bluuebunny/crossref_metadata_2025 huggingface dataset:
Are you a True Patriot? Twentieth‐century Dominican State Formation in the Ecuadorian Amazon
Authors: Fischer William T.
Published: May 2024

This article examines the role played by Dominican missions in Ecuador's Amazonian territory from approximately 1930–1970. In the Dominicans' own monthly magazine, they claimed not only the roles of infrastructural development, “civilisation” of indigenous peoples, and nationalisation of territory, as did Catholic missions elsewhere; but also the roles of mediator of competing interests and redeemer of the entire country. The central Pastaza River region and important cities like Mera and Puyo were administered and developed chiefly by the Dominican missions ahead of massive colonisation and economic development linked to agriculture and oil drilling. This research contributes to our understanding of the role of Catholic missions in Ecuador's twentieth century by demonstrating that print media allowed them to be more than just frontier institutions. It also illustrates how Ecuador's “Oriente” came to be more fully integrated into the nation prior to the oil boom of the 1970s.
Beta‐hCG–producing malignant phyllodes tumour
Authors: Leung Laura Lok Wa , Marabi Monalyn , Tsoi Violet Yee Kei
Published: May 2024

Phyllodes tumours (PTs) of the breasts are rare fibroepithelial tumours accounting for less than 1% of all breast tumours. They have a wide range of presentations, ranging from benign‐natured tumours that behave similarly to fibroadenomas, to aggressive malignant tumours that can rapidly advance both locally and distally. Histologically, PTs are classified into benign, borderline, or malignant based on a combination of the following five features: degree of stromal cellularity, stromal cell atypia, mitotic activity, infiltrative or circumscribed margins, and presence or absence of stromal overgrowth. Malignant tumours demonstrate high levels of stromal cellularity and atypia, infiltrative margins, high mitotic rate (>10 mitoses per 10 high‐power fields), and the presence of stromal overgrowth. Treatment predominantly relies on complete excision of the lesion, although treatment regimens for malignant PTs with adjuvant chemoradiation lack standardization as a result of its rarity. Malignant tumours are also often associated with paraneoplastic syndromes such as recurrent hypoglycaemia and hypertrophic osteoarthropathy. Here, we report a case of recurrent malignant PT with serum beta‐human chorionic gonadotrophin secretion.
Threat, safety, safeness and social safeness 30 years on: Fundamental dimensions and distinctions for mental health and well‐being
Authors: Gilbert Paul
Published: May 2024

In 1993, the British Journal of Clinical Psychology published my paper titled ‘Defence and safety: Their function in social behaviour and psychopathology’. The paper highlights that to understand people's sensitivity to threat, we also need to understand their ability to identify what is safe. This paper offers an update on these concepts, highlighting distinctions that were implicit but not clearly defined at the time. Hence, the paper seeks to clarify distinctions between: (i) threat detection and response, (ii) safety and safety seeking, (iii) safeness and (iv) their social and non‐social functions and forms. Threat detection and response are to prevent or minimize harm (e.g., run from a predator or fire). Safety checking relates to monitoring for the absence and avoidance of threat, while safety seeking links to the destination of the defensive behaviour (e.g., running home). Safety seeking also relates to maintaining vigilance to the appearance of potential harms and doing things believed to avoid harm. Threat‐defending and safety checking and seeking are regulated primarily through evolved threat processing systems that monitor the nature, presence, controllability and/or absence of threat (e.g., amygdala and sympathetic nervous system). Safeness uses different monitoring systems via different psychophysiological systems (e.g., prefrontal cortex, parasympathetic system) for the presence of internal and external resources that support threat‐coping, risk‐taking, resource exploration. Creating brain states that recruit safeness processing can impact how standard evidence‐based therapies (e.g., exposure, distress tolerance and reappraisal) are experienced and produce long‐term change.
Digitisation of Sibling and Social Relationships of Vulnerable Children in the Czech Republic: Implications for Digital Social Work
Authors: Bražinová Ivana , Caletková Lenka
Published: May 2024

