bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of fleQ Deficiency on Resource Allocation and Heterologous Gene Expression in Pseudomonas putida Across Various Growth Media
Authors: Kim Junyoung , Lee Sooyeon , Darlington Alexander P. S. , Kim Juhyun 
Published: November 2024

ABSTRACTPseudomonas putida is widely used in industrial applications, including the recombinant proteins production, because of its natural advantageous properties. In this study, the gene encoding FleQ, the primary regulator of flagellar synthesis, was deleted to construct a new non‐motile P. putida KT2440‐derived strain (ΔfleQ). The non‐motile cells showed reduced biofilm formation and enhanced expression of a heterologous gene in nutrient‐rich media compared with the wild‐type (WT) strain, attributed to the reallocation of cellular resources from flagellar synthesis and cellular motility. Additionally, the ΔfleQ strain exhibited enhanced tolerance to chloramphenicol, indicating higher ribosome production, confirmed by a higher RNA/protein ratio relative to the WT. While the WT strain showed decreased growth and a three‐fold increase in reporter gene activity in minimal media, the ΔfleQ strain maintained consistent reporter gene expression and exhibited a relatively higher growth rate. This suggests that the FleQ is involved in modulating proteome allocation based on nutrient quality. The removal of FleQ allows for more flexible resource allocation, creating a chassis strain with nutrient quality‐independent gene expression capacity, which could be valuable in industrial applications where consistent output is essential.
Residual microglia following short‐term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy
Authors: Kodali Maheedhar , Madhu Leelavathi N. , Somayaji Yogish , Attaluri Sahithi , Huard Charles , Panda Prashanta Kumar , Shankar Goutham , Rao Shama , Shuai Bing , Gonzalez Jenny J. , Oake Chris , Hering Catherine , Babu Roshni Sara , Kotian Sanya , Shetty Ashok K. 
Published: November 2024

AbstractWhile moderately activated microglia in Alzheimer's disease (AD) are pivotal in clearing amyloid beta (Aβ), hyperactivated microglia perpetuate neuroinflammation. Prior investigations reported that the elimination of ~80% of microglia through inhibition of the colony‐stimulating factor 1 receptor (CSF1R) during the advanced stage of neuroinflammation in 5xFamilial AD (5xFAD) mice mitigates synapse loss and neurodegeneration. Furthermore, prolonged CSF1R inhibition diminished the development of parenchymal plaques. Nonetheless, the effects of short‐term CSF1R inhibition during the early stages of neuroinflammation on residual microglia are unknown. Therefore, we investigated the effects of 10‐day CSF1R inhibition using PLX5622 in three‐month‐old female 5xFAD mice, a stage characterized by the onset of neuroinflammation and minimal Aβ plaques. We observed ~65% microglia depletion in the hippocampus and cerebral cortex. The leftover microglia displayed a noninflammatory phenotype with reduced NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3) inflammasome complexes. Moreover, plaque‐associated microglia were reduced with diminished Clec7a expression. Additionally, phosphorylated S6 ribosomal protein and the protein sequestosome 1 analysis suggested reduced mechanistic targets of rapamycin (mTOR) signaling and autophagy in microglia and neurons within the hippocampus and cerebral cortex. Biochemical assays validated the inhibition of NLRP3 inflammasome activation, decreased mTOR signaling in the hippocampus and cerebral cortex, and enhanced autophagy in the hippocampus. However, short‐term CSF1R inhibition did not influence Aβ plaques, soluble Aβ‐42 levels, astrocyte hypertrophy, or hippocampal neurogenesis. Thus, short‐term CSF1R inhibition during the early stages of neuroinflammation in 5xFAD mice promotes the retention of homeostatic microglia with diminished inflammasome activation and mTOR signaling, alongside increased autophagy.
More rTMS pulses or more sessions? The impact on treatment outcome for treatment resistant depression
Authors: Oostra E. , Jazdzyk P. , Vis V. , Dalhuisen I. , Hoogendoorn A. W. , Planting C. H. M. , van Eijndhoven P. F. , van der Werf Y. D. , van den Heuvel O. A. , van Exel E. 
Published: November 2024

