bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternate wetting and drying: a water-saving technology for sustainable rice production in Burkina Faso?
Authors: Johnson Jean-Martial , Becker Mathias , Kaboré Jean Eric P. , Dossou-Yovo Elliott Ronald , Saito Kazuki
Published: July 2024

With emerging water scarcity and rising fertilizer prices, optimising future water use while maintaining yield and nutrient efficiency in irrigated rice is crucial. Alternate wetting and moderate soil drying irrigation (i.e., re-irrigation when the water level reaches 15 cm below the soil surface) has proven to be an efficient water-saving technology in semi-arid zones of West Africa, reducing water inputs without yield penalty. Alternate wetting and severe soil drying (AWD30), by re-irrigating fields only when the water table reaches 30 cm below the soil surface, may further reduce water inputs compared to farmers’ irrigation practices (FP). However, acute soil drying may impair fertilizer use efficiency and reduce the bio-availability of some key nutrients. This study assessed the potentials and risks associated with AWD30 for smallholder rice farmers in the semi-arid zones of West Africa. We conducted 30 on-farm field trials over three seasons (wet and dry seasons of 2019, and dry season of 2020), in Kou Valley, Burkina Faso. We assessed yield, water productivity, nutrient uptake, and use efficiency under AWD30 and FP. In FP, farmers maintained their fields submerged as frequently as possible according to the scheme-dependent water provision schedule. With AWD30, irrigation frequency was reduced by 30%, however, soils were seldom completely dried due to a shallow groundwater table. Compared to FP, AWD30 reduced irrigation water input by 37% with no significant effects on grain yields (average of 4.5 Mg ha−1), thus increasing average water productivity by 39%. Both irrigation management practices provided comparable crop uptake of N, P, and K, and use efficiencies of applied N and P. However, the N content in straw and the P concentration in grain generally increased with total water input (rain + irrigation). We conclude that at locations with a shallow groundwater table, AWD30 can effectively save irrigation water without significantly reducing the grain yield and the use efficiency of applied mineral nutrients.
The effects of plant invasion, floral resources and soil characteristics on ground-nesting bees
Authors: Pellaton Raoul , Szigeti Viktor , Fenesi Annamária , Roberts Stuart , Török Edina , Kovács-Hostyánszki Anikó
Published: July 2024

Ground-nesting bees are susceptible to disturbances that affect foraging resources, vegetation structure and soil characteristics. We studied the effects of 12 invasive alien plant species on environmental variables and directly on ground-nesting bees to reveal their specific importance. We sampled bees along transects; flowers, vegetation, bare ground and litter in quadrats, as well as soil characteristics. Our results suggested that plant invasion reduced overall and flowering plant richness and positively affected the height of native vegetation. However, this did not affect ground-nesting bees’ abundance or species richness. Although we found invaded plots to have altered soil chemical characteristics compared to control plots, there was no correlation between soil characteristics and ground-nesting bees. The large explanatory potential of the random factors suggests that there were large differences in the abundance and species richness of ground-nesting bee species among the different habitat types and before and during the flowering of the invasive species. Although our study lacked a direct sampling of nesting bees, our results show the adverse effects of plant invasion on foraging and some nesting characteristics of ground-nesting bees. Future studies should put effort into the investigation of the number of nest holes and additional soil characteristics to get a better picture of the effects of plant invasion on ground-nesting activity.
Design Considerations for the Optimization of $$\lambda$$-SQUIDs
Authors: Schuster Constantin , Kempf Sebastian
Published: July 2024

Cryogenic microcalorimeters are key tools for high-resolution X-ray spectroscopy due to their excellent energy resolution and quantum efficiency close to 100%. Multiple types of microcalorimeters exist, some of which have already proven outstanding performance. Nevertheless, they cannot yet compete with cutting-edge grating or crystal spectrometers. For this reason, novel microcalorimeter concepts are continuously developed. One such concept is based on the strong temperature dependence of the magnetic penetration depth of a superconductor operated close to its transition temperature. This so-called $$\lambda$$
λ
-SQUID provides an in-situ tunable gain and promises to reach sub-eV energy resolution. Here, we present some design considerations with respect to the optimization of such a detector that are derived by analytic means. We particularly show that for this detector concept the heat capacity of the sensor should match the heat capacity of the absorber.
Measuring the impacts of university-industry R&D collaborations: a systematic literature review
Authors: Cohen Maria , Fernandes Gabriela , Godinho Pedro
Published: July 2024

