bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabricating and examining nanocomposite of P3HT- Graphene- MoS2 by laser ablation method
Authors: Obaid Nagham M , Al-Nafiey Amer , Majeed Hassan A , Ali Al-Dahash Ghaleb
Published: June 2024

This study presents the first successful synthesis of a nanocomposite comprising Poly (3-hexylthiophene) (P3HT), graphene (G), and molybdenum disulfide (MoS2) via laser ablation, using a Q-switch Nd-YAG laser with a repetition rate of 1 (Hz) and different laser pulses of 200, 500, and 800 for both graphene and MoS2, the morphological and optical properties of the samples was thoroughly investigated by various analytical techniques including Transmission electron microscopy (TEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR), and spectrophotometer UV-Vis. Transmission electron microscopy showed that the graphene and molybdenum nanoparticles were semispherical or ball-shaped, with diameters ranging from 6.7 to 61.7 nm. The UV-Vis findings show that the absorbance and absorption coefficient increase with the number of pulses due to the increased concentration of nanoparticles. The FTIR results confirm strong bonding between the P3HT-G800P/MoS2 800P nanocomposite bonds. The indirect energy gap of the Nanocomposite is estimated to be 1.99 (eV), making it attractive for optoelectronic applications.
Implementation of standardized patient safety and quality improvement rounds in a tertiary care paediatric centre
Authors: Pianosi Kiersten D , McKelvie Brianna L , Kilgar Jennifer , Abdulsatar Farah , Strychowsky Julie E
Published: June 2024

Introduction

Patient safety is increasingly becoming a major priority for healthcare institutions, and various models of these rounds exist. The Ottawa M&M Model (OM3) is a structured and standardized approach to patient safety and quality improvement rounds that has been implemented at other institutions across Canada with good success.

Methods

This quality improvement project invited divisions within the Children’s Hospital in London, Ontario to participate in the implementation of the OM3 for M&M rounds. The project aligned with the Institute for Health Improvement’s Model for Improvement. Baseline needs assessments and facilitator training were performed. The main outcome was implementation of a version of the OM3 for PSQI rounds, action items generated from these rounds, and systemic hospital changes.

Results

The baseline needs assessment showed that 18 (66.7%) respondents were members of divisions with pre-existing M&M rounds. Most found their rounds at least valuable, but only two-thirds found that action items were generated following each meeting. After implementation of the OM3, 58.3% (21 of 36) of action items submitted to the CH-QCC were partially or completed actioned by the end of 2022. A post-implementation survey showed that of the 11 division representatives who responded, 7 (64%) were still participating in PSQI rounds and using the new OM3 format, which they agreed was more organized.

Conclusions

We were able to successfully implement a new standardized approach to Patient Safety and Quality Improvement Rounds that has led to systemic changes within the paediatrics hospital and continues to be used today.
Sleep deprivation in adolescent mice impairs long-term memory till early adulthood via suppression of hippocampal astrocytes
Authors: Kang Ji-Yun , Lee Jin-Seok , Wang Jing-Hua , Son Chang-Gue
Published: June 2024

Sleep deficiency is a rampant issue in modern society, serving as a pathogenic element contributing to learning and memory impairment, with heightened sensitivity observed in children. Clinical observations suggest that learning disabilities associated with insufficient sleep during adolescence can persist through adulthood, but experimental evidence for this is lacking. In this study, we examined the impact of early-life sleep deprivation (SD) on both short-term and long-term memory, tracking the effects sequentially into adulthood. We employed a modified multiple-platform method mouse model to investigate these outcomes. SD induced over a 14-day period, beginning on postnatal day 28 (PND28) in mice, led to significant impairment in long-term memory (while short-term memory remained unaffected) at PND42. Notably, this dysfunction persisted into adulthood at PND85. The specific impairment observed in long-term memory was elucidated through histopathological alterations in hippocampal neurogenesis, as evidenced by bromodeoxyuridine (BrdU) signals, observed both at PND42 and PND85. Furthermore, the hippocampal region exhibited significantly diminished protein expressions of astrocytes, characterized by lowered levels of aquaporin 4 (AQP4), a representative molecule involved in brain clearance processes, and reduced protein expressions of brain-derived neurotrophic factors. In conclusion, we have presented experimental evidence indicating that sleep deficiency-related impairment of long-term memory in adolescence can endure into adulthood. The corresponding mechanisms may indicate that the modification of astrocyte-related molecules has led to changes in hippocampal neurogenesis.
“Healthy Points” Gaming to Teach Social Determinants of Health
Authors: Campbell Suzie
Published: June 2024

Social determinants of health (SDOH) and population health are critical to prelicensure nursing education. Game-based learning is a strategy to increase student engagement. A gaming activity was created by faculty to increase student interaction and have students gain a deeper understanding of the SDOH. The game has students experience events that impact health, represented by “healthy points.” Faculty observed deeper student engagement and more robust discussion in class when using the game, with students reporting that the game was fun and engaging. Teaching methods such as gaming can be effective for teaching SDOH and preparing students to promote health equity.
Fostering Clinical Judgment and Promoting Transition Into First Clinical Rotation Through Active Learning
Authors: York Ashley , Wynn Laura
Published: June 2024

Undergraduate nursing education builds on knowledge obtained from previous semesters to grow critical thinking skills and promote clinical judgment attainment. Transitioning knowledge from the classroom to the clinical setting is often difficult. Students finishing their first semester of courses in a BSN program participated in a novel, interactive classroom activity to help them practice critical thinking, transfer their learning, and develop clinical judgment by applying concepts to patient scenarios. Using an engaging student experience promotes long-term deep learning in hopes that students will remain successful in their progression through the curriculum.
Genetic landscape of atopic dermatitis
Authors: Paternoster Lavinia
Published: June 2024

Purpose of review

This review summarizes recent advances in identifying genetic risk factors for atopic dermatitis and how these genetic associations are being used to explore the causal relationships between atopic dermatitis and potential risk factors and downstream outcomes.

