bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of age‐associated alpha‐synuclein aggregation in a conditional transgenic mouse model of Parkinson's disease: Implications for Lewy body formation
Authors: Li Jiahua , Ng Ka Wai , Sung Chun Chau , Chung Kenny K. K. 
Published: May 2024

AbstractParkinson's disease (PD) is a common neurodegenerative disorder that is affecting an increasing number of older adults. Although PD is mostly sporadic, genetic mutations have been found in cohorts of families with a history of familial PD (FPD). The first such mutation linked to FPD causes a point mutation (A53T) in α‐synuclein (α‐syn), a major component of Lewy bodies, which are a classical pathological hallmark of PD. These findings suggest that α‐syn is an important contributor to the development of PD. In our previous study, we developed an adenoviral mouse model of PD and showed that the expression of wild‐type (WT) α‐syn or a mutant form with an increased propensity to aggregate, designated as WT‐CL1 α‐syn, could be used to study how α‐syn aggregation contributes to PD. In this study, we established a transgenic mouse model that conditionally expresses WT or WT‐CL1 α‐syn in dopaminergic (DA) neurons and found that the expression of either WT or WT‐CL1 α‐syn was associated with an age‐dependent degeneration of DA neurons and movement dysfunction. Using this model, we were able to monitor the process of α‐syn aggregate formation and found a correlation between age and the number and sizes of α‐syn aggregates formed. These results provide a potential mechanism by which age‐dependent α‐syn aggregation may lead to the formation of Lewy bodies in PD pathogenesis.image
New Zealand public transport agencies' responses to COVID‐19: Understanding public transport services, infrastructure and communication measures
Authors: Whale Jonty , Imran Muhammad 
Published: May 2024

AbstractCOVID‐19 brought public health challenges to the public transport system throughout the world. As a result, a range of response measures were implemented to ensure the safety of passengers while maintaining a functioning system. This paper explores the responses of public transport agencies in New Zealand's metropolitan cities (Auckland, Christchurch and Wellington) to the COVID‐19 pandemic by examining their physical and communication measures. We analysed public transport agencies' websites to understand the response measures implemented, including the accessibility of COVID‐19‐related information, and the communication of information via websites and social media platforms. The results show that 13 service responses were implemented across the three public transport agencies, with Auckland implementing the most measures. Seven infrastructural responses were implemented, with Christchurch implementing all seven. Wellington was found to be the public transport agency that used social media the most during the pandemic. The website accessibility findings suggest that the more accessible a public transport agency's website was, the less information was present. The research concludes that all three public transport agencies in New Zealand performed reasonably well and were able to maintain a safe and responsive public transport system.
The economic and societal impact of periodontal and peri‐implant diseases
Authors: Saleh Muhammad H. A. , Dias Debora R. , Kumar Purnima 
Published: May 2024

AbstractPeriodontal and peri‐implant diseases result from a chronic inflammatory response to dysbiotic microbial communities and are characterized by inflammation in the soft tissue and the ensuing progressive destruction of supporting bone, resulting in tooth or implant loss. These diseases' high prevalence, multifactorial etiology, extensive treatment costs, and significant detriment to patients' quality‐of‐life underscore their status as a critical public health burden. This review delineates the economic and sociocultural ramifications of periodontal and peri‐implant diseases on patient welfare and healthcare economics. We delve into the implications of diagnosis, treatment, supportive care, and managing destructive tissue consequences, contrasting these aspects with healthy patients.
Ukrainian versus Pan‐Russian Identities: The Roots of Russia's Invasion of Ukraine
Authors: Kuzio Taras 
Published: May 2024