Measuring the impacts of collaborative projects between industry and academia raises significant challenges. It involves stakeholders with different outlooks and impact expectations. Moreover, the multidimensional nature of the impacts themselves means they are tangible and intangible, short- and long-term, direct and indirect, positive and negative, making their measurement process very complex. To gain a deeper understanding of how university-industry R&D collaborations (UICs) impact society, this study conducts a systematic review, using thematic analysis of 92 selected articles published between 2000 and 2022. The paper identifies and categorizes the impacts resulting from UICs, examines the challenges associated with measuring these impacts, and explores the strategies that can be employed to overcome such challenges. Finally, the paper integrates all such findings into a comprehensive framework. This study contributes to the theoretical advancement of impact measurement within the field of UICs, providing a foundation for the development of methodologies aimed at assessing impacts. Furthermore, it highlights important avenues for future research.
Which Capital Flow Surge Methods Are Better at Predicting Reversals and Sudden Stops?: Balancing Type 1 and Type 2 Errors
Authors: Choi Yongseok , Efremidze Levan , Sula Ozan , Willett Thomas D.
Published: July 2024

Capital flow surges have become a major source of concern as they have been often followed by disruptive reversals and sudden stops. We introduce F-score methodology which evaluates how well particular capital flow surge method can predict reversals and sudden stops. F-scores consider both type 1 and type 2 errors and provide policy makers a framework to weigh economic costs of false negative and false positive signals. We construct and compare a large number of commonly used surge identification approaches, including several machine-learning methods, to investigate which types of formulations best help explain which surges are more likely to be reversed. While considerable literature has investigated the determinants of capital flow reversals and sudden stops with surges being included as one of the independent variables, so far little research attention has been focused directly on attempting to determine the likelihood that particular surge will result in reversals or sudden stops. This is the most important question for policies toward capital inflows since the optimal responses to capital flow surges would be quite different depending on whether the flows are likely to be reversed or not. Unfortunately, theory does not offer a clear guide to identifying surges other than that they are unusually large inflows. We emphasize that appropriate evaluation should involve not only precision in predicting reversals but also accuracy in not giving false alarms by predicting reversals that do not occur. In other words, attention needs to be paid to both type 1 and type 2 errors.
Temperature Dependence of Viscoelasticity of Lubricating Oil with Adsorptive Polymer Additives Sheared in Nanogaps
Authors: Nozue Takumi , Itoh Shintaro , Okubo Naoya , Fukuzawa Kenji , Zhang Hedong , Azuma Naoki
Published: July 2024

Adsorptive polymer additives have been reported to improve the retention capacity of oil films under hydrodynamic lubrication and to reduce friction under boundary lubrication. These effects are believed to result from the formation of a polymer adsorption film on the surface that acts as a lubricious coating. Polymer adsorption films have become dominant in nanometer-order microscopic gaps. However, their mechanical properties are difficult to quantify. This hinders the development of polymer additives. In our previous study, we successfully measured the shear viscoelasticity of lubricants (base oils) sheared in nanogaps using an originally developed measurement method called the fiber wobbling method (FWM). In this study, we measured the shear viscoelasticity of polymer-added lubricants in nanogaps by using FWM. In addition, we developed a heating stage in the FWM to quantify the temperature dependence of shear viscoelasticity in nanogaps. As a result, the viscosity index improved and elasticity was observed in the nanogap, where the polymer adsorption film was dominant. Furthermore, our results indicated that the elasticity of the adsorbed polymer film originated from entropic elasticity.

Graphical Abstract
Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles
Authors: Ucak Seren , Dissanayake Hasthi U. , Sutherland Kate , Yee Brendon J. , Kairaitis Kristina , Wheatley John R. , Piper Amanda J. , de Chazal Philip , Cistulli Peter A. ,   on behalf of the Sydney Sleep Biobank Investigators, Sarkissian Nina , Bin Yu Sun , Chow Chin Moi , Chan Andrew , Lowth Aimee , Graham Jacob , Wood William , Cohen Gary , Bennett Callum , Ahmadi Mohammad , Yee Brendon , Piper Amanda , Wong Keith , Melehan Kerri , Chan Margaret , Wang David , Gauthier Gislaine
Published: July 2024

Purpose

In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles.

Methods

HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep.

Results

Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001).

