bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Digital PCR Assays for Multiplexed Microbial Source Tracking in Surface Waters
Authors: Ghosh Shimul , Bivins Aaron 
Published: September 2024

AbstractDigital PCR (dPCR) shows great promise for precise, sensitive, and inhibition-resilient measurement of nucleic acids in surface water, providing an advantage for applications such as microbial source tracking (MST). Herein, we describe our empirical optimization of two triplex format dPCR reactions (Triplex 1 - Cow M2, Rum2Bac, Cow M3; Triplex 2 - HF183/BacR287, Pig2Bac, Entero1a) on the QIAcuity One system for MST. Each triplex produced gene copy measurements similar to single-plex format assays for a standard reference material (SRM 2917) at a fixed concentration and along a concentration gradient. For achieved water samples previously tested by single-plex assays, each triplex also produced MST marker measurements comparable to the single-plex results. The triplexes described here can be directly adopted for MST on the QIAcuity, or the optimization protocol we demonstrate can be used to develop additional multiplex assays on the QIAcuity system.
Endophilin A1 facilitates organization of the GABAergic postsynaptic machinery to maintain excitation-inhibition balance
Authors: Chen Xue , Pan Deng , Liu Jia-Jia , Yang Yanrui 
Published: September 2024

AbstractThe assembly and operation of neural circuits in the brain rely on the coordination and balance of excitatory and inhibitory activities. Inhibitory synapses are key regulators of the functional balance of neural circuits. However, due to the diversity of inhibitory presynaptic neurons, the complex composition of postsynaptic receptor subunits and the lack of typical postsynaptic dense structure, there are relatively few studies on the regulatory mechanisms for inhibitory synaptic structure and function, and insufficient understanding of the cellular and molecular abnormalities of inhibitory synapses in neurological and neuropsychiatric disorders. Here, we report a crucial role for endophilin A1 in inhibitory synapses. We show that endophilin A1 directly interacts with the inhibitory postsynaptic scaffold protein gephyrin in excitatory neurons, and promotes organization of the inhibitory postsynaptic density and synaptic recruitment/stabilization of the γ-aminobutyric acid type A receptors via its plasma membrane association and actin polymerization promoting activities. Loss of endophilin A1 by gene knockout in mouse hippocampal CA1 pyramidal cells weakens inhibitory synaptic transmission and causes imbalance in the excitatory/inhibitory function of neural circuits, leading to increased susceptibility to epilepsy. Our findings identify endophilin A1 as an iPSD component and provide new insights into the organization and stabilization of inhibitory postsynapses to maintain E/I balance as well as the pathogenesis of epilepsy.
Human transferrin and lactoferrin cooperatively supportNeisseria meningitidiscolonization in the murine nasopharynx
Authors: Lee Isaac S. , Fegan Jamie E. , Currie Elissa G. , Bojagora Anna , Leung Nelly Y. , Rancourt Derrick , Taha Muhamed-Kheir , Schryvers Anthony B. , Gray-Owen Scott D. 
Published: September 2024

ABSTRACTNeisseria meningitidisis a human-restricted bacteria that is a normal nasopharyngeal resident, yet it can also disseminate, causing invasive meningococcal disease. Meningococci are highly adapted to life in humans, with human-specific virulence factors contributing to bacterial adhesion, nutrient acquisition and immune evasion. While these factors have been explored in isolation, their relative contribution during infection has not been considered due to their absence in small animal models and their expression by different human cell types not readily combined in eitherin vitroorex vivosystems. Herein, we show that transgenic expression of the iron-binding glycoproteins human transferrin and lactoferrin can each facilitateN. meningitidisreplication in mouse serum but that transferrin was required to support infection-induced sepsis. While these host proteins are insufficient to allow nasopharyngeal colonization alone, mice co-expressing these and human CEACAM1 support robust colonization. In this case, meningococcal colonization elicits an acute elevation in both transferrin and lactoferrin levels within the upper respiratory mucosa, with transferrin levels remaining elevated while lactoferrin returns to basal levels after establishment of infection. Competitive infection of triple transgenic animals with transferrin- and lactoferrin- binding protein mutants selects for bacteria expressing the transferrin receptor, implicating the critical contribution of transferrin-based iron acquisition to support colonization. These transgenic animals have thus allowed us to disentangle the relative contribution of three virulence factors during colonization and invasive disease, and provides a novelin vivomodel that can support extended meningococcal colonization, opening a new avenue to explore the meningococcal lifestyle within its primary niche.
Vps4 substrate binding and coupled mechanisms of Vps4p substrate recruitment and release from autoinhibition
Authors: Wienkers HJ , Han H , Whitby FG , Hill CP 
Published: September 2024

