bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement-induced collective vibrational quantum coherence under spontaneous Raman scattering in a liquid
Authors: Vento Valeria , Tarrago Velez Santiago , Pogrebna Anna , Galland Christophe
Published: May 2023

Spontaneous vibrational Raman scattering is a ubiquitous form of light–matter interaction whose description necessitates quantization of the electromagnetic field. It is usually considered as an incoherent process because the scattered field lacks any predictable phase relationship with the incoming field. When probing an ensemble of molecules, the question therefore arises: What quantum state should be used to describe the molecular ensemble following spontaneous Stokes scattering? We experimentally address this question by measuring time-resolved Stokes–anti-Stokes two-photon coincidences on a molecular liquid consisting of several sub-ensembles with slightly different vibrational frequencies. When spontaneously scattered Stokes photons and subsequent anti-Stokes photons are detected into a single spatiotemporal mode, the observed dynamics is inconsistent with a statistical mixture of individually excited molecules. Instead, we show that the data are reproduced if Stokes–anti-Stokes correlations are mediated by a collective vibrational quantum, i.e. a coherent superposition of all molecules interacting with light. Our results demonstrate that the degree of coherence in the vibrational state of the liquid is not an intrinsic property of the material system, but rather depends on the optical excitation and detection geometry.
Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis
Authors: Jenner Matthew , Hai Yang , Nguyen Hong H. , Passmore Munro , Skyrud Will , Kim Junyong , Garg Neil K. , Zhang Wenjun , Ogorzalek Loo Rachel R. , Tang Yi
Published: May 2023

Siderophores belonging to the ferrichrome family are essential for the viability of fungal species and play a key role for virulence of numerous pathogenic fungi. Despite their biological significance, our understanding of how these iron-chelating cyclic hexapeptides are assembled by non-ribosomal peptide synthetase (NRPS) enzymes remains poorly understood, primarily due to the nonlinearity exhibited by the domain architecture. Herein, we report the biochemical characterization of the SidC NRPS, responsible for construction of the intracellular siderophore ferricrocin. In vitro reconstitution of purified SidC reveals its ability to produce ferricrocin and its structural variant, ferrichrome. Application of intact protein mass spectrometry uncovers several non-canonical events during peptidyl siderophore biosynthesis, including inter-modular loading of amino acid substrates and an adenylation domain capable of poly-amide bond formation. This work expands the scope of NRPS programming, allows biosynthetic assignment of ferrichrome NRPSs, and sets the stage for reprogramming towards novel hydroxamate scaffolds.
Rubisco deactivation and chloroplast electron transport rates co-limit photosynthesis above optimal leaf temperature in terrestrial plants
Authors: Scafaro Andrew P. , Posch Bradley C. , Evans John R. , Farquhar Graham D. , Atkin Owen K.
Published: May 2023

Net photosynthetic CO2 assimilation rate (An) decreases at leaf temperatures above a relatively mild optimum (Topt) in most higher plants. This decline is often attributed to reduced CO2 conductance, increased CO2 loss from photorespiration and respiration, reduced chloroplast electron transport rate (J), or deactivation of Ribulose-1,5-bisphosphate Carboxylase Oxygenase (Rubisco). However, it is unclear which of these factors can best predict species independent declines in An at high temperature. We show that independent of species, and on a global scale, the observed decline in An with rising temperatures can be effectively accounted for by Rubisco deactivation and declines in J. Our finding that An declines with Rubisco deactivation and J supports a coordinated down-regulation of Rubisco and chloroplast electron transport rates to heat stress. We provide a model that, in the absence of CO2 supply limitations, can predict the response of photosynthesis to short-term increases in leaf temperature.
Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9
Authors: Martin Gregory M. , Fernández-Quintero Monica L. , Lee Wen-Hsin , Pholcharee Tossapol , Eshun-Wilson Lisa , Liedl Klaus R. , Pancera Marie , Seder Robert A. , Wilson Ian A. , Ward Andrew B.
Published: May 2023

A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations revealed a critical role of the L9 light chain in integrity of the homotypic interface, which likely impacts PfCSP affinity and protective efficacy. These findings reveal the molecular mechanism of the unique NPNV selectivity of L9 and emphasize the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.
A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes
Authors: Wilson F. Perry , Yamamoto Yu , Martin Melissa , Coronel-Moreno Claudia , Li Fan , Cheng Chao , Aklilu Abinet , Ghazi Lama , Greenberg Jason H. , Latham Stephen , Melchinger Hannah , Mansour Sherry G. , Moledina Dennis G. , Parikh Chirag R. , Partridge Caitlin , Testani Jeffrey M. , Ugwuowo Ugochukwu
Published: May 2023