AbstractThis article critically analyses commonly used descriptions of Ukrainian politics as divided between ‘nationalist’ versus ‘pro‐Russian’, and ‘ethnic’ versus ‘civic’ forces which do not adequately explain Ukrainian politics or understand the roots of Russian military aggression against Ukraine in 2014 and 2022. An alternative framework is provided of competition between Ukrainian identity, which believes Ukrainians are a distinct people different to Russians, and pan‐Russian identity, which believes Russians and Ukrainians are ‘fraternal brothers’ who have always been and always will be united in the Russian World. The Euromaidan Revolution, Russian military aggression in 2014, increasing domination of Ukrainian identity policies and weakness of pro‐Russian political parties led to the progressive marginalisation of pan‐Russian identity in Ukraine. The marginalisation of pan‐Russian identity and unwillingness of Presidents Petro Poroshenko and Volodymyr Zelenskyy to implement the Russian version of the 2014‐2015 Minsk Accords, which would have transformed Ukraine into a Russian satellite, led to the Kremlin's decision to launch a full‐scale invasion on 24 February 2022. The goals of Russia's full‐scale invasion were and remain regime change (i.e., installation of a pro‐Russian puppet regime), destruction of Ukrainian identity (i.e., de‐nazification) and its replacement with a hegemonic pan‐Russian identity in a truncated (i.e., without Crimea and New Russia [southeast Ukraine]) Little Russian satellite controlled by Russia (i.e., de‐militarisation).
Transitions curriculum impact on students and care
Authors: Maddaleni Geeda , Ardolino Eric , Weinstein Amy R. 
Published: May 2024

AbstractBackgroundTransitions of patient care from the inpatient to outpatient setting is a high‐risk time often resulting in medical errors and adverse events. Transitions of care programmes have been demonstrated to reduce negative outcomes. Several professional societies have highlighted care transitions as a central pillar of patient care and therefore a crucial aspect of health professional education; however, little data exist on medical student education in this area.ApproachThe Transitions of Care Curriculum was developed and delivered to all Harvard Medical School Core I Internal Medicine Clerkship students at Beth Israel Deaconess Medical Center, Boston, MA between January 2017 and March 2019, where 12–14 students participated each quarter and included didactic teaching followed by experiential learning. Student data were collected via postclerkship survey. Patient data were collected via chart review. Student self‐reported comfort level with transitions in care skills and medical errors were analysed.EvaluationAll student measures related to comfort with transitions in care skills demonstrated statistically significant improvement after curriculum participation(p < 0.001). Of the patients with a completed postdischarge note, students identified ≥1 postdischarge related issue in 33 of 70 patients, with multiple issues identified in many of these patients. Seventy‐six total issues were identified.ImplicationsThe Transitions of Care Curriculum demonstrated promising student and patient outcomes, suggesting that students can successfully learn and advance clinical skills while having a positive impact on a highly needed and important aspect of patient care by reducing postdischarge errors and adverse events.
Cucumber (Cucumis sativus L.) translationally controlled tumor protein interacts with CsRab11A and promotes activation of target of rapamycin in response to Podosphaera xanthii
Authors: Chen Qiumin , Zhou Shuang , Qu Mengqi , Yang Yun , Chen Qinglei , Meng Xiangnan , Fan Haiyan 
Published: May 2024

SUMMARYThe target of rapamycin (TOR) kinase serves as a central regulator that integrates nutrient and energy signals to orchestrate cellular and organismal physiology in both animals and plants. Despite significant advancements having been made in understanding the molecular and cellular functions of plant TOR kinases, the upstream regulators that modulate TOR activity are not yet fully elucidated. In animals, the translationally controlled tumor protein (TCTP) is recognized as a key player in TOR signaling. This study reveals that two TCTP isoforms from Cucumis sativus, when introduced into Arabidopsis, are instrumental in balancing growth and defense mechanisms against the fungal pathogen Golovinomyces cichoracearum. We hypothesize that plant TCTPs act as upstream regulators of TOR in response to powdery mildew caused by Podosphaera xanthii in Cucumis. Our research further uncovers a stable interaction between CsTCTP and a small GTPase, CsRab11A. Transient transformation assays indicate that CsRab11A is involved in the defense against P. xanthii and promotes the activation of TOR signaling through CsTCTP. Moreover, our findings demonstrate that the critical role of TOR in plant disease resistance is contingent upon its regulated activity; pretreatment with a TOR inhibitor (AZD‐8055) enhances cucumber plant resistance to P. xanthii, while pretreatment with a TOR activator (MHY‐1485) increases susceptibility. These results suggest a sophisticated adaptive response mechanism in which upstream regulators, CsTCTP and CsRab11A, coordinate to modulate TOR function in response to P. xanthii, highlighting a novel aspect of plant–pathogen interactions.
Characterization of activating cis‐regulatory elements from the histone genes of Chlamydomonas reinhardtii
Authors: Lihanova Yuliia , Nagel Raimund , Jakob Torsten , Sasso Severin 
Published: May 2024

