bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch signaling sculpts the stem cell niche
Authors: Zamfirescu Ana-Maria , Yatsenko Andriy S. , Shcherbata Halyna R.
Published: December 2022

Adult stem cells depend on their niches for regulatory signaling that controls their maintenance, division, and their progeny differentiation. While communication between various types of stem cells and their niches is becoming clearer, the process of stem cell niche establishment is still not very well understood. Model genetic organisms provide simplified systems to address various complex questions, for example, how is a stem cell niche formed? What signaling cascades induce the stem cell niche formation? Are the mechanisms of stem cell niche formation conserved? Notch signaling is an evolutionarily conserved pathway first identified in fruit flies, crucial in fate acquisition and spatiotemporal patterning. While the core logic behind its activity is fairly simple and requires direct cell–cell interaction, it reaches an astonishing complexity and versatility by combining its different modes of action. Subtleties such as equivalency between communicating cells, their physical distance, receptor and ligand processing, and endocytosis can have an effect on the way the events unfold, and this review explores some important general mechanisms of action, later on focusing on its involvement in stem cell niche formation. First, looking at invertebrates, we will examine how Notch signaling induces the formation of germline stem cell niche in male and female Drosophila. In the developing testis, a group of somatic gonadal precursor cells receive Delta signals from the gut, activating Notch signaling and sealing their fate as niche cells even before larval hatching. Meanwhile, the ovarian germline stem cell niche is built later during late larval stages and requires a two-step process that involves terminal filament formation and cap cell specification. Intriguingly, double security mechanisms of Notch signaling activation coordinated by the soma or the germline control both steps to ensure the robustness of niche assembly. Second, in the vast domains of mammalian cellular signaling, there is an emerging picture of Notch being an active player in a variety of tissues in health and disease. Notch involvement has been shown in stem cell niche establishment in multiple organs, including the brain, muscle, and intestine, where the stem cell niches are essential for the maintenance of adult stem cells. But adult stem cells are not the only cells looking for a home. Cancer stem cells use Notch signaling at specific stages to gain an advantage over endogenous tissue and overpower it, at the same time acquiring migratory and invasive abilities to claim new tissues (e.g., bone) as their territory. Moreover, in vitro models such as organoids reveal similar Notch employment when it comes to the developing stem cell niches. Therefore, a better understanding of the processes regulating stem cell niche assembly is key for the fields of stem cell biology and regenerative medicines.
Naphthalimide-based conjugated macrocycles possessing tunable self-assembly and supramolecular binding behaviours
Authors: An Dongyue , Sun Yutao , Chang Dongdong , Zhu Jiangyu , Chen Shumin , Lu Xuefeng
Published: December 2022

The special geometric configurations and optoelectronic properties of p-conjugated macrocycles have always been the focus of materials science. The incorporation of building moieties with different features into macrocycles can not only change their geometric configurations, but also realize the regulation of intramolecular charge transfer, which is expected to bring unusual performance in supramolecular chemistry and optoelectronic devices. Herein, four novel p-conjugated macrocycles based on typical electron acceptor units naphthalimide (NMI) with aryl or alkyl substitutions were reported. The different substitutions on NMI had greatly affected the self-assembly behaviours of these macrocycles. Alkyl substituted NP2b and NP3b showed obvious self-aggregation in solution, while similiar phenomenon was not found in aryl substituted macrocycles NP2a and NP3a, which can be attributed to the steric hindrance caused by rigid aryl groups that could affect the aggregation of macrocycles in solution. In addition, all the macrocycles exhibited supramolecular encapsulation with C70, in which the larger macrocycles NP3a and NP3b with twisted geometries showed stronger binding affinity towards C70 than the corresponding small-size macrocycles NP2a and NP2b with near-planar geometries. Our studies have greatly extended the family of macrocycles based on NMI, pointing out the direction for further supramolecular studies and applications on p-conjugated macrocycles.
Outcomes of treatment for right atrial isomerism with functional single ventricle and extracardiac total anomalous pulmonary venous connection beyond neonatal period: Delayed surgical treatment, improving outcomes
Authors: Chen Weidan , Lu Ye , Ma Li , Yang Shengchun , Zou Minghui , Li Wenlei , Chen Xinxin
Published: December 2022

Objective

Total anomalous pulmonary venous connection (TAPVC) is frequently associated with right atrial isomerism (RAI), which is commonly complicated with an unbalanced atrioventricular canal with contralateral hypoplasia, complex systemic and pulmonary venous anatomy, and conotruncal abnormalities, resulting in increased risk of mortality. This study aimed to review the outcomes of delayed surgical treatment for patients with RAI complicated with functional single ventricle (FSV) and TAPVC at a single center.

Methods

In this retrospective study, we reviewed the medical records of 24 consecutive patients with RAI complicated with FSV and TAPVC who underwent initial surgical palliation after 5-month old between September 2008 and June 2019. Demographic data, concomitant anomalies, age at initial palliation, and surgical interventions were extracted and analyzed using the Cox proportional hazard model to assess risk factors for mortality and the Kaplan-Meier method to assess survival.

