bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders
Authors: Buzas Dora , Sun Huan , Toelzer Christine , Yadav Sathish K. N. , Borucu Ufuk , Gautam Gunjan , Gupta Kapil , Bufton Josh , Capin Julien , Sessions Richard B. , Garzoni Frederic , Berger Imre , Schaffitzel Christiane 
Published: September 2023

SummaryAdenovirus-derived dodecamer (ADDomer) nanoparticles comprise 60 copies of Adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport and deployment of ADDomer-based therapeutics independent of a cold-chain. To expand the scope of ADDomer nanoparticles for new applications, we engineered ADDobodies. ADDobodies represent the crown domain of the PBP, genetically separated from its multimerization domain. We inserted heterologous sequences into hyper-variable loops in the crown domain. The resulting ADDobodies were expressed at high yields inEscherichia coli,are monomeric and maintain thermostability. We solved the X-ray structure of an ADDobody prototype validating our design. We demonstrated that ADDobodies can be used to select a specific binder against a target inin vitroselection experiments using ribosome display, with an enrichment factor of ∼104-fold in one selection round. We show that ADDobodies can be converted back into ADDomers by genetically reconnecting the selected ADDobody with the PBP multimerization domain from a different species, giving rise to a multivalent nanoparticle, called Chimera, confirmed by a 2.2 Å structure determined by cryogenic electron microscopy (cryo-EM). Chimera comprises 60 binding sites, resulting in ultra-high, picomolar avidity to the target.
A role for APP in the development of astrocyte morphological complexity
Authors: Saint-Martin Margaux , Goda Yukiko 
Published: September 2023

AbstractThe amyloid precursor protein (APP), whose proteolytic cleavage gives rise to amyloid-βpeptide, has been extensively studied for its role in Alzheimer’s disease, but its physiological function remains less understood. In neurons, APP and its two homologs, the amyloid precursor-like protein 1 (APLP1) and 2 (APLP2), are present in the synaptic compartment and promote synaptogenesis. Over recent years, astrocytes, an abundant glial cell in the brain, have attracted much attention for their role in regulating synapse formation and function. Although APP is also found in astrocytes, its role in these cells remains largely unexplored. Here we have sought to investigate the expression and function of APP in rodent astrocytesin vitroandin vivo. We find that APP along with its family members, APLP1 and APLP2, are expressed in astrocytesin vitroandin vivo. In primary hippocampal cultures, shRNA-mediated knockdown of astrocytic APP, APLP1 or APLP2 compromises astrocyte morphological elaboration to varying degrees. We have then focused on APP to characterize its role in astrocyte development in the intact brain. We show that astrocytic APP shapes the morphological complexity of astrocyte processesin vivoand may also modulate postsynaptic assembly. Our results highlight a role of astrocytic APP and possibly of APLPs that could potentially impact neuronal functions.
NAD+depletion and altered mitochondrial function are key to the establishment of placental dysfunction in an inflammatory-driven subclass of preeclampsia
Authors: Jahan Fahmida , Vasam Goutham , Cariaco Yusmaris , Nik-Akhtar Abolfazl , Green Alex , Menzies Keir J. , Bainbridge Shannon A. 
Published: September 2023

AbstractPreeclampsia (PE) is a pregnancy associated hypertensive disease. It is one of the major causes of pregnancy-related maternal/perinatal adverse health outcomes, with a lack of highly effective preventative strategies and/or therapeutic interventions. Our group has previously identified distinct subclasses of pathophysiology underlying a PE diagnosis, one of which exhibits heightened immune activation at the gestational parent-fetal interface, identified as inflammatory-driven PE. In non-pregnant populations, chronic inflammation is associated with reduced cellular availability of NAD+, a vitamin B3-derived metabolite involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammatory-driven PE, we observed increased activity of NAD+-consuming PARP enzymes and reduced NAD+content. Moreover, these placentas had decreased expression of several mitochondrial oxidative phosphorylation (OXPHOS) proteins and evidence of oxidative damage. This human data was supported by cell culture findings, which likewise demonstrated increased PARP activity, coupled to decreased mitochondrial respiration rates and decreased invasive function of cultured HTR8 human trophoblast cells, following inflammatory induction by TNF-α. Importantly, these adverse inflammatory effects were attenuated by boosting cellular NAD+levels with nicotinamide riboside (NR). Finally, using an LPS-induced rodent model of inflammatory-driven PE, we demonstrated that NR administration (200mg/kg/day) from gestational day (GD) 1-19 could prevent the development of maternal hypertension and fetal/placental growth restriction, improve placental mitochondrial function, reduce placental inflammation and oxidative stress. Thus, this study demonstrates the critical role of NAD+metabolism in maintaining healthy placental function and identifies NAD+boosting as a promising preventative strategy for the inflammatory-driven subclass of PE.One sentence summaryBoosting NAD+levels prevent inflammatory-driven preeclampsia by improving placental mitochondrial function.
A frequency peak at 3.1 kHz obtained from the spectral analysis of the cochlear implant electrocochleography noise
Authors: Herrada Javiera , Medel Vicente , Dragicevic Constantino , Maass Juan C. , Stott Carlos E. , Delano Paul H. 
Published: September 2023