Recent findings

A recent large-scale GWAS meta-analysis has identified 91 genetic loci associated with atopic dermatitis. Rare variant studies have also identified new gain-of-function or loss-of-function variants implicated in atopic dermatitis, particularly for FLG and STAT6/JAK1. Finally, there has been a surge in utilizing genetic association data to investigate the causal relationships between atopic dermatitis and other traits. Mendelian randomization studies have found that various metabolites and gut microbiota are causal for atopic dermatitis and have causally implicate atopic dermatitis in the development of alopecia areata, diabetes, vascular dementia and some cancers.

The past year has seen a huge increase in the genes implicated for atopic dermatitis and in the use of genetics to explore causal relationships. The latter requires caution in implementation and interpretation, but is a promising area of research. In the coming years, increasing the ethnic diversity of atopic dermatitis genetic studies would be very welcome and the translation of current genetic findings into new drugs will be an exciting area of development.
Designing and Implementing Effective Remote Simulation
Authors: Hrdy Michael , Moadel Tiffany , Bentley Suzanne , Chen Tina
Published: June 2024

The COVID-19 pandemic necessitated rapid innovations in distance learning.1 Simulation is a valuable medical education strategy for learners to translate abstract knowledge to clinical application and can be facilitated remotely. This AM Last Page presents common challenges in delivering remote simulation, practical solutions, and unique opportunities afforded by this novel educational format.
Increasing Diversity in Academic Medicine Via a Strategic Intermural Housestaff Leadership Development Program
Authors: Galvan Eva , Ahn Christina E. , Hansen Marissa , Evoh Vanessa , Gebreyohanns Yohanna , Estelle Carolee , Cryer Byron , Yin Helen , Harris Toi Blakley , Collins Chiquita A. , Okorodudu Dale O.
Published: June 2024

Problem

By 2055, the United States will no longer have a single race or ethnic majority. As the nation’s demographics change, the field of medicine must also change to meet the needs of diverse patients.

Approach

In 2013, UT Southwestern Medical Center implemented the Housestaff Emerging Academy of Leaders (HEAL) program, which provides leadership development skills and training to underrepresented in medicine physician residents in preparation for academic medicine careers. Program leaders hypothesized that by providing housestaff with structured mentorship, career coaching, and individualized development plans, HEAL would increase interest in pursuing academic careers and prepare residents for faculty positions. HEAL has since expanded to graduate medical education programs nationwide.

Outcomes

From 2013 to 2018, HEAL included housestaff at UT Southwestern and other Texas medical centers, totaling 392 enrollees. In 2019, the program increased to include housestaff from around the country. The first HEAL USA program had 39 housestaff, which increased to 173 in 2019, including 60 faculty from 31 U.S. academic medical centers. The 2019 HEAL USA preassessment survey (32 trainee responses) revealed that 10 (31%) of the housestaff were “extremely interested” in academic medicine, but only 1 (3%) felt “extremely confident” to pursue an academic medicine career. Postassessment responses to these same items (5 trainee responses) were 3 (60%) and 1 (20%), respectively, with 3 (60%) also feeling “extremely prepared” (1 [20%]) or “very prepared” (2 [40%]) to pursue an academic medicine career. Of 70 evaluable participants who attended at least 2 sessions and have graduated from residency, 47 (67%) have attained academic faculty positions, whereas 23 (33%) have pursued positions at nonacademic centers.

Next Steps

The next steps for HEAL USA will be continued expansion to additional medical centers and effective delivery of career development and leadership training to encourage participants to pursue academic medical careers.
Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units
Authors: Foote Henry P. , Thomassy Haley , Baquero Leonardo , Cayli Mina , Jacobs Elijah , Paladugu Anish , Roy Anisha , Heyward Elizabeth , Clark Reese H. , Hornik Christoph P. , Benjamin Daniel K. , Benjamin Jr Daniel K. , Greenberg Rachel G.
Published: June 2024

Background:

Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis.

Methods:

We performed a multicenter cohort study of infants in neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2020. We included all infants who received acyclovir with complete dosing information. Our primary outcome was the proportion of courses with dosing within 80%–120% of the PopPK recommended daily dose and at the recommended dosing frequency. We compared dosing before and after the publication of the 2014 PopPK recommendations using linear probability modeling.

