bluuebunny/crossref_metadata_2025 huggingface dataset:
Short to midterm follow-up of multi-system inflammatory syndrome in children with special reference to cardiac involvement
Authors: Aziz Omeir A. , Sadiq Masood , Qureshi Ahmad U. , Hyder Najam , Kazmi Uzma , Batool Afsheen , Naz Samia , Mushtaq Asma , Bari Attia , Rashid Junaid
Published: March 2022

Objectives:

We aim to describe the early and upto 16 months follow-up of post-coronavirus disease (COVID), multi-system inflammatory syndrome in children (MIS-C), with special reference to cardiac involvement.

Study design:

This cohort non-interventional descriptive study included patients <18 years admitted between May, 2020 and April, 2021. Based on underlying similarities, children were classified as post-COVID MIS-C with overlapping Kawasaki Disease, MIS-C with no overlapping Kawasaki Disease, and MIS-C with shock. Post-discharge, patients were followed at 1, 3, 6, 12, and 16 months.

Results:

Forty-one patients predominantly males (73%), at median age of 7 years (range 0.2–16 years) fulfilled the World Health Organisation criteria for MIS-C. Cardiac involvement was seen in 15 (36.5%); impaired left ventricle (LV) function in 5 (12.2%), coronary artery involvement in 10 (24.4%), pericardial effusion in 6 (14.6%) patients, and no arrhythmias. There were two hospital deaths (4.9%), both in MIS-C shock subgroup (2/10, 20%). At 1 month, there was persistent LV dysfunction in 2/5, coronary artery abnormalities in 7/10, and pericardial effusion resolved completely in all patients. By 6 months, LV function returned to normal in all but coronary abnormalities persisted in two patients. At last follow-up (median 9.8 months, interquartile range 2–16 months), in 36/38 (94.7%) patients, coronary artery dilatation was persistent in 2 (20%) patients.

Conclusions:

Children with MIS-C have a good early outcome, though MIS-C with shock can be life-threatening subgroup in a resource-constrained country setting. On midterm follow-up, there is normalisation of LV function in all and recovery of coronary abnormalities in 80% of patients.
Coronary fibromuscular dysplasia with three-vessel involvement: a rare cause of ischaemic dilated cardiomyopathy in a very young male
Authors: Călburean Paul-Adrian , Hadadi László , Rudzik Roxana , Dobreanu Dan
Published: March 2022

Coronary artery disease of non-atherosclerotic aetiology, while rare in incidence, can have a wide aetiology, such as fibromuscular dysplasia, which is a non-inflammatory arteriopathy of numerous histopathological types of fibromuscular tissue accumulation. This brief report describes the case of a 22-year-old male with a recently developed dilated cardiomyopathy and a history of aborted cardiac arrest at the age of 14 years. Coronary angiogram revealed severe three vessels disease, while optical coherence tomography established fibromuscular dysplasia as aetiology. Balloon and stent angioplasty was performed guided by fractional flow reserve with acceptable angiographic result.
Lost in translation, apparently: Bilingual language processing of evidentiality in a Turkish–English Translation and judgment task
Authors: Tosun Sümeyra , Filipović Luna
Published: March 2022

We investigated how bilingual speakers process evidentiality information in a dual language activation setting (Green & Abutalebi, 2013) using a translation production and confidence judgment task. Due to interaction of multiple factors in bilingual processing a multifactor model CASP (Complex Adaptive System Principles) for Bilingualism (Filipović & Hawkins, 2019) was used as a theoretical frame. Evidentiality indicates the source of information about past events, i.e., whether they were witnessed firsthand or non-firsthand and it is marked obligatorily in the grammar of Turkish and optionally in English using verbs, adverbs or constructions. The results show that firsthand information is translated more correctly than the non-firsthand in both directions and that different bilingual populations all gravitate towards a shared pattern in both languages but in different ways due to the different proficiency (English vs. Turkish as the stronger (L1) language) and different acquisition histories (early heritage vs. migrant late bilingualism).
Validation of the nutrient-rich foods index estimated by 24-h dietary recall method among adults in Henan province of China
Authors: Zhai Junya , Ma Baihui , Lyu Quanjun , Guo Lijun , Khatun Pipasha , Liang Rui , Cong Minghua , Kong Yongxia
Published: March 2022

Objective:

A family of nutrient-rich food (NRF) indices was validated against the mean adequacy ratio (MAR) and their associations with obesity were tested.

Design:

Cross-sectional study. NRF indices include nutrients to encourage ranging from 6–11 (protein; fibre; vitamin A, vitamin C, vitamin E and vitamin B12; Ca; Fe; K; Mg; Zn) and two nutrients to limit (saturated fat and Na), described as NRFn.2 (where n 6–11), based on reference amount of 100 g or 100 kcal using the NRF index family of algorithms. The percentage of variation in MAR (R2) was the criteria of index performance. Logistic regression models were applied to predict the association between NRF index and obesity.

Setting:

Three communities in Zhengzhou city, Henan province, China.

Participants:

A total of 656 adults were recruited from Henan as the subjects.