Results

The in-hospital mortality was 12.5% (three out of 24). The causes of death were pulmonary arterial hypertension and low cardiac output syndrome. Average follow-up was 65.2 ± 40.3 months (7–137 months). Another 4 patients died during the follow-up due to low cardiac output syndrome, protein-losing enteropathy and pulmonary arterial hypertension, respectively. Kaplan-Meier estimated survival at 1 and 5 years were 83.1 and 69.4%, respectively. Fontan completion was 45.8% (11/24). The mortality for patients with pulmonary venous obstruction (PVO) was 66.7% (4/6). Cox multivariate regression analysis indicated that preoperative PVO was the only risk factor for mortality (p = 0.032; hazard ratio, 10.000; CI 1.222–81.811).

Conclusion

Outcomes of delayed surgical treatment for patients with RAI complicated with FSV and TAPVC have improved significantly. The survival and Fontan completion were higher. However, preoperative PVO was still the risk factor for mortality.
Evaluating homogeneity and trends in extreme daily precipitation indices in a semiarid region of Brazil
Authors: Silva Isamara de Mendonça , Medeiros Deusdedit Monteiro , Sakamoto Meiry Sayuri , Leal João Bosco Verçosa , Mendes David , Ambrizzi Tercio
Published: December 2022

A regional investigation of precipitation extremes could help the local authorities to develop strategies against potential climatic disasters, especially in regions of large climate vulnerability. In this context, this study focused on the homogeneity and trend analysis of eleven extreme precipitation indices from a daily rainfall dataset of rain gauges of the state of Ceará, located in the north of Northeast Brazil, from 1974 to 2018 at annual and seasonal time scales. The data were first submitted to gap-filling and quality control processes. Homogeneity, trend, and correlation coefficient were performed subsequently. Homogeneity results showed that most of the precipitation series were classified as “useful.” Significant break years in the series agreed well with moderate and very strong El Niño and La Niña events, suggesting a further investigation of this possible connection. Wet and dry day precipitation indices mainly indicated a decrease in the rainfall regime and an increase in dry days, mainly in the central-eastern, northwestern, and southern regions of the Ceará, especially during the annual time scale and the rainy season. The Locally Weighted Scatterplot Smoothing (LOWESS) curve showed changes in almost all series during the 1980s and 1990s, coinciding with the homogeneity breaks and years of severe droughts that strongly hit the region. Correlation coefficients were strong and significant between rainfall total index and the other precipitation indices.
An equitable and scalable approach to track fidelity of implementation in partnership with teachers
Authors: Spacciapoli Megan , Viana Mara , Saunders Wilder Oliver , Sullivan Jillian , McCallum Tia , Wilder-Smith Barbara
Published: December 2022

Social and emotional learning (SEL) is a key focus of early childhood education. A significant body of research demonstrates the critical impact of fidelity of SEL curriculum and intervention implementation on child outcomes; however, few widely-used curricula regularly assess classroom-level implementation fidelity outside of the context of research or correlate fidelity with key areas of children’s development of these skills. Fidelity measurement often focuses on easy-to-quantify variables such as classroom environment or lesson plan adherence, and is a periodic snapshot used as a moderator or co-variate when assessing child outcomes, rather than being intentionally leveraged as a systematic, ongoing process to evaluate and support implementation. In this paper, we present a novel approach to capturing fidelity data as a core component of professional development. We outline our findings from a pilot of our approach using short, teacher-recorded videos submitted across the school year as a vehicle for capturing and sharing real-time data related to professional learning, implementation, and curricula impact, as well as a framework for building equitable partnerships with teachers. Results from the initial pilot of this approach in several hundred classrooms across the US demonstrate feasibility and utility and suggest that teacher-recorded videos can offer a scalable means to collect continuous samples of fidelity data, providing a richer view of professional learning, while simultaneously creating the opportunity to provide ongoing feedback and engage teachers in partnership in reflecting on practice and its impact on children’s development. We developed and piloted an approach where teachers record and upload videos of teaching practices and children engaging with their peers in specific classroom activities via a mobile application. Each video submission has a focal activity and associated set of indicators which are shared with teachers in advance to create an equitable feedback system in which both curriculum staff and teachers engage in reflecting on children’s interactions and the application of the curricular approach in their classroom. Videos are viewed and coded on these sets of indicators by both the teachers and curricular coaches who provide targeted feedback in an interactive exchange on a dashboard accessible by teachers and their curricular coach.
Learning engagement in massive open online courses: A systematic review
Authors: Wang Rui , Cao Jie , Xu Yachen , Li Yanyan
Published: December 2022

