bluuebunny/crossref_metadata_2025 huggingface dataset:
The elimination of two restriction enzyme genes allows for electroporation-based transformation and CRISPR-Cas9-based base editing in the non-competent Gram-negative bacterium
Acinetobacter
sp. Tol 5
Authors: Ishikawa Masahito , Hori Katsutoshi
Published: May 2024

Environmental isolates are promising candidates for new chassis of synthetic biology because of their inherent capabilities, which include efficiently converting a wide range of substrates into valuable products and resilience to environmental stresses; however, many remain genetically intractable and unamenable to established genetic tools tailored for model bacteria.
Acinetobacter
sp. Tol 5, an environmentally isolated Gram-negative bacterium, possesses intriguing properties for use in synthetic biology applications. Despite the previous development of genetic tools for the engineering of strain Tol 5, its genetic manipulation has been hindered by low transformation efficiency via electroporation, rendering the process laborious and time-consuming. This study demonstrated the genetic refinement of the Tol 5 strain, achieving efficient transformation via electroporation. We deleted two genes encoding type I and type III restriction enzymes. The resulting mutant strain not only exhibited marked efficiency of electrotransformation but also proved receptive to both
in vitro
and
in vivo
DNA assembly technologies, thereby facilitating the construction of recombinant DNA without reliance on intermediate
Escherichia coli
constructs. In addition, we successfully adapted a CRISPR-Cas9-based base-editing platform developed for other
Acinetobacter
species. Our findings provide genetic modification strategies that allow for the domestication of environmentally isolated bacteria, streamlining their utilization in synthetic biology applications.

IMPORTANCE

Recent synthetic biology has sought diverse bacterial chassis from environmental sources to circumvent the limitations of laboratory
Escherichia coli
strains for industrial and environmental applications. One of the critical barriers in cell engineering of bacterial chassis is their inherent resistance to recombinant DNA, propagated either
in vitro
or within
E. coli
cells. Environmental bacteria have evolved defense mechanisms against foreign DNA as a response to the constant threat of phage infection. The ubiquity of phages in natural settings accounts for the genetic intractability of environmental isolates. The significance of our research is in demonstrating genetic modification strategies for the cell engineering of such genetically intractable bacteria. This research marks a pivotal step in the domestication of environmentally isolated bacteria, promising candidates for emerging synthetic biology chassis. Our work thus significantly contributes to advancing their applications across industrial, environmental, and biomedical fields.
Group A
Streptococcus
induces lysosomal dysfunction in THP-1 macrophages
Authors: Nishioka Scott T. , Snipper Joshua , Lee Jimin , Schapiro Joshua , Zhang Robert Z. , Abe Hyewon , Till Andreas , Okumura Cheryl Y. M.
Published: May 2024

The human-specific bacterial pathogen group A
Streptococcus
(GAS) is a significant cause of morbidity and mortality. Macrophages are important to control GAS infection, but previous data indicate that GAS can persist in macrophages. In this study, we detail the molecular mechanisms by which GAS survives in THP-1 macrophages. Our fluorescence microscopy studies demonstrate that GAS is readily phagocytosed by macrophages, but persists within phagolysosomes. These phagolysosomes are not acidified, which is in agreement with our findings that GAS cannot survive in low pH environments. We find that the secreted pore-forming toxin Streptolysin O (SLO) perforates the phagolysosomal membrane, allowing leakage of not only protons but also large proteins including the lysosomal protease cathepsin B. Additionally, GAS recruits CD63/LAMP-3, which may contribute to lysosomal permeabilization, especially in the absence of SLO. Thus, although GAS does not inhibit fusion of the lysosome with the phagosome, it has multiple mechanisms to prevent proper phagolysosome function, allowing for persistence of the bacteria within the macrophage. This has important implications for not only the initial response but also the overall functionality of the macrophages, which may lead to the resulting pathologies in GAS infection. Our data suggest that therapies aimed at improving macrophage function may positively impact patient outcomes in GAS infection.
Expanding science skills: teaching tissue culture, data analysis, and reporting through imaging the actin cytoskeleton
Authors: Harrison Adrian , Evans Gareth , Blanco Gonzalo
Published: May 2024

Within the eukaryotic cell, the actin cytoskeleton is a crucial structural framework that maintains cellular form, regulates cell movement and division, and facilitates the internal transportation of proteins and organelles. External cues induce alterations in the actin cytoskeleton primarily through the activation of Rho GTPases, which then bind to a diverse array of effector proteins to promote the local assembly or disassembly of actin. We have harnessed the extensively studied functions of RhoA in the dynamics of the actin cytoskeleton to craft a practical series for Stage 2 Biology students. This series not only imparts essential tissue culture laboratory skills but also reinforces them through repetition. These activities are presented in a scenario designed for students to explore the function of a hypothetical RhoA family member. Students produce slides from transfected cells, undertake fluorescence microscopy, process the images using ImageJ, and compile their findings in a comprehensive scientific report. The composition of the report requires independent acquisition of new knowledge and synoptic learning. According to student feedback, this early experience greatly aids in solidifying and honing the skills required to report on more extensive and intricate research projects, such as capstone projects.
Effectiveness and cost-effectiveness of community-based directly observed treatment (DOT) versus health facility-based DOT of tuberculosis in Africa: protocol for a systematic review and meta-analysis
Authors: Baye Tenaw , Kassaw Abebe Tarekegn , Gebrie Desye , Girmaw Fentaw , Ashagrie Getachew
Published: May 2024

Background

Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO’s End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain.