Acute kidney injury is common among hospitalized individuals, particularly those exposed to certain medications, and is associated with substantial morbidity and mortality. In a pragmatic, open-label, National Institutes of Health-funded, parallel group randomized controlled trial (clinicaltrials.gov NCT02771977), we investigate whether an automated clinical decision support system affects discontinuation rates of potentially nephrotoxic medications and improves outcomes in patients with AKI. Participants included 5060 hospitalized adults with AKI and an active order for any of three classes of medications of interest: non-steroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system inhibitors, or proton pump inhibitors. Within 24 hours of randomization, a medication of interest was discontinued in 61.1% of the alert group versus 55.9% of the usual care group (relative risk 1.08, 1.04 – 1.14, p = 0.0003). The primary outcome – a composite of progression of acute kidney injury, dialysis, or death within 14 days - occurred in 585 (23.1%) of individuals in the alert group and 639 (25.3%) of patients in the usual care group (RR 0.92, 0.83 – 1.01, p = 0.09). Trial Registration Clinicaltrials.gov NCT02771977.
The experience of Anxiety for people with Parkinson’s disease
Authors: Blundell Emma. K. , Grover Laura. E. , Stott Joshua , Schrag Anette
Published: May 2023

Anxiety is a common non-motor symptom of Parkinson’s disease (PD) associated with increased disability and reduced quality of life. However, anxiety is poorly understood, underdiagnosed, and undertreated. To date, little research has explored how anxiety is experienced by patients themselves. This study explored the experience of anxiety for people with Parkinson’s (PWP) to inform future research and interventions. Semi-structured interviews with 22 PWP (aged 43-80, 50% female) were conducted and analysed using inductive thematic analysis. Four main themes were extracted: conceptualising anxiety; anxiety and the body; anxiety and social identity; and coping with anxiety. Sub-themes revealed inconsistent perceptions: anxiety was in body and mind, part of disease and human nature, part of self-identity and a threat to it. The symptoms described were diverse. Many perceived their anxiety as more incapacitating than motor symptoms or capable of amplifying them, and described that anxiety restricted their lifestyle. All perceived anxiety as connected to PD, and ultimately persistent: dominant aspirations were coping and acceptance rather than cures, with medications strongly resisted. Findings highlight the complexity and high importance of anxiety for PWP. Implications for therapeutic approaches are discussed.
The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China
Authors: Sun Yi-Min , Zhou Xin-Yue , Liang Xiao-Niu , Lin Jin-Ran , Xu Yi-Dan , Chen Chen , Wei Si-Di , Chen Qi-Si , Liu Feng-Tao , Zhao Jue , Tang Yi-Lin , Shen Bo , Gan Lin-Hua , Lu Boxun , Ding Zheng-Tong , An Yu , Wu Jian-Jun , Wang Jian
Published: May 2023

So far, over 20 causative genes of monogenic Parkinson’s disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early onset age or family history. A total of 832 patients initially diagnosed with PD were enrolled, of which, 636 were classified into the early-onset group and 196 were classified into the familial late-onset group. The genetic testing included the multiplex ligation-dependent probe amplification and next generation sequencing (target sequencing or whole-exome sequencing). The dynamic variants of spinocerebellar ataxia were tested in probands with family history. In the early-onset group, 30.03% of patients (191/636) harbored pathogenic/likely pathogenic (P/LP) variants in known PD-related genes (CHCHD2, DJ-1, GBA (heterozygous), LRRK2, PINK1, PRKN, PLA2G6, SNCA and VPS35). Variants in PRKN were the most prevalent, accounting for 15.72% of the early-onset patients, followed by GBA (10.22%), and PLA2G6 (1.89%). And 2.52% (16/636) had P/LP variants in causative genes of other diseases (ATXN3, ATXN2, GCH1, TH, MAPT, GBA (homozygous)). In the familial late-onset group, 8.67% of patients (17/196) carried P/LP variants in known PD-related genes (GBA (heterozygous), HTRA2, SNCA) and 2.04% (4/196) had P/LP variants in other genes (ATXN2, PSEN1, DCTN1). Heterozygous GBA variants (7.14%) were the most common genetic cause found in familial late-onset patients. Genetic testing is of vital importance in differential diagnosis especially in early-onset and familial PD. Our findings may also provide some clues to the nomenclature of genetic movement disorders.
Th1-dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses
Authors: den Hartog Yvette , Malahe S. Reshwan K. , Rietdijk Wim J. R. , Dieterich Marjolein , Gommers Lennert , Geers Daryl , Bogers Susanne , van Baarle Debbie , Diavatopoulos Dimitri A. , Messchendorp A. Lianne , van der Molen Renate G. , Remmerswaal Ester B. M. , Bemelman Frederike J. , Gansevoort Ron T. , Hilbrands Luuk B. , Sanders Jan-Stephan , GeurtsvanKessel Corine H. , Kho Marcia M. L. , Reinders Marlies E. J. , de Vries Rory D. , Baan Carla C. ,   on behalf of RECOVAC Consortium
Published: May 2023

Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4+ and CD8+ memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)1 (IL-2, TNF-α, and IFN-γ) and Th2 (IL-4, IL-5, IL-13) cytokines, and low levels of Th17 (IL-17A, IL-22) and Th9 (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th1 cytokines upon re-stimulation, with lower levels or absence of Th2, Th17, and Th9 cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th1 and Th2 cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.
Succession of bacterial biofilm communities following removal of chloramine from a full-scale drinking water distribution system
Authors: Rosenqvist Tage , Danielsson Mikael , Schleich Caroline , Ahlinder Jon , Brindefalk Björn , Pullerits Kristjan , Dacklin Ingrid , Salomonsson Emelie N. , Sundell David , Forsman Mats , Keucken Alexander , Rådström Peter , Paul Catherine J.
Published: May 2023

Monochloramine is used to regulate microbial regrowth in drinking water distribution systems (DWDS) but produces carcinogenic disinfection byproducts and constitutes a source of energy for nitrifying bacteria. This study followed biofilm-dispersed microbial communities of a full-scale DWDS distributing ultrafiltered water over three years, before and after removal of monochloramine. Communities were described using flow cytometry and amplicon sequencing, including full-length 16S rRNA gene sequencing. Removal of monochloramine increased total cell counts by up to 440%. Increased abundance of heterotrophic bacteria was followed by emergence of the predatory bacteriaBdellovibrio, and a community potentially metabolizing small organic compounds replaced the nitrifying core community. No increased abundance ofMycobacteriumorLegionellawas observed. Co-occurrence analysis identified a network ofNitrosomonas,Nitrospira,SphingomonasandHyphomicrobium, suggesting that monochloramine supported this biofilm community. While some species expanded into the changed niche, no immediate biological risk to consumers was indicated within the DWDS.
Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma
Authors: Naghavian Reza , Faigle Wolfgang , Oldrati Pietro , Wang Jian , Toussaint Nora C. , Qiu Yuhan , Medici Gioele , Wacker Marcel , Freudenmann Lena K. , Bonté Pierre-Emmanuel , Weller Michael , Regli Luca , Amigorena Sebastian , Rammensee Hans-Georg , Walz Juliane S. , Brugger Silvio D. , Mohme Malte , Zhao Yingdong , Sospedra Mireia , Neidert Marian C. , Martin Roland
Published: May 2023

Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors1,2. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4+ T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.
Responses of pyramidal cell somata and apical dendrites in mouse visual cortex over multiple days
Authors: Gillon Colleen J. , Lecoq Jérôme A. , Pina Jason E. , Ahmed Ruweida , Billeh Yazan N. , Caldejon Shiella , Groblewski Peter , Henley Timothy M. , Kato India , Lee Eric , Luviano Jennifer , Mace Kyla , Nayan Chelsea , Nguyen Thuyanh V. , North Kat , Perkins Jed , Seid Sam , Valley Matthew T. , Williford Ali , Bengio Yoshua , Lillicrap Timothy P. , Zylberberg Joel , Richards Blake A.
Published: May 2023

The apical dendrites of pyramidal neurons in sensory cortex receive primarily top-down signals from associative and motor regions, while cell bodies and nearby dendrites are heavily targeted by locally recurrent or bottom-up inputs from the sensory periphery. Based on these differences, a number of theories in computational neuroscience postulate a unique role for apical dendrites in learning. However, due to technical challenges in data collection, little data is available for comparing the responses of apical dendrites to cell bodies over multiple days. Here we present a dataset collected through the Allen Institute Mindscope’s OpenScope program that addresses this need. This dataset comprises high-quality two-photon calcium imaging from the apical dendrites and the cell bodies of visual cortical pyramidal neurons, acquired over multiple days in awake, behaving mice that were presented with visual stimuli. Many of the cell bodies and dendrite segments were tracked over days, enabling analyses of how their responses change over time. This dataset allows neuroscientists to explore the differences between apical and somatic processing and plasticity.
Characterizing amblyopic perception under non-rivalrous viewing conditions
Authors: Meier Kimberly , Tarczy-Hornoch Kristina , Boynton Geoffrey M. , Fine Ione
Published: May 2023