Although massive open online courses (MOOCs) increase the number of choices in higher education and enhance learning, their low completion rate remains problematic. Previous studies have shown that learning engagement is a crucial factor influencing learning success and learner retention. However, few literature reviews on learning engagement in MOOCs have been conducted, and specific data analysis methods are lacking. Moreover, the internal and external factors that affect learning engagement have not been fully elucidated. Therefore, this systematic literature review summarized articles pertaining to learning engagement in MOOCs published from 2015 to 2022. Thirty articles met the inclusion and quality assurance criteria. We found that (1) learning engagement can be measured through analysis of log, text, image, interview, and survey data; (2) measures that have been used to analyze learning engagement include self-report (e.g., the Online Learning Engagement Scale, Online Student Engagement Questionnaire, and MOOC Engagement Scale) and automatic analysis methods [e.g., convolutional neural network (CNN), bidirectional encoder representations from transformers-CNN, K-means clustering, and semantic network analysis]; and (3) factors affecting learning engagement can be classified as internal (learning satisfaction, etc.) or external (curriculum design, etc.). Future research should obtain more diverse, multimodal data pertaining to social engagement. Second, researchers should employ automatic analysis methods to improve measurement accuracy. Finally, course instructors should provide technical support (“scaffolding”) for self-regulated learning to enhance student engagement with MOOCs.
Combined evaluation of corporate ecological and environmental responsibility: Evidence for forest preservation from Chinese forestry companies
Authors: Long Fengjiao , Strielkowski Wadim , Liu Xiaomin , Uppal Raminder Singh , Chen Qin
Published: December 2022

The ecological benefit of forest has an important influence on the sustainable development of society, thus, forest management has become a critical strategic action. Forest preservation is an inclusive process which depends on collaboration among a wide range of stakeholders. Forestry companies, who own and manage forest resources, are responsible for forest preservation and ecological construction, which is called corporate ecological environmental responsibility (CEER). Most existing analyses, however, were limited to corporate environmental responsibility (CER) and ignored the ecological responsibility of forestry enterprises. Therefore, in order to better play the role of forestry companies in forest preservation, it is urgent to define the content and the measurement of CEER. This paper established a CEER index system based on the characteristics of forestry enterprises. Furthermore, evaluated the CEER level of forestry enterprises using the combined evaluation method based on the GINI criterion, which is more effective and reasonable. It is found that forestry ecological environmental responsibility emphasizes ecological improvement and has shifted from traditional environmental protection to ecological construction. Qingshan Paper, Sun Paper, and Yong’an Forestry perform the best in CEER among all forestry companies. In addition, the results showed a low level but an obvious upward trend in forestry CEER and a noticeable heterogeneity in the performance of CEER in different forestry industries. Our findings can be useful for further promoting the ecological benefits of forest companies and developing relevant policies.
Assessing the broadscale effects of wildfire under extreme drought conditions to boreal peatlands
Authors: Bourgeau-Chavez Laura L. , Graham Jeremy A. , Vander Bilt Dorthea J. L. , Battaglia Michael J.
Published: December 2022

Climate warming and changing fire regimes in the North American boreal zone have the capacity to alter the hydrology and ecology of the landscape with long term consequences to peatland ecosystems and their traditional role as carbon sinks. It is important to understand how peatlands are affected by wildfire in relation to both extent of burn and severity of burn to the organic soil (peat) layers where most of the C is stored. Peatlands cover more than 75% of the landscape in the southern Northwest Territories, Canada where extreme drought led to widespread wildfires in 2014–2015. To assess the wildfire effects across a 14.6 million ha study area including 136 wildfire events, we used an integration of field data collection, land cover mapping of peatland and upland ecotypes, Landsat-8-based mapping of burn severity to the soil organic layers, and MODIS-hotspot mapping of fire progression for season of burning. The intersection of these geospatial products allows for a broadscale assessment of wildfire effects across gradients of ecotype, ecoregions, seasons, and year of burn. Using a series of chi-squared goodness of fit tests, we found that peatlands are more susceptible to wildfire on the Taiga shield where they are smaller and hydrologically isolated by the rocky landscape. There burning affected proportionally larger peat areas with an evenness of burn severity to the organic soil layers which may lead to less spatial diversity in post-fire recovery, making the landscape less resilient to future fire. The most resilient peatlands are expected to be hydrologically well-connected to both ground water systems and larger peatland complexes such as those on the Taiga plains which exhibited large unburned and singed patches across the landscape, and greater variability in burn severity across seasons and ecotypes. Understanding the tipping point of drought conditions at which the landscape becomes connected, and peatlands are susceptible to wildfire with deeper burning of the organic soil layers is important for understanding the potential future effects of climate change and projected increases in wildfire on peatlands. This is critical for C accounting and climate mitigation strategies.
Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience
Authors: Shamriz Oded , Rubin Limor , Simon Amos J. , Lev Atar , Barel Ortal , Somech Raz , Korem Maya , Matza Porges Sigal , Freund Tal , Hagin David , Garty Ben Zion , Nahum Amit , Molho Pessach Vered , Tal Yuval
Published: December 2022

Background

Autosomal dominant hyper-IgE syndrome (AD-HIES) caused by dominant negative (DN) variants in the signal transducer and activator of transcription 3 gene (STAT3) is characterized by recurrent Staphylococcal abscesses, severe eczema, chronic mucocutaneous candidiasis (CMC), and non-immunological facial and skeletal features.