AbstractThe ESCRT pathway’s AAA+ ATPase, Vps4p, remodels ESCRT-III complexes to drive membrane fission. Here, we use peptide binding assays to further the understanding of substrate specificity and the mechanism of autoinhibition. Our results reveal unexpected sequence preference to the substrate binding groove and an elegant mechanism of regulation that couples localization to substrate with release from autoinhibition.
Modelling mucus clearance in sinuses: thin-film flow inside a fluid-producing cavity lined with an active surface
Authors: Desai Nikhil , Lauga Eric 
Published: September 2024

AbstractThe paranasal sinuses are a group of hollow spaces within the human skull, surrounding the nose. They are lined with an epithelium that contains mucusproducing cells and tiny hairlike active appendages called cilia. The cilia beat constantly to sweep mucus out of the sinus into the nasal cavity, thus maintaining a clean mucus layer within the sinuses. This process, called mucociliary clearance, is essential for a healthy nasal environment and disruption in mucus clearance leads to diseases such as chronic rhinosinusitis, specifically in the maxillary sinuses, which are the largest of the paranasal sinuses. We present here a continuum mathematical model of mucociliary clearance inside the human maxillary sinus. Using a combination of analysis and computations, we study the flow of a thin fluid film inside a fluid-producing cavity lined with an active surface: fluid is continuously produced by a wall-normal flux in the cavity and then is swept out, against gravity, due to an effective tangential flow induced by the cilia. We show that a steady layer of mucus develops over the cavity surface only when the rate of ciliary clearance exceeds a threshold, which itself depends on the rate of mucus production. We then use a scaling analysis, which highlights the competition between gravitational retention and cilia-driven drainage of mucus, to rationalise our computational results. We discuss the biological relevance of our findings, noting that measurements of mucus production and clearance rates in healthy sinuses fall within our predicted regime of steady-state mucus layer development.
Mis-regulation of GSK-3β causes axonal microtubule curling through Shot and Tau
Authors: Voelzmann Andre , Nuhu-Soso Lubna , Roof Alex , Patel Sanjai , Bennett Hayley , Adamson Antony , Bentley Marvin , Evans Gareth J. O. , Hahn Ines 
Published: September 2024

AbstractGlycogen Synthase Kinase 3β (GSK-3β) is a key coordinator of neuronal development and maintenance; overactive GSK-3β is linked to neurodevelopmental and -degenerative diseases making it a highly promising therapeutic target. One of GSK-3β’s key roles in neurons is to coordinate the cytoskeleton by directly phosphorylating microtubule binding proteins. However, how GSK-3β orchestrates the activities of a range of microtubule regulators, to jointly maintain microtubule bundles is not well understood. We study the function of GSK-3β using fly primary neurons, a uniquely tractable system which has allowed us to unravel the function of >50 cytoskeletal regulators in the past. Here we report a novel function of GSK-3β. We find that kinase activity needs to be tightly regulated to maintain parallel microtubule bundles in axons. Functional up-as well as down-regulation of GSK-3β leads to axons forming pathological swellings where microtubule bundles disintegrate into criss-crossed curling microtubules. Mechanistically, we have identified Shot and Tau as key GSK-3β targets, providing a means to change microtubule behaviours in a time and location-specific manner. By modifying the ability of Shot and Tau to attach to microtubules and Eb1, both hyperactivity as well as inhibition of GSK-3β leads to the loss of Eb1-Shot-mediated guidance of polymerising microtubules into parallel bundles, thus causing disorganisation. Our findings provide new explanations how overactivity of GSK-3β could lead to neurodegeneration in neurodegenerative diseases and why global inhibition of GSK-3β has not been successful in clinical trials for those disorders.
Topology-Driven Discovery of Transmembrane ProteinS-Palmitoylation
Authors: Forrester Michael T. , Egol Jacob R. , Ozbay Sinan , Singh Rohit , Tata Purushothama Rao 
Published: September 2024

