferred graft volume and mass (1.3 ± 0.4 g) were measured using the liquid overflow method and precision scales at the end of the study. Routine hematoxylin and eosin staining and immunohistochemistry against perilipin were performed for semiqualitative analysis and H-score for viable adipose cells, respectively.

Results:

Collected fat grafts measured significantly less in weight and volume and the survival rate was lower in the control group (P < 0.01). The control group exhibited a reduction in TAC, whereas all groups receiving antioxidants had an increase in TAC during the first week (P = 0.02, P = 0.008, and P = 0.004 for melatonin, zinc, and vitamins, respectively). Immunohistochemistry of the antioxidant group demonstrated a statistically significant excess and reactivity of cells staining with perilipin antibodies.

Conclusion:

In this animal study, the beneficial effect of antioxidants on fat graft survival can be related to the significant increase in TAC following the first week of their administration.

Clinical Relevance Statement:

Antioxidants improve fat graft survival and quality in this rat model, by increasing total antioxidant capacity in the first week of administration.
Upper Eyelid Ptosis Correction with Levator Advancement Using the Levator Musculoaponeurotic Junction Formula in White Patients
Authors: Wong Chin-Ho , Hsieh Michael Ku Hung , Mendelson Bryan
Published: June 2023

Background:

Upper eyelid ptosis correction is a challenging procedure. The authors report a novel approach to this procedure that is more accurate and predictable compared with conventional approaches.

Methods:

A preoperative system of assessment has been formulated to more accurately estimate the amount of levator advancement required. The levator advancement was referenced from a constant landmark: the musculoaponeurotic junction of the levator palpebrae superioris. The factors considered include the amount of upper lid elevation required, the degree of compensatory brow elevation present, and eye dominance. The preoperative assessment and surgical technique are presented in a series of detailed operative videos. The levator advancement is performed as planned preoperatively with final adjustment made intraoperatively to achieve correct lid height and symmetry.

Results:

Seventy-seven patients (154 eyelids) were analyzed prospectively in this study. The authors found this approach to be reliable and accurate in predicting the required amount of levator advancement. Intraoperatively, the formula correctly predicted the exact required fixation location in 63% of eyelids, and to within ±1 mm in 86% of cases. This may be used for patients with ptosis of varying severity, ranging from mild to severe eyelid ptosis. The revision rate was 4%.

Conclusion:

This approach is accurate in determining the fixation location needed, enabling levator advancement for ptosis correction to be performed with more precision and predictability.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Impact of Robotic Assistance on Complications in Bariatric Surgery at Expert Laparoscopic Surgery Centers
Authors: Caiazzo Robert , Bauvin Pierre , Marciniak Camille , Saux Patrick , Jacqmin Geoffrey , Arnoux Raymond , Benchetrit Salomon , Dargent Jerome , Chevallier Jean-Marc , Frering Vincent , Gugenheim Jean , Lechaux David , Msika Simon , Sterkers Adrien , Topart Philippe , Baud Grégory , Pattou François ,   For the SOFFCO-mm Study Group
Published: June 2023

Objective:

To investigate the way robotic assistance affected rate of complications in bariatric surgery at expert robotic and laparoscopic surgery facilities.

Background:

While the benefits of robotic assistance were established at the beginning of surgical training, there is limited data on the robot’s influence on experienced bariatric laparoscopic surgeons.

Methods:

We conducted a retrospective study using the BRO clinical database (2008–2022) collecting data of patients operated on in expert centers. We compared the serious complication rate (defined as a Clavien score≥3) in patients undergoing metabolic bariatric surgery with or without robotic assistance. We used a directed acyclic graph to identify the variables adjustment set used in a multivariable linear regression, and a propensity score matching to calculate the average treatment effect (ATE) of robotic assistance.

Results:

The study included 35,043 patients [24,428 sleeve gastrectomy (SG); 10,452 Roux-en-Y gastric bypass (RYGB); 163 single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S)], with 938 operated on with robotic assistance (801 SG; 134 RYGB; 3 SADI-S), among 142 centers. Overall, we found no benefit of robotic assistance regarding the risk of complications (average treatment effect=−0.05, P=0.794), with no difference in the RYGB+SADI group (P=0.322) but a negative trend in the SG group (more complications, P=0.060). Length of hospital stay was decreased in the robot group (3.7±11.1 vs 4.0±9.0 days, P<0.001).

Conclusions:

Robotic assistance reduced the length of stay but did not statistically significantly reduce postoperative complications (Clavien score≥3) following either GBP or SG. A tendency toward an elevated risk of complications following SG requires more supporting studies.
What Happens on Call Doesn’t Stay on Call. The Effects of In-house Call on Acute Care Surgeons’ Sleep and Burnout
Authors: Coleman Jamie J. , Robinson Caitlin K. , von Hippel William , Holmes Kristen E. , Kim Jeongeun , Pearson Samuel , Lawless Ryan A. , Hubbard Alan E. , Cohen Mitchell J.
Published: June 2023

Objective:

We sought to quantify the effects of in-house call(IHC) on sleep patterns and burnout among acute care surgeons (ACS).