Conclusion

Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk.
CT colonography has advantages over colonoscopy for size measurement of colorectal polyps
Authors: Tsurumaru Daisuke , Nishimuta Yusuke , Nanjo Katsuya , Kai Satohiro , Miyasaka Mitsutoshi , Muraki Toshio , Ishigami Kousei
Published: July 2024

Purpose

The aim of this study was to compare the accuracy of colonoscopy (CS) and CT colonography (CTC) in the measurement of colorectal polyps using pathological size as a reference.

Materials and methods

The analysis included 61 colorectal polyps in 28 patients who underwent preoperative CTC at our institution. All polyps were endoscopically resected. Polyp sizes were measured by CS and CTC. Endoscopic polyp size was extracted from endoscopy records written by one of two endoscopists (A with 11 and B with 6 years of endoscopic experience, respectively), who estimated the size visually/categorically without any measuring devices. After matching the location, the polyp size was measured on CTC using manual three-dimensional (3D) measurement on a workstation. The sizes of resected polyps were also measured after pathological inspection. Differences of the polyp size between CTC and histology, and between CS and histology were compared using paired t tests. Differences in measurement between the two endoscopists were also analyzed.

Results

The mean diameters of polyps measured using CS, CTC, and pathology were 10.5 mm, 9.2 mm, and 8.4 mm, respectively. There was a significant correlation between CS and pathology, as well as between CTC and pathology (both P < 0.0001). The correlation coefficient for CS (r = 0.86) was lower than that for CTC (r = 0.96). The correlations between CS and pathology for endoscopists A and B were 0.90 and 0.89, respectively.

Conclusion

Measurements of polyp size using CTC were closer to the pathological measurements compared to those by CS, which exhibited greater variability. This suggests that CTC may be more suitable for polyp size measurements in the clinical setting if patients undergo CTC concurrently with colonoscopy.
Exploring the Experiences of Family Caregivers in the Management of Stroke Among the Older Adults in Nigeria: A Qualitative Study
Authors: Farombi Temitope H. , Khan Hafiz T. A. , Lawal Muili
Published: July 2024

Stroke, a significant neurological condition, often results in stroke survivors who are older adults relying on family caregivers, including children and spouses, leading to increased challenges for caregivers. This study investigates the experiences of family caregivers caring for stroke survivors who are older adults, focusing on the context of stroke management. Participants were purposively sampled, and three focus group discussions involving family caregivers (n = 18) of older adults who had experienced strokes were conducted. Conversations were recorded, translated, transcribed, and subjected to thematic analysis utilizing NVivo (version 12 pro) software. Thematic analysis yielded five distinct themes. The first theme illuminated family caregivers’ insights regarding the management of stroke in their members or significant others. The second theme emphasized the support and information received at the medical facility. The third theme showcased the perceived value of the information provided. The fourth theme highlighted unmet needs for both information and training in social support. The final theme illuminated the participants’ preferences for how they would like to receive information and training. This study highlights family caregivers’ experiences, encompassing a range of burdens, stresses, and challenges while caring for stroke survivors who are older adults. Findings emphasize the necessity for formal caregivers to provide adequate information, support, and training to family caregivers, thereby alleviating their burdens and enhancing stroke management in a home environment.
Advancing mental health predictions through sleep posture analysis: a stacking ensemble learning approach
Authors: Nouman Muhammad , Khoo Sui Yang , Mahmud M. A. Parvez , Kouzani Abbas Z.
Published: July 2024

Sleep posture is closely related to sleep quality, and can offer insights into an individual’s health. This correlation can potentially aid in the early detection of mental health disorders such as depression and anxiety. Current research focuses on embedding pressure sensors in bedsheets, attaching accelerometers on a subject’s chest, and installing cameras in bedrooms for sleep posture monitoring. However, such solutions sacrifice either the user's sleep comfort or privacy. This study explores the effectiveness of using contactless ultra-wideband (UWB) sensors for sleep posture monitoring. We employed a UWB dataset that is composed of the measurements from 12 volunteers during sleep. A stacking ensemble learning method is introduced for the monitoring of sleep postural transitions, which constitute two levels of learning. At the base-learner level, six transfer learning models (VGG16, ResNet50V2, MobileNet50V2, DenseNet121, VGG19, and ResNet101V2) are trained on the training dataset for initial predictions. Then, the logistic regression is employed as a meta-learner which is trained on the predictions gained from the base-learner to obtain final sleep postural transitions. In addition, a sleep posture monitoring algorithm is presented that can give accurate statistics of total sleep postural transitions. Extensive experiments are conducted, achieving the highest accuracy rate of 86.7% for the classification of sleep postural transitions. Moreover, time-series data augmentation is employed, which improves the accuracy by 13%. The privacy-preserving sleep monitoring solution presented in this paper holds promise for applications in mental health research.
Change in Mindfulness Profiles After Mindfulness-Based Cognitive Therapy for Major Depressive Disorder
Authors: Lubbers Jelle , Spinhoven Philip , Cladder-Micus Mira B. , Spijker Jan , Speckens Anne E. M. , Geurts Dirk E. M.
Published: July 2024