Objectives

To describe our experience with the diagnosis and treatment of adult patients with AD-HIES induced by DN-STAT3 variants.

Methods

The medical records of adult patients (>18 years) treated at the Allergy and Clinical Immunology Clinic of Hadassah Medical Center, Jerusalem, Israel, were retrospectively analyzed. Immune and genetic workups were used to confirm diagnosis.

Results

Three adult patients (2 males; age 29-41 years) were diagnosed with DN-STAT3 variants. All patients had non-immunological features, including coarse faces and osteopenia. Serious bacterial infections were noted in all patients, including recurrent abscesses, recurrent pneumonia, and bronchiectasis. CMC and diffuse dermatophytosis were noted in two patients. Two patients had severe atopic dermatitis refractory to topical steroids and phototherapy. Immune workup revealed elevated IgE in three patients and eosinophilia in two patients. Whole exome sequencing revealed DN-STAT3 variants (c.1166C>T; p.Thr389Ile in two patients and c.1268G>A; p. Arg423Gln in one patient). Variants were located in DNA-binding domain (DBD) and did not hamper STAT3 phosphorylation Treatment included antimicrobial prophylaxis with trimethoprim/sulfamethoxazole (n=2) and amoxycillin-clavulanic acid (n=1), and anti-fungal treatment with fluconazole (n=2) and voriconazole (n=1). Two patients who had severe atopic dermatitis, were treated with dupilumab with complete resolution of their rash. No adverse responses were noted in the dupilumab-treated patients.

Discussion

Dupilumab can be used safely as a biotherapy for atopic dermatitis in these patients as it can effectively alleviate eczema-related symptoms. Immunologists and dermatologists treating AD-HIES adult patients should be aware of demodicosis as a possible manifestation. DN-STAT3 variants in DBD do not hamper STAT3 phosphorylation.
HLA variants have different preferences to present proteins with specific molecular functions which are complemented in frequent haplotypes
Authors: Karnaukhov Vadim , Paes Wayne , Woodhouse Isaac B. , Partridge Thomas , Nicastri Annalisa , Brackenridge Simon , Shcherbinin Dmitrii , Chudakov Dmitry M. , Zvyagin Ivan V. , Ternette Nicola , Koohy Hashem , Borrow Persephone , Shugay Mikhail
Published: December 2022

Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and code for proteins that play a key role in guiding adaptive immune responses by presenting foreign and self peptides (ligands) to T cells. Each person carries up to 6 HLA class I variants (maternal and paternal copies of HLA-A, HLA-B and HLA-C genes) and also multiple HLA class II variants, which cumulatively define the landscape of peptides presented to T cells. Each HLA variant has its own repertoire of presented peptides with a certain sequence motif which is mainly defined by peptide anchor residues (typically the second and the last positions for HLA class I ligands) forming key interactions with the peptide-binding groove of HLA. In this study, we aimed to characterize HLA binding preferences in terms of molecular functions of presented proteins. To focus on the ligand presentation bias introduced specifically by HLA-peptide interaction we performed large-scale in silico predictions of binding of all peptides from human proteome for a wide range of HLA variants and established which functions are characteristic for proteins that are more or less preferentially presented by different HLA variants using statistical calculations and gene ontology (GO) analysis. We demonstrated marked distinctions between HLA variants in molecular functions of preferentially presented proteins (e.g. some HLA variants preferentially present membrane and receptor proteins, while others – ribosomal and DNA-binding proteins) and reduced presentation of extracellular matrix and collagen proteins by the majority of HLA variants. To explain these observations we demonstrated that HLA preferentially presents proteins enriched in amino acids which are required as anchor residues for the particular HLA variant. Our observations can be extrapolated to explain the protective effect of certain HLA alleles in infectious diseases, and we hypothesize that they can also explain susceptibility to certain autoimmune diseases and cancers. We demonstrate that these differences lead to differential presentation of HIV, influenza virus, SARS-CoV-1 and SARS-CoV-2 proteins by various HLA alleles. Taking into consideration that HLA alleles are inherited in haplotypes, we hypothesized that haplotypes composed of a combination of HLA variants with different presentation preferences should be more advantageous as they allow presenting a larger repertoire of peptides and avoiding holes in immunopeptidome. Indeed, we demonstrated that HLA-A/HLA-B and HLA-A/HLA-C haplotypes which have a high frequency in the human population are comprised of HLA variants that are more distinct in terms of functions of preferentially presented proteins than the control pairs.
Interaction between the parasitic barnacle Polyascus planus (Cirripedia: Rhizocephala) and its brachyuran host Metopograpsus thukuhar during the development of the externa of the parasite: Control of the gonadal development and vitellogenin synthesis of the host
Authors: Chen Hsiang-Yin , Lee Chien-Hsun , Tsai Chih-Cheng , Liu Hung-Chang , Yang Su-Ling , Lee Chi-Ying
Published: December 2022