Results:

The NRF9·2 index, based on nine beneficial nutrients and two nutrients to limit, using the algorithm based on sums and 100 kcal, had the higher R2 values (R2 = 0·232). The OR for overweight (defined by BMI) in the 4th quartile (Q4) v. the 1st quartile (Q1) of the NRF9·2 index was 0·61 (95 % CI = 0·37, 0·98) after multiple adjustments.

Conclusion:

NRF9·2 index using the algorithm based on sums and 100 kcal gave the best predicted model for diet quality. NRF9·2 index score was associated with overweight defined by BMI, but it was not associated with central obesity. The NRF9·2 index is a valid tool to assess the overall diet quality among adults in Henan province of China.
Seasonal Variations in the Digestive Tract of the Little Owl, Athene noctua: Anatomical, Histological, and Scanning Electron Microscopical Studies
Authors: Shawki Nahed A. , Mahmoud Fatma A. , Mohamed Mayada Y.
Published: March 2022

The digestive tract of the little owl, Athene noctua (Strigiformes: Strigidae), is described in two different seasons. The digestive tract of this bird follows the basic model for that of a predatory bird. The cervical esophagus is not expanded to form a crop. The internal surface of the esophagus forms numerous longitudinal folds provided with numerous mucous glands. These longitudinal folds increase in number and vary in depth posteriorly. The folds of the proventriculus are composed of simple branched tubular glands. The ventriculus is lined by a thin layer of koilin. The number of goblet cells gradually increases from the duodenum to the rectum, and the lymphatic tissue diffuses within the lamina propria. The esophageal glands secrete acid mucopolysaccharides, while the gastric glands of the stomach, the goblet cells, and crypts of Lieberkühn secrete acid mucopolysaccharides. Proteins were observed in the different histological structures of the digestive tract. Morphometric and histometric studies showed differences between summer and winter in the esophagus and glandular stomach (especially in winter), but no seasonal differences were seen in the muscular stomach, or small and large intestines.
Effectiveness of four interventions in improving community health workers’ performance in western Kenya: a quasi-experimental difference-in-differences study using a longitudinal data
Authors: Kawakatsu Yoshito , Sugishita Tomohiko , Aiga Hirotsugu , Oruenjo Kennedy , Wakhule Steve , Honda Sumihisa
Published: March 2022

Background:

Community health workers (CHWs) are up-front health workers delivering the most effective life-saving health services to communities. They are the key driver to achieve Universal Health Coverage. However, maintaining CHWs’ performance is one of the challenges in sustaining their effectiveness. This article assessed the effectiveness of the four interventions and their combinations on the CHWs’ performance in terms of health knowledge, job satisfaction, and household coverage.

Methods:

We used the longitudinal survey data collected in western Kenya. Our study participants were the representative of all CHWs working in the four districts, Kenya. The four types of interventions were composed of a basic core intervention (i.e., refresher training with/without defaulter tracing) and three supplementary interventions (i.e., provision of a bicycle, frequent supportive supervision, and financial incentives). We performed the three fixed-effect models to assess the effectiveness of the four interventions and their combinations on the three performance indicators.

Results:

Three single and combination interventions significantly increased CHWs’ health knowledge: refresher training only [Coef.: 48.43, 95% CI: 42.09–54.76, P < 0.001]; refresher training plus defaulter-tracing [Coef.: 38.80, 95% CI: 32.71–44.90, P < 0.001]; combination of refresher training plus defaulter-tracing and frequent supervision [Coef.: 17.02, 95% CI: 7.90–26.15, P < 0.001]. Financial support was the only intervention that significantly increased job satisfaction among CHWs [Coef.: 4.97, 95% CI: 0.20–9.75, P = 0.041]. There was no single intervention that significantly increased household coverage. Yet, the combinations of the interventions significantly increased household coverage.

Conclusions:

There was no single intervention to improve all the aspects of CHWs’ performance. The refresher training significantly improved their health knowledge, while financial incentive enhanced the level of their job satisfaction. The combinations of regular refresher training and other intervention(s) are the recommended as the effective interventions in improving and further sustaining CHWs’ performance.
Business Structures, Stereotypes and Knowledge of Discrimination: Understanding Employers’ Support to Paid Family Leave in Hong Kong
Authors: Dai Haijing , Jung Nahri , Li Nanxun
Published: March 2022

Hong Kong society has put family-friendly workplace policies under serious discussion, but the investigation of the views of employers remains insufficient. Adopting the structure-agency paradigm, this study used survey data to examine how structural constraints in business and the subjective world of individual employers influence their support to paid family leave. We found that industry categories were significantly associated with employers’ support but not the size of their enterprises. Employers’ personal stereotypes of family caregivers and their awareness of relevant laws did not exert significant independent effects on their policy support, but the significant interaction of the two suggested that employers with knowledge of regulations were less likely to formulate attitudes towards paid family leave based on their own stereotypes. Policy practices therefore need to consider the rationality of employers in the local contexts of Hong Kong, and aim to integrate legal education with de-stigmatisation of family caregivers in advocacy programs.
Evaluation of resistance against anthracnose (Colletotrichum capsiciandC. gloeosporioides) in chilli landraces collected from the northeastern region of India
Authors: Dwivedi Neeraj , Tirkey Dipti S , Katoch Shabnam , Prasad Lakshman
Published: March 2022