Objective

To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings.

Methods

We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted.

Ethics and dissemination

Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals.

PROSPERO registration number

CRD42023443260.
Rare variant association analyses reveal the significant contribution of carbohydrate metabolic disturbance in severe adolescent idiopathic scoliosis
Authors: Wen Wen , Zhao Zhengye , Zheng Zhifa , Zhao Sen , Zhao Hengqiang , Cheng Xi , Du Huakang , Li Ziquan , Wang Shengru , Qiu Guixing , Wu Zhihong , Zhang Terry Jianguo , Wu Nan
Published: May 2024

Background

Adolescent idiopathic scoliosis (AIS), the predominant genetic-influenced scoliosis, results in spinal deformities without vertebral malformations. However, the molecular aetiology of AIS remains unclear.

Methods

Using genome/exome sequencing, we studied 368 patients with severe AIS (Cobb angle >40°) and 3794 controls from a Han Chinese cohort. We performed gene-based and pathway-based weighted rare variant association tests to assess the mutational burden of genes and established biological pathways. Differential expression analysis of muscle tissues from 14 patients with AIS and 15 controls was served for validation.

Results

SLC16A8
, a lactate transporter linked to retinal glucose metabolism, was identified as a novel severe AIS-associated gene (p=3.08E-06, false discovery rate=0.009). Most AIS cases with deleterious
SLC16A8
variants demonstrated early onset high myopia preceding scoliosis. Pathway-based burden test also revealed a significant enrichment in multiple carbohydrate metabolism pathways, especially galactose metabolism. Patients with deleterious variants in these genes demonstrated a significantly larger spinal curve. Genes related to catabolic processes and nutrient response showed divergent expression between AIS cases and controls, reinforcing our genomic findings.

Conclusion

This study uncovers the pivotal role of genetic variants in carbohydrate metabolism in the development of AIS, unveiling new insights into its aetiology and potential treatment.
SF-36v2 and FACIT-Fatigue quality of life improvements with organ-specific SELENA-SLEDAI response and belimumab treatment in patients with systemic lupus erythematosus
Authors: Rendas-Baum Regina , Chen Wen-Hung , Gairy Kerry , Anderson Seth , Henning Christine , Hammer Anne , Kosinski Mark
Published: May 2024

Objective

Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment.

Methods

Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID).

Results

In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely <MID. Most organ system responders had improved FACIT-Fatigue scores versus non-responders, with cardiovascular and respiratory responders having improvements ≥MID. Musculoskeletal and renal responders receiving belimumab had greater improvements in several SF-36v2 domains than responders receiving placebo (>MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab.

Conclusions

SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.
Systematic review and meta-analysis of birth weight and perfluorohexane sulfonate exposures: examination of sample timing and study confidence
Authors: Ru Hongyu , Lee Alexandra L , Rappazzo Kristen M , Dzierlenga Michael , Radke Elizabeth , Bateson Thomas F , Wright J Michael
Published: May 2024

We examined the association between mean birth weight (BW) differences and perfluorohexane sulfonate (PFHxS) exposure biomarkers.

We fit a random effects model to estimate the overall pooled effect and for different strata based on biomarker sample timing and overall study confidence. We also conducted an analysis to examine the impact of a continuous measure of gestational age sample timing on the overall pooled effect.

We detected a −7.9 g (95% CI −15.0 to –0.7; pQ=0.85; I2=0%) BW decrease per ln ng/mL PFHxS increase based on 27 studies. The 11 medium confidence studies (β=−10.0 g; 95% CI −21.1 to 1.1) showed larger deficits than 12 high (β=−6.8 g; 95% CI −16.3 to 2.8) and 4 low confidence studies (β=−1.5 g; 95% CI −51.6 to 48.7). 10 studies with mid-pregnancy to late-pregnancy sampling periods showed smaller deficits (β=−3.9 g; 95% CI −17.7 to 9.9) than 5 post-partum studies (β=−28.3 g; 95% CI −69.3 to 12.7) and 12 early sampling studies (β=−7.6 g; 95% CI −16.2 to 1.1). 6 of 12 studies with the earliest sampling timing showed results closer to the null.