SUMMARYRegulation of gene expression in eukaryotes is controlled by cis‐regulatory modules (CRMs). A major class of CRMs are enhancers which are composed of activating cis‐regulatory elements (CREs) responsible for upregulating transcription. To date, most enhancers and activating CREs have been studied in angiosperms; in contrast, our knowledge about these key regulators of gene expression in green algae is limited. In this study, we aimed at characterizing putative activating CREs/CRMs from the histone genes of the unicellular model alga Chlamydomonas reinhardtii. To test the activity of four candidates, reporter constructs consisting of a tetramerized CRE, an established promoter, and a gene for the mCerulean3 fluorescent protein were incorporated into the nuclear genome of C. reinhardtii, and their activity was quantified by flow cytometry. Two tested candidates, Eupstr and Ehist cons, significantly upregulated gene expression and were characterized in detail. Eupstr, which originates from highly expressed genes of C. reinhardtii, is an orientation‐independent CRE capable of activating both the RBCS2 and β2‐tubulin promoters. Ehist cons, which is a CRM from histone genes of angiosperms, upregulates the β2‐tubulin promoter in C. reinhardtii over a distance of at least 1.5 kb. The octamer motif present in Ehist cons was identified in C. reinhardtii and the related green algae Chlamydomonas incerta, Chlamydomonas schloesseri, and Edaphochlamys debaryana, demonstrating its high evolutionary conservation. The results of this investigation expand our knowledge about the regulation of gene expression in green algae. Furthermore, the characterized activating CREs/CRMs can be applied as valuable genetic tools.
Innate phase production of IFN-γ by memory and effector T cells expressing early activation marker CD69 during infection with
Cryptococcus deneoformans
in the lungs
Authors: Miyahara Anna , Umeki Aya , Sato Ko , Nomura Toshiki , Yamamoto Hideki , Miyasaka Tomomitsu , Tanno Daiki , Matsumoto Ikumi , Zong Tong , Kagesawa Takafumi , Oniyama Akiho , Kawamura Kotone , Yuan Xiaoliang , Yokoyama Rin , Kitai Yuki , Kanno Emi , Tanno Hiromasa , Hara Hiromitsu , Yamasaki Sho , Saijo Shinobu , Iwakura Yoichiro , Ishii Keiko , Kawakami Kazuyoshi 
Published: May 2024