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) is effective for treatment‐resistant depression (TRD). Optimal rTMS parameters remain unclear, especially whether number of sessions or amount of pulses contribute more to treatment outcome. We hypothesize that treatment outcome depends on the number of sessions rather than on the amount of pulses.MethodsWe searched databases for randomized clinical trials (RCTs) on high‐frequent (HF) or low‐frequent (LF)‐rTMS targeting the left or right DLPFC for TRD. Treatment efficacy was measured using standardized mean difference (SMD), calculated from pre‐ and post‐treatment depression scores. Meta‐regressions were used to explore linear associations between SMD and rTMS pulses, pulses/session and sessions for HF and LF‐rTMS, separately for active and sham‐rTMS. If these variables showed no linear association with SMD, we divided the data into quartiles and explored subgroup SMDs.ResultsEighty‐seven RCTs were included: 67 studied HF‐rTMS, eleven studied LF‐rTMS, and nine studied both. No linear association was found between SMD and amount of pulses or pulses/session for HF and LF‐rTMS. Subgroup analyses showed the largest SMDs for 1200–1500 HF‐pulses/session and 360–450 LF‐pulses/session. The number of sessions was significantly associated with SMD for active HF (β = 0.09, p < 0.05) and LF‐rTMS (β = 0.06, p < 0.01). Thirty was the maximal number of sessions, in the included RCTs.ConclusionMore rTMS sessions, but not more pulses, were associated with improved treatment outcome, in both HF and LF‐rTMS. Our findings suggest that 1200–1500 HF‐pulses/session and 360–450 LF‐pulses/session are already sufficient, and that a treatment course should consist of least 30 sessions for higher chance of response.
Elites, the aid curse, and Chinese development finance: A conjoint survey experiment on elites’ aid preferences in 141 low‐ and middle‐income countries
Authors: Blair Robert A. , Custer Samantha , Roessler Philip 
Published: November 2024

AbstractWhy do elites in low‐ and middle‐income countries (LMICs) favor some foreign aid projects and partners over others? Research on the “aid curse” and Chinese development finance suggests elites should prefer aid that can be easily captured, with few conditionalities, regulations, or transparency requirements. We administer a conjoint survey experiment across 141 LMICs to elicit the aid preferences of elites who are uniquely close to development policy debates. Perhaps unsurprisingly, we find that elites favor larger over smaller projects, grants over loans, and transportation infrastructure projects over initiatives focused on civil society or tax collection capacity. But contrary to the aid curse theory, elites also prefer projects with transparent terms and labor, corruption, and environmental regulations, and are at worst indifferent towards good governance conditionalities. These preferences hold even in corrupt and autocratic countries and even among high‐level government officials who might be expected to favor “no‐strings‐attached” aid regimes.
Possible welfare benefits of basic income support: Evidence from a benefit incidence analysis in South Africa
Authors: Chisadza Carolyn , Chitiga‐Mabugu Margaret , Mabugu Ramos Emmanuel , Nicholls Nicky , Omotoso Kehinde Oluwaseun , Yitbarek Eleni 
Published: November 2024

AbstractThe study investigates the potential welfare effect of basic income support (BIS) in reducing poverty and inequality in South Africa. Using the 2017 labour force survey and a benefit incidence analysis, we consider three BIS scenarios: (i) universal income support for those aged between 18 and 59; (ii) only those who are unemployed receive the benefit; and (iii) only unemployed individuals in extremely poor households defined by the food poverty line receive the benefit. Results show that BIS can reduce poverty and inequality. However, the specific effects of the BIS will depend on the targeting scenario considered. The universal BIS is more costly and has higher leakage, with more benefits going to the non‐poor. However, this universal support has the biggest overall impact on poverty and inequality reduction because more South Africans receive income support under this scenario. Meanwhile, targeting only the unemployed and the impoverished makes the BIS more pro‐poor and progressive, as well as mitigating the leakage of the benefit to the non‐poor. This would, however, require that an appropriate targeting mechanism be in place.
Melle but not Melle? A mine’s mint as a hub for Carolingian silver coinage recycling
Authors: Sarah Guillaume 
Published: November 2024