Overall, we detected a small but statistically significant BW deficit across 27 studies. We saw comparable BW deficit magnitudes in both the medium and high confidence studies as well as the early pregnancy group. Despite no definitive pattern by sample timing, larger deficits were seen in postpartum studies. We also saw results closer to the null for a subset of studies restricted to the earliest biomarker collection times. Serial pregnancy sampling, improved precision in gestational age estimates and more standardised reporting of sample variation and exposure units in future epidemiologic research may offer a greater understanding of the relationship between PFHxS on BW and any potential impact of pregnancy haemodynamics.
Supportive and palliative care needs in advanced non-malignant liver disease: systematic review
Authors: Haire Ellen , Mann Mala , Yeoman Andrew , Atkinson Clea , Wright Mark , Noble Simon
Published: May 2024

Advanced cirrhosis confers a significant symptom burden and has a 50% 2-year mortality rate in those with decompensated disease. There is increasing demand for supportive and palliative care (SAPC) for these patients, yet no consensus on the best model of delivery. It is necessary to identify the needs of such patients and their carers, and evaluate whether they are being met.

A literature search was conducted using key words pertaining to adult patients with liver cirrhosis and their SAPC needs. Study quality was assessed and findings grouped by theme. 51 full texts were selected for inclusion, 8 qualitative studies, 33 quantitative studies, 7 systematic reviews, 2 mixed methods studies and 1 Delphi methods. Key findings were grouped into three main themes: SAPC needs, access to SAPC and models of care.

Patients with cirrhosis have significant psychological and physical symptom burden with many unmet needs. These data failed to identify the best service model of care. The impact of specialist palliative care (SPC) referral was limited by small numbers and late referrals. With the majority of studies conducted in the USA, it is unclear how well these findings translate to other healthcare systems. Comparison between hepatology led services and SPC was limited by inconsistent outcome measures and prevented pooling of data sets. These data also had limited evaluation of patient-reported outcome measures. We propose the development of a core outcome set to ensure consistent and meaningful evaluation of the SAPC needs of patients with advanced non-malignant liver cirrhosis.
A semi-analytic approximation for a single-particle continuum wavefunction
Authors: Shakeshaft Robin
Published: May 2024

A moderately simple approximation to the radial wavefunction of an unbound particle which carries arbitrary angular momentum l( l + 1) and which scatters from any physical potential, including one with a Coulomb tail, is presented. The approximate wavefunction has the form of a linear combination of short- and long-range analytical functions that satisfies the correct boundary conditions at both the origin and at large distances. The coefficients of the short-range functions are determined by solving a matrix equation whose elements are highly suited to numerical quadrature, and which are hardly more difficult to evaluate for l ≫ 1 than for l = 0. The coefficients of the long-range functions are determined by both the nature of the interaction at large distances and the cusp condition on the wavefunction at the origin. This wavefunction has been tested by application to pure Coulomb scattering and to electron scattering from hydrogen within the 1s–2s–2p close coupling framework.
Spooky action at a distance? A two-phase study into learners’ views of quantum entanglement
Authors: Brang Michael , Franke Helena , Greinert Franziska , Ubben Malte S. , Hennig Fabian , Bitzenbauer Philipp
Published: May 2024

Quantum entanglement is a challenging concept within the field of physics education, often eluding a full grasp by both educators and learners alike. In this paper, we report findings from a two-phase empirical study into the views of entanglement held by pre-service physics teachers and physics students from various universities. In the first phase, we utilized a questionnaire consisting of open-ended questions which was completed by 31 pre-service physics teachers. The study participants’ ideas were explored using qualitative content analysis which led to the creation of rating scale items used in study phase 2. These items were administered to a broader cohort including 73 physics university students in order to capture the learners’ agreement or disagreement with the questionnaire statements, and hence, helped to validate and substantiate the in-depth insights from study phase 1. Key findings revealed widespread accurate notions, like the need to consider the entire system when examining entangled states. However, less elaborated views were also identified, including ideas such as that measurements of entangled states always show perfect (anti-)correlation. Another striking observation was the confusion between quantum entanglement and superposition. In the case of quantum teleportation, many participants seemed to have a basic grasp of the concept, although a number of misconceptions were apparent, notably the idea that quantum entanglement enables faster-than-light communication. Practically, the findings can assist educators in anticipating and addressing widespread (mis-)conceptions, paving the way for more effective instruction in quantum mechanics and its real-world applications, such as quantum cryptography and computing.
Multi-Scale Attention and Dilated Convolutional Neural Network-Based 3D Scene Reconstruction for Moving Objects
Authors: Bian Fuluo , Zhang Wentai
Published: May 2024