AbstractIntroductionThe functional evaluation of auditory-nerve activity in spontaneous conditions has remained elusive in humans. In animals, the frequency analysis of the round-window electrical noise recorded by means of electrocochleography yields a frequency peak at around 900 to 1000 Hz, which has been proposed to reflect auditory-nerve spontaneous activity. Here, we studied the spectral components of the electrical noise obtained from cochlear implant electrocochleography in humans.MethodsWe recruited adult cochlear implant recipients from the Clinical Hospital of the Universidad de Chile, between the years 2021 and 2022. We used the AIM System from Advanced Bionics® to obtain single trial electrocochleography signals from the most apical electrode in cochlear implant users. We performed a protocol to study spontaneous activity and auditory responses to 0.5 and 2 kHz tonesResultsTwenty subjects including 12 females, with a mean age of 57.9 ± 12.6 years (range between 36 and 78 years) were recruited. The electrical noise of the single trial cochlear implant electrocochleography signal yielded a reliable peak at 3.1 kHz in 55% of the cases (11 out of 20 subjects), while an oscillatory pattern that masked the spectrum was observed in seven cases. In the other two cases, the single-trial noise was not classifiable. Auditory stimulation at 0.5 kHz and 2.0 kHz did not change the amplitude of the 3.1 kHz frequency peak.ConclusionWe found two main types of noise patterns in the frequency analysis of the single-trial noise from cochlear implant electrocochleography, including a peak at 3.1 kHz that might reflect auditory-nerve spontaneous activity, while the oscillatory pattern probably corresponds to an artifact.
Oligomeric states of an Influenza-encoded PB1-F2 viroporin
Authors: Jamal Sehrish , Moin Syed Tarique , Haider Shozeb 
Published: September 2023

ABSTRACTInfluenza Viruses have always been a major health concern due to their highly contagious nature. The PB1-F2 viroporin encoded by the influenza A virus is known to be a pro-apoptotic protein involved in cell death induction of the host immune cells. The structural arrangement and the mode of action of PB1-F2 viroporin have not been fully understood. In this study, we report on the most probable oligomeric structural existences of PB1-F2, investigated by Molecular Dynamics Simulations with improved sampling of conformational states. The simulations provide a channel framework to study the mitochondrial membrane permeation pathway which could initiate the leakage of mitochondrial contents like cytochrome C and induce apoptosis. The structural attributes of the oligomeric states were rigorously evaluated by comparing the experimental reports. Our results reveal a tetrameric form as the preferable state in the lipid environment. This further fulfills the ion transportation criteria by providing a less energetic barrier to ions/water molecules crossing the membrane.
What is the prevalence of orthostatic hypotension in an Australasian emergency department population?
Authors: Clemensen Ellie , Lau Gabriel T , Popovic Gordana 
Published: September 2023

