bluuebunny/crossref_metadata_2025 huggingface dataset:
In a World of Warners, Be Like Elle: The Benefits of a Prosocial Community Focus to Being a Lawyer (as Explored through Legally Blonde)
Authors: Phillipa Paige Tamsin , Butchart Catherine , Merrifield Liam
Published: June 2023

The toxicity and abuses of power that occur within the legal profession are well-known, and a long-standing problem. In this paper we explore how kindness and community building in the study and practice of law can lead to better outcomes for all concerned. We do this through an examination of literature addressing the legal profession and law school, and behavioural research on the impacts of prosocial behaviour, which leads us to conclude that Elle Woods in the role model that any lawyer or law student who is interested in kindness should look to for inspiration. While this approach may not solve the wholesale cultural issues faced in law school in the legal profession, we suggest it might create pockets of alternate reality for those who love the law but hate the culture of the legal profession.
Mixtec Pictography and Immigrant Labor Resistance in the Comic Undocumented: A Worker’s Fight
Authors: Maldonado Jennifer Caroccio
Published: June 2023

The comic Undocumented: A Worker’s Fight (2018) by Duncan Tonatiuh (pronounced toh-nah-tee-YOU) depicts the fictional narrative of Juan, a Mixtec immigrant from Mexico. My article examines the use of Mixteco in the comic to make apparent how Indigenous Latinx workers in the United States are often left out of the larger narrative of immigration policy and reform. I argue that comics studies scholarship should include more Mesoamerican and Latin American art, history, and writing so that there is no question of image-texts in contemporary western comics as having their own distinct writing system. A Worker’s Fight’s Mixtec style art and lack of borders forces readers to consider an anti-colonial reading practice. Tonatiuh accomplishes this feat by shifting events in the narrative from a linear sequentiality (cause and effect) to make apparent the simultaneous issues of labor and immigration. The temporality and materiality of the comic in Tonatiuh’s rejection of drawn borders is thus also a rejection of the legitimacy of national borders. A Worker’s Fight is a spectacular comic as well as a valuable teaching tool. The feeling of intimacy in Juan’s personal story is significant. The graphic narrative places comics and sequential art in a longer writing tradition that has always included images.
ВЕРА В НАРОДНОЙ ЖИЗНИ XIX–XXI веков: НА ПРИМЕРЕ ТЕМРЮКСКОГО РАЙОНА КРАСНОДАРСКОГО КРАЯ
Authors: Гетманская София Николаевна
Published: June 2023

В статье на основе полевых материалов Кубанских фольклорно-этнографических экспедиций 2004 г. рассматриваются различные аспекты проявления веры у православных жителей Темрюкского р-на Краснодарского края. Современное православное население этого района – потомки запорожских казаков, переселившихся сюда в конце XVIII в. Они основали станицы Тамань, Старотитаровскую, Ахтанизовскую, Вышестеблиевскую. Впоследствии сюда переселялись также малороссийские казаки из Харьковской, Черниговской и Полтавской губерний. На данный момент для старожилов этих населенных пунктов и жителей станиц, основанных впоследствии, характерно соблюдение не только старинных религиозных традиций, но и сравнительно новых, привнесенных более поздними переселенцами.
In the article based on the field materials of the Kuban folklore and ethnographic expeditions of 2004. Various aspects of the manifestation of faith among the Orthodox residents of the Temryuk district of the Krasnodar Region are considered. The basis of the modern Orthodox tradition of this area is the religious tradition of the Zaporizhzhian Cossacks, who moved here at the end of the 18th century. They founded the villages of Taman, Starotitarovskaya, Akhtanizovskaya, Vyshesteblievskaya. Subsequently, the population of the region was replenished with immigrants from the Little Russian Cossacks of Kharkov, Chernigov and Poltava provinces. At the moment, the old-timers of these and other villages, of a later foundation, retain some of the old religious traditions, and new ones are introduced.
ИМЯСЛАВИЕ НА ЮГЕ РОССИИ: БИОГРАФИИ ЛИДЕРОВ ДВИЖЕНИЯ, СУДЬБА ОБЩИН В ДОВОЕННЫЙ ПЕРИОД
Authors: Радионов Александр Петрович
Published: June 2023

Статья раскрывает базовую терминологию поставленной темы, характеризует основные вехи возникновения и развития споров вокруг почитания имени Божия, описывает локализацию мест скопления монашествующих и мирян из среды имяславцев в первой трети XX в. Показаны основные факты биографий лидеров имяславия. Сделан вывод об их вкладе в организацию имяславского движения на юге России. Показана судьба общин имяславцев в период антирелигиозных гонений, проанализированы доводы следствия в отношении обвиняемых.