Developmental profile of the female reproductive apparatus (the externa) of Polyascus planus parasitizing the thukuhar shore-crab Metopograpsus thukuhar is described. The development is divided into 4 stages, which are named based on the distinct color of the externa at each stage. The effects of parasitism on the gonad and hepatopancreas of the host were then examined. The ovary was heavily infiltrated by the rootlet of the parasite, with the oocytes being arrested at the pre-vitellogenic state, whereas the testis, not being infiltrated, still contained abundant amounts of spermatozoa. The hepatopancreas of the hosts of both sexes was heavily infiltrated by the rootlets. Regarding the synthesis of vitellogenin (Vg), the hemolymph precursor of the major yolk protein (vitellin, Vn), expression of host Vg gene was detected in the ovary and hepatopancreas of both non-parasitized and parasitized females, and, importantly, its expression found to be induced in the hepatopancreas of parasitized males. Furthermore, results of quantitative gene expression assays showed that expression levels of the host Vg in the ovary and hepatopancreas did not change significantly among the various parasitization status (i.e., host bearing externa of different developmental stages), nor did those of the parasite Vg in the externa among the developmental stage of the externa. The Vg expression levels in the hepatopancreas of parasitized males and in the externa were however negatively correlated. Finally, analysis of tryptic peptide fragments derived from hemolymph proteins of high molecular weight in the parasitized males confirmed the induction of synthesis of the host Vg, whereas analysis of externa proteins of similar molecular weight revealed that Vg of both host and parasite origins contributes to the formation of parasite Vn. The combined results indicate that the parasitized hosts, regardless of sex, synthesize Vg for the ovarian maturation of the parasite, to which Vg of parasite origin also contributes. Discussion is also made with regard to the strategy the parasite adopts toward hosts of different sexes. The profile of the development of externa established would serve as a temporal framework against which studies of host/parasite interaction can be conducted in a developmental context.
Creating climate-informed physician leaders: The evolution of a physician fellowship in climate and health science policy
Authors: Wheat Stefan , Chekuri Bhargavi , Sorensen Cecilia , Rochford Rosemary , Lemery Jay
Published: December 2022

Climate change poses numerous near and long-term challenges for our society, and the human health consequences are increasingly recognized as unprecedented. Responding to these health hazards requires a healthcare workforce composed of climate-informed clinicians. As trusted messengers, physicians play a vital role in informing and preparing the public for health impacts of climate change. We describe an evolving graduate medical education fellowship for physicians from all specialties capable of training leaders in this field. Our program pairs fellows with federal and non-governmental partners to provide expertise in climate policy and empower them to be change agents. The accelerating response to climate change from the federal government coupled with an increased recognition of the impacts of climate hazards on health demands a climate-informed clinical workforce. The expansion of this fellowship to accommodate trainees from multiple specialties and its innovative structure leveraging local and national partnerships sets a standard for how similar programs can be developed in addressing the greatest public health threat and opportunity of the century.
ADTKD-UMOD in a girl with a de novo mutation: A case report
Authors: Li Meng-shi , Li Yang , Jiang Lei , Song Zhuo-ran , Yu Xiao-juan , Wang Hui , Ren Ya-li , Wang Su-xia , Zhou Xu-jie , Yang Li , Zhang Hong
Published: December 2022

Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). An autosomal dominant inheritance is the general rule, but de novo UMOD mutations have been reported. It was reported that the median age of ESKD was 47 years (18–87 years) and men were at a much higher risk of progression to ESKD. Here, we reported a 13-year-old young girl with unexplained chronic kidney disease (CKD) (elevated serum creatine) and no positive family history. Non-specific clinical and histological manifestations and the absence of evidence for kidney disease of other etiology raised strong suspicion for ADTKD. Trio whole-exome sequencing confirmed that she carried a de novo heterozygous mutation c.280T > C (p.Cys94Arg) in the UMOD gene. The functional significance of the novel mutation was supported by a structural biology approach. With no targeted therapy, she was treated as CKD and followed up regularly. The case underscores the clinical importance of a gene-based unifying terminology help to identify under-recognized causes of CKD, and it demonstrates the value of whole-exome sequencing in unsolved CKD.
Deciphering the global roles of Cold shock proteins in Listeria monocytogenes nutrient metabolism and stress tolerance
Authors: Muchaamba Francis , von Ah Ueli , Stephan Roger , Stevens Marc J. A. , Tasara Taurai
Published: December 2022