Background:

Many ACS take INC, which leads to disrupted sleep and high levels of stress and burnout.

Methods:

Physiological and survey data of 224 ACS with IHC were collected over 6 months. Participants continuously wore a physiological tracking device and responded to daily electronic surveys. Daily surveys captured work and life events as well as feelings of restfulness and burnout. The Maslach Burnout Inventory (MBI) was administered at the beginning and end of the study period.

Results:

Physiological data were recorded for 34,135 days, which includes 4389 nights of IHC. Feelings of moderate, very, or extreme burnout occurred 25.7% of days and feelings of being moderately, slightly, or not at all rested occurred 75.91% of days. Decreased amount of time since the last IHC, reduced sleep duration, being on call, and having a bad outcome all contribute to greater feelings of daily burnout (P<0.001). Decreased time since last call also exacerbates the negative effect of IHC on burnout (P<0.01).

Conclusions:

ACS exhibit lower quality and reduced amount of sleep compared with an age-matched population. Furthermore, reduced sleep and decreased time since the last call led to increased feelings of daily burnout, accumulating in emotional exhaustion as measured on the MBI. A reevaluation of IHC requirements and patterns as well as identification of countermeasures to restore homeostatic wellness in ACS is essential to protect and optimize our workforce.
Diversity and Scale: Genetic Architecture of 2,068 Traits in the VA Million Veteran Program
Authors: Verma Anurag , Huffman Jennifer E , Rodriguez Alex , Conery Mitchell , Liu Molei , Ho Yuk-Lam , Kim Youngdae , Heise David A , Guare Lindsay , Panickan Vidul Ayakulangara , Garcon Helene , Linares Franciel , Costa Lauren , Goethert Ian , Tipton Ryan , Honerlaw Jacqueline , Davies Laura , Whitbourne Stacey , Cohen Jeremy , Posner Daniel C , Sangar Rahul , Murray Michael , Wang Xuan , Dochtermann Daniel R , Devineni Poornima , Shi Yunling , Nandi Tarak Nath , Assimes Themistocles L , Brunette Charles A , Carroll Robert J , Clifford Royce , Duvall Scott , Gelernter Joel , Hung Adriana , Iyengar Sudha K , Joseph Jacob , Kember Rachel , Kranzler Henry , Levey Daniel , Luoh Shiuh-Wen , Merritt Victoria C , Overstreet Cassie , Deak Joseph D , Grant Struan F A , Polimanti Renato , Roussos Panos , Sun Yan V , Venkatesh Sanan , Voloudakis Georgios , Justice Amy , Begoli Edmon , Ramoni Rachel , Tourassi Georgia , Pyarajan Saiju , Tsao Philip S , O’Donnell Christopher J , Muralidhar Sumitra , Moser Jennifer , Casas Juan P , Bick Alexander G , Zhou Wei , Cai Tianxi , Voight Benjamin F , Cho Kelly , Gaziano Michael J , Madduri Ravi K , Damrauer Scott M , Liao Katherine P
Published: June 2023

Genome-wide association studies (GWAS) have underrepresented individuals from non-European populations, impeding progress in characterizing the genetic architecture and consequences of health and disease traits. To address this, we present a population-stratified phenome-wide GWAS followed by a multi-population meta-analysis for 2,068 traits derived from electronic health records of 635,969 participants in the Million Veteran Program (MVP), a longitudinal cohort study of diverse U.S. Veterans genetically similar to the respective African (121,177), Admixed American (59,048), East Asian (6,702), and European (449,042) superpopulations defined by the 1000 Genomes Project. We identified 38,270 independent variants associating with one or more traits at experiment-wide (P < 4.6x10-11) significance; fine-mapping 6,318 signals identified from 613 traits to single-variant resolution. Among these, a third (2,069) of the associations were found only among participants genetically similar to non-European reference populations, demonstrating the importance of expanding diversity in genetic studies. Our work provides a comprehensive atlas of phenome-wide genetic associations for future studies dissecting the architecture of complex traits in diverse populations.

One Sentence Summary

To address the underrepresentation of non-European individuals in genome-wide association studies (GWAS), we conducted a population-stratified phenome-wide GWAS across 2,068 traits in 635,969 participants from the diverse U.S. Department of Veterans Affairs Million Veteran Program, with results expanding our knowledge of variant-trait associations and highlighting the importance of genetic diversity in understanding the architecture of complex health and disease traits.
CohortDiagnostics: phenotype evaluation across a network of observational data sources using population-level characterization
Authors: Rao Gowtham A. , Shoaibi Azza , Makadia Rupa , Hardin Jill , Swerdel Joel , Weaver James , Voss Erica A , Conover Mitchell M. , Fortin Stephen , Sena Anthony G. , Knoll Chris , Hughes Nigel , Gilbert James P. , Blacketer Clair , Andryc Alan , DeFalco Frank , Molinaro Anthony , Reps Jenna , Schuemie Martijn J , Ryan Patrick B
Published: June 2023

Objective

This paper introduces a novel framework for evaluating phenotype algorithms (PAs) using the open-source tool, Cohort Diagnostics.