Results:

We identified 6862 infants with complete dosing information across 308 centers. Dosing met PopPK recommendations for 41% of treatment courses for infants <30 weeks postmenstrual age (PMA), 71% for infants 30 to <36 weeks PMA and <1% for infants ≥ 36 weeks PMA. Comparison of dosing from 1997 to 2013 with that from 2015 to 2020 showed a significant increase in dosing meeting PopPK recommendations for infants <30 weeks PMA (P = 0.008) and infants 30 to <36 weeks PMA (P = 0.02) but not infants ≥ 36 weeks PMA (P = 0.29). No significant increase in dosing meeting PopPK recommendations was seen for any PMA group when comparison was limited to more recent years (2008–2013 vs. 2015–2020).

Conclusions:

Dosing meeting PopPK recommendations increased over time for some PMA groups, but dosing different than PopPK recommendations remains common. More research is needed to clarify optimal dosing strategies in these infants.
Health-related quality of life outcomes in children after congenital heart disease surgery in low-middle-income countries: a systematic review and meta-analysis
Authors: Luitel Prajjwol , Yadav Rukesh , Neupane Nischal , Paudel Sujan , Adhikari Niranjan , Punukollu Rachana
Published: June 2024

Introduction:

Improved treatments for children with congenital heart disease (CHD) have led to a growing interest in long-term functional outcomes such as health-related quality of life (HRQOL). Studies on HRQOL in children with CHD have yielded contradictory results. In this study, we aimed to perform a systematic review and meta-analysis to analyze the effect of surgery on HRQOL outcomes in children with CHD in low-income and middle-income countries.

Methods:

A comprehensive search for articles was performed using the Medline (PubMed), Scopus, and Embase databases from their inception to September 5, 2023. Studies reporting QOL outcomes in children <18 years and published in English were included.

Results:

Of the 1239 records screened, 10 studies, including 1721 participants, were included in the study. The overall QOL was significantly better in the control group than in the children who underwent surgery for CHD (P=0.04, standard mean difference of −0.62, 95% CI: −1.2 to −0.04), and the overall QOL was significantly better in the children with CHD after surgery than before surgery (P=0.05, standard mean difference of −0.56, 95% CI: −1.11 to −0.01).

Conclusion:

The QOL of children from low-income and middle-income countries who undergo surgery for CHD is significantly poorer than that of controls in all dimensions except the emotional domain. Meanwhile, surgery has the greatest impact on improving the physical domain in children with CHD after surgery. Strategies to improve HRQOL in this subgroup of patients should be further investigated.
Knowledge, attitude, practice, and associated factors of health professionals towards cardiopulmonary resuscitation at Ayder Comprehensive Specialized Hospital, 2023, Tigray, Ethiopia
Authors: Hadush Yared , Mulaw Abara , Belay Aregawi , Ayalew Assefa , Bitsa Yihdego , Berhane Haftom
Published: June 2024

Background:

Cardiopulmonary resuscitation (CPR) is a crucial medical technique that is performed manually to preserve intact brain function. Early initiation of CPR manoeuvres and activation of the chain of survival are key factors in the prognosis of patients with cardiorespiratory arrest (CRA). Inadequacy in any step of CPR due to a lack of knowledge or skill is associated with a poor return of spontaneous circulation and a decreased survival rate.

Objective:

To assess the knowledge, attitude, practice, and factors associated with health towards CPR at Ayder Comprehensive Specialized Hospital 2023.

Methods:

Institution-based cross-sectional study was conducted to assess the knowledge, attitude, and practice of health professionals towards cardiopulmonary CPR in Ayder Comprehensive Specialized Hospital Of Tigray, Ethiopia from 1 May to 30 August 2023. Data were collected using structured questionnaires by Two BSC anaesthesia staff and One MSc. as supervisor. A stratified random sampling technique was used to select the study participants. The Data were entered and analyzed using SPSS version 23. Variables with P value less than 0.20 were fitted into multivariate logistic regression. Descriptive statistics such as frequencies, median, interquartile range, percentages, tables, graphs and charts were used to present the results.

Result:

A total of 262 Of 277 healthcare providers were included in the study, with a response rate of 93.3%. Knowledge, attitude, practice of health professionals towards CPR was 22.5%, 39% and 31.5%, respectively. MSc degree in level of education [adjusted odds ratio (AOR): 8.561 95% CI=2.109–34.746], CPR training (AOR: 2.157, 95%, 1.005, 4.631), and Work experience 6–10years and more than 10 (AOR =0.195, 95% CI, 0.071–0.539) and AOR =0.148 195 95% CI, 0.017, 1.285) were significantly associated with knowledge. The Anaesthetist and Medical doctors were 5.5 times (AOR, 5.50, 95% CI 1.263–23.93) and 2.125 times (AOR: 2.125, 95% CI, 0.865–5.216) respectively more likely to have favourable attitude than the midwives. Regarding to practice participants with CPR training (AOR: 1.804 95% CI=0.925–3.518), good knowledge (AOR: 2.766 95% CI=1.312–5.836) and favourable attitude (AOR: 1.931, 95% CI=0.995–3.749) were significantly associated with safe practice.