The aim of the research was to determine the impacts of digital technology use on the sibling and other social relationships of vulnerable children from their perspective as well as from the perspective of their parents and social workers. The research employed a qualitative research strategy and thematic analysis. We carried out semi‐structured interviews with 10 children and their parents (7) and 10 social workers. The main topics related to the impact of digital technology use were identified as (1) children's addiction to digital technology, (2) digital technology and the online environment as an unlimited leisure and socialisation tool, (3) the shift of risky behaviours to the online environment and the threat of other online ‘risks’ and (4) digital technology as a modern tool for communication with children or their parents. Discussion provides recommendations on how digital technology can be used in social work practice with vulnerable children and their families.
Primary localized cutaneous lichen myxedematosus with light chain‐restricted plasma cells: A distinct variant of the localized form of lichen myxedematosus
Authors: Liu Shuo S. , Park Lily , Karim Rehan , Serralta Victoria , Ciocca Giovanna , Susa Joseph S. , Hanly Andrew , Karai Laszlo J.
Published: May 2024

Lichen myxedematosus (LM) is a chronic cutaneous mucinosis that can present as a localized skin lesion or as a generalized systemic disease termed scleromyxedema. The differential diagnosis is determined by a combination of clinical presentation, serological studies, and histopathological examination. Currently, well‐established and accepted histopathological features to distinguish localized LM from scleromyxedema have not been elucidated. Our recent publication, together with a retrospective literature review, suggests that the presence of groups of light chain‐restricted plasma cells represents a distinct histopathological clue for the diagnosis of localized LM. In this report, we provide two additional cases of localized LM with lambda light chain‐restricted plasma cells, together with clinical and histopathological findings that are similar to our previous publication. These cases support our theory that the light chain‐restricted plasmacytic microenvironment is primarily attributed to the pathogenesis of localized LM. Therefore, we consider these cases to constitute a clinically and pathologically new variant of localized LM and name it primary localized cutaneous LM with light chain‐restricted plasma cells.
Risk factors for postgastric endoscopic submucosal dissection bleeding in direct oral anticoagulant users
Authors: Kagawa Tomo , Ishikawa Shigenao , Hidaka Yu , Colvin Hugh Shunsuke , Nakanishi Akira , Ohkawa Jumpei , Negishi Shin , Yasutomi Eriko , Yamauchi Kenji , Okamoto Kunio , Sakakihara Ichiro , Izumikawa Koichi , Yamamoto Kumiko , Takahashi Sakuma , Tanaka Shigetomi , Matsuura Mihoko , Wato Masaki , Hasui Toshimi , Inaba Tomoki
Published: May 2024

Objectives

Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post‐ESD bleeding and drug differences in patients taking DOACs.

Methods

We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri‐cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post‐ESD bleeding.

Results

The incidence of post‐ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post‐ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post‐ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran.

Conclusions

The administration of DOACs was shown to be a possible factor involved in post‐ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.
Cat's cradle traction during endoscopic submucosal dissection of early gastric cancer
Authors: Hamamoto Hidetaka , Igarashi Kimihiro , Matsuda Tomoki
Published: May 2024

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A novel animal model for understanding secondary traumatic stress and visceral pain in male rats
Authors: Lannon Adam S. , Brocka Marta , Collins James M. , Fitzgerald Patrick , O'Mahony Siobhain M. , Cryan John F. , Moloney Rachel D.
Published: May 2024

Empathetic relationships and the social transference of behaviours have been shown to occur in humans, and more recently through the development of rodent models, where both fear and pain phenotypes develop in observer animals. Clinically, observing traumatic events can induce ‘trauma and stressor‐related disorders’ as defined in the DSM 5. These disorders are often comorbid with pain and gastrointestinal disturbances; however, our understanding of how gastrointestinal – or visceral – pain can be vicariously transmitted is lacking. Visceral pain originates from the internal organs, and despite its widespread prevalence, remains poorly understood. We established an observation paradigm to assess the impact of witnessing visceral pain. We utilised colorectal distension (CRD) to induce visceral pain behaviours in a stimulus rodent while the observer rodent observed. Twenty four hours post‐observation, the observer rodent's visceral sensitivity was assessed using CRD. The observer rodents were found to have significant hyperalgesia as determined by lower visceral pain threshold and higher number of total pain behaviours compared with controls. The behaviours of the observer animals during the observation were found to be correlated with the behaviours of the stimulus animal employed. We found that observer animals had hypoactivity of the hypothalamic–pituitary–adrenal (HPA) axis, highlighted by reduced corticosterone at 90 minutes post‐CRD. Using c‐Fos immunohistochemistry we showed that observer animals also had increased activation of the anterior cingulate cortex, and decreased activation of the paraventricular nucleus, compared with controls. These results suggest that witnessing another animal in pain produces a behavioural phenotype and impacts the brain–gut axis.
Time‐dependent interaction modification generated from plant–soil feedback
Authors: Zou Heng‐Xing , Yan Xinyi , Rudolf Volker H. W.
Published: May 2024