Listeria monocytogenes (Lm) accounts for serious public health and food safety problems owing to its stress resilience and pathogenicity. Based on their regulatory involvement in global gene expression events, cold-shock domain family proteins (Csps) are crucial in expression of various stress fitness and virulence phenotypes in bacteria. Lm possesses three Csps (CspA, CspB, and CspD) whose regulatory roles in the context of the genetic diversity of this bacterium are not yet fully understood. We examined the impacts of Csps deficiency on Lm nutrient metabolism and stress tolerance using a set of csp deletion mutants generated in different genetic backgrounds. Phenotype microarrays (PM) analysis showed that the absence of Csps in ∆cspABD reduces carbon (C-) source utilization capacity and increases Lm sensitivity to osmotic, pH, various chemical, and antimicrobial stress conditions. Single and double csp deletion mutants in different Lm genetic backgrounds were used to further dissect the roles of individual Csps in these phenotypes. Selected PM-based observations were further corroborated through targeted phenotypic assays, confirming that Csps are crucial in Lm for optimal utilization of various C-sources including rhamnose and glucose as well as tolerance against NaCl, β-phenyethylamine (PEA), and food relevant detergent stress conditions. Strain and genetic lineage background-based differences, division of labour, epistasis, and functional redundancies among the Csps were uncovered with respect to their roles in various processes including C-source utilization, cold, and PEA stress resistance. Finally, targeted transcriptome analysis was performed, revealing the activation of csp gene expression under defined stress conditions and the impact of Csps on expression regulation of selected rhamnose utilization genes. Overall, our study shows that Csps play important roles in nutrient utilization and stress responses in Lm strains, contributing to traits that are central to the public health and food safety impacts of this pathogen.
The role of upper and lower genital tract microbiota alterations in term chorionamnionitis: A prospective study
Authors: Li Meng , Huang Zhenyu , Tao Zhi , Meng Yiting , Wen Jia , Zhang Qiongqiong , Liu Ying , Shang Mengyuan , Wang Ying , Wang Yufeng , Chen Rui , Wang Xiaoqian , Cao Yang , Zhang Lei , Liao Qinping
Published: December 2022

Objective

This study aimed to compare the dynamics of lower and upper genital tract microbiota in normal term pregnancy, histological chorioamnionitis (HCA), and clinical chorioamnionitis (CCA) patients to provide a reference for the diagnosis and treatment of chorioamnionitis (CAM) patients.

Methods

We prospectively collected vaginal and cervical secretions, as well as placenta tissues, fetal membranes, and amniotic fluid from normal-term pregnant women, HCA and CCA patients. Then, we performed genomic DNA extraction and PCR amplification for all samples. The eligible samples were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Additionally, all placenta tissues were histopathologically examined, and neonatal pharyngeal swabs and placenta tissues from the HCA and CCA groups were subjected to microbial culture.

Results

A total of 85 term pregnant women were enrolled in this study, including 34 in the normal group (N), 37 in the HCA group, and 14 in the CCA group. A total of 171 qualified samples were analyzed by 16S rRNA sequencing. The results suggested that the cervical microbiota was highly similar to the vaginal microbiota in normal term parturients, with Lactobacillus as the dominant bacterium. Moreover, there was no difference in the alpha and beta diversity of vaginal microbiota between the N, HCA, and CCA groups at the genus level. Besides, no significant differences were detected in cervical microbiome among the three groups. Regarding intrauterine microorganisms, the N and HCA groups had similar microbial composition but were different from the CCA group. No microbe was detected in the placental tissue of normal term parturients, while some microorganisms were found in the intrauterine amniotic fluid and fetal membrane samples. Regardless of cultivation or 16S rRNA sequencing, an extremely low microbial positive rate was detected in HCA and CCA intrauterine samples. Compared to the normal group, Lactobacillus was significantly reduced in the CCA group intrauterine, and Ureaplasma and Enterococcus increased with no statistically significant.

Conclusion

The N, HCA and CCA groups had similar composition of vaginal and cervical microflora. Some normal-term pregnant women can harbor non-pathogenic microbiota in the uterine cavity. Sterile inflammation is more frequent than microbial-associated inflammation in term HCA and CCA parturients.
Pre-analytical processing of plasma and serum samples for combined proteome and metabolome analysis
Authors: Gegner Hagen M. , Naake Thomas , Dugourd Aurélien , Müller Torsten , Czernilofsky Felix , Kliewer Georg , Jäger Evelyn , Helm Barbara , Kunze-Rohrbach Nina , Klingmüller Ursula , Hopf Carsten , Müller-Tidow Carsten , Dietrich Sascha , Saez-Rodriguez Julio , Huber Wolfgang , Hell Rüdiger , Poschet Gernot , Krijgsveld Jeroen
Published: December 2022

