bluuebunny/crossref_metadata_2025_split huggingface dataset:
The NO Answer for Autism Spectrum Disorder
Authors: Tripathi Manish Kumar , Ojha Shashank Kumar , Kartawy Maryam , Hamoudi Wajeha , Aran Adi , Amal Haitham 
Published: January 2023

AbstractAutism spectrum disorders (ASDs) include a range of developmental disorders that share a core of neurobehavioral deficits manifested by abnormalities in social interactions, deficits in communication, restricted interests, and repetitive behaviors. Several reports showed that mutations in different high-risk ASD genes, includingSHANK3andCNTNAP2, lead to ASD. However, to date, the underlying molecular mechanisms have not been deciphered, and no effective pharmacological treatment has been established for ASD. Recently, we reported a dramatic increase of nitric oxide (NO) in ASD mouse models. NO is a multifunctional neurotransmitter that plays a key role in different neurological disorders. However, its role in ASD has not yet been investigated. To reveal the novel molecular, cellular, and behavioral role of NO in ASD, we conducted multidisciplinary experiments using cellular and mouse models as well as clinical samples. First, we treated WT mice with an NO donor, which led to an autism-like phenotype. Next, we measured and found high levels of nitrosative stress biomarkers in both theShank3andCntnap2ASD mouse models. Treating both mouse models with a selective neuronal NO synthase (nNOS) inhibitor led to a reversal in the molecular, synaptic, and behavioral ASD phenotypes. Using a primary neuronal cell culture, we confirmed that NO is specifically involved in neurons in ASD pathology. Next, using genetic manipulations in the human SH-SY5Y cell line, we found that nNOS plays a key role in the pathology. Finally, we examined human plasma samples from 19 low-functioning ASD patients, compared to 20 typically developed volunteers, and found a significant elevation in the NO levels in the ASD patients. Furthermore, using the SNOTRAP technology, which is an innovative mass spectrometric method to identify the SNO-proteome (SNO: NO-mediated post-translational modification), we revealed that the complement systems in the synaptic and neuronal development processes are enriched in the ASD group. This work indicates, for the first time, that NO plays a pathological role in ASD development. Our findings will open future and novel directions to examine NO in diverse mutations on the autism spectrum as well as other neurodevelopmental disorders and psychiatric diseases. Most importantly, it suggests a novel treatment strategy for ASD.One sentence summaryNitric oxide plays a key role in ASD pathology development and progression, and targeting its production leads to a reversal in the autistic phenotype.
Fertility decline in female mosquitoes is regulated by theorcoolfactory co-receptor
Authors: David Olayinka G. , Sanchez Kevin M. , Arce Andrea V. , Costa-da-Silva Andre Luis , Bellantuono Anthony J. , DeGennaro Matthew 
Published: January 2023

SUMMARYFemaleAedes aegyptimosquitoes undergo multiple rounds of reproduction, known as gonotrophic cycles. These cycles span the period from blood meal intake to oviposition. Understanding how reproductive success is maintained across gonotrophic cycles allows for the identification of molecular targets to reduce mosquito population growth. Odorant receptor co-receptor (orco) encodes a conserved insect-specific transmembrane ion channel that complexes with tuning odorant receptors (ORs) to form a functional olfactory receptor.orcoexpression has been identified in the male and female mosquito germline, but its role is unclear. We report anorco-dependent, maternal effect reduction in fertility after the first gonotrophic cycle. This decline was rescued by repairing theorcomutant locus. Eggs deposited byorcomutant females are fertilized but the embryos reveal developmental defects, reduced hatching, and changes in ion channel signaling gene transcription. We present an unexpected role for an olfactory receptor pathway in mosquito reproduction.HIGHLIGHTSLoss of theorcoolfactory co-receptor promotes female mosquito fertility decline.After their first reproductive cycle completes,Ae. aegypti orcomutant females produce embryos with disrupted development and reduced hatching.CRISPR/Cas9-mediated repair of theorcomutation rescues the fertility defect.Gene expression profiling of embryos fromorcomutant females supports a role for ion channel signaling in mosquito development.
Scalable Apparatus to Measure Posture and Locomotion (SAMPL): a high-throughput solution to study unconstrained vertical behavior in small animals
Authors: Zhu Yunlu , Auer Franziska , Gelnaw Hannah , Davis Samantha N. , Hamling Kyla R. , May Christina E. , Ahamed Hassan , Ringstad Niels , Nagel Katherine I. , Schoppik David 
Published: January 2023