Pairwise interactions between species can be modified by other community members, leading to emergent dynamics contingent on community composition. Despite the prevalence of such higher‐order interactions, little is known about how they are linked to the timing and order of species' arrival. We generate population dynamics from a mechanistic plant–soil feedback model, then apply a general theoretical framework to show that the modification of a pairwise interaction by a third plant depends on its germination phenology. These time‐dependent interaction modifications emerge from concurrent changes in plant and microbe populations and are strengthened by higher overlap between plants' associated microbiomes. The interaction between this overlap and the specificity of microbiomes further determines plant coexistence. Our framework is widely applicable to mechanisms in other systems from which similar time‐dependent interaction modifications can emerge, highlighting the need to integrate temporal shifts of species interactions to predict the emergent dynamics of natural communities.
Impact of root canal disinfection on the bacteriome present in primary endodontic infection: A next generation sequencing study
Authors: Alquria Theeb Abdullah , Acharya Aneesha , Tordik Patricia , Griffin Ina , Martinho Frederico C.
Published: May 2024

Aim

To investigate the bacteriome present in teeth with primary endodontic infection (PEI) and apical periodontitis (AP) and to determine quantitatively and qualitatively the impact of chemomechanical preparation (CMP) using 2.5% sodium hypochlorite NAOCl on the bacteriome found in PEI with AP using the Illumina MiSeq platform.

Methodology

Thirty‐six paired samples from 18 patients were successfully sequenced and analysed. Samples were collected at two sampling times: before (s1) and after (s2) CMP using 2.5% NaOCl. The DNA was extracted from s1 and s2 samples and quantified using quantitative PCR (qPCR). All 36 samples were sequenced using the Illumina MiSeq platform. Raw V3–V4 amplicon sequencing data were processed with the DADA2 pipeline to generate amplicon sequence variants (ASVs). Alpha diversity metrics representing abundance (Chao1) and diversity and evenness (Shannon, Simpson) were computed. The paired‐sample Wilcoxon's test was used to compare alpha diversity metrics and qPCR counts between s1 and s2. The PERMANOVA method (with 999 permutations) was applied to compare community composition between sample types (s1 versus s2) and between patient IDs. ALDEx2 (ANOVA‐like differential expression tool for high‐throughput sequencing data) to investigate differentially abundant taxa between s1 and s2. A paired‐sample Wilcoxon's test was used to compare alpha diversity metrics and qPCR counts between s1 and s2.

Results

The qPCR counts were significantly higher in s1 compared to s2 (p = .0007). The Chao1 index indicated no difference in alpha diversity (p < .7019); whereas Shannon (p = .0056) and Simpson (p = .02685) indexes showed higher values in s2. The PERMANOVA test using Adonis2 showed a significant effect of sample time on community composition (R2 = .0630, p = .012). Patient ID also showed a significant effect on community composition (R2 = .6961, p = .001). At the genus level, Dialister, Mogibacterium, Prevotella, and Olsenella were differentially enriched at s1, while Actinomyces, Stenotrophomonas_unclassified, Enterococcus_unclassified, and Actinomyces_unclassified were differentially enriched in s2.