Objectives

Mindfulness-Based Cognitive Therapy (MBCT) reduces recurrence and current depressive symptoms in patients with major depressive disorder (MDD). To understand how and for whom MBCT works, a person-centered approach focusing on mindfulness profiles can be useful. Four mindfulness profiles, each associated differently with mental health outcomes, have previously been identified. So far, no studies have examined whether profiles change after MBCT and whether these changes are related to treatment outcome.

Method

Latent transition analysis (LTA) was performed on pre- and post-MBCT subscale scores of the Five Facet Mindfulness Questionnaire (FFMQ) in patients with current or remitted MDD (n=500). LTA allowed the assessment of individual changes in mindfulness profile after MBCT and the relation between profile change and corresponding changes in measures of mental health, including depressive symptoms, overall functional impairment, worry, and self-compassion.

Results

LTA re-established the four profiles previously identified cross-sectionally: “Very low mindfulness” (VLM), “Non-judgmentally aware” (NJA), “Judgmentally observing” (JO), and “High mindfulness” (HM). For 71 out of 168 patients with VLM profiles changed to NJA and for another 30 to HM. For 49 out of the 129 patients with NJA and for 37 out of 141 patients with JO profiles changed to HM. All 61 patients starting with HM kept HM. In general, change was related to greater than average improvement in mental health, while no change in profile was related to less than average improvement in mental health (except for HM).

Conclusions

Our findings indicate that changes in mindfulness profile after MBCT was differentially related to clinical change. These results from a person-centered approach offer new avenues to further elucidate the working mechanism of MBCT and improve its outcome.

Preregistration

This study was not preregistered.
The structures control the evolution of molasse basins and alteration zones occurrences in the northwestern sector of the Central Eastern Desert of Egypt
Authors: Abd El-Wahed Mohamed A. , Kassem Osama M. K. , Abudeif Abdelbaset M. , Abdelhameed Mohammed , Attia Mohamed
Published: July 2024

Integration between the analyses of both fieldwork and remote sensing dataset were employed to assess the structural evolution of molasse basins and explore gold mineral deposits in the El Qash area, Central Eastern Desert of Egypt. Sandstone, mudstones, wacke, and pebbly conglomerates make up most of the sediments in the molasse basins. The younger basins (595–575 Ma) are small, less weathered, and mostly Dokhan detritus-filled basins compared to the larger older basins (> 625–605 Ma), which have more weathered sources mainly of arc metavolcanics. The molasse basins appear to have originated in a north–south regional extensional setting, characterized by a prolonged period of left-lateral transtension combined with the formation of NNE-trending synformal folds during an ENE–WSW compression phase. Notably, en-echelon arrays of normal faults, oriented perpendicular to the boundary of the strike-slip shear zone, are a recurring feature in basins formed through transtension. Furthermore, oblique NE-SW compression played a role in generating SW-dipping thrust faults and regional folding with NW–SE orientation, along with the reactivation of transtensional normal faults in a reverse manner. Multispectral satellite imagery data and radar data are used to map the relevant lithological units, structures, and hydrothermal alteration zones. This study concludes that the regions where gold deposits may be explored in connection with prospecting alteration minerals include the area around the ophiolitic assemblages, and the granitic intrusions, in addition to the felsite and the molasse sediments contacts.
Noncoding RNA regulates the expression of Krm1 and Dkk2 to synergistically affect aortic valve lesions
Authors: Xian Gaopeng , Huang Rong , Xu Minhui , Zhao Hengli , Xu Xingbo , Chen Yangchao , Ren Hao , Xu Dingli , Zeng Qingchun
Published: July 2024