Current assessments of interocular interactions in amblyopia often use rivalrous stimuli, with conflicting stimuli in each eye, which does not reflect vision under typical circumstances. Here we measure interocular interactions in observers with amblyopia, strabismus with equal vision, and controls using a non-rivalrous stimulus. Observers used a joystick to continuously report the perceived binocular contrast of dichoptic grating stimuli, identical except that the stimulus was contrast-modulated independently in each eye over time. Consistent with previous studies, a model predicting the time-course of perceived contrast found increased amblyopic eye attenuation, and reduced contrast normalization of the fellow eye by the amblyopic eye, in amblyopic participants compared to controls. However, these suppressive interocular effects were weaker than those found in previous studies, suggesting that rivalrous stimuli may overestimate the effects of amblyopia on interocular interactions during naturalistic viewing conditions.
Effects of folic acid supplementation in pregnant mice on glucose metabolism disorders in male offspring induced by lipopolysaccharide exposure during pregnancy
Authors: Sun Wan-Xiao , Shu Yi-Ping , Yang Xin-Yu , Huang Wei , Chen Jing , Yu Ning-Ning , Zhao Mei
Published: May 2023

The DOHaD theory suggests that adverse environmental factors in early life may lead to the development of metabolic diseases including diabetes and hypertension in adult offspring through epigenetic mechanisms such as DNA methylation. Folic acid (FA) is an important methyl donor in vivo and participates in DNA replication and methylation. The preliminary experimental results of our group demonstrated that lipopolysaccharide (LPS, 50 µg/kg/d) exposure during pregnancy could lead to glucose metabolism disorders in male offspring, but not female offspring; however, the effect of folic acid supplementation on glucose metabolism disorders in male offspring induced by LPS exposure remains unclear. Therefore, in this study, pregnant mice were exposed to LPS on gestational day (GD) 15–17 and were given three doses of FA supplementation (2 mg/kg, 5 mg/kg, or 40 mg/kg) from mating to lactation to explore its effect on glucose metabolism in male offspring and the potential mechanism. This study confirmed that FA supplementation of 5 mg/kg in pregnant mice improved glucose metabolism in LPS-exposed offspring during pregnancy by regulating gene expression.
Effect of cetrimonium carrier micelles on bacterial membranes and extracellular DNA, an in silico study
Authors: Puelles Jhonatan Soto , Ghorbani Mahdi , Tuck Benjamin , Machuca Laura L. , Ackland M. Leigh , Chen Fangfang , Somers Anthony E. , Forsyth Maria
Published: May 2023

Microorganisms do not live as dispersed single cells but rather they form aggregates with extracellular polymeric substances at interfaces. Biofilms are considered efficient life forms because they shield bacteria from biocides and collect dilute nutrients. This is a big concern in industry since the microorganisms can colonize a wide range of surfaces, accelerating material deterioration, colonizing medical devices, contaminating ultrapure drinking water, increasing energy costs and creating focus of infection. Conventional biocides that target a specific component of the bacteria are not effective in the presence of biofilms. Efficient biofilm inhibitors are based on a multitarget approach interacting with the bacteria and the biofilm matrix. Their rationale design requires a thorough understanding of inhibitory mechanisms that are still largely lacking today. Herein we uncover via molecular modelling the inhibition mechanism of cetrimonium 4-OH cinnamate (CTA-4OHcinn). Simulations show that CTA-4OH micelles can disrupt symmetric and asymmetric bilayers, representative of inner and outer bacterial membranes, following three stages: adsorption, assimilation, and defect formation. The main driving force for micellar attack is electrostatic interactions. In addition to disrupting the bilayers, the micelles work as carriers facilitating the trapping of 4OH cinnamate anions within the bilayer upper leaflet and overcoming electrostatic repulsion. The micelles also interact with extracellular DNA (e-DNA), which is one of the main components of biofilms. It is observed that CTA-4OHcinn forms spherical micelles on the DNA backbone; which hinders their ability to pack. This is demonstrated by modelling the DNA along the hbb histone-like protein, showing that in the presence of CTA-4OHcinn, DNA does not pack properly around hbb. The abilities of CTA-4OHcinn to cause cell death through membrane disruption and to disperse a mature, multi-species biofilm are also confirmed experimentally.
Evolutionary success of the thrifty genotype depends on both behavioral adaptations and temporal variability in the food environment
Authors: Batta Erasmo , Stephens Christopher R.
Published: May 2023

Obesity is a result of a long-term energy imbalance due to decisions associated with energy intake and expenditure. Those decisions fit the definition of heuristics: cognitive processes with a rapid and effortless implementation which can be very effective in dealing with scenarios that threaten an organism’s viability. We study the implementation and evaluation of heuristics, and their associated actions, using agent-based simulations in environments where the distribution and degree of richness of energetic resources is varied in space and time. Artificial agents utilize foraging strategies, combining movement, active perception, and consumption, while also actively modifying their capacity to store energy—a “thrifty gene” effect—based on three different heuristics. We show that the selective advantage associated with higher energy storage capacity depends on both the agent’s foraging strategy and heuristic, as well as being sensitive to the distribution of resources, with the existence and duration of periods of food abundance and scarcity being crucial. We conclude that a ”thrifty genotype” is only beneficial in the presence of behavioral adaptations that encourage overconsumption and sedentariness, as well as seasonality and uncertainty in the food distribution.
A Doppler-exclusive non-invasive computational diagnostic framework for personalized transcatheter aortic valve replacement
Authors: Bahadormanesh Nikrouz , Tomka Benjamin , Abdelkhalek Mohamed , Khodaei Seyedvahid , Maftoon Nima , Keshavarz-Motamed Zahra
Published: May 2023