The article reveals the basic terminology of the topic, characterizes the main milestones in the emergence and development of disputes around the veneration of the name of God, describes the localization of gathering places of monastics and laity from among the imyaslavists in the first third of the 20th century. The main facts of the biographies of the leaders of imyaslavie are shown. The conclusion is made about their contribution to the organization of the imyaslav movement in the south of Russia. The fate of the imyaslavists communities during the period of anti-religious persecution is shown, the arguments of the investigation against the accused are analyzed.
Multipatch stochastic epidemic model for the dynamics of a tick-borne disease
Authors: Maliyoni Milliward , Gaff Holly D. , Govinder Keshlan S. , Chirove Faraimunashe
Published: June 2023

Spatial heterogeneity and migration of hosts and ticks have an impact on the spread, extinction and persistence of tick-borne diseases. In this paper, we investigate the impact of between-patch migration of white-tailed deer and lone star ticks on the dynamics of a tick-borne disease with regard to disease extinction and persistence using a system of Itô stochastic differential equations model. It is shown that the disease-free equilibrium exists and is unique. The general formula for computing the basic reproduction number for all patches is derived. We show that for patches in isolation, the basic reproduction number is equal to the largest patch reproduction number and for connected patches it lies between the minimum and maximum of the patch reproduction numbers. Numerical simulations for a two-patch deterministic and stochastic differential equation models are performed to illustrate the dynamics of the disease for varying migration rates. Our results show that the probability of eliminating or minimizing the disease in both patches is high when there is no migration unlike when it is present. The results imply that the probability of disease extinction can be increased if deer and tick movement are controlled or even prohibited especially when there is an outbreak in one or both patches since movement can introduce a disease in an area that was initially disease-free. Thus, screening of infectives in protected areas such as deer farms, private game parks or reserves, etc. before they migrate to other areas can be one of the intervention strategies for controlling and preventing disease spread.
Structure-preserving model reduction for port-Hamiltonian systems based on separable nonlinear approximation ansatzes
Authors: Schulze Philipp
Published: June 2023

We discuss structure-preserving model order reduction for port-Hamiltonian systems based on a nonlinear approximation ansatz which is linear with respect to a part of the state variables of the reduced-order model. In recent years, such nonlinear approximation ansatzes have gained more and more attention especially due to their effectiveness in the context of model reduction for transport-dominated systems which are challenging for classical linear model reduction techniques. We demonstrate that port-Hamiltonian reduced-order models can often be obtained by a residual minimization approach where a suitable weighted norm is used for the residual. Moreover, we discuss sufficient conditions for the resulting reduced-order models to be stable. Finally, the methodology is illustrated by means of two transport-dominated numerical test cases, where the ansatz functions are determined based on snapshot data of the full-order state.
Mesenchymal stem cells can improve discogenic pain in patients with intervertebral disc degeneration: a systematic review and meta-analysis
Authors: Zhang Wupeng , Wang Daofeng , Li Hua , Xu Gaoxiang , Zhang Hao , Xu Cheng , Li Jiantao
Published: June 2023

Background: The meta-analysis aimed to estimate the efficacy of mesenchymal stem cells on lumbar discogenic pain in patients with intervertebral disc degeneration.

Methods: A comprehensive literature search was conducted in the PubMed, Web of Science, Embase and Cochrane Library databases with predetermined search strategy up to 18 September 2022. The clinical studies focusing on evaluating the efficacy and safety of mesenchymal stem cells in patients with intervertebral disc degeneration were identified. The primary outcomes were changes of pain score and Oswestry Disability Index. The Newcastle-Ottawa Scale for cohort studies was used for quality assessment. Review Manager was used to conduct the statistical analysis. Pooled risk ratios were calculated based on the random effect model. Heterogeneity, subgroup, and publication bias analyses were also performed.