Three-dimensional (3D) scene reconstruction for moving objects remains a challenging research topic. It is crucial to effectively capture feature representations from dynamic and complex scenarios. Consequently, this work introduces the integration of multi-scale attention and dilated convolution to create an enhanced deep-learning structure for this purpose. Therefore, this paper proposes a 3D reconstruction method for moving objects based on multi-scale attention and a dilated convolutional neural network (CNN). Specifically, a multi-scale attention algorithm framework that incorporates dilated CNNs is designed to extract multi-scale features of moving targets. The dilated CNN is incorporated to enhance the model’s perception ability and receptive field while maintaining a lightweight structure. This integrated design aims to achieve automatic learning targeted at features and scene information at different scales. By increasing the effective range of information perception and further enhancing the quality of reconstruction results, a coordinate system is established for 3D scene reconstruction of moving targets. Finally, a comparative analysis of subjective vision, visualization, and reconstruction algorithms is conducted using real-world cases. The experimental results demonstrate that the proposed method exhibits significant advantages in the 3D scene reconstruction task of moving targets compared to traditional methods.
Discoidal carbonaceous compressions from the early Mesoproterozoic Gaoyuzhuang Formation: a fossil example of microbial biofilm
Authors: Chen Kai , Miao Lanyun , Zhao Fangchen , Zhu Maoyan
Published: May 2024

Discoidal carbonaceous compressions are the most common type of Precambrian macrofossil, with a long temporal range starting from the late Paleoproterozoic. However, their unsolved biological nature restricts our understanding of the early evolution of macroscopic life. Here, we report an assemblage of well-preserved discoidal carbonaceous macrofossils from the early Mesoproterozoic Gaoyuzhuang Formation in North China, which provides insights into this problem. They are preserved in round to elliptical shapes ranging in size from millimetres to several centimetres. Petrographic thin sections show that the macrofossils consist of laminated structures with alternating laminae of organic matter, along with clay minerals and dolomites. Neither cellular structures nor individual microfossils were identified within them, but their regular shape, internal structures and associated mineral constituents suggest that they are probably the remains of microbial biofilms, rather than multicellular organisms. This assemblage presents a well-preserved fossil example of macroscopic microbial biofilms with a regular overall morphology. It implies a possible origin of microbial biofilms for some of the early carbonaceous macrofossils and calls for a detailed re-examination of those macrofossils to exclude such a possibility. Our findings are consistent with previous studies that showed biofilms may have had an important role in the survival of early microorganisms in the Precambrian ecosystem.

Thematic collection:
This article is part of the The North China Craton as a window to Earth’s middle age collection available at:
https://www.lyellcollection.org/topic/collections/the-north-china-craton-as-a-window-to-earths-middle-age
Synthetic Data for Deep Learning in Computer Vision & Medical Imaging: A Means to Reduce Data Bias
Authors: Paproki Anthony , Salvado Olivier , Fookes Clinton
Published: May 2024

Deep-learning (DL) performs well in computer-vision and medical-imaging automated decision-making applications. A bottleneck of DL stems from the large amount of labelled data required to train accurate models that generalise well. Data scarcity and imbalance are common problems in imaging applications that can lead DL models towards biased decision making. A solution to this problem is synthetic data. Synthetic data is an inexpensive substitute to real data for improved accuracy and generalisability of DL models. This survey reviews the recent methods published in relation to the creation and use of synthetic data for computer-vision and medical-imaging DL applications. The focus will be on applications that utilised synthetic data to improve DL models by either incorporating an increased diversity of data that is difficult to obtain in real life, or by reducing a bias caused by class imbalance. Computer-graphics software and generative networks are the most popular data generation techniques encountered in the literature. We highlight their suitability for typical computer-vision and medical-imaging applications, and present promising avenues for research to overcome their computational and theoretical limitations.
Deep Domain Adaptation With Max-Margin Principle for Cross-Project Imbalanced Software Vulnerability Detection
Authors: Nguyen Van , Le Trung , Tantithamthavorn Chakkrit , Grundy John , Phung Dinh
Published: May 2024

Software vulnerabilities (SVs) have become a common, serious, and crucial concern due to the ubiquity of computer software. Many AI-based approaches have been proposed to solve the software vulnerability detection (SVD) problem to ensure the security and integrity of software applications (in both the development and testing phases). However, there are still two open and significant issues for SVD in terms of (i) learning automatic representations to improve the predictive performance of SVD, and (ii) tackling the scarcity of labeled vulnerability datasets that conventionally need laborious labeling effort by experts. In this paper, we propose a novel approach to tackle these two crucial issues. We first exploit the automatic representation learning with deep domain adaptation for SVD. We then propose a novel cross-domain kernel classifier leveraging the max-margin principle to significantly improve the transfer learning process of SVs from imbalanced labeled into imbalanced unlabeled projects.
Our approach is the first work that leverages solid body theories of the max-margin principle, kernel methods, and bridging the gap between source and target domains for imbalanced domain adaptation (DA) applied in cross-project SVD
. The experimental results on real-world software datasets show the superiority of our proposed method over state-of-the-art baselines. In short, our method obtains a higher performance on F1-measure, one of the most important measures in SVD, from 1.83% to 6.25% compared to the second highest method in the used datasets.
Fairness Testing of Machine Translation Systems
Authors: Sun Zeyu , Chen Zhenpeng , Zhang Jie , Hao Dan
Published: May 2024