Conclusion

The bacteriome present in teeth with PEI with AP is complex and diverse. CMP using 2.5% NaOCl showed a high quantitatively and qualitatively disinfectant impact on the bacteriome present in PEI with AP.
Second‐order cone programming models for the unitary weighted Weber problem and for the minimum sum of the squares clustering problem
Authors: Linhares Marcella Braga de Assis , Pinto Renan Vicente , Maculan Nelson , Negreiros Marcos
Published: May 2024

In this work, new mixed integer nonlinear optimization models are proposed for two clustering problems: the unitary weighted Weber problem and the minimum sum of squares clustering. The proposed formulations are convex quadratic models with linear and second‐order cone constraints that can be efficiently solved by interior point algorithms. Their continuous relaxation is convex and differentiable. The numerical experiments show the proposed models are more efficient than some classical models for these problems known in the literature.
Macrophage M2 polarization promotes pulpal inflammation resolution during orthodontic tooth movement
Authors: Li Jichang , Ren Huiying , Zhang Zijie , Zhang Jin , Wei Fulan
Published: May 2024

Mechanical force induces hypoxia in the pulpal area by compressing the apical blood vessels of the pulp, triggering pulpal inflammation during orthodontic tooth movement. However, this inflammation tends to be restorable. Macrophages are recognized as pivotal immunoreactive cells in the dental pulp. Whether they are involved in the resolution of pulpal inflammation in orthodontic teeth remains unclear. In this study, we investigated macrophage polarization and its effects during orthodontic tooth movement. It was demonstrated that macrophages within the dental pulp polarized to M2 type and actively participated in the process of pulpal inflammation resolution. Inflammatory reactions were generated and vascularization occurred in the pulp during orthodontic tooth movement. Macrophages in orthodontic pulp show a tendency to polarize towards M2 type as a result of pulpal hypoxia. Furthermore, by blocking M2 polarization, we found that macrophage M2 polarization inhibits dental pulp‐secreting inflammatory factors and enhances VEGF production. In conclusion, our findings suggest that macrophages promote pulpal inflammation resolution by enhancing M2 polarization and maintaining dental health during orthodontic tooth movement.
MIDAS and dividend growth predictability: Revisiting the excess volatility puzzle
Authors: Quaye Enoch , Tunaru Radu , Voukelatos Nikolaos
Published: May 2024

We examine dividend growth predictability and the excess volatility puzzle across a large sample of international equity markets using a mixed‐frequency data sampling (MIDAS) regression approach. We find that accounting for dividend seasonality under the MIDAS framework significantly improves dividend growth predictability compared to simple regressions with annually aggregated data. Moreover, variance bounds tests that allow for nonstationary dividends consistently fail to reject the market efficiency hypothesis across all countries. Our findings suggest that the common rejection of market efficiency in the literature is most likely driven by the annual aggregation of dividend data as well as by the assumption of stationary dividends.
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

Parkinson'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.

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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

COVID‐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

Periodontal 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

This 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

Background

Transitions 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.

Approach

The 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.

Evaluation

All 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.

Implications

The 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

The 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

Regulation 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.
In Other Journals
Authors: Stern Peter , Ray L. Bryan , Smith H. Jesse , Stajic Jelena , Uzogara Ekeoma , Ash Caroline , Funk Michael A.
Published: May 2024

Editors’ selections from the current scientific literature
Journals investigating Nobel winner’s papers
Authors: Else Holly
Published: May 2024

Thomas Südhof’s lab is facing scrutiny after admitting mistakes in 15 publications
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

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

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

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

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.
Recurrent spontaneous pneumothorax in an NF1 patient with a novel causative variant: broadening genotype–phenotype correlations
Authors: Paoloni-Giacobino Ariane , Blouin Jean-Louis , Nouspikel Thierry , Zgheib Omar
Published: May 2024

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance, most commonly known to affect the skin and eyes. Although lung involvement in the form of cysts and bullae occurs in up to 20% of adults, the seemingly intuitive association of NF1 and spontaneous pneumothorax is not widely recognised among clinicians. Here, we report the second case of recurring spontaneous pneumothorax in the context of NF1 with a confirmed molecular diagnosis. In both cases, the NF1 variants featured a premature stop codon in the C-terminal protein domain. Interestingly, our patient had mild skin symptoms, suggesting that spontaneous pneumothorax may not be correlated with cutaneous disease severity. More genotype–phenotype correlation studies are needed for NF1 in general and for its link to spontaneous pneumothorax in particular.
Intramedullary spinal cord metastasis from breast cancer: an ambiguous entity
Authors: Ben Kridis Wala , Nefzi Issaad , Souissi Basma , Ben Mahfoudh Kheireddine , Dammak Mariem , Daoud Jamel , Khanfir Afef
Published: May 2024