Conclusion and recommendation:

The overall level of health professionals, knowledge, attitude, practices, and factors associated towards CPR in Ayder Comprehensive Specialized Hospital at Tigray, Ethiopia were insufficient, favourable and safe enough. Regular CPR training is recommended to increase the knowledge, attitude, and practice of healthcare professionals towards CPR.
Congenital Flexor Contracture of Ulnar Digits Masquerading as Volkmann Ischemic Contracture
Authors: Kumar Rajesh , Saini Parampreet Singh
Published: June 2024

Congenital flexion contracture of ulnar digits is a rare entity with few cases reported in medical literature. This condition is often misdiagnosed as Volkmann ischemic contracture as both have similar presentation. The patient history, physical examination, radiological investigation, and intra-operative findings can differentiate these 2 conditions clearly. A 14-year-old female presented to a tertiary care hospital with flexion deformity of the left long, ring, and little fingers without neurological deficit since she was 3 years old. Patient had decreased handspan with difficulty in grasping daily life objects. Finger flexion deformity was also not aesthetically acceptable due to social stigma. Patient finger contracture was managed with flexor pronator slide (Max-Page) operation. The muscle slide operation was done using concealed medial incision. Aesthetic and functional correction was achieved with no recurrence at subsequent follow-ups.
Applying a synergistic mindsets intervention to an esports context
Authors: Behnke Maciej , Lakens Daniel , Petrova Kate , Chwiłkowska Patrycja , Białek Szymon Jęśko , Kłoskowski Maciej , Krzyżaniak Wadim , Maciejewski Patryk , Kaczmarek Lukasz D. , Szymański Kacper , Jamieson Jeremy P. , Gross James J.
Published: June 2024

Affective responses during stressful, high-stakes situations can play an important role in shaping performance. For example, feeling shaky and nervous at a job interview can undermine performance, whereas feeling excited during that same interview can optimize performance. Thus, affect regulation—the way people influence their affective responses—might play a key role in determining high-stakes outcomes. To test this idea, we adapted a synergistic mindsets intervention (SMI) (Yeager
et al
. 2022
Nature
607
, 512–520 (doi:
10.1038/s41586-022-04907-7
)) to a high-stakes esports context. Our approach was motivated by the idea that (i) mindsets both about situations and one’s stress responses to situations can be shaped to help optimize stress responses, and (ii) challenge versus threat stress responses will be associated with improved outcomes. After a baseline performance task, we randomly assigned gamers (
n
= 300) either to SMI or a control condition in which they learned brain facts. After two weeks of daily gaming, gamers competed in a cash-prize tournament. We measured affective experiences before the matches and cardiovascular responses before and throughout the matches. Contrary to predictions, gamers did not experience negative affect (including feeling stressed), thus limiting the capacity for the intervention to regulate physiological responses and optimize performance. Compared with the control participants, synergistic mindsets participants did not show greater challenge responses or improved performance outcomes. Though our adaptation of Yeager
et al
.’s SMI did not optimize esports performance, our findings point to important considerations regarding the suitability of an intervention such as this to different performance contexts of varying degrees of stressfulness.
Multimode multiple wave scattering in suspensions of solid particles in viscous liquids: part 2: numerical validation
Authors: Pinfield Valerie J. , Valier-Brasier Tony
Published: June 2024

In the first paper in this series, we presented asymptotic results for the effective wavenumber of the coherent longitudinal waves propagating through a system of pseudo-randomly distributed spherical elastic scatterers in a viscous medium. The analysis was based on multi-modal multiple scattering theory to account for both longitudinal and shear waves in the viscous embedding medium, arising from wave conversions at the scatterers surface, and identified asymptotic results in the long wavelength limit of the longitudinal waves. In this second paper, we present numerical validation of the various asymptotic approximations presented previously, including truncation of the number of partial wave orders and the use of the low concentration expansion of the dispersion relation. We explore the important contributions of wave conversion and of correlations in particle positions to the effective attenuation and to the frequency of the dipolar resonance of the scatterers. A comparison of the experimental results obtained with water containing sub-micrometric silica beads shows the very good validity of the model, particularly in the vicinity of the dipolar resonance.
Moth resonant mechanics are tuned to wingbeat frequency and energetic demands
Authors: Wold Ethan S. , Aiello Brett , Harris Manon , bin Sikandar Usama , Lynch James , Gravish Nick , Sponberg Simon
Published: June 2024

An insect’s wingbeat frequency is a critical determinant of its flight performance and varies by multiple orders of magnitude across Insecta. Despite potential energetic benefits for an insect that matches its wingbeat frequency to its resonant frequency, recent work has shown that moths may operate off their resonant peak. We hypothesized that across species, wingbeat frequency scales with resonance frequency to maintain favourable energetics, but with an offset in species that use frequency modulation as a means of flight control. The moth superfamily Bombycoidea is ideal for testing this hypothesis because their wingbeat frequencies vary across species by an order of magnitude, despite similar morphology and actuation. We used materials testing, high-speed videography and a model of resonant aerodynamics to determine how components of an insect’s flight apparatus (stiffness, wing inertia, muscle strain and aerodynamics) vary with wingbeat frequency. We find that the resonant frequency of a moth correlates with wingbeat frequency, but resonance curve shape (described by the Weis-Fogh number) and peak location vary within the clade in a way that corresponds to frequency-dependent biomechanical demands. Our results demonstrate that a suite of adaptations in muscle, exoskeleton and wing drive variation in resonant mechanics, reflecting potential constraints on matching wingbeat and resonant frequencies.
Svornostia abyssi gen. nov., sp. nov. isolated from the world’s deepest silver–uranium mine currently devoted to the extraction of radon-saturated water
Authors: Kapinusova Gabriela , Suman Jachym , Strejcek Michal , Pajer Petr , Cajthaml Tomas , Ulbrich Pavel , Neumann-Schaal Meina , Uhlik Ondrej
Published: June 2024