AbstractObjectiveOrthostatic hypotension (OH) is associated with increased morbidity and there is limited research on the prevalence in the Australian ED population. The aim was to determine the prevalence of OH in an Australian ED population. Secondary outcomes included any associations of OH with symptoms, presenting complaints, patient demographics, or hospital admission, and the timing of OH findings.MethodsPatients presenting to a regional Australasian ED underwent orthostatic measurements at 1, 3 and 5 min of standing following 5 min of supine bed rest. OH was defined as a drop in systolic and/or diastolic blood pressure by ≥20 and ≥10 mmHg, respectively.ResultsOf the 312 patients who were enrolled in the study, 69 (22.1%, 95% confidence interval 17.7–27.2%) had OH and 76.8% of cases were detected after 3 min of standing. There was evidence of difference in the prevalence of OH with age (P < 0.001). Similarly, there was evidence of a difference in supine systolic and diastolic blood pressure measurements (P = 0.012 and P < 0.001, respectively) between orthostatic and normotensive subjects. No association was found with OH and hospital admission, presenting complaints or comorbid medical illnesses.ConclusionsIn this single Australian ED population, there was a high prevalence of OH (22.1%) with most cases detected within 3 min of standing. A higher‐powered study across multiple sites would better substantiate these findings.
Genomics, transcriptomics, and peptidomics of the greater wax moth Galleria mellonella neuropeptides and their expression in response to lead stress
Authors: Luo Li‐Lin , Lin Yang , Linghu Jun‐Hong , Gong Wei , Luo Yuan‐Hong , Liu Man , Jin Dao‐Chao , Smagghe Guy , Liu Tong‐Xian , Gui Shun‐Hua , Yi Tian‐Ci 
Published: September 2023

AbstractNeuropeptides are crucial in regulation of a rich variety of developmental, physiological, and behavioral functions throughout the life cycle of insects. Using an integrated approach of multiomics, we identified neuropeptide precursors in the greater wax moth Galleria mellonella, which is a harmful pest of honeybee hives with a worldwide distribution. Here, a total of 63 and 67 neuropeptide precursors were predicted and annotated in the G. mellonella genome and transcriptome, in which 40 neuropeptide precursors were confirmed in the G. mellonella peptidome. Interestingly, we identified 12 neuropeptide precursor genes present in G. mellonella but absent in honeybees, which may be potential novel pesticide target sites. Honeybee hives were contaminated with heavy metals such as lead, enabling its bioaccumulation in G. mellonella bodies through the food chain, we performed transcriptome sequencing to analyze the effects of Pb stress on the mRNA expression level of G. mellonella neuropeptide precursors. After treatment by Pb, the expression of neuropeptide F1 was found to be significantly downregulated, implying that this neuropeptide might be associated with responding to the heavy metal stress in G. mellonella. This study comprehensively identified neuropeptide precursors in G. mellonella, and discussed the effects of heavy metals on insect neuropeptides, with the example of G. mellonella. The results are valuable for future elucidation of how neuropeptides regulate physiological functions in G. mellonella and contribute to our understanding of the insect's environmental plasticity and identify potential new biomarkers to assess heavy metal toxicity in insects.
Alcohol and cannabis dual use among Black adults: Associations with alcohol use, use‐related problems, and race‐based discrimination
Authors: Buckner Julia D. , Zvolensky Michael J. , Scherzer Caroline R. 
Published: September 2023

AbstractBackground and ObjectivesBlack adults who drink alcohol appear at risk for poor alcohol‐related outcomes, yet little research has examined whether cannabis use among those who consume alcohol (alcohol‐cannabis dual use) is related to worse alcohol‐related consequences, as observed in predominantly White samples. Further, it may be that experiencing more race‐based discrimination may be related to using multiple substances to cope with such experiences; however, no known studies have examined the impact of race‐based discrimination on alcohol‐cannabis dual use.MethodsParticipants were 270 Black undergraduates who endorsed past‐month drinking, 112 of whom endorsed alcohol‐cannabis dual use.ResultsThe dual use group reported heavier drinking, more drinking‐related problems, and more race‐based microaggressions (but not overt racism) than the alcohol‐only group.ConclusionsThe use of cannabis among Black young adults who drink alcohol was related to heavier drinking and more alcohol‐related problems. Further, experiencing more microaggressions may place these individuals at risk for using multiple substances, presumably to cope with these experiences.Scientific SignificanceConsidering models suggesting that the dual use of cannabis may result in less alcohol use, the current study highlights that for Black adults who consume alcohol, cannabis dual use is related to heavier drinking and more alcohol‐related problems, which can inform intervention and treatment efforts.
Opioid and benzodiazepine misuse in the United States: The impact of socio‐demographic characteristics
Authors: Haider Mohammad Rifat , Jayawardhana Jayani 
Published: September 2023