Anthracnose or fruit rot disease caused byColletotrichumspp. leads to substantial economic losses in chilli (Capsicum annuumL.) production worldwide. In the present study, 24 different Bhut Jolokia chilli landraces and sevenCapsicum annuumcultivars have been collected from the northeastern region of India and subsequently screened underin vitroandin vivoconditions againstColletotrichum capsiciandC. gloeosporiodesinfections. During field evaluation, eight chilli genotypes (CC0164, CC0165, CC0191, CC0192, CC0202, CC0206, CC0209 and CC0218) were highly resistant and 12 genotypes (CC0154, CC0179, CC0181, CC0183, CC0186, CC0189, CC0193, CC0198, CC0205, CC0210, CC0213 and CC0217) were found in resistant category againstC. capsiciinfection. Duringin-vitrogermplasm evaluation, 11 and 12 landraces were found to be highly resistant toC. capsiciandC. gloeosporioidesinfections, respectively. According to the findings, the majority of Bhut Jolokia chilli landraces are resistant to anthracnose. Given the difficulties farmers experience as a result of excessive use of fungicides and pesticides, germplasm screening for host resistance has already begun. The resistant lines identified in the current study offers better choices to tackle anthracnose and could be used effectively in breeding programs to develop anthracnose resistant varieties.
Weak constitutionalism and the legal dimension of the constitution
Authors: Melero Mariano C
Published: March 2022

This article offers a critical discussion of two influential positions in contemporary legal and political theory, which will be referred to as ‘political constitutionalism’ and ‘strong popular sovereignty’. Despite their important differences, both share a sceptical approach to the dominant constitutional practice in liberal democracies, hence they are brought together here under the term ‘weak constitutionalism’. They both highlight the political dimension of the constitution, arguing that democratic legitimacy requires institutional arrangements that give the people and/or their representatives the last word in settling fundamental issues of political morality. By contrast, this article underlines the legal dimension of the constitution as the repository of the moral principles that make possible a practice of public justification in constitutional states. It is from this second constitutional dimension that the critical arguments are developed, both against the desire to take the constitution away from the courts and the aspiration to recognize the constituent power as pre-legal constitution-making faculty.
Positive-Negative Asymmetry in Self-Related Processing
Authors: Wang Nan , Li Jiwen , Zeng Mei , Yang Juan
Published: March 2022

Abstract. People have different tendencies when responding to positive and negative self-related stimuli, which can be referred to as positive-negative asymmetry. People are generally biased toward self-positivity on the one hand and display a self-focus on negative information on the other. Studies found that the positive-negative asymmetry exists in the cognitive processing of the self, but research on emotional self-related processing has been scant. In the current study, 635 participants rated the extent to which an adjective describes themselves and how much pride or shame they feel during such an evaluation. For positive items, results showed an increasing tendency in participants’ self-descriptive ratings, from 1 (= very low) to 7 (=  very high), which can positively predict pride but negatively predict shame. Meanwhile, for negative items, participants’ ratings, which show a decreasing trend, can positively predict pride and shame. Overall, the current study suggests a valence asymmetry in both cognitive and emotional self-related processing.
An Assimilating Model Using Broad Learning System for Incorporating Multi‐Source Precipitation Data With Environmental Factors Over Southeast China
Authors: Zhou Yuanyuan , Li Xu , Tang Qiuhong , Kuok Sin Chi , Fei Kai , Gao Liang
Published: March 2022

Remote sensing technique is beneficial for rainfall data retrievals, however, enhancing the accuracy remains a challenge. In this study, a novel framework based on a broad learning system (BLS) was proposed to assimilate multi‐source data. The dataset includes six satellite‐based rainfall products (3B42V7, 3B42RT, IMERG, CBLD, GSMaP, and PCDR), gauge‐based rainfall, and environmental data (temperature, specific humidity, wind speed, and locations) from 1 March 2014 to 31 December 2017 over southeast China (SEC). Leave‐one‐year‐out cross‐validation (LOYOCV) and independent validation were used to evaluate the BLS assimilating model. The proposed BLS model outperformed six original satellite‐based products on Pearson's correlation coefficient (CC), root‐mean‐square error (RMSE), and Nash‐Sutcliffe coefficient of efficiency (NSE) in each test year of LOYOCV. BLS model considering the environmental factors performed better on CC, RMSE, and NSE compared to that without environmental factors. Seasonal variations of daily gauge‐based precipitation were accurately captured by BLS‐based estimates. BLS method outperformed satellites on CC, RMSE, and NSE at most validation sites at low altitudes (0–1000 m). According to the independent validation, more accurate daily precipitation estimates could be obtained at more than half of the validation sites using the proposed model compared to the source datasets. The BLS‐based framework considering environmental factors has the potential to improve estimates over SEC and is expected to be applied to other regions.
Pre‐ and Co‐Eruptive Analysis of the September 2021 Eruption at Cumbre Vieja Volcano (La Palma, Canary Islands) Through DInSAR Measurements and Analytical Modeling
Authors: De Luca C. , Valerio E. , Giudicepietro F. , Macedonio G. , Casu F. , Lanari R.
Published: March 2022