Results: There were 2,392 studies were identified in the initial search, and 9 eligible studies with 245 patients were eventually included in this review. The Visual Analogue Scale score was significantly lower in patients after receiving mesenchymal stem cells therapy (mean difference = 41.62; 95% confidence interval 24.32 to 58.93; Heterogeneity: I2 = 98%; p < 0.01). And the pooled mean difference of Oswestry Disability Index was 22.04 from baseline to final follow-up points (95% confidence interval 8.75 to 35.33; p = 0.001; Heterogeneity: I2 = 98%; p < 0.001). The pooled reoperation proportion was 0.074 (95% confidence interval 0.009 to 0.175; Heterogeneity: I2 = 72%; p < 0.01). There were no serious related adverse events associated with the therapy.

Conclusion: The findings of this meta-analysis indicated that mesenchymal stem cells therapy may be effective in relieving pain and improving Oswestry Disability Index significantly in patients with lumbar discogenic pain. Mesenchymal stem cells therapy may also be associated with a lower risk of adverse events and reoperation rates.
One-half century (or more) of study of cell death: origins, present, and perhaps future
Authors: Lockshin Richard A.
Published: June 2023

The concept of biological cell death—that is, cell death that is neither accidental nor chaotic—has existed and has been obvious since at least the beginning of the 20th C, but it was noticed by other than specialists apt choices of words that caught the spirit of the time, “programmed cell death” and “apoptosis” caught the attention of a wider range of scientists. Then, by the early 1990s the recognition of at least two genes that were important to cancer and other diseases by controlling cell death (p53, Bcl-2, and Fas); recognition that cell death could be controlled by a highly conserved family of proteases; and the development of rapid and easy means of measuring cell death, led to the explosion of the field as a subject of research. Today we recognize many variations on the theme of biological cell death, but many mysteries remain. The most important of these remaining mysteries is that we recognize many of the penultimate and ultimate steps to kill cells, but it is rarely clear how and why these steps are activated. Most likely they are activated by an interaction of several metabolic steps, but we will need more high-powered analysis to determine how this interaction functions.
Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD
Authors: Petrelli B. , Oztürk A. , Pind M. , Ayele H. , Fainsod A. , Hicks G. G.
Published: June 2023

Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%–5% of the Western population. In Xenopus laevis studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. Gsc+/Cyp26A1 mouse embryos have a reduced RA domain and expression in the developing frontonasal prominence region and delayed HoxA1 and HoxB1 expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. Gsc+/Cyp26A1 mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD.
DNA structural properties of DNA binding sites for 21 transcription factors in the mycobacterial genome
Authors: Dey Upalabdha , Olymon Kaushika , Banik Anikesh , Abbas Eshan , Yella Venkata Rajesh , Kumar Aditya
Published: June 2023

Mycobacterium tuberculosis, the causative agent of tuberculosis, has evolved over time into a multidrug resistance strain that poses a serious global pandemic health threat. The ability to survive and remain dormant within the host macrophage relies on multiple transcription factors contributing to virulence. To date, very limited structural insights from crystallographic and NMR studies are available for TFs and TF–DNA binding events. Understanding the role of DNA structure in TF binding is critical to deciphering MTB pathogenicity and has yet to be resolved at the genome scale. In this work, we analyzed the compositional and conformational preference of 21 mycobacterial TFs, evident at their DNA binding sites, in local and global scales. Results suggest that most TFs prefer binding to genomic regions characterized by unique DNA structural signatures, namely, high electrostatic potential, narrow minor grooves, high propeller twist, helical twist, intrinsic curvature, and DNA rigidity compared to the flanking sequences. Additionally, preference for specific trinucleotide motifs, with clear periodic signals of tetranucleotide motifs, are observed in the vicinity of the TF–DNA interactions. Altogether, our study reports nuanced DNA shape and structural preferences of 21 TFs.
Information guided adaptation of complex biological systems
Authors: Herndon R. Craig
Published: June 2023

Introduction: Functional information transmission through a complex biological system is introduced as a method for biological response (bioresponse) adaptation using qualified biological marker (biomarker) data.