AbstractThe mines at Melle in Deux‐Sèvres, France, are known as the only significant source of silver for the early Middle Ages until the 10th century. Though it was not a major locality, the settlement possessed a mint in the Merovingian period that became one of the major centres of coin production under the Carolingians in the ninth century. Following the decrease in Carolingian power and increase in the autonomy of local authorities from c.900, the counts of Poitou started minting a coinage in the name of Melle that remained with the same typology for the next two hundred years. This paper presents an examination of the trace elements (Au and Bi) determined by laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) in nearly 2000 silver coins covering four centuries over the Merovingian, Carolingian and Feudal periods. It has two main objectives: first, identifying the patterns of trace elements for the coinages attributed to Melle by comparing them with those of the same periods from other mints; and second, establishing the general evolution of the trace elements in coins from Poitou and other areas are scrutinized to evaluate the contribution of fresh silver from Melle, in order to identify the silver stocks available. One main result is that part of the silver minted at Melle in the ninth century does not present the trace element patterns that characterize Melle silver, suggesting the use of the Melle mint as a hub for coining not only local silver from the mines but also for recycling and refining silver previously coined elsewhere.
The Effect of NiTi Brush, Polishing Brush, and Chemical Agent on the Dental Implant Surface Morphology and Cytocompatibility
Authors: Brunello Giulia , Becker Kathrin , Rauch Nicole , Schwarz Frank , Becker Jürgen 
Published: November 2024

ABSTRACTObjectivesTo in vitro investigate the effect of different implant surface decontamination methods and treatment storing conditions on implant surface morphology and cell viability.Materials and MethodsTitanium disks with a sand‐blasted and acid‐etched surface (Promote, PRO) were treated with diamond polishing brushes (BRUSH), nickel‐titanium brushes (NITI), or phenol and sulfuric acid‐gel (GEL). The disks were stored in saline (‐S) or left exposed to air overnight (‐A). Untreated (PRO) and machined (MACHINED) disks were used as controls. GEL samples were treated for the 60 s, while the operative time was recorded for BRUSH and NITI. The samples were subjected to scanning electron microscopy (SEM), surface roughness measurements, and cell viability (SaOS‐2 cells, 7 days) assessment.ResultsThe operative time was shorter for NITI than for BRUSH (p = 0.017). The original surface morphology (PRO) was not altered in the GEL group, in contrast with what was observed for BRUSH and NITI. The type of storage did not influence the surface morphology. No significant differences in Sa and Sz were observed among the groups, except for MACHINED, which presented lower Sa values (p < 0.05). Cells were able to proliferate on all surfaces. NITI‐S showed significantly higher cell viability compared to all groups (p ≤ 0.001), except for NITI‐A and MACHINED. Among the treated groups, only one additional significant difference was found, as NITI‐A performed better than GEL‐S.ConclusionsNone of the investigated protocols compromised the cytocompatibility of the titanium dental implant surface. The best results were registered in the NITI group when the samples were stored in saline. Future studies should confirm the effectiveness of the proposed methods in removing bacterial biofilm from contaminated implant surfaces.
A Retrospective Study on the Gender Differences in Clinical Manifestations of Bell's Palsy
Authors: Yon Dong Keon , Kim Dokyoung , Yoo Myung Chul , Kim Sung Soo , Rim Hwa Sung , Kim Sang Hoon , Byun Jae Yong , Yeo Seung Geun 
Published: November 2024

ABSTRACTObjectivesAlthough many studies have assessed the clinical features and the factors affecting treatment outcomes of Bell's palsy, few have analysed differences between men and women. This study therefore evaluated whether the clinical features and treatment results, and the factors affecting them, differ between men and women with Bell's palsy.MethodsThis retrospective study included 1708 patients (791 men and 917 women) who presented with facial palsy to the otolaryngology department between January 1986 and December 2022. Clinical features and treatment outcomes were compared in men and women diagnosed with Bell's palsy.ResultsAge distribution, side affected by facial palsy, House‐Brackmann (HB) Grade, underlying disease such as diabetes and hypertension, electroneuronography (ENoG) results, electromyography (EMG) results, and treatment methods did not differ significantly between men and women with Bell's palsy (p > 0.05 each). Factors significantly associated with better prognosis in men included milder initial facial palsy and better electromyography (EMG) results (p < 0.05). Factors significantly associated with better prognosis in women included younger age, milder initial facial palsy, and better EMG results (p < 0.05). Women had significantly better prognosis than men when treated with steroids within 3 days of the onset of paralysis (p < 0.05).ConclusionMilder initial facial palsy and better EMG results were associated with better prognosis in both men and women with Bell's palsy. Younger age at onset and early stage treatment with steroids were associated with a higher recovery rate in women, but not in men.
Targeting Hsp90α to inhibit HMGB1‐mediated renal inflammation and fibrosis
Authors: Wei Huizhi , Ren Jinhong , Feng Xiue , Zhao Chengxiao , Zhang Yuanlin , Yuan Hongxia , Yang Fan , Li Qingshan 
Published: November 2024