We investigate the 19 September 2021 eruption of the Cumbre Vieja volcano (La Palma, Canary Islands, Spain). In particular, we analyze the Differential Interferometric Synthetic Aperture Radar (DInSAR) measurements obtained by processing Sentinel‐1 images acquired from both ascending and descending orbits. First, we show the importance, for oceanic islands like La Palma, of investigating DInSAR products retrieved from time series, instead of single interferograms, to effectively remove possible atmospheric artifacts within the displacement measurements. Subsequently, we invert the retrieved data through analytical modeling. Our results highlight that a sill–like source was active in the pre–eruptive phase (8–16 September), whereas the action of two dikes prevailed during the co‐eruptive phase (17–22 September). This evolution suggests a process of magma rising through a network of interconnected sills and dikes. The seismicity, that preceded and accompanied the onset of the eruption, is consistent with our findings.
Juxtamembrane 2 mimic peptide competitively inhibits mitochondrial trafficking and activates ROS-mediated apoptosis pathway to exert anti-tumor effects
Authors: He Dan , Ma Zhijie , Xue Ke , Li Haiyan
Published: March 2022

Our previous study demonstrates that a juxtamembrane 2 (JM2) mimic peptide can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism remains unclear. In this study, JM2 is found to suppress the growth of 4T1 breast tumors by inducing apoptosis and inhibiting the proliferation of 4T1 tumor cells. Further study indicates that JM2 can stimulate the mitochondria to gather near the microtubule-organizing center of tumor cells and subsequently induce ROS-induced ROS release responses, which results in mitochondrial dysfunction and mitochondria-mediated apoptosis. In addition, JM2 can arrest cell cycle in S phase by regulating the expression of cell cycle-related proteins and consequently inhibit proliferation of tumor cells. Then, a previously designed JM2 grafted hyaluronic acid (HA) injectable hydrogel system (HA-JM2) is injected in a breast tumor-resected model and the HA-JM2 hydrogel can inhibit the malignant proliferation of residual tumor cells and suppress the breast tumor recurrence. These findings not only confirm the application potentials of JM2 in anti-tumor therapy and tumor post-surgery treatments but also provide greater understanding on the mechanisms by which JM2 inhibits tumor growth.
STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS)
Authors: Messaoud-Nacer Yasmine , Culerier Elodie , Rose Stéphanie , Maillet Isabelle , Rouxel Nathalie , Briault Sylvain , Ryffel Bernhard , Quesniaux Valerie F. J. , Togbe Dieudonnée
Published: March 2022

Stimulator of interferon genes (STING) contributes to immune responses against tumors and may control viral infection including SARS-CoV-2 infection. However, activation of the STING pathway by airway silica or smoke exposure leads to cell death, self-dsDNA release, and STING/type I IFN dependent acute lung inflammation/ARDS. The inflammatory response induced by a synthetic non-nucleotide-based diABZI STING agonist, in comparison to the natural cyclic dinucleotide cGAMP, is unknown. A low dose of diABZI (1 µg by endotracheal route for 3 consecutive days) triggered an acute neutrophilic inflammation, disruption of the respiratory barrier, DNA release with NET formation, PANoptosis cell death, and inflammatory cytokines with type I IFN dependent acute lung inflammation. Downstream upregulation of DNA sensors including cGAS, DDX41, IFI204, as well as NLRP3 and AIM2 inflammasomes, suggested a secondary inflammatory response to dsDNA as a danger signal. DNase I treatment, inhibition of NET formation together with an investigation in gene-deficient mice highlighted extracellular DNA and TLR9, but not cGAS, as central to diABZI-induced neutrophilic response. Therefore, activation of acute cell death with DNA release may lead to ARDS which may be modeled by diABZI. These results show that airway targeting by STING activator as a therapeutic strategy for infection may enhance lung inflammation with severe ARDS.
Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics
Authors: Hadland Brandon , Varnum-Finney Barbara , Dozono Stacey , Dignum Tessa , Nourigat-McKay Cynthia , Heck Adam M. , Ishida Takashi , Jackson Dana L. , Itkin Tomer , Butler Jason M. , Rafii Shahin , Trapnell Cole , Bernstein Irwin D.
Published: March 2022

Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.
MERS-CoV ORF4b employs an unusual binding mechanism to target IMPα and block innate immunity
Authors: Munasinghe Thilini S. , Edwards Megan R. , Tsimbalyuk Sofiya , Vogel Olivia A. , Smith Kate M. , Stewart Murray , Foster Justin K. , Bosence Loretta A. , Aragão David , Roby Justin A. , Basler Christopher F. , Forwood Jade K.
Published: March 2022