Machine translation is integral to international communication and extensively employed in diverse human-related applications. Despite remarkable progress, fairness issues persist within current machine translation systems. In this article, we propose FairMT, an automated fairness testing approach tailored for machine translation systems. FairMT operates on the assumption that translations of semantically similar sentences, containing protected attributes from distinct demographic groups, should maintain comparable meanings. It comprises three key steps: (1) test input generation, producing inputs covering various demographic groups; (2) test oracle generation, identifying potential unfair translations based on semantic similarity measurements; and (3) regression, discerning genuine fairness issues from those caused by low-quality translation. Leveraging FairMT, we conduct an empirical study on three leading machine translation systems–Google Translate, T5, and Transformer. Our investigation uncovers up to 832, 1,984, and 2,627 unfair translations across the three systems, respectively. Intriguingly, we observe that fair translations tend to exhibit superior translation performance, challenging the conventional wisdom of a fairness-performance tradeoff prevalent in the fairness literature.
Centralized and Federated Models for the Analysis of Clinical Data
Authors: Li Ruowang , Romano Joseph D. , Chen Yong , Moore Jason H.
Published: May 2024

The progress of precision medicine research hinges on the gathering and analysis of extensive and diverse clinical datasets. With the continued expansion of modalities, scales, and sources of clinical datasets, it becomes imperative to devise methods for aggregating information from these varied sources to achieve a comprehensive understanding of diseases. In this review, we describe two important approaches for the analysis of diverse clinical datasets, namely the centralized model and federated model. We compare and contrast the strengths and weaknesses inherent in each model and present recent progress in methodologies and their associated challenges. Finally, we present an outlook on the opportunities that both models hold for the future analysis of clinical data.
Adverse Food Reactions: Physiological and Ecological Perspectives
Authors: Korn Lisa L. , Kutyavin Vassily I. , Bachtel Nathaniel D. , Medzhitov Ruslan
Published: May 2024

While food is essential for survival, it can also cause a variety of harmful effects, ranging from intolerance to specific nutrients to celiac disease and food allergies. In addition to nutrients, foods contain myriads of substances that can have either beneficial or detrimental effects on the animals consuming them. Consequently, all animals evolved defense mechanisms that protect them from harmful food components. These “antitoxin” defenses have some parallels with antimicrobial defenses and operate at a cost to the animal's fitness. These costs outweigh benefits when defense responses are exaggerated or mistargeted, resulting in adverse reactions to foods. Additionally, pathological effects of foods can stem from insufficient defenses, due to unabated toxicity of harmful food components. We discuss the structure of antitoxin defenses and how their failures can lead to a variety of adverse food reactions.
Diversifying laboratory assessment modes broadens engagement with practical competencies in life science students
Authors: Drumm Bernard T. , Bree Ronan , Griffin Caoimhin S. , O’Leary Niall
Published: May 2024

This study suggests that undergraduate life science students can benefit significantly from a holistic assessment strategy that complements reports with performance-based approaches that incorporate broader competencies and allow for greater student engagement and expression in undergraduate modules.
Insights into posttranslational regulation of skeletal muscle contractile function by the acetyltransferases, p300 and CBP
Authors: Meyer Gretchen A. , Ferey Jeremie L. A. , Sanford James A. , Fitzgerald Liam S. , Greenberg Akiva E. , Svensson Kristoffer , Greenberg Michael J. , Schenk Simon
Published: May 2024

The mechanism underlying dramatic loss of muscle contractile function with inducible deletion of both E1A binding protein p300 (p300) and cAMP-response element-binding protein binding protein (CBP) in skeletal muscle remains unknown. Here, we find that impairments in mitochondrial function or cross-bridge cycling are not the underlying mechanism of action. Future work will investigate other aspects of excitation-contraction coupling, such as Ca2+ handling and membrane excitability, as contractile function could be rescued by permeabilizing skeletal muscle, which provides exogenous Ca2+ and bypasses membrane depolarization.
LAMA improves tissue oxygenation more than LABA in patients with COPD
Authors: Perez-Bogerd Silvia , Van Muylem Alain , Zengin Selim , El Khloufi Yasmina , Maufroy Emilie , Faoro Vitalie , Malinovschi Andrei , Michils Alain
Published: May 2024

Long-acting muscarinic antagonists (LAMAs) significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with β2-agonists (LABAs). The mechanisms involved may differ between drugs: increased peripheral ventilation for LABA and likely lung capillary blood volume for LAMA. This could argue for LAMA as the first therapeutic choice in COPD.
Understanding coenzyme Q
Authors: Wang Ying , Lilienfeldt Noah , Hekimi Siegfried
Published: May 2024