Metabolomic and proteomic analyses of human plasma and serum samples harbor the power to advance our understanding of disease biology. Pre-analytical factors may contribute to variability and bias in the detection of analytes, especially when multiple labs are involved, caused by sample handling, processing time, and differing operating procedures. To better understand the impact of pre-analytical factors that are relevant to implementing a unified proteomic and metabolomic approach in a clinical setting, we assessed the influence of temperature, sitting times, and centrifugation speed on the plasma and serum metabolomes and proteomes from six healthy volunteers. We used targeted metabolic profiling (497 metabolites) and data-independent acquisition (DIA) proteomics (572 proteins) on the same samples generated with well-defined pre-analytical conditions to evaluate criteria for pre-analytical SOPs for plasma and serum samples. Time and temperature showed the strongest influence on the integrity of plasma and serum proteome and metabolome. While rapid handling and low temperatures (4°C) are imperative for metabolic profiling, the analyzed proteomics data set showed variability when exposed to temperatures of 4°C for more than 2 h, highlighting the need for compromises in a combined analysis. We formalized a quality control scoring system to objectively rate sample stability and tested this score using external data sets from other pre-analytical studies. Stringent and harmonized standard operating procedures (SOPs) are required for pre-analytical sample handling when combining proteomics and metabolomics of clinical samples to yield robust and interpretable data on a longitudinal scale and across different clinics. To ensure an adequate level of practicability in a clinical routine for metabolomics and proteomics studies, we suggest keeping blood samples up to 2 h on ice (4°C) prior to snap-freezing as a compromise between stability and operability. Finally, we provide the methodology as an open-source R package allowing the systematic scoring of proteomics and metabolomics data sets to assess the stability of plasma and serum samples.
Dual-task related frontal cerebral blood flow changes in older adults with mild cognitive impairment: A functional diffuse correlation spectroscopy study
Authors: Udina Cristina , Avtzi Stella , Mota-Foix Miriam , Rosso Andrea L. , Ars Joan , Kobayashi Frisk Lisa , Gregori-Pla Clara , Durduran Turgut , Inzitari Marco
Published: December 2022

Introduction

In a worldwide aging population with a high prevalence of motor and cognitive impairment, it is paramount to improve knowledge about underlying mechanisms of motor and cognitive function and their interplay in the aging processes.

Methods

We measured prefrontal cerebral blood flow (CBF) using functional diffuse correlation spectroscopy during motor and dual-task. We aimed to compare CBF changes among 49 older adults with and without mild cognitive impairment (MCI) during a dual-task paradigm (normal walk, 2- forward count walk, 3-backward count walk, obstacle negotiation, and heel tapping). Participants with MCI walked slower during the normal walk and obstacle negotiation compared to participants with normal cognition (NC), while gait speed during counting conditions was not different between the groups, therefore the dual-task cost was higher for participants with NC. We built a linear mixed effects model with CBF measures from the right and left prefrontal cortex.

Results

MCI (n = 34) showed a higher increase in CBF from the normal walk to the 2-forward count walk (estimate = 0.34, 95% CI [0.02, 0.66], p = 0.03) compared to participants with NC, related to a right- sided activation. Both groups showed a higher CBF during the 3-backward count walk compared to the normal walk, while only among MCI, CFB was higher during the 2-forward count walk.

Discussion

Our findings suggest a differential prefrontal hemodynamic pattern in older adults with MCI compared to their NC counterparts during the dual-task performance, possibly as a response to increasing attentional demand.
Comparison of the efficacy of acupuncture-related Therapies for post-stroke motor aphasia: A Bayesian network meta-analysis
Authors: Feng Sisi , Tang Mingzhi , Huang Gan , Wang Jumei , Lv Yulan , He Sijin , Liu Duo , Gu Lihua
Published: December 2022

Background

Motor aphasia, which can affect the communication ability of patients and even triggers severe psychological disorders, is one of the most common sequelae after stroke. Acupuncture (a typical complementary alternative therapy) is frequently combined with speech training (ST) to treat post-stroke motor aphasia (PSMA) and presents significant efficacy. However, the most effective acupuncture intervention is still unknown. This study aims to analyze the efficacy of several acupuncture approaches combined with ST for PSMA to identify the best intervention for clinical decision-making by using network meta-analysis (NMA).

Methods

Eight major databases were searched from the time of their establishment to March 2022. Clinical efficacy rate (CER) was used as the primary outcome indicator. R software (version 4.13.0) and STATA software (version 16.0) were used to analyze the data.

Results

A total of 29 randomized controlled trials (RCTs) and six treatment regimens were included in this study. In the pair-wise meta-analysis, we found that the efficacy of scalp-tongue acupuncture (STA) combined with ST [OR = 8.30; 95% Credible interval (CrI): 3.87, 17.33], tongue acupuncture (TA) combined with ST (OR = 3.95; 95% CrI: 2.27, 6.89), scalp-body acupuncture (SBA) combined with ST (OR = 3.75; 95% CrI: 2.26, 6.22), scalp acupuncture (SA) combined with ST (OR = 2.95; 95% CrI: 1.74, 5.0), and body acupuncture (BA) combined with ST (OR = 2.30; 95% CrI: 1.26, 4.19) were significantly superior to that of ST. In addition, the efficacy of STA + ST was significantly superior to that of SA +ST (OR = 2. 82; 95% CrI: 1.24, 6.38) and BA + ST (OR = 3.61; 95% CrI: 1.40, 9.29). According to the surface under the cumulative ranking curve (SUCRA), STA + ST (SUCRA = 97.9%) may be the best treatment regimen to improve the clinical outcome in patients with PSMA.