Methods: This information guided adaptation methodology traverses the series of complex connections, defined by disparate bioresponse and biomarkers data sets, by placing both data sets on the common platiorm defined by information. The absolute uncertainty associated with these data sets can be defined in terms of decimal digits of information. This relationship between the data’s absolute uncertainty and its information entropy is used to decompose information entropy into functional and relative uncertainty components, where the functional component quantifies the function or meaning of a data set in units of information.

Results: Application of functional information to adapt patient medical treatments using the information values for the bioresponse model and the biomarker model are outlined in detail and presented tabularly.

Discussion: Functional information provides a mathematical connection between a bioresponse model and a biomarker model by quantifying both data sets in the units of information and thereby providing the means to implement precision therapeutic plans by quantitatively adapting patient treatments using their biomarker measurements.
Pixel-wise statistical analysis of myocardial injury in STEMI patients with delayed enhancement MRI
Authors: Duchateau Nicolas , Viallon Magalie , Petrusca Lorena , Clarysse Patrick , Mewton Nathan , Belle Loic , Croisille Pierre
Published: June 2023

Objectives

Myocardial injury assessment from delayed enhancement magnetic resonance images is routinely limited to global descriptors such as size and transmurality. Statistical tools from computational anatomy can drastically improve this characterization, and refine the assessment of therapeutic procedures aiming at infarct size reduction. Based on these techniques, we propose a new characterization of myocardial injury up to the pixel resolution. We demonstrate it on the imaging data from the Minimalist Immediate Mechanical Intervention randomized clinical trial (MIMI: NCT01360242), which aimed at comparing immediate and delayed stenting in acute ST-Elevation Myocardial Infarction (STEMI) patients.

Methods

We analyzed 123 patients from the MIMI trial (62 ± 12 years, 98 male, 65 immediate 58 delayed stenting). Early and late enhancement images were transported onto a common geometry using techniques inspired by statistical atlases, allowing pixel-wise comparisons across population subgroups. A practical visualization of lesion patterns against specific clinical and therapeutic characteristics was also proposed using state-of-the-art dimensionality reduction.

Results

Infarct patterns were roughly comparable between the two treatments across the whole myocardium. Subtle but significant local differences were observed for the LCX and RCA territories with higher transmurality for delayed stenting at lateral and inferior/inferoseptal locations, respectively (15% and 23% of myocardial locations with a p-value <0.05, mainly in these regions). In contrast, global measurements were comparable for all territories (no statistically significant differences for all-except-one measurements before standardization / for all after standardization), although immediate stenting resulted in more subjects without reperfusion injury.

Conclusion

Our approach substantially empowers the analysis of lesion patterns with standardized comparisons up to the pixel resolution, and may reveal subtle differences not accessible with global observations. On the MIMI trial data as illustrative case, it confirmed its general conclusions regarding the lack of benefit of delayed stenting, but revealed subgroups differences thanks to the standardized and finer analysis scale.
Diagenesis and reservoir quality of Neoproterozoic dolomitized microbialites following multi-stage diagenetic fluid activity: a case study of the Sinian Dengying Formation, China
Authors: Dong Shuyi , Fu Meiyan , Song Rongcai , Guo Hengwei , Shen Qiuyuan
Published: June 2023