A Gram-stain-positive, rod-shaped, aerobic, motile bacterium, J379T, was isolated from radioactive water spring C1, located in a former silver–uranium mine in the Czech Republic. This slow-growing strain exhibited optimal growth at 24–28 °C on solid media with <1 % salt concentration and alkaline pH 8–10. The only respiratory quinone found in strain J379T was MK-7(H4). C18 : 1 ω9c (60.9 %), C18 : 0 (9.4 %), C16 : 0 and alcohol-C18 : 0 (both 6.2 %) were found to be the major fatty acids. The peptidoglycan contained directly cross-linked meso-diaminopimelic acid. Phylogenetic reconstruction based on the 16S rRNA gene sequences and the core-genome analysis revealed that strain J379T forms a separate phylogenetic lineage within the recently amended order Solirubrobacterales. A comparison of the 16S rRNA gene sequences between strain J379T and other members of the order Solirubrobacterales showed <96 % similarity. This analysis revealed that the closest type strains were Parviterribacter kavangonensis D16/0 /H6T (95.2 %), Capillimicrobium parvum 0166_1T (94.9 %) and Conexibacter arvalis KV-962T (94.5 %). Whole-genome analysis showed that the closest type strain was Baekduia soli BR7-21T with an average nucleotide identity of 78 %, average amino acid identity of 63.2 % and percentage of conserved proteins of 48.2 %. The G+C content of the J379T genomic DNA was 71.7 mol%. Based on the phylogenetic and phylogenomic data, as well as its physiological characteristics, strain J379T is proposed to represent a type strain (DSM 113746T=CCM 9300T) of Svornostia abyssi gen. nov. sp. nov. within the family Baekduiaceae.
An AINTEGUMENTA phospho-switch controls bilateral stem cell activity during secondary growth
Authors: Xiao Wei , Yang Ling , Molina David , Chen Houming , Yu Shan , Miao Yingjing , Ripper Dagmar , Deng Shulin , Bayer Martin , De Rybel Bert , Ragni Laura
Published: June 2024

Plant stem cells have the remarkable ability to give rise to distinct tissues and organs throughout development. Two concentric cylinders of actively dividing stem cells are the main drivers of radial thickening during secondary growth, each producing distinct vascular cell types towards the inside and the outside. While the molecular mechanisms underlying their initiation have been well studied, it remains unclear how these stem cell layers determine which cell type is generated. Here, we demonstrate that the cross-talk between the ERECTA (ER) receptor pathway and auxin signalling controls the amount and choice of output tissue in these two stem cell regions. Mechanistically, we show that the ER pathway phosphorylates the transcription factor ANTEGUMENTA, thereby modulating bilateral stem cell activity and favouring the differentiation of only one type of cell. Our results thus show that the phosphorylation status of ANT regulates root girth and biomass accumulation by influencing bilateral stem cell production. This highlights the critical role of post-translational modifications in plant growth and development.
Gene-modified NK Cells Expressing CD64 and Pre-loaded with HIV-specific BNAbs Target Autologous HIV-1 Infected CD4+T Cells by ADCC
Authors: Tomescu Costin , Ortiz Adiana Ochoa , Lu Lily D. , Kong Hong , Riley James L. , Montaner Luis J.
Published: June 2024

NK cells can efficiently mediate antibody-dependent cellular cytotoxicity (ADCC) of antibody coated target cells via the low-affinity Fc-receptor, CD16, but cannot retain antibodies over time. To increase antibody retention and facilitate targeted ADCC, we genetically modified human NK cells with the high-affinity Fc receptor, CD64, so that we could pre-load them with HIV-specific BNAbs and enhance their capacity to target HIV infected cells via ADCC. Purified NK cells from the peripheral blood of Control Donors or Persons Living with HIV (PLWH) were activated with IL-2/IL-15/IL-21 cytokines and transduced with a lentivirus encoding CD64. High levels of CD64 surface expression were maintained for multiple weeks on NK cells and CD64 transduced NK cells were similar to control NK cells with strong expression of CD56, CD16, NKG2A, NKp46, CD69, HLA-DR, CD38, and CD57. CD64 transduced NK cells exhibited significantly greater capacity to bind HIV-specific BNAbs in short-term antibody binding assay as well as retain the BNAbs over time (1 week antibody retention assay) compared to Control NK cells only expressing CD16. BNAb pre-loaded CD64 transduced NK cells showed a significantly enhanced capacity to mediate ADCC against autologous HIV-1 infected CD4+primary T cells in both a short term 3 hour degranulation assay as well as a 24 hour HIV p24 HIV Elimination Assay when compared to control NK cells. A chimeric CD64 enhanced NK cell strategy (NK EnhancementStrategy, “NuKES”) retaining bound HIV-specific antibody and targeted ADCC represents a novel autologous primary NK cell immuno-therapy strategy against HIV.
A vacuolar invertase geneSlVImodulates sugar metabolism and postharvest fruit quality and resistance in tomato
Authors: Wu Yu , Chen Haonan , Wu Mengbo , Zhou Yuanyi , Yu Chuying , Yang Qihong , Rolland Filip , Van de Poel Bram , Bouzayen Mondher , Hu Nan , Wang Yikui , Liu Mingchun
Published: June 2024