ABSTRACT

Cryptococcus deneoformans
is a yeast-type fungus that causes fatal meningoencephalitis in immunocompromised patients and evades phagocytic cell elimination through an escape mechanism. Memory T (Tm) cells play a central role in preventing the reactivation of this fungal pathogen. Among these cells, tissue-resident memory T (T
RM
) cells quickly respond to locally invaded pathogens. This study analyzes the kinetics of effector T (Teff) cells and Tm cells in the lungs after cryptococcal infection. Emphasis is placed on the kinetics and cytokine expression of T
RM
cells in the early phase of infection. CD4
+
Tm cells exhibited a rapid increase by day 3, peaked at day 7, and then either maintained their levels or exhibited a slight decrease until day 56. In contrast, CD8
+
Tm cells reached their peak on day 3 and thereafter decreased up to day 56 post-infection. These Tm cells were predominantly composed of CD69
+
T
RM
cells and CD69
+
CD103
+
T
RM
cells. Disruption of the CARD9 gene resulted in reduced accumulation of these T
RM
cells and diminished interferon (IFN) -γ expression in T
RM
cells. T
RM
cells were derived from T cells with T cell receptors non-specific to ovalbumin in OT-II mice during cryptococcal infection. In addition, T
RM
cells exhibited varied behavior in different tissues. These results underscore the importance of T cells, which produce IFN-γ in the lungs during the early stage of infection, in providing early protection against cryptococcal infection through CARD9 signaling.
Phenotypic and transcriptional changes in peripheral blood mononuclear cells during alphavirus encephalitis in mice
Authors: Nguyen Benjamin H. , Bartlett Maggie L. , Troisi Elizabeth M. , Stanley Elise , Griffin Diane E. 
Published: May 2024

ABSTRACT

Sindbis virus (SINV) infection of mice provides a model system for studying the pathogenesis of alphaviruses that infect the central nervous system (CNS) to cause encephalomyelitis. While studies of human viral infections typically focus on accessible cells from the blood, this compartment is rarely evaluated in mice. To bridge this gap, single-cell RNA sequencing (scRNAseq) was combined with flow cytometry to characterize the transcriptional and phenotypic changes of peripheral blood mononuclear cells (PBMCs) from SINV-infected mice. Twenty-one clusters were identified by scRNAseq at 7 days after infection, with a unique cluster and overall increase in naive B cells for infected mice. Uninfected mice had fewer immature T cells and CCR9
+
CD4 T cells and a unique immature T cell cluster. Gene expression was most altered in the Ki67
+
CD8 T cell cluster, with chemotaxis and proliferation-related genes upregulated. Global analysis indicated metabolic changes in myeloid cells and increased expression of
Ccl5
by NK cells. Phenotypes of PBMCs and cells infiltrating the CNS were analyzed by flow cytometry over 14 days after infection. In PBMCs, CD8 and Th1 CD4 T cells increased in representation, while B cells showed a transient decrease at day 5 in total, Ly6a
+
, and naive cells, and an increase in activated B cells. In the brain, CD8 T cells increased for the first 7 days, while Th1 CD4 T cells and naive and Ly6a
+
B cells continued to accumulate for 14 days. Therefore, dynamic immune cell changes can be identified in the blood as well as the CNS during viral encephalomyelitis.

IMPORTANCE
The outcome of viral encephalomyelitis is dependent on the host immune response, with clearance and resolution of infection mediated by the adaptive immune response. These processes are frequently studied in mouse models of infection, where infected tissues are examined to understand the mechanisms of clearance and recovery. However, studies of human infection typically focus on the analysis of cells from the blood, a compartment rarely examined in mice, rather than inaccessible tissue. To close this gap, we used single-cell RNA sequencing and flow cytometry to profile the transcriptomic and phenotypic changes of peripheral blood mononuclear cells (PBMCs) before and after central nervous system (CNS) infection in mice. Changes to T and B cell gene expression and cell composition occurred in PBMC and during entry into the CNS, with CCL5 being a differentially expressed chemokine. Therefore, dynamic changes occur in the blood as well as the CNS during the response of mice to virus infection, which will inform the analysis of human studies.
Flavomycin restores colistin susceptibility in multidrug-resistant Gram-negative bacteria
Authors: Huang Ying , Zhu Yan , Yue Hui-Ying , Liu Yi-Yun , Deng Li-Min , Lv Luchao , Wang Chengzhen , Yang Jun , Liu Jian-Hua 
Published: May 2024

ABSTRACT

Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time–kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on
Escherichia coli
(
E. coli
) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the
E. coli
outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy.
In vivo
studies confirmed the efficacy of colistin combined with flavomycin against MDR
E. coli
infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria.