Materials and Methods

The method is based on several diagnostic criteria to evaluate a patient cohort returned by a PA. Diagnostics include estimates of incidence rate, index date entry code breakdown, and prevalence of all observed clinical events prior to, on, and after index date. We test our framework by evaluating one PA for systemic lupus erythematosus (SLE) and two PAs for Alzheimer’s disease (AD) across 10 different observational data sources.

Results

By utilizing CohortDiagnostics, we found that the population-level characteristics of individuals in the cohort of SLE closely matched the disease’s anticipated clinical profile. Specifically, the incidence rate of SLE was consistently higher in occurrence among females. Moreover, expected clinical events like laboratory tests, treatments, and repeated diagnoses were also observed. For AD, although one PA identified considerably fewer patients, absence of notable differences in clinical characteristics between the two cohorts suggested similar specificity.

Discussion

We provide a practical and data-driven approach to evaluate PAs, using two clinical diseases as examples, across a network of OMOP data sources. Cohort Diagnostics can ensure the subjects identified by a specific PA align with those intended for inclusion in a research study.

Conclusion

Diagnostics based on large-scale population-level characterization can offer insights into the misclassification errors of PAs.
Phylogenomics including new sequence data of phytoplankton-infecting chytrids reveals multiple independent lifestyle transitions across the phylum
Authors: Thomé Pauline C. , Wolinska Justyna , Van Den Wyngaert Silke , Reñé Albert , Ilicic Doris , Agha Ramsy , Grossart Hans-Peter , Garcés Esther , Monaghan Michael T. , Strassert Jürgen F. H.
Published: June 2023

Parasitism is the most common lifestyle on Earth and has emerged many times independently across the eukaryotic tree of life. It is frequently found among chytrids (Chytridiomycota), which are early-branching unicellular fungi that feed osmotrophically via rhizoids as saprotrophs or parasites. Chytrids are abundant in most aquatic and terrestrial environments and fulfil important ecosystem functions. As parasites, they can have significant impacts on host populations. They cause global amphibian declines and influence the Earth’s carbon cycle by terminating algal blooms. To date, the evolution of parasitism within the chytrid phylum remains unclear due to the low phylogenetic resolution of rRNA genes for the early diversification of fungi, and because few parasitic lineages have been cultured and genomic data for parasites is scarce. Here, we combine transcriptomics, culture-independent single-cell genomics and a phylogenomic approach to overcome these limitations. We newly sequenced 29 parasitic taxa and combined these with existing data to provide a robust backbone topology for the diversification of Chytridiomycota. Our analyses reveal multiple independent lifestyle transitions between parasitism and saprotrophy among chytrids, multiple host shifts by parasites, and suggest that the chytrid last common ancestor was a parasite of phytoplankton.
Bipartite left-right sided endocrine system: processing of contralateral effects of brain injury
Authors: Watanabe Hiroyuki , Kobikov Yaromir , Nosova Olga , Sarkisyan Daniil , Galatenko Vladimir , Carvalho Liliana , Maia Gisela H. , Lukoyanov Nikolay , Lavrov Igor , Hallberg Mathias , Schouenborg Jens , Zhang Mengliang , Bakalkin Georgy
Published: June 2023

The crossed descending neural tracts set a basis for contralateral effects of brain injury. In addition, the left-right side-specific effects of the unilateral brain lesions may be mediated by neurohormones through the humoral pathway as discovered in animals with disabled descending motor tracts. We here examined if counterparts of the endocrine system that convey signals from the left and right brain injuries differ in neural and molecular mechanisms. In rats with completely transected cervical spinal cords a unilateral injury of the hindlimb sensorimotor cortex produced hindlimb postural asymmetry with contralateral hindlimb flexion, a proxy for neurological deficit. The effects of the left and right side brain lesions were differently inhibited by antagonists of the δ-, κ- and µ-opioid receptors suggesting differential neuroendocrine control of the left-right side-specific hormonal signaling. Bilateral deafferentation of the lumbar spinal cord eliminated hormone-mediated effects of the left-side brain injury but not the right-side lesion suggesting their afferent and efferent mechanisms, respectively. Analysis of gene-gene co-expression patterns identified the left and right side-specific gene regulatory networks that were coordinated across the hypothalamus and lumbar spinal cord through the humoral pathway. The coordination was ipsilateral and perturbed by brain injury. These findings suggest that the neuroendocrine system that conveys left-right side-specific hormonal messages from injured brain is bipartite, contributes to contralateral neurological deficits through asymmetric neural mechanisms, and enables ipsilateral coordination of molecular processes across neural areas along the neuraxis.