AbstractBackground and ObjectivesIn 2021, drug overdose deaths in the United States reached a new record of 107,622. Misuse of opioids and benzodiazepines accounts for a large portion of drug overdose deaths. However, the effects of socio‐demographic characteristics on misuse of opioids and benzodiazepines are not evident. Thus, this study examines the socio‐demographic characteristics associated with misuse of opioids and benzodiazepines among adults in the United States.MethodsData from 2015–2019 National Survey on Drug Use and Health was utilized in the multinomial logistic regression analysis and included 202,935 adults ages ≥18 years.ResultsDuring 2015–2019, 3.3% of the adults misused opioids, 1.2% misused benzodiazepines, and 0.9% misused both drugs in the preceding year of the survey. Those who were younger, bisexual, non‐Hispanic White, had a history of delinquency in the past year, had alcohol dependence/abuse, marijuana dependence/abuse, nicotine dependence and use, and experienced major depressive episodes were more likely to misuse opioids, benzodiazepines, or both.Conclusion and Scientific SignificanceA large portion of US adults are misusing opioids, benzodiazepines, and both drugs. Specifically, bisexual individuals experience higher odds of opioid misuse, benzodiazepine misuse and misuse of both drugs compared with heterosexuals, while males are experiencing lower odds of benzodiazepine misuse compared with females. Individuals aged 26–49 experience the highest odds of opioid misuse, though misuse of both drugs was higher among the 18–25 age group. Findings underscore the use of targeted preventive measures to reduce misuse of these drugs among at‐risk populations identified in this study.
Where Motivated Reasoning Withers and Looms Large: Fear and Partisan Reactions to the COVID‐19 Pandemic
Authors: Mehlhaff Isaac D. , Ryan Timothy J. , Hetherington Marc J. , MacKuen Michael B. 
Published: September 2023

AbstractContemporary American politics has been largely characterized by hyperpartisanship and polarization, with partisan‐motivated reasoning a thematic concern. Theories of emotions in politics suggest that anxiety might interrupt partisan heuristics and encourage citizens to reason more evenhandedly—but in what domains and to what extent? We use original panel data to assess how anxiety about becoming seriously ill from COVID‐19 interacted with partisan attachments to shape political judgment during the COVID‐19 pandemic. The structure of our data allows us to assess large‐scale implications of politically relevant emotions in ways that so far have not been possible. We find large effects on policy attitudes: Republicans who were afraid of getting sick rejected signals from copartisan leaders by supporting mask mandates and the like. Effects on vote choice for Republicans were muted in comparison, but fear's large effect on independents may have been pivotal.
Artificial intelligence quantifying endoscopic severity of ulcerative colitis in gradation scale
Authors: Takabayashi Kaoru , Kobayashi Taku , Matsuoka Katsuyoshi , Levesque Barrett G. , Kawamura Takuji , Tanaka Kiyohito , Kadota Takeaki , Bise Ryoma , Uchida Seiichi , Kanai Takanori , Ogata Haruhiko 
Published: September 2023

ObjectivesExisting endoscopic scores for ulcerative colitis (UC) objectively categorize disease severity based on the presence or absence of endoscopic findings; therefore, it may not reflect the range of clinical severity within each category. However, inflammatory bowel disease (IBD) expert endoscopists categorize the severity and diagnose the overall impression of the degree of inflammation. This study aimed to develop an artificial intelligence (AI) system that can accurately represent the assessment of the endoscopic severity of UC by IBD expert endoscopists.MethodsA ranking‐convolutional neural network (ranking‐CNN) was trained using comparative information on the UC severity of 13,826 pairs of endoscopic images created by IBD expert endoscopists. Using the trained ranking‐CNN, the UC Endoscopic Gradation Scale (UCEGS) was used to express severity. Correlation coefficients were calculated to ensure that there were no inconsistencies in assessments of severity made using UCEGS diagnosed by the AI and the Mayo Endoscopic Subscore, and the correlation coefficients of the mean for test images assessed using UCEGS by four IBD expert endoscopists and the AI.ResultsSpearman's correlation coefficient between the UCEGS diagnosed by AI and Mayo Endoscopic Subscore was approximately 0.89. The correlation coefficients between IBD expert endoscopists and the AI of the evaluation results were all higher than 0.95 (P < 0.01).ConclusionsThe AI developed here can diagnose UC severity endoscopically similar to IBD expert endoscopists.
Intergenerational differences in healthy eating beliefs among British Pakistanis with type 2 diabetes
Authors: Iqbal Syka , Iqbal Halima , Kagan Carolyn 
Published: September 2023