ABSTRACTProteinS-palmitoylation is a reversible lipophilic posttranslational modification regulating a diverse number of signaling pathways. Within transmembrane proteins (TMPs),S-palmitoylation is implicated in conditions from inflammatory disorders to respiratory viral infections. Many small-scale experiments have observedS-palmitoylation at juxtamembrane Cys residues. However, most large-scaleS-palmitoyl discovery efforts rely on trypsin-based proteomics within which hydrophobic juxtamembrane regions are likely underrepresented. Machine learning– by virtue of its freedom from experimental constraints – is particularly well suited to address this discovery gap surrounding TMPS-palmitoylation. Utilizing a UniProt-derived feature set, a gradient boosted machine learning tool (TopoPalmTree) was constructed and applied to a holdout dataset of viralS-palmitoylated proteins. Upon application to the mouse TMP proteome, 1591 putativeS-palmitoyl sites (i.e. not listed in SwissPalm or UniProt) were identified. Two lung-expressedS-palmitoyl candidates (synaptobrevin Vamp5 and water channel Aquaporin-5) were experimentally assessed. Finally, TopoPalmTree was used for rational design of anS-palmitoyl site on KDEL-Receptor 2. This readily interpretable model aligns the innumerable small-scale experiments observing juxtamembraneS-palmitoylation into a proteomic tool for TMPS-palmitoyl discovery and design, thus facilitating future investigations of this important modification.
Relationship between nonexercise activity and mood in patients with eating disorders
Authors: Olfermann Robin , Schlegel Sabine , Vogelsang Anna , Ebner‐Priemer Ulrich , Zeeck Almut , Reichert Markus 
Published: September 2024

AbstractIntroductionMany patients with eating disorders (EDs) engage in excessive and compulsive physical activity (pathological exercise, PE) to regulate negative mood or to “burn calories.” PE can lead to negative health consequences. Non‐exercise activity (NEA) bears the potential to serve as intervention target to counteract PE and problematic eating behaviors since it has been associated with positive mood effects. However, to date, there is no investigation on whether the positive link between NEA and mood seen in the healthy translates to patients with ED.Material and MethodsTo study potential associations of NEA and mood in ED, we subjected 29 ED‐patients and 35 healthy controls (HCs) to an ambulatory assessment study across 7 days. We measured NEA via accelerometers and repeatedly assessed mood on electronic smartphone diaries via a mixed sampling strategy based on events, activity and time. Within‐ and between‐subject effects of NEA on mood, PE as moderator, and the temporal course of effects were analyzed via multilevel modeling.ResultsNEA increased valence (β = 2.12, p < 0.001) and energetic arousal (β = 4.02, p < 0.001) but showed no significant effect on calmness. The effects of NEA on energetic arousal where significantly stronger for HCs (β
HC = 6.26, p < 0.001) than for EDs (β
ED = 4.02, p < 0.001; β
interaction = 2.24, p = 0.0135). Effects of NEA were robust across most timeframes of NEA and significantly moderated by PE, that is, Lower PE levels exhibited stronger NEA effects on energetic arousal.ConclusionPatients with ED and HC show an affective benefit from NEA, partly depending on the level of PE. If replicated in experimental daily life studies, this evidence may pave the way towards expedient NEA interventions to cope with negative mood. Interventions could be especially promising if delivered as Just‐in‐time adaptive interventions (JITAIs) and should be tailored according to the PE level.
How did the elephant cross the fence? Electric fence crossing by elephants in Udawalawe, Sri Lanka
Authors: Ranjeewa A. D. G. , Thomas R. J. , Weerakoon D. K. , Sandanayake G. H. N. A. , Fernando P. 
Published: September 2024