GRAPHICAL ABSTRACT
Semi-automated retrieval of chemical and phylogenetic information from natural products literature
Authors: Coelho Ana Carolina Lunardello , da Silva Ricardo R.
Published: June 2023

Natural products (NPs) are metabolites of great importance due to their fundamental biological role in performing specialized activities, ranging from basic cellular functions to complex ecological interactions. These metabolites have contributed to innovating fields such as agriculture and medicine due to their optimized biological activities, a consequence of evolution. A key factor in ensuring that isolated NPs are novel is to search scientific literature and compare pre-existing chemical entities with the new isolate. Unfortunately, articles are typically not machine-readable, a problem that hinders efficient searching and increases the chances of unintended rediscovery. In addition, the time required to add new compound discoveries to compound databases hinders computational studies on cell metabolism and Quantitative Structure-Activity Relationships (QSAR). Here, we present a modularized tool that uses text mining techniques to retrieve chemical entities and taxonomic mentions present in scientific literature, called NPMINE (Natural Products MINIng). We were able to analyze 55,382 scientific articles from some of the most important applied chemistry journals from Brazil and the world, consistently recovering the expected taxonomic and structural information. This processing resulted in 120,970 unique InChI Keys potentially associated with 21,526 unique species mentioned. Using the PubChem BioAssay database we show how QSAR models can be used to mine active leads. The results indicate that NPMINE not only facilitates natural products cataloging, but also assists in biological source assignment and structure-activity relationships, a time-consuming task, typically performed in low throughput.
Development of a CMS Classifier for Clinical CRC Samples
Authors: Torang Arezo , van de Weerd Simone , van Lammers Veerle , van Hooff Sander , Koster Jan , Medema Jan Paul
Published: June 2023

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, emphasizing the need for improved predictive biomarkers to guide treatment decisions. A classification system based on gene expression profiles, known as CMS, has shown promise in stratifying CRC into distinct subtypes with varying clinical outcomes. However, the lack of a reliable assay to classify formalin-fixed paraffin-embedded (FFPE) samples poses a challenge for translating this system into routine clinical practice. In this paper, we introduce the NanoClassifier, an NanoString-based CMS classifier to classify both FFPE and Fresh frozen (FF) tumors. We demonstrate the strong accuracy of the NanoClassifier in predicting CMS for CRC samples. By validating its performance on FF and FFPE samples, we highlight the prognostic significance of CMS in CRC.
Adaptive mechanisms of social and asocial learning in immersive collective foraging
Authors: Wu Charley M. , Deffner Dominik , Kahl Benjamin , Meder Björn , Ho Mark H. , Kurvers Ralf H.J.M.
Published: June 2023

Human cognition is distinguished by our ability to adapt to different environments and circumstances. Yet the mechanisms driving adaptive behavior have predominantly been studied in separate asocial and social contexts, with an integrated framework remaining elusive. Here, we use a collective foraging task in a virtual Minecraft environment to integrate these two fields, by leveraging automated transcriptions of visual field data combined with high-resolution spatial trajectories. Our behavioral analyses capture both the structure and temporal dynamics of social interactions, which are then directly tested using computational models sequentially predicting each foraging decision. These results reveal that adaptation mechanisms of both asocial foraging and selective social learning are driven by individual foraging success (rather than social factors). Furthermore, it is the degree of adaptivity—of both asocial and social learning—that best predicts individual performance. These findings not only integrate theories across asocial and social domains, but also provide key insights into the adaptability of human decision-making in complex and dynamic social landscapes.
Rescuable sleep and synaptogenesis phenotypes in aDrosophilamodel of O-GlcNAc transferase intellectual disability
Authors: Czajewski Ignacy , McDowall Laurin , Ferenbach Andrew , van Aalten Daan M. F.
Published: June 2023

O-GlcNAcylation is an essential intracellular protein modification mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations inOGThave been linked to intellectual disability, indicating that this modification is important for the development and functioning of the nervous system. However, the processes that are most sensitive to perturbations in O-GlcNAcylation remain to be identified. Here, we uncover quantifiable phenotypes in the fruit flyDrosophila melanogastercarrying a patient-derived OGT mutation in the catalytic domain. Hypo-O-GlcNAcylation leads to defects in synaptogenesis and reduced sleep stability. Both these phenotypes can be partially rescued by genetically or chemically targeting OGA, suggesting that a balance of OGT/OGA activity is required for normal neuronal development and function.
Characterization of CAR T Cells Manufactured using Genetically Engineered Artificial Antigen Presenting Cells
Authors: Sayadmanesh Ali , Azadbakht Mohammad , Yari Kheirollah , Abedelahi Ali , Shafaei Hajar , Shanehbandi Dariush , Baradaran Behzad , Basiri Mohsen
Published: June 2023

Objective

Chimeric antigen receptor (CAR) T cell therapy has recently emerged as a promising approach for the treatment of different types of cancer. Improving CAR T cell manufacturing in terms of costs and product quality is an important concern for expanding the accessibility of this therapy. One proposed strategy for improving T cell expansion is to use genetically engineered artificial antigen presenting cells (aAPC) expressing a membrane-bound anti-CD3 for T cell activation. In this study, we characterized CAR T cells generated with this approach in terms of expansion efficiency, immunophenotype, and cytotoxicity.

Materials and Methods

In this experimental study, we generated an aAPC line by engineering K562 cells to express a membrane-bound anti-CD3 (mOKT3). T cell activation was performed by culturing PBMCs with either mitomycin C-treated aAPCs or surface-immobilized anti-CD3 and anti-CD28 antibodies. Untransduced and CD19-CAR-transduced T cells were characterized in terms of expansion, activation markers, IFN-γ secretion, CD4/CD8 ratio, memory phenotype, and exhaustion markers. Cytotoxicity of CD19-CAR T cells generated by aAPCs and antibodies was also investigated using a bioluminescence-based co-culture assay.