ABSTRACTBalance and movement are impaired in a wide variety of neurological disorders. Recent advances in behavioral monitoring provide unprecedented access to posture and loco-motor kinematics, but without the throughput and scalability necessary to screen candidate genes / potential therapeutics. We present a powerful solution: a Scalable Apparatus to Measure Posture and Locomotion (SAMPL). SAMPL includes extensible imaging hardware and low-cost open-source acquisition software with real-time processing. We first demonstrate that SAMPL’s hardware and acquisition software can acquire data fromD. melanogaster,C.elegans, andD. rerioas they move vertically. Next, we leverage SAMPL’s throughput to rapidly (two weeks) gather a new zebrafish dataset. We use SAMPL’s analysis and visualization tools to replicate and extend our current understanding of how zebrafish balance as they navigate through a vertical environment. Next, we discover (1) that key kinematic parameters vary systematically with genetic background, and (2) that such background variation is small relative to the changes that accompany early development. Finally, we simulate SAMPL’s ability to resolve differences in posture or vertical navigation as a function of effect size and data gathered – key data for screens. Taken together, our apparatus, data, and analysis provide a powerful solution for laboratories using small animals to investigate balance and locomotor disorders at scale. More broadly, SAMPL is both an adaptable resource for laboratories looking process video-graphic measures of behavior in real-time, and an exemplar of how to scale hardware to enable the throughput necessary for screening.
A humanizedCaenorhabditis elegansmodel of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4
Authors: Gümüşderelioğlu Selin , Resch Lauren , Brock Trisha ,   Undiagnosed Diseases Network, Luxton G.W. Gant , Tan Queenie K-G , Hopkins Christopher , Starr Daniel A. 
Published: January 2023

AbstractHereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified a variant in human kinesin light chainKLC4that is suspected to be associated with autosomal dominant HSP. How this and other variants relate to pathologies is unknown. We created a humanizedC. elegansmodel whereklc-2 was replaced with humanKLC4and assessed the extent to whichhKLC4retained function in the worm. We observed a slight decrease in motility but no nuclear migration defects in the humanized worms, suggesting thathKLC4retains much of the function ofklc-2. FivehKLC4variants were introduced into the humanized model. The clinical variant led to early lethality with significant defects in nuclear migration when homozygous, and a weak nuclear migration defect when heterozygous, possibly correlating with the clinical finding of late onset HSP when the proband was heterozygous. Thus, we were able to establish humanizedC. elegansas an animal model for HSP and use it to test the significance of five variants of uncertain significance in the human geneKLC4.Summary StatementWe identified a variant inKLC4associated with Hereditary Spastic Paraplegia. The variant had physiological relevance in a humanizedC. elegansmodel where we replacedklc-2with humanKLC4.
Ex VivoBiomechanical Characterization of Umbilical Vessels: Possible Shunts in Congenital Heart Palliation
Authors: Murtada S-I. , Ramachandra A.B. , Humphrey J.D 
Published: January 2023

AbstractChildren born with single ventricle defects undergo staged palliative surgeries to reconstruct the circulation to improve transport of deoxygenated blood to the lungs. As part of the first surgery, a temporary shunt (Blalock-Thomas-Taussig) is often created in neonates to connect a systemic and a pulmonary artery. Standard-of-care shunts are synthetic, which can lead to thrombosis, and much stiffer than the two host vessels, which can cause adverse mechanobiological responses. Moreover, the neonatal vasculature can undergo significant changes in size and structure over a short period, thus constraining the use of a non-growing synthetic shunt. Recent studies suggest that autologous umbilical vessels could serve as improved shunts, but there has not been a detailed biomechanical characterization of the four primary vessels – subclavian artery, pulmonary artery, umbilical vein, and umbilical artery. Herein, we biomechanically phenotype umbilical veins and arteries from prenatal mice (E18.5) and compare them to subclavian and pulmonary arteries harvested at two critical postnatal developmental ages (P10, P21). Comparisons include age-specific physiological conditions and simulated ‘surgical-like’ shunt conditions. Results suggest that the intact umbilical vein is a better choice as a shunt than the umbilical artery due to concerns with lumen closure and constriction related-intramural damage in the latter. Yet, decellularization of umbilical arteries may be a viable alternative, with the possibility of host cellular infiltration and subsequent remodeling. Given recent efforts using autologous umbilical vessels as Blalock-Thomas-Taussig shunts in a clinical trial, our findings highlight aspects of the associated biomechanics that deserve further investigation.
Follicle stimulating hormone signaling opposes the DRL-1/FLR-4 MAP Kinases to balance p38-mediated growth and lipid homeostasis inC. elegans
Authors: Torzone Sarah K. , Park Aaron Y. , Breen Peter C. , Cohen Natalie R. , Dowen Robert H. 
Published: January 2023