Calcific aortic valve disease (CAVD) is becoming an increasingly important global medical problem, but effective pharmacological treatments are lacking. Noncoding RNAs play a pivotal role in the progression of cardiovascular diseases, but their relationship with CAVD remains unclear. Sequencing data revealed differential expression of many noncoding RNAs in normal and calcified aortic valves, with significant differences in circHIPK3 and miR-182-5p expression. Overexpression of circHIPK3 ameliorated aortic valve lesions in a CAVD mouse model. In vitro experiments demonstrated that circHIPK3 inhibits the osteogenic response of aortic valve interstitial cells. Mechanistically, DEAD-box helicase 5 (DDX5) recruits methyltransferase 3 (METTL3) to promote the N6-methyladenosine (m6A) modification of circHIPK3. Furthermore, m6A-modified circHIPK3 increases the stability of Kremen1 (Krm1) mRNA, and Krm1 is a negative regulator of the Wnt/β-catenin pathway. Additionally, miR-182-5p suppresses the expression of Dickkopf2 (Dkk2), the ligand of Krm1, and attenuates the Krm1-mediated inhibition of Wnt signaling. Activation of the Wnt signaling pathway significantly contributes to the promotion of aortic valve calcification. Our study describes the role of the Krm1-Dkk2 axis in inhibiting Wnt signaling in aortic valves and suggests that noncoding RNAs are upstream regulators of this process.
NLRP3 inflammasome: a key player in the pathogenesis of life-style disorders
Authors: Ramachandran Rajath , Manan Abdul , Kim Jei , Choi Sangdun
Published: July 2024

Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body’s defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease.
Genome-resolved metagenomics: a game changer for microbiome medicine
Authors: Kim Nayeon , Ma Junyeong , Kim Wonjong , Kim Jungyeon , Belenky Peter , Lee Insuk
Published: July 2024

Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy. Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities. There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut. Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones.
MAST4 regulates stem cell maintenance with DLX3 for epithelial development and amelogenesis
Authors: Lee Dong-Joon , Kim Pyunggang , Kim Hyun-Yi , Park Jinah , Lee Seung-Jun , An Haein , Heo Jin Sun , Lee Min-Jung , Ohshima Hayato , Mizuno Seiya , Takahashi Satoru , Jung Han-Sung , Kim Seong-Jin
Published: July 2024

The asymmetric division of stem cells permits the maintenance of the cell population and differentiation for harmonious progress. Developing mouse incisors allows inspection of the role of the stem cell niche to provide specific insights into essential developmental phases. Microtubule-associated serine/threonine kinase family member 4 (Mast4) knockout (KO) mice showed abnormal incisor development with low hardness, as the size of the apical bud was decreased and preameloblasts were shifted to the apical side, resulting in amelogenesis imperfecta. In addition, Mast4 KO incisors showed abnormal enamel maturation, and stem cell maintenance was inhibited as amelogenesis was accelerated with Wnt signal downregulation. Distal-Less Homeobox 3 (DLX3), a critical factor in tooth amelogenesis, is considered to be responsible for the development of amelogenesis imperfecta in humans. MAST4 directly binds to DLX3 and induces phosphorylation at three residues within the nuclear localization site (NLS) that promotes the nuclear translocation of DLX3. MAST4-mediated phosphorylation of DLX3 ultimately controls the transcription of DLX3 target genes, which are carbonic anhydrase and ion transporter genes involved in the pH regulation process during ameloblast maturation. Taken together, our data reveal a novel role for MAST4 as a critical regulator of the entire amelogenesis process through its control of Wnt signaling and DLX3 transcriptional activity.
Phospholipase C-β3 is dispensable for vascular constriction but indispensable for vascular hyperplasia
Authors: Jin Seo Yeon , Ha Jung Min , Kum Hye Jin , Ma Ji Soo , Ha Hong Koo , Song Sang Heon , Yang Yong Ryoul , Lee Ho , Bae Yoon Soo , Yamamoto Masahiro , Suh Pann-Ghill , Bae Sun Sik
Published: July 2024