Sugars act as signaling molecules to modulate various growth processes and enhance plant tolerance to various abiotic and biotic stresses. Moreover, sugars contribute to the post-harvest flavor in fleshy fruit crops. To date, the regulation of sugar metabolism and its effect in plant growth, fruit ripening, postharvest quality and resistance remains not fully understood. In this study, we investigated the role of tomato gene encoding a vacuolar invertase, hydrolyzing sucrose to glucose and fructose.SlVIis specifically expressed during the tomato fruit ripening process. We found that overexpression ofSlVIresulted in increased leaf size and early flowering, while knockout ofSlVIled to increased fruit sucrose content, enhanced fruit firmness, elevated resistance of postharvest fruit toBotrytis cinerea.Moreover, the content of naringenin and total soluble solids was significantly increased inSlVIknockout fruit at postharvest stage. Transcriptome analysis showed a negative feedback regulation triggered by sucrose accumulation inSlVIknockout fruit resulting in a downregulation ofBAM3andAMY2,which are critical for starch degradation. Moreover, genes associated with cell wall, cutin, wax, and flavonoid biosynthesis and pathogen resistance were upregulated inSlVIknockout fruit. Conversely, the expression levels of genes involved in cell wall degradation were decreased in knockout fruit. These results are consistent with the enhanced postharvest quality and resistance. Our findings not only provide new insights into the relationship between tomato fruit sucrose content and postharvest fruit quality, but also suggest new strategies to enhance fruit quality and extend postharvest shelf life.
A genome-wide study of ruminants reveals two endogenous retrovirus families still active in goats
Authors: Verneret Marie , Leroux Caroline , Faraut Thomas , Navratil Vincent , Lerat Emmanuelle , Turpin Jocelyn
Published: June 2024

Background: Endogenous retroviruses (ERV) are traces of ancestral retroviral germline infections that constitute a significant portion of mammalian genomes and function as LTR-retrotransposons. ERVs remain understudied in ruminants and usually focus on specific families, highlighting a need for comprehensive and thorough exploration of the ERV landscape in these species. Results: We characterized 23 de novo Class I and II ERV families across four reference assemblies of domestic and wild sheep and goats, and one assembly of cattle. Among these families, 15 were shared by the five ruminant species, while six were exclusive to small ruminants and two were exclusive to cattle. The presence of these families in other ruminant species revealed multiple endogenization events over 40 million years. We identified a total of 113,812 ERV insertions across the five genomes, representing between 0.5 and 1% of their genomes. Solo-LTRs account for 84.5% of the annotated copies demonstrating that most of the ERVs are relics of past events. Although Class I ERVs showed similar sequence divergence landscapes between species, Class II ERVs displayed contrasting evolutionary dynamics. Families II-3 and II-5 showed higher abundance and copy conservation in small ruminants. Family II-5 was closely related to circulating exogenous retroviruses and was identified with 22 copies sharing identical LTRs and 12 with complete coding capacities in the domestic goat. Conclusions: Our results indicate that two ERV families may have retain their transpositional activity within ruminants, particularly in domestic goats, illustrating distinct evolutionary dynamics among ruminant species. This work highlights the ongoing influence of ERVs on genomic landscapes and provides further insights into their evolutionary trajectories in ruminant genomes.
A holistic quantitative understanding of state transition in plant photosynthesis
Authors: Oung Hui Ming Olivia , Koochak Haniyeh , Krysiak Malgorzata , Svoboda Vaclav , Kirchhoff Helmut
Published: June 2024

Efficient and safe harvesting of sunlight by photosynthesis in plant thylakoid membranes requires that both photosystems (PS)I and PSII operate with similar electron turnover rates. This is realized by state transition encompassing the redistribution of light-harvesting complexes II (LHCII) between the spatially separated PSII (mainly in stacked grana thylakoids) and PSI (mainly in unstacked domains). Here, we provide a quantitative holistic view on lateral protein and pigment reorganizations within the thylakoid membrane network induced by state transitions and the role of reversible protein phosphorylation for this process. The data reveals that plants can perfectly balance electron fluxes through both photosystems by the redistribution of a certain pool of hyperphosphorylated LHCII from PSII in stacked to PSI in unstacked thylakoid membranes. Force balance analysis predicts that the photosystems antenna reorganization is not realized by a phosphorylation induced stimulation of lateral mobility of LHCII but likely by vertical unstacking. Shuffling of phospho-LHCII during state transition results in remodeling of the PSI supercomplex landscape but not of the PSII landscape supporting the notion that only a loosely bound pool of LHCIIs is involved in state transition.
Hexa-acylated lipopolysaccharides from the gut microbiota enhance cancer immunotherapy responses
Authors: Beresford-Jones Benjamin S. , Sardar Puspendu , Xia Wangmingyu , Shabana Omar , Suyama Satoshi , Jesus Faustino Ramos Ruben J. , Soderholm Amelia T. , Tourlomousis Panagiotis , Kuo Paula , Evans Alexander C. , Imianowski Charlotte J. , Conti Alberto G. , Wesolowski Alexander J. , Okkenhaug Klaus , Whiteside Sarah K. , Roychoudhuri Rahul , Bryant Clare E. , Cross Justin R. , Pedicord Virginia A.
Published: June 2024