Results

Our findings showed that the engineered aAPC line has the potential to expand CAR T cells similar to that of the antibody-based method. Although activation with aAPCs leads to a higher ratio of CD8+and effector memory T cells in the final product, we did not observe a significant difference in IFN-γ secretion cytotoxic activity or exhaustion between CAR T cells generated with aAPC or antibodies.

Conclusion

Our results show that despite the differences in the immunophenotypes of aAPC and antibody-based CAR T cells, both methods can be used to manufacture potent CAR T cells. These findings can be instrumental for the improvement of the T cell manufacturing process and future applications of aAPC-derived CAR T cells.
Encoding and context-dependent control of reward consumption within the central nucleus of the amygdala
Authors: Fraser Kurt M. , Kim Tabitha H. , Castro Matilde , Drieu Céline , Padovan-Hernandez Yasmin , Chen Bridget , Pat Fiona , Ottenheimer David J. , Janak Patricia H.
Published: June 2023

The ability to evaluate and select a preferred option among a variety of available offers is an essential aspect of goal-directed behavior. Dysregulation of this valuation process is characteristic of alcohol use disorder, with the central amygdala being implicated in persistent alcohol pursuit. However, the mechanism by which the central amygdala encodes and promotes the motivation to seek and consume alcohol remains unclear. We recorded single-unit activity in male Long-Evans rats as they consumed 10% ethanol or 14.2% sucrose. We observed significant activity at the time of approach to alcohol or sucrose, as well as lick-entrained activity during the ongoing consumption of both alcohol and sucrose. We then evaluated the ability of central amygdala optogenetic manipulation time-locked to consumption to alter ongoing intake of alcohol or sucrose, a preferred non-drug reward. In closed two-choice scenarios where rats could drink only sucrose, alcohol, or quinine-adulterated alcohol with or without central amygdala stimulation, rats drank more of stimulation-paired options. Microstructural analysis of licking patterns suggests these effects were mediated by changes in motivation, not palatability. Given a choice among different options, central amygdala stimulation enhanced consumption if the stimulation was associated with the preferred reward while closed-loop inhibition only decreased consumption if the options were equally valued. However, optogenetic stimulation during consumption of the less-preferred option, alcohol, was unable to enhance overall alcohol intake while sucrose was available. Collectively, these findings indicate that the central amygdala processes the motivational value of available offers to promote pursuit of the most preferred available option.
Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)
Authors: Frieg Benedikt , Han Mookyoung , Giller Karin , Dienemann Christian , Riedel Dietmar , Becker Stefan , Andreas Loren B. , Griesinger Christian , Schröder Gunnar F.
Published: June 2023

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions.
Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways
Authors: Herrmannová Anna , Jelínek Jan , Pospíšilová Klára , Kerényi Farkas , Vomastek Tomáš , Watt Kathleen , Brábek Jan , Mohammad Mahabub Pasha , Wagner Susan , Topisirovic Ivan , Valášek Leoš Shivaya
Published: June 2023

Protein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes. To comprehensively study the effects of eIF3 remodeling, we contrasted the impact of eIF3d, eIF3e or eIF3h depletion on the translatome of HeLa cells using Ribo-seq. Depletion of eIF3d or eIF3e, but not eIF3h reduced the levels of multiple components of the MAPK signaling pathways. Surprisingly, however, depletion of all three eIF3 subunits increased MAPK/ERK pathway activity. Depletion of eIF3e and partially eIF3d also increased translation of TOP mRNAs that encode mainly ribosomal proteins and other components of the translational machinery. Moreover, alterations in eIF3 subunit stoichiometry were often associated with changes in translation of mRNAs containing short uORFs, as in the case of the proto-oncogene MDM2 and the transcription factor ATF4. Collectively, perturbations in eIF3 subunit stoichiometry exert specific effect on the translatome comprising signaling and stress-related transcripts with complex 5’ UTRs that are implicated in homeostatic adaptation to stress and cancer.
Relationship between the colors of the rivers in the Amazon and the incidence of malaria
Authors: Fonseca Fernanda , Martinez Jean-Michel , Balieiro Antônio , Orellana Jesem , Filizola Naziano
Published: June 2023

Background

Malaria is an infection caused by parasites of the genus Plasmodium, which are transmitted to humans via the bite of the female Anopheles mosquito. In Brazil, approximately 99% of malaria cases are concentrated in the Amazon region. Os rios desempenham um papel importante no ciclo de vida da malária, uma vez que o vetor se reproduz em ambiente aquático. The waters of the rivers in the Amazon have distinct chemical characteristics and this prompted us to analyze the influence of the color of the waters of the rivers in the Amazon on the distribution of malaria.

Methodology

This study was conducted for a period of seventeen years (2003-2019) in 50 municipalities in the state of Amazonas, Brazil. A generalized linear mixed model was developed to analyze the association of malaria incidence and three types of river color: white, black and mixed.