The MERS coronavirus (MERS-CoV) is a highly pathogenic, emerging virus that produces accessory proteins to antagonize the host innate immune response. The MERS-CoV ORF4b protein has been shown to bind preferentially to the nuclear import adapter IMPα3 in infected cells, thereby inhibiting NF-κB-dependent innate immune responses. Here, we report high-resolution structures of ORF4b bound to two distinct IMPα family members. Each exhibit highly similar binding mechanisms that, in both cases, lack a prototypical Lys bound at their P2 site. Mutations within the NLS region dramatically alter the mechanism of binding, which reverts to the canonical P2 Lys binding mechanism. Mutational studies confirm that the novel binding mechanism is important for its nuclear import, IMPα interaction, and inhibition of innate immune signaling pathways. In parallel, we determined structures of the nuclear binding domain of NF-κB component p50 bound to both IMPα2 and α3, demonstrating that p50 overlaps with the ORF4b binding sites, suggesting a basis for inhibition. Our results provide a detailed structural basis that explains how a virus can target the IMPα nuclear import adapter to impair immunity, and illustrate how small mutations in ORF4b, like those found in closely related coronaviruses such as HKU5, change the IMPα binding mechanism.
The landscape of receptor-mediated precision cancer combination therapy via a single-cell perspective
Authors: Ahmadi Saba , Sukprasert Pattara , Vegesna Rahulsimham , Sinha Sanju , Schischlik Fiorella , Artzi Natalie , Khuller Samir , Schäffer Alejandro A. , Ruppin Eytan
Published: March 2022

Mining a large cohort of single-cell transcriptomics data, here we employ combinatorial optimization techniques to chart the landscape of optimal combination therapies in cancer. We assume that each individual therapy can target any one of 1269 genes encoding cell surface receptors, which may be targets of CAR-T, conjugated antibodies or coated nanoparticle therapies. We find that in most cancer types, personalized combinations composed of at most four targets are then sufficient for killing at least 80% of tumor cells while sparing at least 90% of nontumor cells in the tumor microenvironment. However, as more stringent and selective killing is required, the number of targets needed rises rapidly. Emerging individual targets include PTPRZ1 for brain and head and neck cancers and EGFR in multiple tumor types. In sum, this study provides a computational estimate of the identity and number of targets needed in combination to target cancers selectively and precisely.
Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine
Authors: Arévalo-Herrera Myriam , Gaitán Xiomara , Larmat-Delgado Michelle , Caicedo María Alejandra , Herrera Sonia M. , Henao-Giraldo Juliana , Castellanos Angélica , Devaud Jean-Christophe , Pannatier André , Oñate José , Corradin Giampietro , Herrera Sócrates
Published: March 2022

A randomized, double-blind, controlled vaccine clinical trial was conducted to assess, as the primary outcome, the safety and protective efficacy of thePlasmodium vivaxcircumsporozoite (CS) protein in healthy malaria-naïve (phase IIa) and semi-immune (phase IIb) volunteers. Participants (n = 35) were randomly selected from a larger group (n = 121) and further divided into naïve (n = 17) and semi-immune (n = 18) groups and were immunized at months 0, 2, and 6 withPvCS formulated in Montanide ISA-51 adjuvant or placebo (adjuvant alone). Specific antibodies and IFN-γ responses toPvCS were determined as secondary outcome; all experimental volunteers developed specific IgG and IFN-γ. Three months after the last immunization, all participants were subjected to controlled human malaria infection. All naive controls became infected and drastic parasitemia reduction, including sterile protection, developed in several experimental volunteers in phase IIa (6/11) (54%, 95% CI 0.25–0.84) and phase IIb (7/11) (64%, 95% CI 0.35–0.92). However, no difference in parasitemia was observed between the phase IIb experimental and control subgroups. In conclusion, this study demonstrates significant protection in both naïve and semi-immune volunteers, encouraging furtherPvCS vaccine clinical development. Trial registration number NCT 02083068. This trial was funded by Colciencias (grant 529-2009), NHLBI (grant RHL086488 A), and MVDC/CIV Foundation (grant 2014-1206).
The architecture of assisted colonisation in sea turtles: building new populations in a biodiversity crisis
Authors: Barbanti Anna , Blumenthal Janice M. , Broderick Annette C. , Godley Brendan J. , Prat-Varela Alejandro , Turmo Maria , Pascual Marta , Carreras Carlos
Published: March 2022

Due to changing environmental conditions, many species will have to migrate or occupy new suitable areas to avoid potential extinction in the current biodiversity crisis. Long-lived animals are especially vulnerable and ex-situ conservation actions can provide solutions through assisted colonisations. However, there is little empirical evidence on the process of founding new populations for such species or the feasibility of assisted colonisations as a viable conservation measure. Here, we combined genetics with reproductive data to study the rise of two wild populations of green turtles (Chelonia mydas) in the Cayman Islands as a possible outcome of a reintroduction program started 50 years ago. We show that both populations are highly related to the captive population but rapidly diverged due to genetic drift. Individuals from the reintroduced populations showed high levels of nest fidelity, within and across nesting seasons, indicating that philopatry may help reinforce the success of new populations. Additionally, we show that reintroduction from captive populations has not undermined the reproductive fitness of first generation individuals. Sea turtle reintroduction programs can, therefore, establish new populations but require scientific evaluation of costs and benefits and should be monitored over time to ensure viability in the long-term.
Topoarchitected polymer networks expand the space of material properties
Authors: Liu Xiao , Wu Jingping , Qiao Keke , Liu Guohan , Wang Zhengjin , Lu Tongqing , Suo Zhigang , Hu Jian
Published: March 2022