Given the associated risks with transcatheter aortic valve replacement (TAVR), it is crucial to determine how the implant will affect the valve dynamics and cardiac function, and if TAVR will improve or worsen the outcome of the patient. Effective treatment strategies, indeed, rely heavily on the complete understanding of the valve dynamics. We developed an innovative Doppler-exclusive non-invasive computational framework that can function as a diagnostic tool to assess valve dynamics in patients with aortic stenosis in both pre- and post-TAVR status. Clinical Doppler pressure was reduced by TAVR (52.2 ± 20.4 vs. 17.3 ± 13.8 [mmHg], p < 0.001), but it was not always accompanied by improvements in valve dynamics and left ventricle (LV) hemodynamics metrics. TAVR had no effect on LV workload in 4 patients, and LV workload post-TAVR significantly rose in 4 other patients. Despite the group level improvements in maximum LV pressure (166.4 ± 32.2 vs 131.4 ± 16.9 [mmHg], p < 0.05), only 5 of the 12 patients (41%) had a decrease in LV pressure. Moreover, TAVR did not always improve valve dynamics. TAVR did not necessarily result in a decrease (in 9 out of 12 patients investigated in this study) in major principal stress on the aortic valve leaflets which is one of the main contributors in valvedegeneration and, consequently, failure of heart valves. Diastolic stresses increased significantly post-TAVR (34%, 109% and 81%, p < 0.001) for each left, right and non-coronary leaflets respectively. Moreover, we quantified the stiffness and material properties of aortic valve leaflets which correspond with the reduced calcified region average stiffness among leaflets (66%, 74% and 62%; p < 0.001; N = 12). Valve dynamics post-intervention should be quantified and monitored to ensure the improvement of patient conditions and prevent any further complications. Improper evaluation of biomechanical valve features pre-intervention as well as post-intervention may result in harmful effects post-TAVR in patients including paravalvular leaks, valve degeneration, failure of TAVR and heart failure.
Urban structure reinforces attitudes towards tsunami evacuation
Authors: Makinoshima Fumiyasu , Oishi Yusuke , Imamura Fumihiko
Published: May 2023

Evacuation is a critical life-saving action, especially in devastating natural hazards such as near-field tsunamis. However, the development of effective evacuation measures remains challenging to the extent that a successful example has been referred to as a ‘miracle’. Here we show that urban structures have the potential to reinforce attitudes towards evacuation and significantly influence the success of tsunami evacuation. Agent-based evacuation simulations revealed that a distinctive root-like urban structure formed in ria coasts reinforces positive evacuation attitudes by effectively gathering evacuation flows and leads to higher evacuation rates compared to typical grid-like urban structures, which can explain the regional differences in the number of casualties in the 2011 Tohoku tsunami. Although a grid-like structure reinforces negative attitudes under low evacuation tendencies, with leading evacuees, its dense feature helps to propagate positive attitudes and drastically improve evacuation tendencies. These findings pave the way for making successful evacuation inevitable through harmonised urban and evacuation plannings.
Liver-specific overexpression of HKDC1 increases hepatocyte size and proliferative capacity
Authors: Pusec Carolina M. , Ilievski Vladimir , De Jesus Adam , Farooq Zeenat , Zapater Joseph L. , Sweis Nadia , Ismail Hagar , Khan Md Wasim , Ardehali Hossein , Cordoba-Chacon Jose , Layden Brian T.
Published: May 2023

A primary role of the liver is to regulate whole body glucose homeostasis. Glucokinase (GCK) is the main hexokinase (HK) expressed in hepatocytes and functions to phosphorylate the glucose that enters via GLUT transporters to become glucose-6-phosphate (G6P), which subsequently commits glucose to enter downstream anabolic and catabolic pathways. In the recent years, hexokinase domain-containing-1 (HKDC1), a novel 5th HK, has been characterized by our group and others. Its expression profile varies but has been identified to have low basal expression in normal liver but increases during states of stress including pregnancy, nonalcoholic fatty liver disease (NAFLD), and liver cancer. Here, we have developed a stable overexpression model of hepatic HKDC1 in mice to examine its effect on metabolic regulation. We found that HKDC1 overexpression, over time, causes impaired glucose homeostasis in male mice and shifts glucose metabolism towards anabolic pathways with an increase in nucleotide synthesis. Furthermore, we observed these mice to have larger liver sizes due to greater hepatocyte proliferative potential and cell size, which in part, is mediated via yes-associated protein (YAP) signaling.
Alpha radiation from polymetallic nodules and potential health risks from deep-sea mining
Authors: Volz Jessica B. , Geibert Walter , Köhler Dennis , van der Loeff Michiel M. Rutgers , Kasten Sabine
Published: May 2023