IMPORTANCE
Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs.
From genome to evolution: investigating type II methylotrophs using a pangenomic analysis
Authors: Samanta Dipayan , Rauniyar Shailabh , Saxena Priya , Sani Rajesh K. 
Published: May 2024

ABSTRACT

A comprehensive pangenomic approach was employed to analyze the genomes of 75 type II methylotrophs spanning various genera. Our investigation revealed 256 exact core gene families shared by all 75 organisms, emphasizing their crucial role in the survival and adaptability of these organisms. Additionally, we predicted the functionality of 12 hypothetical proteins. The analysis unveiled a diverse array of genes associated with key metabolic pathways, including methane, serine, glyoxylate, and ethylmalonyl-CoA (EMC) metabolic pathways. While all selected organisms possessed essential genes for the serine pathway,
Methylooceanibacter marginalis
lacked serine hydroxymethyltransferase (SHMT), and
Methylobacterium variabile
exhibited both isozymes of SHMT, suggesting its potential to utilize a broader range of carbon sources. Notably,
Methylobrevis
sp. displayed a unique serine-glyoxylate transaminase isozyme not found in other organisms. Only nine organisms featured anaplerotic enzymes (isocitrate lyase and malate synthase) for the glyoxylate pathway, with the rest following the EMC pathway.
Methylovirgula
sp. 4MZ18 stood out by acquiring genes from both glyoxylate and EMC pathways, and
Methylocapsa
sp. S129 featured an A-form malate synthase, unlike the G-form found in the remaining organisms. Our findings also revealed distinct phylogenetic relationships and clustering patterns among type II methylotrophs, leading to the proposal of a separate genus for
Methylovirgula
sp. 4M-Z18 and
Methylocapsa
sp. S129. This pangenomic study unveils remarkable metabolic diversity, unique gene characteristics, and distinct clustering patterns of type II methylotrophs, providing valuable insights for future carbon sequestration and biotechnological applications.

IMPORTANCE

Methylotrophs have played a significant role in methane-based product production for many years. However, a comprehensive investigation into the diverse genetic architectures across different genera of methylotrophs has been lacking. This study fills this knowledge gap by enhancing our understanding of core hypothetical proteins and unique enzymes involved in methane oxidation, serine, glyoxylate, and ethylmalonyl-CoA pathways. These findings provide a valuable reference for researchers working with other methylotrophic species. Furthermore, this study not only unveils distinctive gene characteristics and phylogenetic relationships but also suggests a reclassification for
Methylovirgula
sp. 4M-Z18 and
Methylocapsa
sp. S129 into separate genera due to their unique attributes within their respective genus. Leveraging the synergies among various methylotrophic organisms, the scientific community can potentially optimize metabolite production, increasing the yield of desired end products and overall productivity.
Constraining new physics models from $$\mu \rightarrow e $$ observables in bottom-up EFT
Authors: Ardu Marco , Davidson Sacha , Lavignac Stéphane 
Published: May 2024

AbstractUpcoming experiments will improve the sensitivity to $$\mu \rightarrow e$$

μ
→
e

processes by several orders of magnitude, and could observe lepton flavour-changing contact interactions for the first time. In this paper, we investigate what could be learned about New Physics from the measurements of these $$\mu \rightarrow e$$

μ
→
e

observables, using a bottom-up effective field theory (EFT) approach and focusing on three popular models with new particles around the TeV scale (the type II seesaw, the inverse seesaw and a scalar leptoquark). We showed in a previous publication that $$\mu \rightarrow e$$

μ
→
e

observables have the ability to rule out these models because none can fill the whole experimentally accessible parameter space. In this work we give more details on our EFT formalism and present more complete results. We discuss the impact of some observables complementary to $$\mu \rightarrow e$$

μ
→
e

transitions (such as the neutrino mass scale and ordering, and LFV $$\tau $$
τ
decays) and draw attention to the interesting appearance of Jarlskog-like invariants in our expressions for the low-energy Wilson coefficients.