Immune checkpoint inhibitors (ICI), such as anti-PD-1, have revolutionized cancer treatment, but they are only effective for a minority of patients. The gut microbiome plays a crucial role in modulating immunotherapy treatment responses, and previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis. However, LPS from diverse bacterial species have activities ranging from immunostimulatory to inhibitory. By functionally analyzing fecal metagenomes from 112 melanoma patients prior to anti-PD-1 therapy, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in the microbiomes of clinical responders. We confirmed robust activation of the NF-kB pathway by hexa-acylated LPSin vitro, and this activation was significantly inhibited by penta-acylated LPS in a dose-dependent manner. Importantly, oral administration of hexa-acylated LPS augmented anti-PD-1-mediated anti-tumor immunity in anin vivomouse model of cancer immunotherapy. Microbiome hexa-acylated LPS may therefore represent an accessible predictor and potential enhancer of clinical anti- PD-1 immunotherapy responses.

Statement of significance

Functional rather than taxonomic profiling of patient gut microbiomes reveals hexa-acylated LPS as a novel biomarker of responsiveness and a targetable pathway for enhancing responses to anti-PD-1, informing future studies and current patient treatment.
Autism Prevalence in Chile: Unmet Special Education Needs using Data Linkage and Bayesian Analysis of Three Million School-Aged Children
Authors: Roman-Urrestarazu Andres , Tyson Adele , Gatica-Bahamonde Gabriel , van Kessel Robin , Yang Justin , Mansilla Carola , Zuniga Isabel , Mendez-Fadol Alejanda , Larrain Blanca , Garcia Ricardo , Koch Damaris , Groot Wim , Pavlova Milena , Czabanowska Katarzyna , Ford Tamsin
Published: June 2024

Prevalence estimates of autism spectrum disorder (henceforth autism) in Latin America thus far have been limited by a lack of reliable population-level data. We analyzed autism school prevalence across 29 Chilean health service regions for students aged 6–18 years, standardized by age and sex. We validated these results using electronic health records from one of Chile’s largest regional health service, the Servicio de Salud Araucania Sur (SSAS). We then projected Bayesian prevalences, reporting nationally, and by health service, ethnicity, immigration background, and rurality. We found a standardized national school autism prevalence of 0.46% (95% CI, 0.46%-0.47%), with boys having six times higher odds of autism than girls (OR 6.10 [95%CI: 5.82–6.41]). The sex - and age-adjusted clinical prevalence in the SSAS trust was 1.22% (95% CI: 1.16%-1.28%) and the projected Bayesian national autism prevalence was 1.31% (95% Credible Interval: 1.25%-1.38%). Our results indicate a higher autism prevalence than previously reported in the south of the Araucania region with observed disparities in prevalence across sex, ethnic groups, and health services.
Mechanical Strain Activates Planar Cell Polarity Signaling to Coordinate Vascular Cell Dynamics
Authors: Golbach Lieke , Saha Tanumoy , Odenthal-Schnittler Maria , Lücking Jenny , Velic Ana , Akmeric Emir Bora , Bornhorst Dorothee , Popp Oliver , Mertins Philipp , Gunawan Felix , Gerhardt Holger , Macek Boris , Trappmann Britta , Schnittler Hans J. , Galic Milos , Matis Maja
Published: June 2024

Mechanical stimuli, particularly laminar blood flow, play a crucial role in shaping the vascular system. Changes in the rate of blood flow manifest in altered shear stress, which activates signaling cascades that drive vascular remodeling. Consistently, dysregulation of the endothelial response to fluid shear forces and aberrant flow patterns both lead to pathological conditions, including impaired blood vessel development and atherosclerosis. Despite its importance, the mechanisms driving the coordinated cell behavior underlying vascular remodeling are not fully understood. Combining classical cell biological approaches with advanced image analysis, mathematical modeling, biomimetic strategies, and in vivo studies, we identify the planar cell polarity (PCP) protein Vangl1 as an enforcer of flow-dependent cell dynamics in the vascular system. We demonstrate that shear stress triggers the relocation of Vangl1 from an internal reservoir to the plasma membrane at the initiation of cell remodeling. Membrane enrichment of Vangl1 is mediated by a Coronin1C-dependent shift in the equilibrium between endo- and exocytosis and results in the spatial reorganization of another essential PCP protein, Frizzled6 (Fzd6). The resulting mutual exclusion of the core PCP proteins Fzd6 and Vangl1 augments differential junctional and cytoskeletal dynamics along the flow axis. Loss of Vangl1 limits the ability of endothelial cells to respond to shear forces in a coordinated fashion, resulting in irregular cell alignment along the flow direction and erroneous vessel sprouting. Together, these studies introduce core PCP signaling as a determinant of collective cell dynamics and organization of the vascular system.
HOCl Forms LipidN-Chloramines in Cell Membranes of Bacteria and Immune Cells
Authors: Knoke Lisa R. , Abad Herrera Sara , Heinrich Sascha , Lupilov Natalie , Bandow Julia E. , Günther Pomorski Thomas
Published: June 2024