In search for critical elements, polymetallic nodules at the deep abyssal seafloor are targeted for mining operations. Nodules efficiently scavenge and retain several naturally occurring uranium-series radioisotopes, which predominantly emit alpha radiation during decay. Here, we present new data on the activity concentrations of thorium-230, radium-226, and protactinium-231, as well as on the release of radon-222 in and from nodules from the NE Pacific Ocean. In line with abundantly published data from historic studies, we demonstrate that the activity concentrations for several alpha emitters are often higher than 5 Bq g−1 at the surface of the nodules. These observed values can exceed current exemption levels by up to a factor of 1000, and even entire nodules commonly exceed these limits. Exemption levels are in place for naturally occurring radioactive materials (NORM) such as ores and slags, to protect the public and to ensure occupational health and radiation safety. In this context, we discuss three ways of radiation exposure from nodules, including the inhalation or ingestion of nodule fines, the inhalation of radon gas in enclosed spaces and the potential concentration of some radioisotopes during nodule processing. Seen in this light, inappropriate handling of polymetallic nodules poses serious health risks.
Bioaccumulation and biomagnifications of toxic metals in tissues of loggerhead turtles (Caretta caretta) from the Mediterranean Sea coast, Egypt
Authors: Abdallah Maha Ahmed Mohamed
Published: May 2023

Heavy metal concentrations in the different tissues of marine turtles are presented; the most frequently monitored elements are mercury, cadmium, and lead. Concentrations of Hg, Cd, Pb, and As in different organs and tissues (liver, kidney, muscle tissue, fat tissue, and blood) of loggerhead turtle Caretta caretta from the southeastern Mediterranean Sea were determined using Atomic Absorption Spectrophotometer, Shimadzu and mercury vapor unite (MVu 1A) for Hg measurements. The highest levels of cadmium and arsenic were found in the kidney (Cd: 61.17 µg g−1; As: 0.051 µg g−1 dry weight). For lead, the highest level was found in muscle tissue (35.80 µg g−1). Mercury tended to be higher in the liver than in other tissues and organs (0.253 µg g−1 dry weight) which showed a higher accumulation of this element. Fat tissue generally displays the lowest trace element burdens. The concentrations of As remained low in all the considered tissues, possibly the result of low trophic levels in sea turtles. In contrast, the diet of loggerhead turtles would result in significant exposure to Pb. This is the first study into metal accumulation in the tissues of a loggerhead turtle from the Egyptian Mediterranean coastline.
Microbial communities and their roles in the Cenozoic sulfurous oil reservoirs in the Southwestern Qaidam Basin, Western China
Authors: Jiao Yue , An Liyun , Wang Wei , Ma Jian , Wu Chaodong , Wu Xiaolei
Published: May 2023

The latest discovery of sulfurous natural gas marked a breakthrough in the Cenozoic natural gas exploration in the southwestern margin of Qaidam Basin. The 16S rRNA analyses were performed on the crude oil samples from H2S-rich reservoirs in the Yuejin, Shizigou and Huatugou profiles, to understand the sulfurous gas origin, which was also integrated with carbon and hydrogen isotopes of alkane and sulfur isotopes of H2S collected from the Yingxiongling Area. Results show that the microorganisms in samples can survive in the hypersaline reservoirs, and can be classified into multiple phyla, including Proteobacteria, Planctomycetes, Firmicutes, Bacteroidetes, and Haloanaerobiaeota. Methanogens are abundant in all of the three profiles, while sulfate-reducing bacteria are abundant in Yuejin and Huatugou profiles, contributing to the methane and H2S components in the natural gas. The carbon, hydrogen and sulfur isotopes of sulfurous natural gas in the Yingxiongling Area show that the natural gas is a mixture of coal-type gas and oil-type gas, which was primarily derived from thermal degradation, and natural gas from the Yuejin and Huatugou profiles also originated from biodegradation. The isotopic analysis agrees well with the 16S rRNA results, i.e., H2S-rich natural gas from the Cenozoic reservoirs in the southwest margin of the Qaidam Basin was primarily of thermal genesis, with microbial genesis of secondary importance.
Ultrasound-Promoted preparation and application of novel bifunctional core/shell Fe3O4@SiO2@PTS-APG as a robust catalyst in the expeditious synthesis of Hantzsch esters
Authors: Shakib Peyman , Dekamin Mohammad G. , Valiey Ehsan , Karami Shahriar , Dohendou Mohammad
Published: May 2023