Angiotensin II (AngII) induces the contraction and proliferation of vascular smooth muscle cells (VSMCs). AngII activates phospholipase C-β (PLC-β), thereby inducing Ca2+ mobilization as well as the production of reactive oxygen species (ROS). Since contraction is a unique property of contractile VSMCs, signaling cascades related to the proliferation of VSMCs may differ. However, the specific molecular mechanism that controls the contraction or proliferation of VSMCs remains unclear. AngII-induced ROS production, migration, and proliferation were suppressed by inhibiting PLC-β3, inositol trisphosphate (IP3) receptor, and NOX or by silencing PLC-β3 or NOX1 but not by NOX4. However, pharmacological inhibition or silencing of PLC-β3 or NOX did not affect AngII-induced VSMC contraction. Furthermore, the AngII-dependent constriction of mesenteric arteries isolated from PLC-β3∆SMC, NOX1−/−, NOX4−/− and normal control mice was similar. AngII-induced VSMC contraction and mesenteric artery constriction were blocked by inhibiting the L-type calcium channel Rho-associated kinase 2 (ROCK2) or myosin light chain kinase (MLCK). The activation of ROCK2 and MLCK was significantly induced in PLC-β3∆SMC mice, whereas the depletion of Ca2+ in the extracellular medium suppressed the AngII-induced activation of ROCK2, MLCK, and vasoconstriction. AngII-induced hypertension was significantly induced in NOX1−/− and PLC-β3∆SMC mice, whereas LCCA ligation-induced neointima formation was significantly suppressed in NOX1−/− and PLC-β3∆SMC mice. These results suggest that PLC-β3 is essential for vascular hyperplasia through NOX1-mediated ROS production but is nonessential for vascular constriction or blood pressure regulation.
FGFR3 drives Aβ-induced tau uptake
Authors: Kim Dong Kyu , Suh Kyujin , Park Junho , Lee Sang-Eun , Han Jihui , Chang Sunghoe , Kim Youngsoo , Mook-Jung Inhee
Published: July 2024

The amyloid cascade hypothesis suggests that amyloid beta (Aβ) contributes to initiating subsequent tau pathology in Alzheimer’s disease (AD). However, the underlying mechanisms through which Aβ contributes to tau uptake and propagation remain poorly understood. Here, we show that preexisting amyloid pathology accelerates the uptake of extracellular tau into neurons. Using quantitative proteomic analysis of endocytic vesicles, we reveal that Aβ induces the internalization of fibroblast growth factor receptor 3 (FGFR3). Extracellular tau binds to the extracellular domain of FGFR3 and is internalized by the FGFR3 ligand, fibroblast growth factor 2 (FGF2). Aβ accelerates FGF2 secretion from neurons, thereby inducing the internalization of tau-attached FGFR3. Knockdown of FGFR3 in the hippocampus reduces tau aggregation by decreasing tau uptake and improving memory function in AD model mice. These data suggest FGFR3 in neurons as a novel tau receptor and a key mediator of Aβ-induced tau uptake in AD.
Interaction of perceived social support and childhood maltreatment on limbic responsivity towards negative emotional stimuli in healthy individuals
Authors: Borgers Tiana , Rinck Anne , Enneking Verena , Klug Melissa , Winter Alexandra , Gruber Marius , Kraus Anna , Dohm Katharina , Leehr Elisabeth J. , Grotegerd Dominik , Förster Katharina , Goltermann Janik , Bauer Jochen , Dannlowski Udo , Redlich Ronny
Published: July 2024

Childhood maltreatment (CM) is associated with increased limbic activity, while social support is linked to decreased limbic activity towards negative stimuli. Our study aimed to explore the interaction of perceived social support with CM, and their combined impact on limbic activity in negative emotion processing. A total of 130 healthy individuals (HC) underwent a negative emotional face processing paradigm. They were divided into two groups based on the Childhood Trauma Questionnaire: n = 65 HC without CM matched with n = 65 HC with CM. In a region-of-interest approach of the bilateral amygdala-hippocampus-complex (AHC), regression analyses investigating the association of CM and perceived social support with limbic activity and a social support x CM ANCOVA were conducted. CM was associated with increased AHC activity, while perceived social support tended to be associated with decreased AHC activity during negative emotion processing. The ANCOVA showed a significant interaction in bilateral AHC activity (pFWE ≤ 0.024) driven by a negative association between perceived social support and bilateral AHC activity in HC without CM. No significant association was observed in HC with CM. Exploratory analyses using continuous CM scores support this finding. Our results suggest that CM moderates the link between perceived social support and limbic activity, with a protective effect of perceived social support only in HC without CM. The lack of this effect in HC with CM suggests that CM may alter the buffering effect of perceived social support on limbic functioning, highlighting the potential need for preventive interventions targeting social perception of HC with CM.
Shared functional specialization in transformer-based language models and the human brain
Authors: Kumar Sreejan , Sumers Theodore R. , Yamakoshi Takateru , Goldstein Ariel , Hasson Uri , Norman Kenneth A. , Griffiths Thomas L. , Hawkins Robert D. , Nastase Samuel A.
Published: July 2024