ABSTRACTAnimals integrate developmental and nutritional signals before committing crucial resources to growth and reproduction; however, the pathways that perceive and respond to these inputs remain poorly understood. Here, we demonstrate that DRL-1 and FLR-4, which share similarity with mammalian mitogen-activated protein kinases, maintain lipid homeostasis in theC. elegansintestine. DRL-1 and FLR-4 function in a protein complex at the plasma membrane to promote development, as mutations indrl-1orflr-4confer slow growth, small body size, and impaired lipid homeostasis. To identify factors that oppose DRL-1/FLR-4, we performed a forward genetic screen for suppressors of thedrl-1mutant phenotypes and identified mutations inflr-2andfshr-1, which encode the orthologues of follicle stimulating hormone and its putative G protein-coupled receptor, respectively. In the absence of DRL-1/FLR-4, neuronal FLR-2 acts through intestinal FSHR-1 and Protein Kinase A signaling to restrict growth. Furthermore, we show that opposing signaling through DRL-1 and FLR-2 coordinates TIR-1 phase transition, which modulates downstream p38/PMK-1 activity, lipid homeostasis, and development. Finally, we identify a surprising noncanonical role for the developmental transcription factor PHA-4/FOXA in the intestine where it restricts growth in response to impaired DRL-1 signaling. Our work uncovers a complex multi-tissue signaling network that converges on p38 signaling to maintain homeostasis during development.
Mechanism of physical force induced human slack channel desensitization
Authors: Zhang Mingfeng , Shan Yuanyue , Pei Duanqing 
Published: January 2023

SummaryHuman Slack (hSlack) channel is abundantly expressed in the central nervous system and regulates numerous physiological processes. Here, we identified hSlack channel is a voltage dependent physical force induced desensitization potassium channel. In the cell-attached mode, hSlack exhibited large voltage dependent potassium currents without significant delayed rectification or C-type inactivation. After breaking the cell membrane resulting the inside-out mode, the potassium currents were largely inhibited and it transited to the strong voltage dependent delayed rectified state. Structural results suggested that the “S6 site” confers the voltage dependent delayed rectification of hSlack channel, like our recent finding in hEag2 channel(In revision). Strikingly, the physical force induced desensitization and gating kinetics transition are mediated by the gatekeeper lipids in the central pore. Our results reported a novel physical force sensing channel through the pore lipids mediating physical force induced desensitization and gating kinetics transition. It opens a new door to understand the molecular basis of mechanobiology.
Decoding CRISPR–Cas9 PAM recognition with UniDesign
Authors: Huang Xiaoqiang , Zhou Jun , Yang Dongshan , Zhang Jifeng , Xia Xiaofeng , Chen Y. Eugene , Xu Jie 
Published: January 2023