In this work, D-(–)-α-phenylglycine (APG)-functionalized magnetic nanocatalyst (Fe3O4@SiO2@PTS-APG) was designed and successfully prepared in order to implement the principles of green chemistry for the synthesis of polyhydroquinoline (PHQ) and 1,4-dihydropyridine (1,4-DHP) derivatives under ultrasonic irradiation in EtOH. After preparing of the nanocatalyst, its structure was confirmed by different spectroscopic methods or techniques including Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDS), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and thermal gravimetric analysis (TGA). The performance of Fe3O4@SiO2@PTS-APG nanomaterial, as a heterogeneous catalyst for the Hantzsch condensation, was examined under ultrasonic irradiation and various conditions. The yield of products was controlled under various conditions to reach more than 84% in just 10 min, which indicates the high performance of the nanocatalyst along with the synergistic effect of ultrasonic irradiation. The structure of the products was identified by melting point as well as FTIR and1H NMR spectroscopic methods. The Fe3O4@SiO2@PTS-APG nanocatalyst is easily prepared from commercially available, lower toxic and thermally stable precursors through a cost-effective, highly efficient and environmentally friendly procedure. The advantages of this method include simplicity of the operation, reaction under mild conditions, the use of an environmentally benign irradiation source, obtaining pure products with high efficiency in short reaction times without using a tedious path, which all of them address important green chemistry principles. Finally, a reasonable mechanism is proposed for the preparation of polyhydroquinoline (PHQ) and 1,4-dihydropyridine (1,4-DHP) derivatives in the presence of Fe3O4@SiO2@PTS-APG bifunctional magnetic nanocatalyst.
Gender specific factors contributing to cognitive resilience in APOE ɛ4 positive older adults in a population-based sample
Authors: Zheng Lidan , Eramudugolla Ranmalee , Cherbuin Nicolas , Drouin Shannon M. , Dixon Roger A. , Anstey Kaarin J.
Published: May 2023

Although APOE ɛ4 has been identified as the strongest genetic risk factor for Alzheimer’s Disease, there are some APOE ɛ4 carriers who do not go on to develop Alzheimer’s disease or cognitive impairment. This study aims to investigate factors contributing to this “resilience” separately by gender. Data were drawn from APOE ɛ4 positive participants who were aged 60 + at baseline in the Personality and Total Health Through Life (PATH) Study (N = 341, Women = 46.3%). Participants were categorised into “resilient” and “non-resilient” groups using Latent Class Analysis based on their cognitive impairment status and cognitive trajectory across 12 years. Logistic regression was used to identify the risk and protective factors that contributed to resilience stratified by gender. For APOE ɛ4 carriers who have not had a stroke, predictors of resilience were increased frequency of mild physical activity and being employed at baseline for men, and increased number of mental activities engaged in at baseline for women. The results provide insights into a novel way of classifying resilience among APOE ɛ4 carriers and risk and protective factors contributing to resilience separately for men and women.
DARPins bind their cytosolic targets after having been translocated through the protective antigen pore of anthrax toxin
Authors: Becker Lukas , Plückthun Andreas
Published: May 2023

Intracellular protein–protein interactions in aberrant signaling pathways have emerged as a prime target in several diseases, particularly cancer. Since many protein–protein interactions are mediated by rather flat surfaces, they can typically not be interrupted by small molecules as they require cavities for binding. Therefore, protein drugs might be developed to compete with undesired interactions. However, proteins in general are not able to translocate from the extracellular side to the cytosolic target site by themselves, and thus an efficient protein translocation system, ideally combining efficient translocation with receptor specificity, is in high demand. Anthrax toxin, the tripartite holotoxin of Bacillus anthracis, is one of the best studied bacterial protein toxins and has proven to be a suitable candidate for cell-specific translocation of cargoes in vitro and in vivo. Our group recently developed a retargeted protective antigen (PA) variant fused to different Designed Ankyrin Repeat Proteins (DARPins) to achieve receptor specificity, and we incorporated a receptor domain to stabilize the prepore and prevent cell lysis. This strategy had been shown to deliver high amounts of cargo DARPins fused behind the N-terminal 254 amino acids of Lethal Factor (LFN). Here, we established a cytosolic binding assay, demonstrating the ability of DARPins to refold in the cytosol and bind their target after been translocated by PA.
Adding virtual plants leads to higher cognitive performance and psychological well-being in virtual reality
Authors: Mostajeran Fariba , Steinicke Frank , Reinhart Sarah , Stuerzlinger Wolfgang , Riecke Bernhard E. , Kühn Simone
Published: May 2023