AbstractElectric fences are widely used in human–elephant conflict mitigation. However, elephants constantly challenge and overcome fences, which is a growing concern. We studied how elephants crossed the perimeter electric fence around the Udawalawe National Park (UWNP), Sri Lanka. Using camera traps, we monitored 18 fence posts and an open gate in the fence over 605 days from 2016 to 2019. Photographs of 3097 fence crossings were analysed to obtain demographic data for fence crossing elephants, crossing methods, and the daily and seasonal timing of fence crossing. We identified 77 adult males and 12 adult females that crossed the fence, which represent about 17% of the adult elephants in UWNP. Most of the crossings were through the open gate at night. Elephants used a variety of crossing methods, comprised of crossing at the open gate, at previously toppled posts, by crashing through wires and stepping over wires, as well as by using the trunk or forefeet to topple posts. Fence voltage was not a determinant of fence crossing. The frequency and timing of fence crossings varied between locations with later exits and less time spent outside, at crossing points bordering human dominated areas. Our results emphasis on the importance of taking into account the problem solving abilities of elephants in fence design and location, such as energising fence posts and constructing exclosure fences at the boundaries of crop fields and settlements, in employing electric fences to mitigate human‐elephant conflict.
The clinical utility of autologous tumor lysate‐loaded dendritic cell vaccination for patients with glioma: A systematic review and meta‐analysis
Authors: Habibi Mohammad Amin , Mirjani Mohammad Sina , Ahmadvand Muhammad Hussain , Delbari Pouria , Arab Shayan , Minaee Poriya , Eazi SeyedMohammad , Ahmadpour Sajjad 
Published: September 2024

AbstractBackgroundDendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta‐analysis examined DC vaccine efficacy and safety for gliomas.MethodsThis systematic review and meta‐analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated.ResultsA total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6‐month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%–100%]. Respectively, 12‐month OS reported 75% [95%CI: 65%–85%] but declined to 32% [95%CI: 20%–43%] for 24‐month OS. 6‐ and 12‐month progression‐free survival reached 49% [95%CI: 21%–77%] and 19% [95%CI:8%–30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%–42%], and 26% [95%CI: 10%–42%], though stable disease reached 33% [95%CI: 15%–51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%–57%].ConclusionsIn gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.
Predicting alcohol consumption: Application of an integrated social cognition model of intentions, habits, and cue consistency
Authors: Simpson‐Rojas Danielle , Phipps Daniel J. , Jenkins Kailas , Fleig Lena , Hagger Martin S. , Hamilton Kyra 
Published: September 2024

AbstractDrinking alcohol in excess is associated with deleterious health outcomes, highlighting the need for research to identify potentially modifiable correlates of excessive alcohol consumption to target in behavioral interventions. The present two‐wave prospective correlational study applied an integrated theoretical model that included theory of planned behavior constructs alongside habit, cue consistency, affective attitudes, and past behavior as predictors of two alcohol‐related behaviors, drinking within safe limits and regular alcohol drinking, in separate samples of Australian undergraduate students (total N = 474). Structural equation models identified direct effects of habit, affective attitude, and subjective norms on intention for both behaviors. Habit at follow‐up, cue consistency, and past behavior directly predicted behavior in both samples, whereas intention predicted behavior only for drinking within safe limits, and affective attitude only predicted behavior for regular drinking. Cue consistency moderated the effects of habit on behavior for both behaviors and moderated the effect of past behavior on regular drinking. Results corroborate past behavior and habit as key correlates of behavior and provide preliminary evidence of the importance of integrating cue consistency, a defining characteristic of habit, as a moderator of habit and past behavior effects an integrated theory test.
Age‐stage, two‐sex life table and transcriptome analysis reveal the adaptation of Liriomyza trifolii to different host plants
Authors: Yan Yu‐Qing , Chang Ya‐Wen , Gong Wei‐Rong , Hu Jie , Du Yu‐Zhou 
Published: September 2024