Coenzyme Q (CoQ), also known as ubiquinone, comprises a benzoquinone head group and a long isoprenoid side chain. It is thus extremely hydrophobic and resides in membranes. It is best known for its complex function as an electron transporter in the mitochondrial electron transport chain (ETC) but is also required for several other crucial cellular processes. In fact, CoQ appears to be central to the entire redox balance of the cell. Remarkably, its structure and therefore its properties have not changed from bacteria to vertebrates. In metazoans, it is synthesized in all cells and is found in most, and maybe all, biological membranes. CoQ is also known as a nutritional supplement, mostly because of its involvement with antioxidant defenses. However, whether there is any health benefit from oral consumption of CoQ is not well established. Here we review the function of CoQ as a redox-active molecule in the ETC and other enzymatic systems, its role as a prooxidant in reactive oxygen species generation, and its separate involvement in antioxidant mechanisms. We also review CoQ biosynthesis, which is particularly complex because of its extreme hydrophobicity, as well as the biological consequences of primary and secondary CoQ deficiency, including in human patients. Primary CoQ deficiency is a rare inborn condition due to mutation in CoQ biosynthetic genes. Secondary CoQ deficiency is much more common, as it accompanies a variety of pathological conditions, including mitochondrial disorders as well as aging. In this context, we discuss the importance, but also the great difficulty, of alleviating CoQ deficiency by CoQ supplementation.
An Investigation of the Acoustic Enclosure of an Air Conditioning Compressor Using Response Surface Analysis and Topological Rigidity Optimization
Authors: Cao Hai-Feng , Yang Cang-Jie , Ma Ren-Lian , Ni Shi-Wei , Song Zheng-Kai , Wang Xi , Chen Yu-Xuan , Jiang Chen-Xing
Published: May 2024

A novel split‐type air conditioning system is introduced to balance usability and portability. Unlike conventional split‐type systems, where the compressor is typically placed outside, this system situates the compressor within the indoor unit, which may expose users to compressor noise. There are prominent peaks in the compressor noise spectrum, particularly at the compressor operating frequency and its harmonics, notably the second and third harmonics. The research presents a multilayered acoustic enclosure specifically designed for air conditioning compressors to address this issue without modifying the compressor or indoor unit casing. In order to get better sound insulation performance, a response surface methodology (RSM) is applied to optimize the thickness ratio, open area ratio, and open area height of the acoustic enclosure with predefined thickness. In addition, topological optimization is employed to strengthen weak areas of the acoustic enclosure. Then, experimental trials using the proposed acoustic enclosure are conducted in a semianechoic chamber. Results demonstrate significant reductions in noise levels, including 7.99 dB(A), 5.69 dB(A), and 5.19 dB(A) reductions in the fundamental frequency, second harmonic, and third harmonic noise of the compressor’s operating frequency, respectively.
Study the Impact of the Anthropogenic Activities on the Marine Environment of Fujairah Offshore Waters of UAE Based on Baseline Surveys and Buoy Data
Authors: Alhmoudi Sabhah Ali Obaid , Aldhanhani Hanan Rashed Alsharari , Ridouane Fouad Lamghari , Ateeg Mohamed , Al Moalla Aseela , Mirza Shaher Bano
Published: May 2024

As Fujairah comprises extremely diverse natural landscapes which enforce us to protect and understand possible risks and challenges faced by the coastal waters of Fujairah, it is critical to mitigate, reduce, and eliminate the risks. The aim of this study is to assess and evaluate the effect of such anthropogenic activities on the offshore waters of Fujairah. Accordingly, two buoys were deployed after conducting a baseline survey for 30 locations targeting areas affected by the anthropogenic activities. Furthermore, two sites were chosen for the buoy deployment, nearshore which is across the desalination plant (Qidfa) and offshore which is across the oil and gas facility port (Skamkam). After analyzing the water quality measurements taken for 1 year from both deployed buoys and compared it with the baseline survey measurements, an indication of water quality deterioration in nearshore and offshore buoys was evinced, and the nearshore site which located in Qidfa has a higher deterioration in water quality measurements compared to the offshore site located in Skamkam. A long-term monitoring program needs to be conducted to gather additional data on water quality over several years to help identify the seasonal variations, trends, and long-term changes in water quality.
Managing Cracked Teeth with Root Extension: A Prospective Preliminary Study Using Biodentine™ Material
Authors: de Toubes Kênia Maria Soares , Corrêa Isabella Sousa , Valadares Regina Célia Lopes , Tonelli Stephanie Quadros , Bruzinga Fábio Fernandes Borém , Silveira Frank Ferreira
Published: May 2024