Many living tissues achieve functions through architected constituents with strong adhesion. An Achilles tendon, for example, transmits force, elastically and repeatedly, from a muscle to a bone through staggered alignment of stiff collagen fibrils in a soft proteoglycan matrix. The collagen fibrils align orderly and adhere to the proteoglycan strongly. However, synthesizing architected materials with strong adhesion has been challenging. Here we fabricate architected polymer networks by sequential polymerization and photolithography, and attain adherent interface by topological entanglement. We fabricate tendon-inspired hydrogels by embedding hard blocks in topological entanglement with a soft matrix. The staggered architecture and strong adhesion enable high elastic limit strain and high toughness simultaneously. This combination of attributes is commonly desired in applications, but rarely achieved in synthetic materials. We further demonstrate architected polymer networks of various geometric patterns and material combinations to show the potential for expanding the space of material properties.
Earlier emergence of a temperature response to mitigation by filtering annual variability
Authors: Samset B. H. , Zhou C. , Fuglestvedt J. S. , Lund M. T. , Marotzke J. , Zelinka M. D.
Published: March 2022

The rate of global surface warming is crucial for tracking progress towards global climate targets, but is strongly influenced by interannual-to-decadal variability, which precludes rapid detection of the temperature response to emission mitigation. Here we use a physics based Green’s function approach to filter out modulations to global mean surface temperature from sea-surface temperature (SST) patterns, and show that it results in an earlier emergence of a response to strong emissions mitigation. For observed temperatures, we find a filtered 2011–2020 surface warming rate of 0.24 °C per decade, consistent with long-term trends. Unfiltered observations show 0.35 °C per decade, partly due to the El Nino of 2015–2016. Pattern filtered warming rates can become a strong tool for the climate community to inform policy makers and stakeholder communities about the ongoing and expected climate responses to emission reductions, provided an effort is made to improve and validate standardized Green’s functions.
Superheating of grain boundaries within bulk colloidal crystals
Authors: Xiao Xiuming , Wang Lilin , Wang Zhijun , Wang Ziren
Published: March 2022

Whether grain boundaries (GBs) premelt is a longstanding question, because of the difficulty of direct experimental tests. Here, we focused an optical beam to locally heat single GBs within bulk hard-sphere colloidal crystals, observing the melting dynamics at single-particle resolution by video microscopy. The melting point is determined by analysing both the Lindemann parameter and the critical nucleus size for homogeneous nucleation. We found that all the GBs, including the high-energy GBs, can be superheated and melt via a heterogeneous nucleation mechanism. Based on the classical nucleation theory of GBs, we measured the incubation time and contact angle of the critical nucleus to compute all relevant kinetic factors, as well as the energy barrier, nucleation rate and the diffusion coefficient at the solid–liquid interface under weak superheating. The superheat limits of GBs with various misorientations have also been measured to further explore the instability mechanism. Under traditional uniform heating, premelting occurs only at triple junctions, whereas GBs retain their original structures up to the melting point. The premelted regions at triple junctions further interrupt high-energy GBs from superheating, through intrusion by uniform liquid layers. Overall, our experiments confirm the existence of superheating of GBs.
Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes
Authors: Frallicciardi Jacopo , Melcr Josef , Siginou Pareskevi , Marrink Siewert J. , Poolman Bert
Published: March 2022

Cell membranes provide a selective semi-permeable barrier to the passive transport of molecules. This property differs greatly between organisms. While the cytoplasmic membrane of bacterial cells is highly permeable for weak acids and glycerol, yeasts can maintain large concentration gradients. Here we show that such differences can arise from the physical state of the plasma membrane. By combining stopped-flow kinetic measurements with molecular dynamics simulations, we performed a systematic analysis of the permeability of a variety of small molecules through synthetic membranes of different lipid composition to obtain detailed molecular insight into the permeation mechanisms. While membrane thickness is an important parameter for the permeability through fluid membranes, the largest differences occur when the membranes transit from the liquid-disordered to liquid-ordered and/or to gel state, which is in agreement with previous work on passive diffusion of water. By comparing our results with in vivo measurements from yeast, we conclude that the yeast membrane exists in a highly ordered and rigid state, which is comparable to synthetic saturated DPPC-sterol membranes.
Crystal Structures of Wolbachia CidA and CidB Reveal Determinants of Bacteria-induced Cytoplasmic Incompatibility and Rescue
Authors: Wang Haofeng , Xiao Yunjie , Chen Xia , Zhang Mengwen , Sun Guangxin , Wang Feng , Wang Lin , Zhang Hanxiao , Zhang Xiaoyu , Yang Xin , Li Wenling , Wei Yi , Yao Deqiang , Zhang Bing , Li Jun , Cui Wen , Wang Fenghua , Chen Cheng , Shen Wei , Su Dan , Bai Fang , Huang Jinhai , Ye Sheng , Zhang Lei , Ji Xiaoyun , Wang Wei , Wang Zefang , Hochstrasser Mark , Yang Haitao
Published: March 2022