AbstractThe critical first step in CRISPR–Cas mediated gene editing is recognizing a preferred protospacer adjacent motif (PAM) on target DNAs by the protein’s PAM-interacting amino acids (PIAAs). Thus, accurate computational modeling of PAM recognition is useful in assisting CRISPR–Cas engineering to relax or tighten PAM requirement for subsequence applications. Here we describe a universal computational protein design framework (UniDesign) for designing protein–nucleic acid interactions. As a proof of concept, we applied UniDesign to decode the PAM–PIAA interactions for eight Cas9 proteins. We show that, given native PIAAs, the UniDesign-predicted PAMs are largely identical to the natural PAMs of all Cas9s. In turn, given natural PAMs, the computationally redesigned PIAA residues largely recapitulated the native PIAAs (>70% and >80% in terms of identity and similarity, respectively). These results demonstrate that UniDesign faithfully captures the mutual preference between natural PAMs and native PIAAs, suggesting it as a useful tool for engineering CRISPR–Cas and other nucleic acid–interacting proteins. UniDesign is open-sourced athttps://github.com/tommyhuangthu/UniDesign.
The effect ofin vitrostarch digestibility on glycemic/insulinemic index of biscuits and bread made from non-conventional wholemeal/wholegrain flour mixtures
Authors: Papadopoulos Charalampos , Anagnostopoulos Constantine , Zisimopoulos Athanasios , Panopoulou Maria , Papazoglou Dimitrios , Grapsa Anastasia , Tente Thaleia , Tentes Ioannis 
Published: January 2023

AbstractBACKGROUNDCarbohydrates as starch are a staple part of the Mediterranean diet. Starch is digested in the small intestine and the resulting glucose is absorbed into the blood, eliciting an insulin response. The digestion and absorption kinetics (rapid or slow) depends on starch structure.OBJECTIVETo study the relationship between thein vivoglycemic and insulinemic index and thein vitrodigestibility characteristics of six bakery products, made from non-conventional wholemeal/wholegrain flours.METHODSWe analyzedin vitrothe rapidly- and slowly- available glucose (RAG and SAG), the rapidly- and slowly- digestible starch (RDS and SDS), and the resistant starch (RS) fraction of the six wholemeal/wholegrain products and one white type of bread. The glycemic and the insulinemic index (GI and II respectively) were estimated byin vivotesting in a group of eleven healthy individuals.RESULTSThe GI of the wholemeal/wholegrain flour biscuits and breads were low, (range 28±3.2 to 41±3.9, Mean±SEM) correlating with the II. RAG positively correlated with both GI and II, with fiber having a marginal correlation.CONCLUSIONSOur findings indicate that both conventional and non-conventional wholemeal/wholegrain bakery products have low GI and moderate II, correlating toin vitrostarch digestibility and the type of processing.
Evolutionarily acquired activity-dependent transformation of the CaMKII holoenzyme
Authors: Tsujioka Shotaro , Sumino Ayumi , Nagasawa Yutaro , Sumikama Takashi , Flechsig Holger , Puppulin Leonardo , Tomita Takuya , Baba Yudai , Kakuta Takahiro , Ogoshi Tomoki , Umeda Kenichi , Kodera Noriyuki , Murakoshi Hideji , Shibata Mikihiro 
Published: January 2023

AbstractCa2+/calmodulin-dependent protein kinase II (CaMKII) has long been central in synaptic plasticity research. CaMKII is a dodecameric serine/threonine kinase that has been essentially conserved across metazoans for over a million years. While the mechanisms of CaMKII activation are well studied, its “behavior” at the molecular level has remained unobserved. Here, high-speed atomic force microscopy was used to visualize the activity-dependent structural dynamics of rat/hydra/C. elegansCaMKII in various states at nanometer resolution. Among the species, rat CaMKII underwent internal kinase domain aggregation in an activity-dependent manner and showed a higher tolerance to dephosphorylation by phosphatase. Our findings suggest that mammalian CaMKII has evolutionarily acquired a new structural form and a tolerance to phosphatase to maintain robust CaMKII activity for proper neuronal function.One-Sentence SummaryHigh-speed atomic force microscopy reveals the activity-dependent structural dynamics of rat/hydra/C. elegansCaMKII
Spillovers between non-commercial traders’ activity and spot prices? Analysis of the financialization mechanism in the crude oil market
Authors: Focacci Antonio 
Published: January 2023

PurposeThe purpose of this stud is to analyze the financialization effect on oil prices.Design/methodology/approachThis study applied the technique of multibreak point analysis with Bai and Perron test plus VAR methodology.FindingsFindings revealed that there was no effect on oil prices.Originality/valueTo the best of the author’s knowledge, this is the first paper combining the multibreakpoint analysis with VAR for the period analyzed in the present work.
The effectiveness of sustainability social marketing use of fear and guilt appeals to influence the behavioural intention of millennials
Authors: van Breda Lise , Terblanche-Smit Marlize , Pelser Theuns 
Published: January 2023

Purpose
This study aims to understand if the appeals often used in social marketing, namely, fear and guilt, are effective in changing South African millennials’ intention to behave more pro-environmentally.