AbstractRenal fibrosis, a terminal manifestation of chronic kidney disease, is characterized by uncontrolled inflammatory responses, increased oxidative stress, tubular cell death, and imbalanced deposition of extracellular matrix. 5,2′‐Dibromo‐2,4′,5′‐trihydroxydiphenylmethanone (LM49), a polyphenol derivative synthesized by our group with excellent anti‐inflammatory pharmacological properties, has been identified as a small‐molecule inducer of extracellular matrix degradation. Nonetheless, the protective effects and mechanisms of LM49 on renal fibrosis remain unknown. Here, we report LM49 could effectively alleviate renal fibrosis and improve filtration function. Furthermore, LM49 significantly inhibited macrophage infiltration, pro‐inflammatory cytokine production and oxidative stress. Interestingly, in HK‐2 cells induced by tumour necrosis factor alpha under oxygen–glucose‐serum deprivation conditions, LM49 treatment similarly yielded a reduced inflammatory response, elevated cellular viability and suppressed cell necrosis and epithelial‐to‐mesenchymal transition. Notably, LM49 prominently suppressed the high‐mobility group box 1 (HMGB1) expression, nucleocytoplasmic translocation and activation. Mechanistically, drug affinity responsive target stability and cellular thermal shift assay confirmed that LM49 could interact with the target heat shock protein 90 alpha family class A member 1 (Hsp90α), disrupting the direct binding of Hsp90α to HMGB1 and inhibiting the nuclear export of HMGB1, thereby suppressing the inflammatory response, cell necrosis and fibrogenesis. Furthermore, molecular docking and molecular dynamic simulation revealed that LM49 occupied the N‐terminal ATP pocket of Hsp90α. Collectively, our findings show that LM49 treatment can ameliorate renal fibrosis through inhibition of HMGB1‐mediated inflammation and necrosis via binding to Hsp90α, providing strong evidence for its anti‐inflammatory and anti‐fibrotic actions.
Positive signs from the history as an aid for early diagnosis in functional movement disorders: The prospective TASMAN study
Authors: Lagrand Tjerk J. , Gelauff Jeannette M. , Brusse‐Keizer Marjolein , Lehn Alexander C. , Tijssen Marina A. J. ,   other individuals of the TASMAN Study Group
Published: November 2024

AbstractBackground and purposeThere has been a concerted move in recent times to shift from an exclusionary to a positive diagnosis of functional movement disorders (FMDs). To date, most of the focus has been on defining positive physical signs. Here the focus was on the diagnostic specificity of specific symptoms and patient characteristics.MethodsFor this prospective cohort study, newly referred patients in the Netherlands and Australia were recruited before their first neurology appointment. Participants completed questionnaires within 2 months prior to their visit at one of the six different clinics. Directly following the first consultation, physicians received a questionnaire about their diagnostic process. Patients were excluded if the diagnosis was not a movement disorder. Univariate and multivariate regression analyses were conducted to identify predictors of FMDs. Subsequently, a predictive model was constructed and assessed using the area under the receiver operating curve.ResultsBetween 1 March 2021 and 1 March 2023, 465 patients were eligible for inclusion, of whom 171 (37%) had an FMD and 294 (63%) a non‐FMD. Distinguishing factors amongst these groups included age at onset, gender, history or family history of a functional and psychiatric disorder, sudden onset, specific triggers, fluctuation patterns throughout the day and over an extended period, pain, fatigue, depression, anxiety and dissociation. Using these, a predictive model was developed, yielding a discriminative accuracy of 88%.ConclusionSpecific symptoms and patient characteristics have high diagnostic discriminative value between FMDs and non‐FMDs, providing an additional tool in positive diagnosis.
Rebuilding and Reference Points Under Compensatory and Depensatory Recruitment: A Meta‐Analysis of Northeast Atlantic Fish Stocks
Authors: Albertsen Christoffer Moesgaard , Perälä Tommi , Cardinale Massimiliano , Winker Henning , Trijoulet Vanessa 
Published: November 2024