AbstractLiriomyza trifolii (Burgess) (Diptera: Agromyzidae) is a polyphagous insect that is widely known for its invasiveness. Understanding the adaptation of L. trifolii to different host plants is critical in formulating effective approaches for integrated pest management (IPM). In this study, the effects of various host plants on L. trifolii were investigated by age‐stage, two‐sex life tables and transcriptome analysis. Our results show that the growth rate of immature L. trifolii on sponge gourd increased significantly relative to bean, but mortality was high. Mature L. trifolii adapted to sponge gourd had significantly increased longevity as compared to flies adapted to bean but exhibited reduced fecundity. The net reproductive rate, the intrinsic rate of increase, and the finite rate of increase of L. trifolii adapted to sponge gourd were significantly lower than those of flies adapted to bean. Transcriptome analysis showed the presence of 150 up‐ and 617 downregulated differentially expressed genes in L. trifolii adapted to sponge gourd as compared to flies adapted to bean. Genes encoding glutathione‐S‐transferase, cytochrome P450, and trypsin were significantly downregulated in L. trifolii adapted to sponge gourd as compared to bean. This study provides valuable insight into host plant effects on L. trifolii and provides a basis for the subsequent development of IPM measures such as push and pull, crop rotation, and biopesticide development.
Characterisation of chicken breast and soy proteins glycated with konjac glucomannan hydrolysate
Authors: Pomsang Pachara , Phumsombat Putthapong , Borompichaichartkul Chaleeda 
Published: September 2024

SummaryThis study investigated the enhancement of food proteins through glycation with bioactive saccharides derived from Konjac glucomannan hydrolysate (KGMH) via the Maillard reaction. The focus was on how the degree of polymerisation (DP) of KGMH influences the glycation process and the properties of conjugates with chicken breast and soy proteins. KGMH samples with low, medium, and high DPs (4.20, 5.21, and 6.11, respectively) were glycated under wet‐heating conditions with varying pH levels (8, 9, and 10) at 70 °C for 15 min to 6 h. Results demonstrated that higher pH and longer reaction times significantly enhanced (P < 0.05) glycation and browning, particularly with lower DP saccharides. The optimal conjugates markedly improved protein solubility (1.3 to 1.9 times), heat stability (1.1 to 2.4 times), and emulsification properties (1.2 to 1.5 times), with the highest DP showing the strongest correlation. Additionally, these conjugates exhibited significantly enhanced in vitro bioaccessibility (58.69% to 66.65%) and antioxidant activity (P < 0.05). This study highlights the novel potential of KGMH‐protein conjugation through the Maillard reaction for developing functional food ingredients with superior quality.
The effect of debittering by sonication in brine, NaOH and water on bioactive compounds, antioxidant activity of caper (Capparis ovata Desf.) young shoot and buds
Authors: Qasem Akram A. , Mohamed Ahmed Isam A. , Mohammed Belal M. , Brennan Charles S. , Özcan Mehmet Musa , Uslu Nurhan 
Published: September 2024

SummaryThe total carotenoid amounts of the caper young shoot and buds debittered by sonication in brine, NaOH and tap water were reported to be between 19.99 (control) and 37.23 μg g−1 (water) to 4.36 (control) and 20.38 μg g−1 (NaOH), respectively. Total phenolic contents of sonicated caper young shoot and buds in brine, NaOH and tap water were specified to be between 34.96 (NaOH) and 299.84 mg gallic acid equivalent (GAE)/100 g (control) to 45.04 (NaOH) and 373.12 mg GAE/100 g (control), respectively. Radical scavenging activity values of sonicated young shoots were measured between 1.26 (NaOH) and 7.58 mmol trolox equivalent (TE) kg−1 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) (control). In addition to DPPH, antioxidant activity values of sonicated caper young shoot and buds were measured to be between 2.06 (NaOH) and 17.72 Ferric reducing antioxidant power (FRAP), mg g−1 (control) to 1.70 (NaOH) and 13.44 FRAP mg g−1 (control), respectively. Kaempferol quantities of sonicated caper young shoot were identified between 40.08 (control) and 53.83 mg/100 g (Brine). In general, the most reduction in phenolic components was observed in caper young shoot and buds sonicated in NaOH solution. The phenolic components of the caper young shoot and buds sonicated in different solutions showed changes on the solution type when compared to the control.