Design/methodology/approach
A primary quantitative research method was followed with a between-subject experimental design approach. The treatment took the form of fear- and guilt-based sustainability advertisements. Questions were asked in the form of a survey with the determinants of the theory of planned behaviour (TPB) model (i.e. attitude, subjective norm and perceived behavioural control) as its constructs.

Findings
Analysis of the collected data revealed that adding the appeal of fear or guilt to advertisements does not significantly change South African millennials’ intention to behave pro-environmentally. Furthermore, a deeper analysis of the TPB model’s determinants showed that attitude had the strongest effect on behavioural intention. Also, the use of fear or guilt in sustainability social marketing does not affect the subjective norms of South African millennials.

Research limitations/implications
The study offers a greater understanding of customer engagement and motivational factors in the mobile instant messaging (MIM) environment. Future studies could consider more complex relationships with customer engagement in using MIM apps focussed on a younger generation.

Practical implications
It is therefore recommended that to significantly increase the South African millennials’ intention to behave pro-environmentally, social marketers should use other advertising tools or appeals, namely, positive attitude change.

Originality/value
The results of this study represent a contribution to the limited literature on TPB determinants and how they drive behavioural intention.
A framework to implement augmented reality based on BIM to improve operation and maintenance of mechanical facilities of commercial complexes
Authors: Alijani Mamaghani Omid , Noorzai Esmatullah 
Published: January 2023

Purpose
The mechanical facilities of large-scale buildings have many complexities, so facility management (FM) encounters a massive amount of information during the operation, and inspection is not implemented efficiently. This study aims to integrate building information modeling (BIM), augmented reality (AR) and sensors to mitigate the operation and maintenance (O&M) problems of mechanical facilities by establishing intelligent management.

Design/methodology/approach
The component-level data of an under-construction commercial complex were implemented in a 3D model in Autodesk Revit and Navisworks. Then, sensors were installed in mechanical facilities to provide vital online information for the model. Moreover, Unity was used on Vuforia for the AR visualization of the devices.

Findings
It was found that FM not only could obtain building information but can also visualize the functioning of mechanical facilities online through a 3D model in BIM. Thus, in the case of a failure, the AR platform is used on tablets, smartphones and smart glasses to show the technician how mechanical facilities can be repaired and maintained.

Originality/value
Previous studies focused on some factors and processes to improve mechanical FM and did not cover the entire aspect. However, this method reduces the average maintenance time, extends the lives of mechanical devices and prevents unpredicted failures.
On thresholds: signs, symbols and significance
Authors: Van der Veer Martens Betsy 
Published: January 2023

PurposeThis paper reviews research developments in semiosis (sign activity) as theorized by Peirce, Eco and Sebeok, focusing specifically on the current study of “semiotic threshold zones,” which range from the origins of life through various nonhuman life forms to artificial life forms, including those symbolic thresholds most familiar to library and information science (LIS) researchers. The intent is to illustrate potential opportunities for LIS research beyond its present boundaries.Design/methodology/approachThe paper provides a framework that describes six semiotic threshold zones (presemiotic, protosemiotic, phytosemiotic, zoosemiotic, symbolic and polysemiotic) and notable work being done by researchers in each.FindingsWhile semiotic researchers are still defining the continuum of semiotic thresholds, this focus on thresholds can provide a unifying framework for significance as human and nonhuman interpretations of a wide variety of signs accompanied by a better understanding of their relationships becomes more urgent in a rapidly changing global environment.Originality/valueThough a variety of semiotic-related topics have appeared in the LIS literature, semiotic thresholds and their potential relationships to LIS research have not been previously discussed there. LIS has traditionally tasked itself with the recording, dissemination and preservation of knowledge, and in a world that faces unprecedented environmental and global challenges for all species, the importance of these thresholds may well be considered as part of our professional obligations in potentially documenting and archiving the critical differences in semiosis that extend beyond purely human knowledge.