Previous research has shown the positive effects of exposure to real and virtual nature. To investigate how such benefits might generalize to ever-more-prevalent virtual workplaces, we examined the effects of the absence or presence of virtual plants in an office environment in Virtual Reality (VR) on users’ cognitive performance and psychological well-being. The results of our user study with 39 participants show that in the presence of virtual plants, participants performed significantly better in both short-term memory and creativity tasks. Furthermore, they reported higher psychological well-being scores, including positive affect and attentive coping, whilst reporting lower feelings of anger and aggression after exposure to virtual plants in VR. The virtual office with plants was also perceived as more restorative and induced a higher sense of presence. Overall, these results highlight how the presence of virtual plants in VR can have positive influences on users, and therefore, constitute important design considerations when developing future working and learning spaces.
Designing continuous equilibrium structures that counteract gravity in any orientation
Authors: Redoutey Maria , Filipov Evgueni T.
Published: May 2023

This paper presents a framework that can transform reconfigurable structures into systems with continuous equilibrium. The method involves adding optimized springs that counteract gravity to achieve a system with a nearly flat potential energy curve. The resulting structures can move or reconfigure effortlessly through their kinematic paths and remain stable in all configurations. Remarkably, our framework can design systems that maintain continuous equilibrium during reorientation, so that a system maintains a nearly flat potential energy curve even when it is rotated with respect to a global reference frame. This ability to reorient while maintaining continuous equilibrium greatly enhances the versatility of deployable and reconfigurable structures by ensuring they remain efficient and stable for use in different scenarios. We apply our framework to several planar four-bar linkages and explore how spring placement, spring types, and system kinematics affect the optimized potential energy curves. Next, we show the generality of our method with more complex linkage systems that carry external masses and with a three-dimensional origami-inspired deployable structure. Finally, we adopt a traditional structural engineering approach to give insight on practical issues related to the stiffness, reduced actuation forces, and locking of continuous equilibrium systems. Physical prototypes support the computational results and demonstrate the effectiveness of our method. The framework introduced in this work enables the stable, and efficient actuation of reconfigurable structures under gravity, regardless of their global orientation. These principles have the potential to revolutionize the design of robotic limbs, retractable roofs, furniture, consumer products, vehicle systems, and more.
Tfap2b acts in GABAergic neurons to control sleep in mice
Authors: Hu Yang , Bringmann Henrik
Published: May 2023

Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b−/− embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b+/− mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b−/− mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b−/− mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep.
Underweight and risk of fractures in adults over 40 years using the nationwide claims database
Authors: Park Sang-Min , Park Jiwon , Han Sangsoo , Jang Hae-Dong , Hong Jae-Young , Han Kyungdo , Kim Ho-Joong , Yeom Jin S.
Published: May 2023

We aimed to investigate how underweight affects the incidence of fractures, as well as the influence of cumulative, longitudinal periods of low body mass index (BMI) and changes in body weight on fracture development. Data on adults aged 40-year and over who had three health screenings between January 1, 2007, and December 31, 2009 were used to determine the incidence of new fractures. The hazard ratios (HRs) for new fractures depending on BMI, total cumulative number of underweight, and weight change over time were calculated using Cox proportional hazard analysis. In this study, 15,955 (2.8%) of the 561,779 adults were diagnosed with fractures more than once over three health examinations. The fully adjusted HR for fractures in underweight individuals was 1.173 (95% Confidence interval [CI] 1.093–1.259). Underweight individuals diagnosed only once, twice, or three times had an adjusted HR of 1.227 (95%CI 1.130–1.332), 1.174 (95%CI 1.045–1.319), and 1.255 (95%CI 1.143–1.379), respectively. Although the adjusted HR was higher in adults who consistently had underweight (HR; 1.250 [95%CI 1.146–1.363]), those with underweight had an increased risk of fractures regardless of weight change (HR; 1.171 [95%CI 1.045–1.312], and 1.203[95%CI 1.075–1.346]). Underweight is a risk factor for fractures in adults over the age of 40 years, even if they returned to normal weight.
Regulation of whole-body angular momentum during human walking
Authors: Negishi Takuo , Ogihara Naomichi
Published: May 2023

In human walking, whole-body angular momentum (WBAM) about the body centre-of-mass is reportedly maintained in a small range throughout a gait cycle by the intersegmental cancellation of angular momentum. However, the WBAM is certainly not zero, which indicates that external moments applied from the ground due to ground reaction forces (GRFs) and vertical free moments (VFMs) counteract the WBAM. This study provides a complete dataset of the WBAM, each segmental angular momentum, and the external moments due to GRFs and VFMs during human walking. This is done to test whether (1) the three components of the WBAM are cancelled by coordinated intersegmental movements, and whether (2) the external moments due to GRFs and VFMs contribute only minimally to WBAM regulation throughout a gait cycle. This study demonstrates that WBAM is regulated in a small range not only by the segment-to-segment cancellation, but also largely through contributions by the GRFs. The magnitude of VFM is significantly smaller than the peak vertical moment generated by the GRFs; however, in the single-support phase during walking, the VFM is possibly critical for coping with the change in the vertical WBAM due to force perturbations and arm or trunk movements.