Principal Findings

The results suggest that there is a trend towards a decrease in malaria cases until 2015, with a possible resumption of the incidence of the disease from 2017 onwards, in all types of river color. In addition, the research indicates that places located near black-or mixed-water rivers have a higher incidence of malaria when compared to places on the banks of white-water rivers.

Conclusions

Historically, the hydrological regime has played an important role in the dynamics of malaria in the Amazon, but little is known about the relationship between river colors and the incidence of the disease. In this sense, our results, by showing a significant association between the colors of the rivers and the incidence of malaria over time, seem to expand the understanding between physical-chemical characteristics of the rivers and the occurrence of malaria.

Author summary

Malaria is a disease that has a major impact on morbidity in tropical and subtropical countries. In Brazil, most of the cases registered in the country are concentrated in the northern region. A variety of factors can contribute to the occurrence of malaria outbreaks or epidemics, and rivers play an important role in the transmission of the disease. The waters of the rivers in the Amazon have distinct chemical characteristics and this study sought to analyze the influence of the color of the waters of the rivers in the Amazon on the distribution of malaria. Data on the incidence of malaria, from 2003 to 2019, in 50 municipalities in the state of Amazonas, Brazil, were associated with three types of river coloration: white, black and mixed. The results demonstrated the existence of a trend towards a decrease in malaria over the years, in all types of river coloration, and that this trend does not seem to be associated with the different types of water. However, the research indicates that places located near black-or mixed-water rivers have a higher incidence of malaria, when compared to places on the banks of white-water rivers.
Predicting Executive Functioning from Brain Networks: Modality Specificity and Age Effects
Authors: Heckner Marisa K. , Cieslik Edna C. , Paas Oliveros Lya K. , Eickhoff Simon B. , Patil Kaustubh R. , Langner Robert
Published: June 2023

Healthy aging is associated with structural and functional network changes in the brain, which have been linked to deterioration in executive functioning (EF), while their neural implementation at the individual level remains unclear. As the biomarker potential of individual resting-state functional connectivity (RSFC) patterns has been questioned, we investigated to what degree individual EF abilities can be predicted from gray-matter volume (GMV), regional homogeneity, fractional amplitude of low-frequency fluctuations (fALFF), and RSFC within EF-related, perceptuo-motor, and whole-brain networks in young and old adults. We examined whether differences in out-of-sample prediction accuracy were modality-specific and depended on age or task-demand levels. Both uni- and multivariate analysis frameworks revealed overall low prediction accuracies and moderate to weak brain–behavior associations (R2< .07,r< .28), further challenging the idea of finding meaningful markers for individual EF performance with the metrics used. Regional GMV, well linked to overall atrophy, carried the strongest information about individual EF differences in older adults, whereas fALFF, measuring functional variability, did so for younger adults. Our study calls for future research analyzing more global properties of the brain, different task-states and applying adaptive behavioral testing to result in sensitive predictors for young and older adults, respectively.
Gle1 is required for tRNA to stimulate Dbp5 ATPase activityin vitroand to promote Dbp5 mediated tRNA exportin vivo
Authors: Rajan Arvind Arul Nambi , Asada Ryuta , Montpetit Ben
Published: June 2023

Cells must maintain a pool of processed and charged transfer RNAs (tRNA) to sustain translation capacity and efficiency. Numerous parallel pathways support the processing and directional movement of tRNA in and out of the nucleus to meet this cellular demand. Recently, several proteins known to control messenger RNA (mRNA) transport were implicated in tRNA export. The DEAD-box Protein 5, Dbp5, is one such example. In this study, genetic and molecular evidence demonstrates that Dbp5 functions parallel to the canonical tRNA export factor Los1.In vivoco-immunoprecipitation data further shows Dbp5 is recruited to tRNA independent of Los1, Msn5 (another tRNA export factor), or Mex67 (mRNA export adaptor), which contrasts with Dbp5 recruitment to mRNA that is abolished upon loss of Mex67 function. However, as with mRNA export, overexpression of Dbp5 dominant-negative mutants indicates a functional ATPase cycle and that binding of Dbp5 to Gle1 is required by Dbp5 to direct tRNA export. Biochemical characterization of the Dbp5 catalytic cycle demonstrates the direct interaction of Dbp5 with tRNA (or double stranded RNA) does not activate Dbp5 ATPase activity, rather tRNA acts synergistically with Gle1 to fully activate Dbp5. These data suggest a model where Dbp5 directly binds tRNA to mediate export, which is spatially regulated via Dbp5 ATPase activation at nuclear pore complexes by Gle1.
Single cell-resolutionin situsequencing elucidates spatial dynamics of multiple sclerosis lesion and disease evolution
Authors: Langseth C. M. , Kukanja P. , Rubio Rodríguez-Kirby L. A. , Agirre E. , Raman A. , Yokota C. , Avenel C. , Tiklová K. , Guerreiro-Cacais A. O. , Olsson T. , Hilscher M. M. , Nilsson M. , Castelo-Branco G.
Published: June 2023