AbstractIntroductionThere are growing concerns on how to prevent, slow down and induce remission of type 2 diabetes mellitus (T2DM). Recent evidence has found diet and lifestyle interventions can cause remission of T2DM, however, there are challenges for diverse groups such as British Pakistanis who are four times more at risk of T2DM. There is a need to understand the food behaviours of different generational groups to develop culturally appropriate strategies to support diabetes prevention programmes.AimsThis study explores beliefs about healthy eating and food practices related to T2DM among British Pakistanis to understand the challenges they face in implementing healthy diets.MethodWe carried out 26 semi‐structured qualitative interviews via telephone and face‐to‐face. The sample included T2DM British Pakistanis living in Bradford (UK), aged between 18 and 71 with a mean age of 50 (SD = 17.04). Among the participants, 14 were women (54%) and 12 were men (46%), with interviews conducted in both English (76%) and Urdu (24%). Participants were grouped under three generation groups based on age (first generation 65+; second generation 40–64; younger generation 18–39 years). There was no biological link between the generational groups, and they were not part of the same family. Data were analysed using qualitative reflexive thematic analysis.ResultsFindings were categorised into three themes: knowledge and awareness of diabetes symptoms; social and family context of food practices and making sense of healthy eating. The family was the fundamental unit of understanding food‐related health behaviours. Eating traditional food was perceived as healthy and deemed practical for first generations who were the initial members of their family to settle in the UK as well as the second generations who had parents born in Pakistan. Younger British Pakistanis were born in the UK and reported that they struggled to eat alternative foods within the home and manage their T2DM.ConclusionThese findings improve our understanding of how three generations of British Pakistanis with T2DM negotiate healthy diets. There is a need for culturally tailored diet modifications and interventions, where different generational needs can be specifically targeted to adopt healthier diets which should be shared and encouraged.
Simultaneous structural replacement of the sphingoid long‐chain base and sterol in budding yeast
Authors: Kono Yushi , Ishibashi Yohei , Fukuda Shizuka , Higuchi Takashi , Tani Motohiro 
Published: September 2023

The basic structures of membrane lipids that compose biomembranes differ among species; i.e., in mammals, the primary structure of long‐chain base (LCB), the common backbone of ceramides and complex sphingolipids, is sphingosine, whereas, in yeast Saccharomyces cerevisiae, it is phytosphingosine, and S. cerevisiae does not have sphingosine. In addition, the sterol, which is coordinately involved in various functions with complex sphingolipids, is cholesterol in mammals, while in yeast it is ergosterol. Previously, it was found that yeast cells are viable when the structure of LCBs is replaced by sphingosine by supplying an exogenous LCB to cells lacking LCB biosynthesis. Here, we characterized yeast cells having sphingosine instead of phytosphingosine (sphingosine cells). Sphingosine cells exhibited a strong growth defect when biosynthesis of ceramides or complex sphingolipids was inhibited, indicating that, in the sphingosine cells, exogenously added sphingosine is required to be further metabolized. The sphingosine cells exhibited hypersensitivity to various environmental stresses and had abnormal plasma membrane and cell wall properties. Furthermore, we also established a method for simultaneous replacement of both LCB and sterol structures with those of mammals (sphingosine/cholesterol cells). The multiple stress hypersensitivity and abnormal plasma membrane and cell wall properties observed in sphingosine cells were also observed in sphingosine/cholesterol cells, suggesting that simultaneous replacement of both LCB and sterol structures with those of mammals cannot prevent these abnormal phenotypes. This is the first study to our knowledge showing that S. cerevisiae can grow even if LCB and sterol structures are simultaneously replaced with mammalian types.