Conclusion

The NMA showed that STA combined with ST may be the best treatment to improve CER, compared with other combination treatments. However, since the overall quality and number of studies are limited, further RCTs with a large sample and multicenter are needed for further validation.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316081, identifier CRD42022316081.
Immediate effects of short-term meditation on sensorimotor rhythm-based brain–computer interface performance
Authors: Kim Jeehyun , Jiang Xiyuan , Forenzo Dylan , Liu Yixuan , Anderson Nancy , Greco Carol M. , He Bin
Published: December 2022

Introduction

Meditation has been shown to enhance a user’s ability to control a sensorimotor rhythm (SMR)-based brain-computer interface (BCI). For example, prior work have demonstrated that long-term meditation practices and an 8-week mindfulness-based stress reduction (MBSR) training have positive behavioral and neurophysiological effects on SMR-based BCI. However, the effects of short-term meditation practice on SMR-based BCI control are still unknown.

Methods

In this study, we investigated the immediate effects of a short, 20-minute meditation on SMR-based BCI control. Thirty-seven subjects performed several runs of one-dimensional cursor control tasks before and after two types of 20-minute interventions: a guided mindfulness meditation exercise and a recording of a narrator reading a journal article.

Results

We found that there is no significant change in BCI performance and Electroencephalography (EEG) BCI control signal following either 20-minute intervention. Moreover, the change in BCI performance between the meditation group and the control group was found to be not significant.

Discussion

The present results suggest that a longer period of meditation is needed to improve SMR-based BCI control.
Melatonin receptors and Per1 expression in the inferior olivary nucleus of the Sapajus apella monkey
Authors: Granado Marcos Donizete Junior , Pinato Luciana , Santiago Jeferson , Barbalho Sandra Maria , Parmezzan Jessica Ellen Lima , Suzuki Lenita Mayumi , Cabrini Mayara Longui , Spressão Daniele Raineri Mesquita Serva , Carneiro de Camargo Ana Letícia , Guissoni Campos Leila Maria
Published: December 2022

Melatonin is a transducer of photic environmental information and participates in the synchronization of various physiological and behavioral phenomena. Melatonin can act directly in several areas of the central nervous system through its membrane receptors coupled to G protein, called MT1 and MT2 receptors. In some structures, such as the retina, hypothalamus and pars tuberalis, the expression of both melatonin receptors shows circadian variations. Melatonin can act in the synchronization of the clock proteins rhythm in these areas. Using the immunohistochemistry technique, we detected the immunoexpression of the melatonin receptors and clock genes clock protein Per1 in the inferior olivary nucleus (ION) of theSapajus apellamonkey at specific times of the light-dark phase. The mapping performed by immunohistochemistry showed expressive immunoreactivity (IR) Per1 with predominance during daytime. Both melatonin receptors were expressed in the ION without a day/night difference. The presence of both melatonin receptors and the Per1 protein in the inferior olivary nucleus can indicate a functional role not only in physiological, as in sleep, anxiety, and circadian rhythm, but also a chronobiotic role in motor control mechanisms.
Blood-nerve barrier disruption and coagulation system activation induced by mechanical compression injury participate in the peripheral sensitization of trigeminal neuralgia
Authors: Zhou Lu-Xi , Lin Shao-Wei , Qiu Rong-Hui , Lin Ling , Guo Yue-Feng , Luo Dao-Shu , Li Yun-Qing , Wang Feng
Published: December 2022

Introduction

The aim of this study was to investigate the effect and possible mechanisms of the blood-nerve barrier (BNB) and the coagulation-anticoagulation system in modulating the mechanical allodynia in a trigeminal neuralgia (TN) rat model induced by chronic compression of the trigeminal root entry zone (TREZ).

Methods

Von Frey filaments were applied to determine the orofacial mechanical allodynia threshold. The BNB permeability was evaluated by Evans blue extravasation test. Immunohistochemical staining and laser confocal microscopy were used to measure the length of the depletion zones of the nodes of Ranvier in the TREZ, the diameter of nerve fibers and the length of the nodal gap. The transcriptional levels of prothrombin and endogenous thrombin inhibitor protease nexin-1 (PN-1) in the TREZ of TN rats were assessed by RT-qPCR. A Western blotting assay was performed to detect the expression of paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) in the TREZ. The spatiotemporal expression pattern of thrombin activated receptor (i.e. protease activated receptor 1, PAR1) in TREZ were defined by immunostaining and immunoblotting assays. PAR1 receptor inhibitors SCH79797 were administrated to TN rats to analyze the effect of thrombin-PAR1 on orofacial hyperalgesia.

Results

A compression injury of a rat’s TREZ successfully induced TN-like behavior and was accompanied by the destruction of the permeability of the BNB and the promotion of prothrombin and thrombin inhibitor protease nexin-1 (PN-1) expression. The expression of the paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) was increased, while the nodal gap length of the nodes of Ranvier was widened and the length of node-depleted zones was shortened. Moreover, the expression of PAR1 within the TREZ was upregulated at an early stage of TN, and administration of the PAR1 antagonist SCH79797 effectively ameliorated orofacial mechanical allodynia.

Conclusion

A compression injury of the TREZ increased the permeability of the BNB and induced disturbances in the local coagulation-anticoagulation system, concomitant with the structural changes in the nodes of Ranvier, thrombin-PAR1 may play a critical role in modulating orofacial mechanical hyperalgesia in a TN rat model.