Multiple sclerosis (MS) is a neurological disease characterised by multifocal lesions and smouldering pathology. While single-cell analyses have provided insights into neuropathology, cellular processes underlying MS remain poorly understood. We modelled the cellular dynamics of MS by examining temporal and regional rates of disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model. By performing single-cell spatial expression profiling usingIn situsequencing, we annotated disease neighbourhoods during lesion evolution and found centrifugal propagation of active lesions. We demonstrated that disease-associated (DA) glia are dynamic and induced independently of lesions, preceding their formation. Single-cell spatial analysis of human archival MS spinal cord confirmed differential distribution of DA-glia, enabled deconvolution of active and inactive lesions into sub-compartments, and identification of new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single-cell resolution, our study unveils the intricate cellular dynamics underlying MS disease evolution.
Elucidating the Impact of Bacterial Lipases, Human Serum Albumin, and FASII Inhibition on the Utilization of Exogenous Fatty Acids byStaphylococcus aureus
Authors: Pruitt Emily L. , Zhang Rutan , Ross Dylan H. , Ashford Nathaniel K. , Chen Xi , Alonzo Francis , Bush Matthew F. , Werth Brian J. , Xu Libin
Published: June 2023

Staphylococcus aureusonly synthesizes straight-chain or branched-chain saturated fatty acids (SCFAs or BCFAs) via the type II fatty acid synthesis (FASII) pathway, but as a highly adaptive pathogen,S. aureuscan also utilize host-derived exogenous fatty acids (eFAs), including SCFAs and unsaturated fatty acids (UFAs).S. aureussecretes three lipases, Geh, sal1, and SAUSA300_0641, which could perform the function of releasing fatty acids from host lipids. Once released, the FAs are phosphorylated by the fatty acid kinase, FakA, and incorporated into the bacterial lipids. In this study, we determined the substrate specificity ofS. aureussecreted lipases, the effect of human serum albumin (HSA) on eFA incorporation, and the effect of FASII inhibitor, AFN-1252, on eFA incorporation using comprehensive lipidomics. When grown with major donors of fatty acids, cholesteryl esters (CEs) and triglycerides (TGs), Geh was found to be the primary lipase responsible for hydrolyzing CEs, but other lipases could compensate for the function of Geh in hydrolyzing TGs. Lipidomics showed that eFAs were incorporated into all majorS. aureuslipid classes and that fatty acid-containing HSA can serve as a source of eFAs. Furthermore,S. aureusgrown with UFAs displayed decreased membrane fluidity and increased production of reactive oxygen species (ROS). Exposure to AFN-1252 enhanced UFAs in the bacterial membrane, even without a source of eFAs, indicating a FASII pathway modification. Thus, the incorporation of eFAs alters theS. aureuslipidome, membrane fluidity, and ROS formation, which could affect host-pathogen interactions and susceptibility to membrane-targeting antimicrobials.

IMPORTANCE

Incorporation of host-derived exogenous fatty acids (eFAs), particularly unsaturated fatty acids (UFAs), byStaphylococcus aureuscould affect the bacterial membrane fluidity and susceptibility to antimicrobials. In this work, we found that Geh is the primary lipase hydrolyzing cholesteryl esters and, to a less extent, triglycerides (TGs) and that human serum albumin (HSA) could serve as a buffer of eFAs, where low levels of HSA facilitate the utilization of eFAs, but high levels of HSA inhibit it. The fact that the FASII inhibitor, AFN-1252, leads to an increase in UFA content even in the absence of eFA suggests that membrane property modulation is part of its mechanism of action. Thus, Geh and/or the FASII system look to be promising targets to enhanceS. aureuskilling in a host environment by restricting eFA utilization or modulating membrane property, respectively.
Effect of La doping on the structure and cycloidal spin ordering in multiferroic BiFeO3
Authors: Pikula Tomasz , Siedliska Karolina , Szumiata Tadeusz , Panek Rafał , Mitsiuk Viktor I. , Ruchomski Leszek , Jartych Elżbieta
Published: June 2023

A series of Bi1–x
La
x
FeO3 samples with 0.00 ≤ x ≤ 0.30 was synthesized by the sol–gel method. The effects of lanthanum concentration on the phase formation, microstructure and cycloidal spin ordering were studied using X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. The crystal structure of the La-doped bismuth ferrite transformed from rhombohedral R3c (x ≤ 0.05) to a mixture of R3c and cubic Pm
3
m (0.07 ≤ x ≤ 0.15) and finally to a mixture of R3c, Pm
3
m and orthorhombic Pbam (0.20 ≤ x ≤ 0.30). The Pbam phase, with characteristic porous microstructure shown by microscopy images, was observed in Bi1–x
La
x
FeO3 compounds for the first time. Based on the Mössbauer spectroscopy, it was found that the cycloidal spin ordering started to disappear at x = 0.07. With increasing La concentration the share of the cycloid decreased from 100% at 0.00 ≤ x ≤ 0.05 to 0% at x = 0.30. At the beginning, for x ≤ 0.02, the anharmonicity parameter, m, of the cycloidal spin ordering was about 0.5, which is typical of a pure BiFeO3 compound. In the range 0.05 ≤ x ≤ 0.25, the m parameter was of the order of 0.1, which indicated the practically harmonic character of the cycloid. The structural transition at x = 0.07 was accompanied by a substantial increase in magnetization.
Implications of the COVID-19 pandemic on internal auditing: a field study
Authors: Jarva Henry , Zeitler Teresa
Published: June 2023

Purpose

The purpose of this paper is to examine the implications of the COVID-19 pandemic on internal auditing as the pandemic forced individual internal auditors and audit teams to conduct the work remotely.