Cytoplasmic incompatibility (CI) results when Wolbachia bacteria-infected male insects mate with uninfected females, leading to embryonic lethality. “Rescue” of viability occurs if the female harbors the same Wolbachia strain. CI is caused by linked pairs of Wolbachia genes called CI factors (CifA and CifB). The co-evolution of CifA-CifB pairs may account in part for the incompatibility patterns documented in insects infected with different Wolbachia strains, but the molecular mechanisms remain elusive. Here, we use X-ray crystallography and AlphaFold to analyze the CI factors from Wolbachia strain wMel called CidAwMel and CidBwMel. Substituting CidAwMel interface residues with those from CidAwPip (from strain wPip) enables the mutant protein to bind CidBwPip and rescue CidBwPip-induced yeast growth defects, supporting the importance of CifA-CifB interaction in CI rescue. Sequence divergence in CidAwPip and CidBwPip proteins affects their pairwise interactions, which may help explain the complex incompatibility patterns of mosquitoes infected with different wPip strains.
Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells
Authors: Kawashima Naomi , Ishikawa Yuichi , Kim Jeong Hui , Ushijima Yoko , Akashi Akimi , Yamaguchi Yohei , Hattori Hikaru , Nakashima Marie , Ikeno Seara , Kihara Rika , Nishiyama Takahiro , Morishita Takanobu , Watamoto Koichi , Ozawa Yukiyasu , Kitamura Kunio , Kiyoi Hitoshi
Published: March 2022

Patient-derived xenografts (PDX) are widely used as human cancer models. Previous studies demonstrated clonal discordance between PDX and primary cells. However, in acute myeloid leukemia (AML)-PDX models, the significance of the clonal dynamics occurring in PDX remains unclear. By evaluating changes in the variant allele frequencies (VAF) of somatic mutations in serial samples of paired primary AML and their PDX bone marrow cells, we identify the skewing engraftment of relapsed or refractory (R/R) AML clones in 57% of PDX models generated from multiclonal AML cells at diagnosis, even if R/R clones are minor at <5% of VAF in patients. The event-free survival rate of patients whose AML cells successfully engraft in PDX models is consistently lower than that of patients with engraftment failure. We herein demonstrate that primary AML cells including potentially chemotherapy-resistant clones dominantly engraft in AML-PDX models and they enrich pre-existing treatment-resistant subclones.
Bound nucleotide can control the dynamic architecture of monomeric actin
Authors: Ali Rustam , Zahm Jacob A. , Rosen Michael K.
Published: March 2022

Polymerization of actin into cytoskeletal filaments is coupled to its bound adenine nucleotides. The mechanism by which nucleotide modulates actin functions has not been evident from analyses of ATP- and ADP-bound crystal structures of the actin monomer. We report that NMR chemical shift differences between the two forms are globally distributed. Furthermore, microsecond–millisecond motions are spread throughout the molecule in the ATP form, but largely confined to subdomains 1 and 2, and the nucleotide binding site in the ADP form. Through these motions, the ATP- and ADP-bound forms sample different high-energy conformations. A deafness-causing, fast-nucleating actin mutant populates the high-energy conformer of ATP-actin more than the wild-type protein, suggesting that this conformer may be on the pathway to nucleation. Together, the data suggest a model in which differential sampling of a nucleation-compatible form of the actin monomer may contribute to control of actin filament dynamics by nucleotide.
PARP inhibition impedes the maturation of nascent DNA strands during DNA replication
Authors: Vaitsiankova Alina , Burdova Kamila , Sobol Margarita , Gautam Amit , Benada Oldrich , Hanzlikova Hana , Caldecott Keith W.
Published: March 2022

Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in the detection and processing of unligated Okazaki fragments and other DNA replication intermediates, highlighting such structures as potential sources of genome breakage induced by PARP inhibition. Here, we show that PARP1 activity is greatly elevated in chicken and human S phase cells in which FEN1 nuclease is genetically deleted and is highest behind DNA replication forks. PARP inhibitor reduces the integrity of nascent DNA strands in both wild-type chicken and human cells during DNA replication, and does so in FEN1−/− cells to an even greater extent that can be detected as postreplicative single-strand nicks or gaps. Collectively, these data show that PARP inhibitors impede the maturation of nascent DNA strands during DNA replication, and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these compounds.
Single-cell RNA sequencing of adult rat testes after Leydig cell elimination and restoration
Authors: Guan Xiaoju , Ji Minpeng , Wen Xin , Huang Fu , Zhao Xingyi , Chen Dan , Shao Jingjing , Wang Jiexia , Xie Jiajia , Tian Jing , Lin Han , Duan Ping , Zirkin Barry R. , Su Zhijian , Chen Haolin
Published: March 2022