Purpose. The authors of this study proposed an innovative approach involving the use of Biodentine™ material as an intraorifice barrier in cracked teeth with root extension to promote internal crack sealing, preventing the possibility of microinfiltration and apical crack propagation. Materials and Methods. The dental records of 11 patients with 12 posterior cracked teeth with root extension were included with a precise protocol performed by a senior endodontist. The treatment protocol included pulp diagnosis, crack identification using a dental operating microscope (DOM), endodontic treatment, placing a Biodentine™ as an intraorifice barrier, and immediate full‐coverage restoration. The effectiveness of the treatment was assessed at two intervals, 6 months, and 1−3 years posttreatment, evaluating clinical, radiographic, and tomographic aspects. The treatment was deemed successful if there were no indications of radiolucency, sinus tracts, edema, or periodontal pockets associated with the crack line. Results. The study observed remarkably positive outcomes during the follow‐up period, which spanned from 1 to 3 years. All the cracked teeth (100%) remained asymptomatic, meaning they were free of pain or discomfort. Furthermore, these teeth were in occlusal function. Both radiographic and tomographic assessments revealed the absence of bone loss along the crack line. This outcome signifies that the treatment effectively prevented further deterioration of the surrounding bone. Conclusions. Integrating advanced biomaterials and conservative restorative techniques has paved the way for innovative approaches in dental care. This protocol suggests a proactive step for managing cracked teeth with root extension. It addresses both biological aspects by sealing internal cracks and mechanical aspects by preventing crack progression, thereby improving these teeth’ prognosis and long‐term survival.
Utility of Pulmonary Angiography by 128-Slice Computed Tomographic Scanner in Diagnosis of Tetralogy of Fallot Cases
Authors: Dwivedi Abhishek , Sharma Ankur , Sharma Rachit , Awasthi Prateek , Choudhary Satveer Singh
Published: May 2024

Tetralogy of Fallot (TOF) is a significant cause of cyanotic congenital heart disease (CHD) encountered in childhood with few cases manifesting in adulthood. It has four classical features (ventricular septal defect, overriding of aorta, hypertrophy of right ventricular hypertrophy, and right ventricular outflow tract obstruction), but the clinical presentation and course can be variable. Due to various anatomical variations and complex anatomy, presurgical planning and postoperative follow-up by pulmonary computed tomographic angiography (CTA) have a very important role. With continued technological advances and the availability of 128-slice computed tomographic (CT) scans, they now play an important role in TOF preoperative evaluation and workup, assisting by minimizing routine invasive digital subtraction catheter angiography. The fast scan of a 128-slice CTA with very sensitive detectors is a very useful modality for studying the complex anatomy and variations as well as its utilization for postoperative management. In this article, we report four cases of TOF where we used a 128-slice scan for performing pulmonary angiography (Optima 660, GE 128, 2180 Premier Row, Orlando, FL 32809, U.S.A.) for preoperative diagnosis and management of three cases and work up for revision surgery for an already operated case with a nonfunctional modified Blalock-Taussig shunt with additional lung parenchymal findings simultaneously. This study will explain the advantageous role of the 128-slice CT scanner over the lesser-slice CT scanners with the ability of pulmonary CTA to facilitate accurate diagnosis and postoperative management.
Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus
Authors: Tang-Siegel Gaoyan G. , Maughan David W. , Frownfelter Milah B. , Light Alan R.
Published: May 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disabling disease with unclear etiology and pathophysiology, whose typical symptoms include prolonged debilitating recovery from fatigue or postexertional malaise (PEM). Disrupted production of adenosine triphosphate (ATP), the intracellular energy that fuels cellular activity, is a cause for fatigue. Here, we present a long-term case of ME/CFS: a 75-year-old Caucasian female patient, whose symptoms of ME/CFS were clearly triggered by an acute infection of the Epstein–Barr virus 24 years ago (mononucleosis). Before then, the patient was a healthy professional woman. A recent DNA sequence analysis identified missense variants of mitochondrial respiratory chain enzymes, including ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V). Protein subunits ATP6 and Cox1 are encoded by mitochondrial DNA outside of the nucleus: the Cox1 gene encodes subunit 1 of complex IV (CIV: cytochrome c oxidase) and the ATP6 gene encodes subunit A of complex V (CV: ATP synthase). CIV and CV are the last two of five essential enzymes that perform the mitochondrial electron transport respiratory chain reaction to generate ATP. Further analysis of the blood sample using transmission electron microscopy demonstrated abnormal, circulating, extracellular mitochondria. These results indicate that the patient had dysfunctional mitochondria, which may contribute directly to her major symptoms, including PEM and neurological and cognitive changes. Furthermore, the identified variants of ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V), functioning at a later stage of mitochondrial ATP production, may play a role in the abnormality of the patient’s mitochondria and the development of her ME/CFS symptoms.
Variations in Bioactive Compounds and Sensory Properties of Flower-Flavored Chardonnay Wine during Floral Maceration and Bottle Aging
Authors: Liang Zijian , Yang Shuge , Xiao Jingning , Chia Ying , Chen Yipeng , Fang Zhongxiang , Zhang Pangzhen
Published: May 2024