ABSTRACTModern management of fish stocks is based on integrating the precautionary approach with the maximum sustainable yield framework. It relies on accurate estimation of precautionary limits, defined as levels of spawning biomass where a stock has reduced reproductive capacity, and harvesting targets aimed to maximise future yields. Therefore, it is heavily depending on productivity assumptions. Most fish stocks are managed assuming that productivity will increase as the stock size decreases (i.e., density dependent compensatory stock and recruitment relationship). However, several biological and ecological processes will result in a decreased productivity below a certain population size, referred to as the Allee effect or depensation. Through a meta‐analysis of 81 Northeast Atlantic fish stocks, we investigated the impact of assuming compensatory recruitment in the presence of depensation in fisheries management. Across life histories, depensation results in a 22% reduction of the fishing mortality rate leading to extinction. On average, the maximum reproductive rate per spawning biomass was found at 35% of BMSY, which was also the biomass where stocks have a 5% risk of extinction without fishing. Finally, the presence of depensation resulted in increased rebuilding times when stock spawning biomass falls below the limit reference point. When depensatory effects are present, assuming increasing productivity at low biomass will generally result in over‐optimistic perceptions of rebuilding and stock status at biomass below 25% and 45% of BMSY in general, and for pelagic stocks respectively. When not accounted for, depensation will potentially lead to unsustainable harvesting practices of marine living resources.
Spontaneous reversal of small molecule‐induced mitochondrial uncoupling: the case of anilinothiophenes
Authors: Kirsanov Roman S. , Khailova Ljudmila S. , Krasnov Vladimir S. , Firsov Alexander M. , Lyamzaev Konstantin G. , Panteleeva Alisa A. , Popova Lyudmila B. , Nazarov Pavel A. , Tashlitsky Vadim N. , Korshunova Galina A. , Kotova Elena A. , Antonenko Yuri N. 
Published: November 2024

Tissue specificity can render mitochondrial uncouplers more promising as leading compounds for creating drugs against serious diseases. In search of tissue‐specific uncouplers, we address anilinothiophenes as possible glutathione‐S‐transferase substrates (GST). Earlier, ‘cyclic’ uncoupling activity was reported for 5‐bromo‐N‐(4‐chlorophenyl)‐3,4‐dinitro‐2‐thiophenamine (BDCT) in isolated rat liver mitochondria (RLM). The mechanism by which BDCT induced two‐phase changes in mitochondrial respiration (stimulation followed by deceleration) was unknown. To clarify this issue, we synthesized BDCT and its two analogues. Among these, 5‐bromo‐3,4‐dinitro‐N‐(4‐nitrophenyl)‐2‐thiophenamine (BDNT) appeared to be the most effective as a mitochondrial uncoupler, decreasing membrane potential and stimulating respiration at submicromolar concentrations. Importantly, BDNT exerted two‐phase changes in both mitochondrial membrane potential and respiration rate of RLM, which were enhanced by the addition of glutathione (GSH) but inhibited by the compounds capable of GSH depleting, such as 1‐chloro‐2,4‐dinitrobenzene (CDNB). By contrast, the phase of recoupling was not observed in rat heart mitochondria (RHM). Remarkably, BDNT elicited mitochondrial depolarization in primary human fibroblasts but not in cultured human liver (HepG2) cells. By detecting proton‐selective electrical current through planar bilayer lipid membranes, we demonstrated the ability of BDCT and BDNT to transfer protons across membranes. BDNT proved to be an anionic protonophore with a pKa of 7.38. By using LC–MS and capillary electrophoresis, we directly showed the formation of BDNT conjugates with GSH upon incubation with RLM but not RHM. Therefore, we hypothesize that GST is involved in the disappearance of the anilinothiophene uncoupling activity in RLM, ensuring the tissue‐specific behavior of the uncoupler.