Spermatogenesis is an efficient, complex, and highly organized proliferation and differentiation process that relies on multiple factors including testosterone produced by the Leydig cells. Although the critical role played by testosterone in spermatogenesis is well recognized, the mechanism by which it works is still not completely understood, partially due to the inability to specifically and precisely monitor testosterone-dependent changes within developing germ cells. Here we present single-cell RNA sequencing data from10,983 adult rat testicular cells after the rats were treated with ethanedimethanesulfonate, which temporarily eliminates Leydig cells. The elimination and recovery of Leydig cells represented a complete testosterone depletion and restoration cycle. The dataset, which includes all developing germ cells from spermatogonia to spermatozoa, should prove useful for characterizing developing germ cells, their regulatory networks, and novel cell-specific markers. The dataset should be particularly useful for exploring the effects of the androgen environment on the regulation of spermatogenesis. As this is the first single-cell RNA-Seq dataset for rat testes, it can also serve as a reference for future studies.
The contribution of daytime sleepiness to impaired quality of life in NAFLD in an ethnically diverse population
Authors: Li Wenhao , Kadler Benjamin Karl , Brindley James Hallimond , Hood Gillian , Devalia Kalpana , Loy John , Syn Wing-kin , Alazawi William
Published: March 2022

Health-related quality of life (HRQoL) is lower in people with NAFLD compared to the general population. Sleep disturbance resulting in daytime sleepiness is common in patients with NAFLD, but the effect of daytime sleepiness on HRQoL in NAFLD is unclear. The prevalence and natural history of NAFLD vary in different ethnic groups, but there has been limited ethnic diversity in HrQoL studies to date. We aimed to assess whether daytime sleepiness is independently associated with reduced HRQoL in an ethnically diverse UK population. We conducted HRQoL assessments using SF-36 version 2 and Epworth Sleepiness Scale (ESS) questionnaires in 192 people with NAFLD. Multivariate linear regression was used to identify factors independently affecting HRQoL scales. People with NAFLD reported significantly reduced physical health-related SF-36 scores compared to the general UK population. South Asian NAFLD patients reported impairment in physical health, but not mental health, approximately a decade before White NAFLD patients. In multivariate linear regression, daytime sleepiness (ESS score > 10), was the most significant independent predictor of reduced physical health. Age, BMI and liver stiffness score were also significantly associated. HRQoL is impaired earlier in patients of South Asian ethnicity. ESS score > 10, indicative of excessive daytime sleepiness, is an independent predictor of reduced HRQoL in people with NAFLD regardless of ethnicity. Daytime sleepiness should be considered as a contributing factor to reduced HRQoL in clinical practice and when evaluating patient-related outcomes in clinical trials.
Sexual dimorphic impacts of systemic vincristine on lower urinary tract function
Authors: Iguchi Nao , Hecht Sarah L. , Gao Dexiang , Wilcox Duncan T. , Malykhina Anna P. , Cost Nicholas G.
Published: March 2022

Vincristine (VCR) is one of the most common chemotherapy agents used in pediatric oncology. Despite the well-known VCR-induced peripheral neuropathy, potential impacts of VCR on lower urinary tract (LUT) function remain poorly defined. We investigated the effects of systemic VCR exposure in childhood on LUT function by using juvenile mice treated with VCR (4 mg/kg) or saline and evaluated at 5 weeks later. VCR induced a decreased urinary frequency with increased functional bladder capacity and non-void contractions. There were no changes in detrusor contractility between the groups. VCR exposure caused sexual dimorphic changes; in females, increased intravesical pressure at micturition and downregulations of a major player in bladder afferent firing, Htr3b, in the bladders, and Cav1.2 in the lumbosacral dorsal root ganglia (Ls-DRG), while male mice displayed increases in bladder compliance and detrusor activity, upregulations of IL-2, Trpa1 and Itga1 in the bladders and neuroinflammation-related genes, P2×4, P2×7, IL-2 and CD68 in the Ls-DRG. These results suggest that that systemic VCR exposure caused sensory neuropathy via sex-dimorphic mechanisms, leading to altered LUT function. These changes might clinically present as gender-specific signs or symptoms of LUT dysfunction, and follow-up urological assessment may be of benefit for pediatric cancer patients treated with VCR.
No indications for altered EEG oscillatory activity in patients with chronic post-burn itch compared to healthy controls
Authors: Millard Samantha K. , Bokelmann Klara , Schalbroeck Rik , van der Wee Nic J. A. , van Loey Nancy E. E. , van Laarhoven Antoinette I. M.
Published: March 2022

A large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot study investigates whether altered cortical oscillatory processes are involved in chronic post-burn itch. Continuous electroencephalography (EEG) data were recorded during rest and stimulation of non-injured skin, inducing itch (histamine and electrical) and cold-pressor task pain for 15 adults with chronic post-burn itch and 15 matched healthy controls. Quantitative metrics comprised oscillatory power and peak frequencies in theta, alpha, and beta bands. No statistical differences between patients and healthy controls were found in oscillatory activity during rest or stimulation, with Bayesian analysis suggesting equivocal evidence. However, post-traumatic stress symptoms and duration of chronic itch may be associated with changes in oscillatory activity. A lack of differences in cortical oscillatory processing and itch levels at non-injured sites, suggests that itch symptoms have a localised character in this sample of patients with post-burn itch. For future studies, a biopsychological approach with integration of peripheral and central nervous system techniques, linear and non-linear EEG analysis, injured and non-injured stimulation sites, and incorporation of individual characteristics is recommended. Insight into pathophysiological mechanisms underlying chronic post-burn itch could improve diagnostics and treatments.