When processing language, the brain is thought to deploy specialized computations to construct meaning from complex linguistic structures. Recently, artificial neural networks based on the Transformer architecture have revolutionized the field of natural language processing. Transformers integrate contextual information across words via structured circuit computations. Prior work has focused on the internal representations (“embeddings”) generated by these circuits. In this paper, we instead analyze the circuit computations directly: we deconstruct these computations into the functionally-specialized “transformations” that integrate contextual information across words. Using functional MRI data acquired while participants listened to naturalistic stories, we first verify that the transformations account for considerable variance in brain activity across the cortical language network. We then demonstrate that the emergent computations performed by individual, functionally-specialized “attention heads” differentially predict brain activity in specific cortical regions. These heads fall along gradients corresponding to different layers and context lengths in a low-dimensional cortical space.
Impacts of ocean warming on fish size reductions on the world’s hottest coral reefs
Authors: Johansen Jacob L. , Mitchell Matthew D. , Vaughan Grace O. , Ripley Daniel M. , Shiels Holly A. , Burt John A.
Published: July 2024

The impact of ocean warming on fish and fisheries is vigorously debated. Leading theories project limited adaptive capacity of tropical fishes and 14-39% size reductions by 2050 due to mass-scaling limitations of oxygen supply in larger individuals. Using the world’s hottest coral reefs in the Persian/Arabian Gulf as a natural laboratory for ocean warming - where species have survived >35.0 °C summer temperatures for over 6000 years and are 14-40% smaller at maximum size compared to cooler locations - we identified two adaptive pathways that enhance survival at elevated temperatures across 10 metabolic and swimming performance metrics. Comparing Lutjanus ehrenbergii and Scolopsis ghanam from reefs both inside and outside the Persian/Arabian Gulf across temperatures of 27.0 °C, 31.5 °C and 35.5 °C, we reveal that these species show a lower-than-expected rise in basal metabolic demands and a right-shifted thermal window, which aids in maintaining oxygen supply and aerobic performance to 35.5 °C. Importantly, our findings challenge traditional oxygen-limitation theories, suggesting a mismatch in energy acquisition and demand as the primary driver of size reductions. Our data support a modified resource-acquisition theory to explain how ocean warming leads to species-specific size reductions and why smaller individuals are evolutionarily favored under elevated temperatures.
HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages
Authors: Virgilio Maria C. , Ramnani Barkha , Chen Thomas , Disbennett W. Miguel , Lubow Jay , Welch Joshua D. , Collins Kathleen L.
Published: July 2024

HIV-1 Vpr promotes efficient spread of HIV-1 from macrophages to T cells by transcriptionally downmodulating restriction factors that target HIV-1 Envelope protein (Env). Here we find that Vpr induces broad transcriptomic changes by targeting PU.1, a transcription factor necessary for expression of host innate immune response genes, including those that target Env. Consistent with this, we find silencing PU.1 in infected macrophages lacking Vpr rescues Env. Vpr downmodulates PU.1 through a proteasomal degradation pathway that depends on physical interactions with PU.1 and DCAF1, a component of the Cul4A E3 ubiquitin ligase. The capacity for Vpr to target PU.1 is highly conserved across primate lentiviruses. In addition to impacting infected cells, we find that Vpr suppresses expression of innate immune response genes in uninfected bystander cells, and that virion-associated Vpr can degrade PU.1. Together, we demonstrate Vpr counteracts PU.1 in macrophages to blunt antiviral immune responses and promote viral spread.
Time-calibrated phylogenetic and chromosomal mobilome analyses of Staphylococcus aureus CC398 reveal geographical and host-related evolution
Authors: Fernandez Javier Eduardo , Egli Adrian , Overesch Gudrun , Perreten Vincent
Published: July 2024