Neutrophils orchestrate a coordinated attack on bacteria, combining phagocytosis with a potent cocktail of oxidants, including the highly toxic hypochlorous acid (HOCl), renowned for its deleterious effects on proteins. Here, we examined the occurrence of lipidN-chloraminesin vivo, their biological activity and neutralization. Using a chemical probe forN-chloramines, we demonstrate their formation in the membranes of bacteria and monocytic cells exposed to physiologically relevant concentrations of HOCl.N-chlorinated model membranes composed of phosphatidylethanolamine, the major membrane lipid inEscherichia coliand an important component of eukaryotic membranes, exhibited oxidative activity towards the redox-sensitive protein roGFP2, suggesting a role for lipidN-chloramines in protein oxidation. Conversely, the cellular antioxidant glutathione neutralized lipidN-chloramines by removing the chlorine moiety. We propose that lipidN-chloramines, like proteinN-chloramines, are involved in inflammation and accelerate the host immune response.
The PIN1-p38-CtIP signaling axis protects stalled replication forks from deleterious degradation
Authors: Vivalda Francesca , Gatti Marco , Manfredi Letizia , Dogan Hülya , Porro Antonio , Collotta Giulio , Ceppi Ilaria , von Aesch Christine , van Ackeren Vanessa , Wild Sebastian , Steger Martin , Canovas Begoña , Cubillos-Rojas Monica , Riera Antoni , Cejka Petr , Nebreda Angel R. , Dibitetto Diego , Rottenberg Sven , Sartori Alessandro A.
Published: June 2024

Human CtIP plays a critical role in homologous recombination (HR) by promoting the resection of DNA double-strand breaks. Moreover, CtIP maintains genome stability through protecting stalled replication forks from nucleolytic degradation. However, the upstream signaling mechanisms governing the molecular switch between these two CtIP-dependent processes remain largely elusive. Here, we show that phosphorylation of CtIP by the p38α stress kinase and subsequent PIN1-mediated CtIPcis-to-transisomerization is required for fork stabilization but dispensable for HR. We found that stalled forks are degraded in cells expressing non-phosphorylatable CtIP or lacking PIN1-p38α activity, while expression of a CtIPtrans-locked mutant overcomes the requirement for PIN1-p38α in fork protection. We further reveal thatBrca1-deficient mammary tumor cells that have acquired PARPi resistance regain chemosensitivity after PIN1 or p38α inhibition. Collectively, our findings identify the PIN1-p38-CtIP signaling pathway as a critical regulator of replication fork integrity.
Piezo1 is a mechanosensor of soft matrix viscoelasticity
Authors: Oliva Mariana A. G. , Ciccone Giuseppe , Luo Jiajun , Voigt Jonah L. , Romani Patrizia , Dobre Oana , Dupont Sirio , Vassalli Massimo , Salmeron-Sanchez Manuel
Published: June 2024

Mechanosensitive ion channels have emerged as fundamental proteins in sensing extracellular matrix (ECM) mechanics. Among those, Piezo1 has been proposed as a key mechanosensor in cells. However, whether and how Piezo1 senses time-dependent ECM mechanical properties (i.e., viscoelasticity) remains unknown. To address this question, we combined an immortalised mesenchymal stem cell (MSC) line with adjustable Piezo1 expression with soft (400 Pa) and stiff (25 kPa) viscoelastic hydrogels with independently tuneable Young’s modulus and stress relaxation. We demonstrate that Piezo1 is a mechanosensor of viscoelasticity in soft ECMs, consistent with the molecular clutch model. By performing RNA sequencing (RNA-seq), we identified the transcriptomic phenotype of MSCs response to matrix viscoelasticity and Piezo1 activity, highlighting gene signatures that drive MSCs mechanobiology in soft and stiff viscoelastic hydrogels.
Unraveling an unknown diversity of archaeal and bacterial tetraether membrane lipid producers in a euxinic marine system
Authors: Boukhchtaber Dina Castillo , von Meijenfeldt F. A. Bastiaan , Canavesi Diana X. Sahonero , Dorhout Denise , Bale Nicole J. , Hopmans Ellen C. , Villanueva Laura
Published: June 2024

Bacterial membrane lipids have been traditionally defined as fatty acids (FAs) bilayers linked through ester bonds, while those of Archaea as ether-linked isoprenoids forming bilayers or monolayers of membrane spanning lipids (MSLs) known as isoprenoidal glycerol dialkyl glycerol tetraethers (isoGDGTs). This paradigm has been challenged with the discovery of branched GDGTs (brGDGTs), membrane spanning ether-bound branched alkyl FAs, that are of bacterial origin but whose specific producers in the environment are often unknown. The limited number of available microbial cultures restricts the knowledge of the biological sources of membrane lipids, which in turn limits their potential applicability as biomarkers. To address this limitation, we detected membrane lipids in the Black Sea using high resolution accurate mass/mass spectrometry and inferred their potential producers by targeting lipid biosynthetic pathways encoded on the metagenome, in metagenome-assembled genomes and unbinned scaffolds. We also detected brGDGTs and overly branched GDGTs in the suboxic and euxinic waters, which are potentially attributed, to members of the Planctomycetota, Cloacimonadota, Desulfobacterota, Chloroflexota, Actinobacteria and Myxococcota—all anaerobic microorganisms. These results open a new chapter in the use of specific brGDGTs as biomarkers of anoxic conditions in marine settings and of the role of these membrane lipids in microbial adaptation.