Design/methodology/approach

Five in-depth semi-structured interviews of internal audit experts that work in German retail and manufacturing industry were conducted between February and April 2021.

Findings

The authors find that the importance of audit technologies did not change significantly due to the pandemic, as audit technologies were already an integral part of internal audits. Interestingly, the transition to remote audits occurred with remarkable speed and efficiency. The presence of well-functioning information and communication technologies emerges as a critical facilitator for effective remote communication, collaboration and data exchange. However, audit technologies can only partially replace physical on-site examinations and human interaction. The main challenges of remote audits are related to the auditing of non-digitalized processes and the inherent limitations of auditee interviews and interactions.

Research limitations/implications

The authors' interview approach does not allow to cover variations between industries and between countries. While internal audit experts provided notably consistent responses during the interviews, acknowledging that the sample size is very small is important.

Practical implications

The COVID-19 pandemic serves as a catalyst for increased digitalization and technology adoption within the realm of internal auditing. A hybrid approach combining the benefits of on-site and remote audits is expected to prevail in the future.

Originality/value

The paper is among the first to document the effects of the COVID-19 pandemic on the work of internal auditing using field-based research methods.
Capital structure and default risk of small and medium enterprises: evidence from Algeria
Authors: Baha Riad , Levy Aldo , Hasnaoui Amir
Published: June 2023

Purpose

This study examines the existence of a causal relationship between the capital structure at the creation of the small and medium-sized enterprise (SME) and its viability after 3 years.

Design/methodology/approach

The empirical strategy consists of proceeding in two stages: first, the use of the Logit model to regress the studied variable reflecting the state of an SME of being in default or not, on the variables likely to significantly explain its default risk. Second, the authors investigate the existence of a relationship between the capital structure at the time of SME creation and viability. The obtained results are analyzed to confirm the initial hypothesis.

Findings

The results obtained indicate that the Logit model performs well in terms of discriminating and classifying SMEs. These findings are consistent with previous studies and support their conclusions regarding the model's strong classification capability. Furthermore, the model demonstrates a noteworthy classification rate of 90% for capital SMEs, specifically joint-stock companies (SpA). Out of the 10 observed SMEs, 8 nonfailing SMEs were still operational three years after the observation period, resulting in a survival rate of 80%.

Practical implications

The results allow bankers to better understand the main determinants of SME default risk and demonstrate the existence of a causal relationship between the capital structure of an SME and its viability. This study is conducted in the construction, public works, and hydraulics sector (second largest sector in Algeria after the services sector). In future works, the authors try to extend the results of this study to other sectors of activity.

Originality/value

The richness of the established Logit model is to consider both financial and non-financial and qualitative variables. Although the qualitative variables are not statistically significant in the results obtained, the authors used the “Legal form” variable to demonstrate the existence of a causal relationship between the capital structure of an SME and its viability.
Essentialising Sex: Hermaphrodites and the Thresholds of Masculinity and Femininity in the Early Modern Catholic Church c.1700
Authors: Röder Brendan
Published: June 2023

This article focuses on four individuals from France and Italy who were viewed as hermaphrodites and their attempts to become members of the Catholic clergy between c.1650 and 1720. Drawing on largely unexplored material from the archive of the Roman Congregation of the Council, this article argues that whether, and how, bodies were problematised as hermaphroditic depended on the different and changing thresholds of masculinity and femininity they were confronted with. Offering a fresh perspective on practices of constructing sex and sex difference, this article suggests that the decades c.1700 saw marked transformations in the defining and assigning of sex both in theory and social practice. Medical and ecclesiastical decision‐makers shifted their attention from a broader spectrum of behavioural and bodily signs to the anatomy of genitalia. The trend towards heightened vigilance and intransigence towards perceived sexual ambiguity was, however, highly asymmetrical, targeting mainly individuals initially believed to be women.
The influence of milk with different compositions on the bioavailability of blackberry polyphenols in model sports nutrition beverages
Authors: van de Langerijt Tessa M , O'Callaghan Yvonne C , Tzima Katerina , Lucey Alice , O'Brien Nora M , O'Mahony James A , Rai Dilip K , Crowley Shane V
Published: June 2023

This study aimed to determine whether the fat and protein content in dairy‐fruit blends prepared using full‐fat, semi‐skimmed, skimmed or high‐protein milk in combination with freeze‐dried blackberry puree influenced the bioaccessibility and bioavailability of blackberry polyphenols and organic acids. Samples were subjected to in vitro digestion, after which bioavailability was analysed with a Caco‐2 cell model. The addition of puree to milk resulted in the formation of protein aggregates, which partially protected anthocyanins during digestion. Milk fat may have increased the bioaccessibility of anthocyanins while reducing permeability through the Caco‐2 cells, leading to a lower bioavailability in tested samples.