An international collection of Staphylococcus aureus of clonal complex (CC) 398 from diverse hosts spanning all continents and a 30 year-period is studied based on whole-genome sequencing (WGS) data. The collection consists of publicly available genomic data from 2994 strains and 134 recently sequenced Swiss methicillin-resistant S. aureus (MRSA) CC398 strains. A time-calibrated phylogeny reveals the presence of distinct phylogroups present in Asia, North and South America and Europe. European MRSA diverged from methicillin-susceptible S. aureus (MSSA) at the beginning of the 1950s. Two major European phylogroups (EP4 and EP5), which diverged approximately 1974, are the main drivers of MRSA CC398 spread in Europe. Within EP5, an emergent MRSA lineage spreading among the European horse population (EP5-Leq) diverged approximately 1996 from the pig lineage (EP5-Lpg), and also contains human-related strains. EP5-Leq is characterized by staphylococcal cassette chromosome mec (SCCmec) IVa and spa type t011 (CC398-IVa-t011), and EP5-Lpg by CC398-SCCmecVc-t011. The lineage-specific antibiotic resistance and virulence gene patterns are mostly mediated by the acquisition of mobile genetic elements like SCCmec, S. aureus Genomic Islands (SaGIs), prophages and transposons. Different combinations of virulence factors are present on S. aureus pathogenicity islands (SaPIs), and novel antimicrobial resistance gene containing elements are associated with certain lineages expanding in Europe. This WGS-based analysis reveals the actual evolutionary trajectory and epidemiological trend of the international MRSA CC398 population considering host, temporal, geographical and molecular factors. It provides a baseline for global WGS-based One-Health studies of adaptive evolution of MRSA CC398 as well as for local outbreak investigations.
De novo atomic protein structure modeling for cryoEM density maps using 3D transformer and HMM
Authors: Giri Nabin , Cheng Jianlin
Published: July 2024

Accurately building 3D atomic structures from cryo-EM density maps is a crucial step in cryo-EM-based protein structure determination. Converting density maps into 3D atomic structures for proteins lacking accurate homologous or predicted structures as templates remains a significant challenge. Here, we introduce Cryo2Struct, a fully automated de novo cryo-EM structure modeling method. Cryo2Struct utilizes a 3D transformer to identify atoms and amino acid types in cryo-EM density maps, followed by an innovative Hidden Markov Model (HMM) to connect predicted atoms and build protein backbone structures. Cryo2Struct produces substantially more accurate and complete protein structural models than the widely used ab initio method Phenix. Additionally, its performance in building atomic structural models is robust against changes in the resolution of density maps and the size of protein structures.
CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment
Authors: Zhang Jie , Hu Gongcheng , Lu Yuli , Ren Huawei , Huang Yin , Wen Yulin , Ji Binrui , Wang Diyang , Wang Haidong , Liu Huisheng , Ma Ning , Zhang Lingling , Pan Guangjin , Qu Yibo , Wang Hua , Zhang Wei , Miao Zhichao , Yao Hongjie
Published: July 2024

The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelerates the maturation of GABAergic neurons, and disrupts neurodevelopmental and synaptic pathways. Additionally, it specifically hinders CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrors the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567W mutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions.
Prefrontal cortex neurons encode ambient light intensity differentially across regions and layers
Authors: Zangen Elyashiv , Hadar Shira , Lawrence Christopher , Obeid Mustafa , Rasras Hala , Hanzin Ella , Aslan Ori , Zur Eyal , Schulcz Nadav , Cohen-Hatab Daniel , Samama Yona , Nir Sarah , Li Yi , Dobrotvorskia Irina , Sabbah Shai
Published: July 2024

While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions’ contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.
Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice
Authors: Demaestri Camila , Pisciotta Margaux , Altunkeser Naira , Berry Georgia , Hyland Hannah , Breton Jocelyn , Darling Anna , Williams Brenna , Bath Kevin G.
Published: July 2024

Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.
Co-immobilization of whole cells and enzymes by covalent organic framework for biocatalysis process intensification
Authors: Zheng Dong , Zheng Yunlong , Tan Junjie , Zhang Zhenjie , Huang He , Chen Yao
Published: July 2024

Co-immobilization of cells and enzymes is often essential for the cascade biocatalytic processes of industrial-scale feasibility but remains a vast challenge. Herein, we create a facile co-immobilization platform integrating enzymes and cells in covalent organic frameworks (COFs) to realize the highly efficient cascade of inulinase and E. coli for bioconversion of natural products. Enzymes can be uniformly immobilized in the COF armor, which coats on the cell surface to produce cascade biocatalysts with high efficiency, stability and recyclability. Furthermore, this one-pot in situ synthesis process facilitates a gram-scale fabrication of enzyme-cell biocatalysts, which can generate a continuous-flow device conversing inulin to D-allulose, achieving space-time yield of 161.28 g L−1 d−1 and high stability (remaining >90% initial catalytic efficiency after 7 days of continuous reaction). The created platform is applied for various cells (e.g., E. coli, Yeast) and enzymes, demonstrating excellent universality. This study paves a pathway to break the bottleneck of extra- and intracellular catalysis, creates a high-performance and customizable platform for enzyme-cell cascade biomanufacturing, and expands the scope of biocatalysis process intensification.