An innovative flavored wine was developed by macerating six different edible flowers into Chardonnay wine, where the physicochemical characteristics (titratable acidity, pH), antioxidant activity (DPPH, FRAP) and volatile profile were modulated. Bottle aging of the flower-flavored wines were performed for 9 months where a significant (p<0.05) increases of total phenolic content and an opposite trend in antioxidant power (assessed by DPPH and FRAP assays) were observed. A total of 37 volatile substances were characterized in the aged flower-flavored wines. The aging process led to a decline in fruity and floral odors. Among the 12 month-aged wines, 1% (w/v) O. fragrans-flavored Chardonnay wine aged for 12 months was perceived as the most-liked product in human sensory analysis. This study manifested a bright future of edible flowers as a novel additive in the development of flavored wine with desirable sensory attributes.
The Efficacy and Safety of Hyperthermic Intravesical Chemotherapy Compared with Other Instillation Methods in Treating Intermediate- and High-Risk Non-Muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis
Authors: Yang Yingying , Liu Hongquan , Chu Yongli , Wang Jipeng , Ma Jian , Ding Guixin , Bao Xingjun , Cui Yuanshan , Wu Jitao
Published: May 2024

Background. In order to prevent the recurrence and progression of intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT), various bladder instillation therapies have been developed in recent years. Among these, device-assisted Hyperthermic Intravesical Chemotherapy (HIVEC) has received a great deal of attention. Objective. To identify the efficacy and safety of HIVEC, we conducted this meta-analysis. Methods. We identified relevant articles from PubMed, Embase, and Cochrane Library databases. All published randomized controlled trials (RCTs) describing the role of bladder instillation for the treatment of intermediate- and high-risk NMIBC were involved. Outcomes included 1–3 years Recurrence-Free Survival (RFS), 1–3 years Progression-Free Survival (PFS), 5 years Overall Survival (OS), Adverse Events (AEs), and relevant subgroup analyses. Result. Our study involved a total of 10 RCTs and 1360 patients. In subgroup analysis, we found that compared to MMC instillation, HIVEC decreased the 1–3 years RFS (OR = 0.51; p=0.009) while not increasing the incidence of AEs (OR = 0.86; p=0.30). Compared with BCG instillation, HIVEC reduced the incidence of serious AEs (OR = 0.21; p=0.04) while bringing the same efficacy (OR = 0.78; p=0.63). Conclusion. HIVEC combined the advantages of efficacy and safety compared with the two recommended instillation modalities. As a potential alternative therapy, its widespread clinical effect remains to be further evaluated.
Table S4 from ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts
Authors: Hu Bomiao , Wiesehöfer Marc , de Miguel Fernando J. , Liu Zongzhi , Chan Lok-Hei , Choi Jungmin , Melnick Mary Ann , Arnal Estape Anna , Walther Zenta , Zhao Dejian , Lopez-Giraldez Francesc , Wurtz Anna , Cai Guoping , Fan Rong , Gettinger Scott , Xiao Andrew , Yan Qin , Homer Robert , Nguyen Don X. , Politi Katerina
Published: May 2024

Upregulated pathways in EGFR mutant cell lines transfected with ASCL1
Figure S8 from ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts
Authors: Hu Bomiao , Wiesehöfer Marc , de Miguel Fernando J. , Liu Zongzhi , Chan Lok-Hei , Choi Jungmin , Melnick Mary Ann , Arnal Estape Anna , Walther Zenta , Zhao Dejian , Lopez-Giraldez Francesc , Wurtz Anna , Cai Guoping , Fan Rong , Gettinger Scott , Xiao Andrew , Yan Qin , Homer Robert , Nguyen Don X. , Politi Katerina
Published: May 2024

Changes in chromatin accessibility in HCC827 and PC9 cells upon ASCL1 expression. Global changes in chromatin accessibility in mutant EGFR lung cancer cell lines following ASCL1 overexpression and osimertinib treatment.
Figure S5 from ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts
Authors: Hu Bomiao , Wiesehöfer Marc , de Miguel Fernando J. , Liu Zongzhi , Chan Lok-Hei , Choi Jungmin , Melnick Mary Ann , Arnal Estape Anna , Walther Zenta , Zhao Dejian , Lopez-Giraldez Francesc , Wurtz Anna , Cai Guoping , Fan Rong , Gettinger Scott , Xiao Andrew , Yan Qin , Homer Robert , Nguyen Don X. , Politi Katerina
Published: May 2024

Characterization of mutant EGFR lung cancer PDXs at single-cell resolution. Workflow for scRNA-seq on PDXs and single cell data for an additional PDX.
Figure S1 from ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts
Authors: Hu Bomiao , Wiesehöfer Marc , de Miguel Fernando J. , Liu Zongzhi , Chan Lok-Hei , Choi Jungmin , Melnick Mary Ann , Arnal Estape Anna , Walther Zenta , Zhao Dejian , Lopez-Giraldez Francesc , Wurtz Anna , Cai Guoping , Fan Rong , Gettinger Scott , Xiao Andrew , Yan Qin , Homer Robert , Nguyen Don X. , Politi Katerina
Published: May 2024

Effects of erlotinib and TKI withdrawal on PDX growth.