Intramedullary spinal cord metastasis (IMSC) from solid tumors is rare. In this report, we describe the case of a patient treated at our center for breast cancer with intramedullary spinal cord metastases without bone and brain metastases or meningitis. Management of the disease remains challenging even with recent advances in the treatment of metastatic breast cancer. Treatment options include surgery, radiotherapy and chemotherapy. The prognosis of these patients still very poor.
Year-round monitoring of three water sources in Québec, Canada, reveals site-specific differences in conditions for Cryptosporidium and Giardia contamination
Authors: Fradette Marie-Stéphanie , Bourque Sandrinne L. , Rodriguez Manuel J. , Charette Steve J.
Published: May 2024

Cryptosporidium and Giardia are protozoan parasites responsible for gastrointestinal illnesses in humans and in animal species. The main way these parasites are transmitted is by ingestion of their (oo)cysts in drinking water. Monitoring (oo)cysts in water sources is beneficial to evaluate the quality of raw water supplying treatment plants. Currently, the only standardized protocol to enumerate these parasites from water samples is United States Environmental Protection Agency (USEPA) Method 1623.1. With this method, we monitored three major water sources in Quebec over a year to assess temporal and geographical variations of these parasite (oo)cysts. These three water sources have independent watersheds despite being in the same region. We found a general pattern for Giardia, with high concentrations of cysts during cold and transition periods, and significantly lower concentrations during the warm period. Cryptosporidium’s concentration was more variable throughout the year. Statistical correlations (Pearson’s correlation coefficients) were established between the concentration of each parasite and various environmental parameters. The three study sites each showed unique factors correlating with the presence of both protozoa, supporting the idea that each water source must be seen as a unique entity with its own particular characteristics and therefore, must be monitored independently. Although some environmental parameters could be interesting proxies to the parasitic load, no parameter was strongly correlated throughout the whole sampling year and none of the parameters could be used as a single proxy for all three studies sources.
Constraining new physics models from $$\mu \rightarrow e $$ observables in bottom-up EFT
Authors: Ardu Marco , Davidson Sacha , Lavignac Stéphane
Published: May 2024

Upcoming 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.
Super Bassian and nearly generalized Bassian Abelian groups
Authors: Danchev Peter , Goldsmith Brendan
Published: May 2024

In connection to two recent publications of ours in Arch. Math. Basel (2021) and Acta Math. Hungar. (2022), respectively, and in regard to the results obtained in Arch. Math. Basel (2012), we have the motivation to study the near property of both Bassian and generalized Bassian groups. Concretely, we prove that if an arbitrary reduced group has the property that all of its proper subgroups are generalized Bassian, then it is also generalized Bassian itself, that is, if G is an arbitrary nearly generalized Bassian group, then either G is a quasi-cyclic group or G is generalized Bassian of finite torsion-free rank. Moreover, we show that there is a complete description of the so-called super Bassian groups that are those groups whose epimorphic images are all Basian, and give their full characterization. Also, we establish that the hereditary property of Bassian groups gives nothing new as it coincides with the ordinary Bassian property.
On Cohen–Macaulay modules over the Weyl algebra
Authors: Hsiao Jen-Chieh , Lin Kuei-Nuan
Published: May 2024

We investigate a definition of Cohen–Macaulay modules over the Weyl algebra D and give a sufficient condition for a GKZ A-hypergeometric D-module to be Cohen–Macaulay.
When some complement of an exact fully invariant submodule is a direct summand
Authors: Tercan Adnan , Yücel Canan Celep
Published: May 2024

In this paper, we study modules with the property that every exact fully invariant submodule has a complement which is a direct summand. This new class of modules properly contains both of classes of FI-extending modules and [Formula: see text]-modules (i.e. modules have [Formula: see text] property for exact submodules). We obtain several module theoretical results including decompositions for the former class of modules.