Neoproterozoic marine microbialites have been targets for exploration and hydrocarbon reservoir development. The original depositional fabric and diagenesis control the pore systems of microbialites, leading to the complicated origin of microbialite reservoirs. This study aimed to reveal the origin of microbialite reservoirs following multi-stage diagenetic fluid activity in the fourth Member of the Dengying Formation in the central Sichuan Basin in southwestern China. The fourth Member of the Sinian Dengying Formation developed dolomitized microbialites, mainly including stromatolites, laminates, and thrombolites. Based on the background of tectonic movement, petrology and geochemistry examinations were executed to analyze the origin of the microbialite reservoir. Based on the cathodoluminescence and the homogenization temperature of the brine inclusions, it is credible that there were four stages of diagenetic fluid activities in the burial diagenesis. In the first stage, the microbialite reservoir was charged by oil in the Silurian period, with evidence from residual asphalt around the pores. In the second stage, dolomite precipitated to incompletely fill the pore spaces. In the third stage, the silica-rich diagenetic fluid with high temperature resulted in the precipitation of authigenic quartz. In the last stage, the oil charged again during the Triassic period, followed by siliceous filling, with residual asphalt filling the pore spaces. There were two stages of subaerial emergence, which occurred in two episodes of the Sinian-Early Cambrian Tongwan movement. The evidence for the two tectonic events includes two phases of dolomites with meteoric water origin, two cycles of V, Sr, and Na element profiles, two instances of negative excursion δ18O isotope, and two cavity layers. By comparison, the karstification of reservoirs in the Tongwan III episode could generate a higher quality of reservoir than that in the Tongwan II episode. As a result, the quality of the microbialite reservoir from the fourth Member of the Dengying Formation was mainly improved by the subaerial exposure in the Tongwan III episode and then was partly destroyed by the siliceous filling. The identification of multi-staged diagenetic fluid charging can illustrate the evolution of the reservoir quality of Neoproterozoic microbialites.
Genetic testing for maturity-onset diabetes of the young resulting in an upgraded genetic classification of an HNF1A gene variant: a case report
Authors: Pollack-Schreiber Naama , Nwosu Benjamin Udoka , Salemi Parissa
Published: June 2023

The frequent misdiagnosis of MODY (Maturity-Onset Diabetes of the Young) subtypes makes it necessary to clarify the clinical spectrum of the disease phenotypes in suspected subjects so that accurate diagnosis and management plans can be introduced as early as possible in the course of the disease. We report the case of a MODY subtype that was initially characterized as variant of uncertain significance (VUS) but was later changed to a likely pathogenic variant following our report of two cases where the full expression of the clinical phenotype was described. HNF1A-MODY (Maturity Onset Diabetes of the Young type 3) is one of the most common subtypes of MODY. Due to its variable clinical presentation, and the concerns with being misdiagnosed as either type 1 or type 2 diabetes, DNA sequencing is needed to confirm the diagnosis. This case report illustrates the clinical scenario leading to the identification of the gene variant c.416T>C(p. Leu139Pro) in the HNF1A gene, initially reported as a VUS and later upgraded to a likely pathogenic variant. Though the mutation was described in two Czech family members in 2020, the clinical course and phenotype was not characterized. Therefore, there was the need to fully describe the spectrum of the disease arising from the mutation. The case report fully describes the clinical spectrum of this mutation and provides much needed clinical management approaches to the wider scientific community.
Molecular characterization and re-interpretation of HNF1A variants identified in Indian MODY subjects towards precision medicine
Authors: Kavitha Babu , Ranganathan Sampathkumar , Gopi Sundaramoorthy , Vetrivel Umashankar , Hemavathy Nagarajan , Mohan Viswanathan , Radha Venkatesan
Published: June 2023

Background

HNF1A is an essential component of the transcription factor network that controls pancreatic β-cell differentiation, maintenance, and glucose stimulated insulin secretion (GSIS). A continuum of protein malfunction is caused by variations in the HNF1A gene, from severe loss-of-function (LOF) variants that cause the highly penetrant Maturity Onset Diabetes of the Young (MODY) to milder LOF variants that are far less penetrant but impart a population-wide risk of type 2 diabetes that is up to five times higher. Before classifying and reporting the discovered variations as relevant in clinical diagnosis, a critical review is required. Functional investigations offer substantial support for classifying a variant as pathogenic, or otherwise as advised by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) ACMG/AMP criteria for variant interpretation.

Objective

To determine the molecular basis for the variations in the HNF1A gene found in patients with monogenic diabetes in India.

Methods

We performed functional protein analyses such as transactivation, protein expression, DNA binding, nuclear localization, and glucose stimulated insulin secretion (GSIS) assay, along with structural prediction analysis for 14 HNF1A variants found in 20 patients with monogenic diabetes.

Results

Of the 14 variants, 4 (28.6%) were interpreted as pathogenic, 6 (42.8%) as likely pathogenic, 3 (21.4%) as variants of uncertain significance, and 1 (7.14%) as benign. Patients harboring the pathogenic/likely pathogenic variants were able to successfully switch from insulin to sulfonylureas (SU) making these variants clinically actionable.

Conclusion

Our findings are the first to show the need of using additive scores during molecular characterization for accurate pathogenicity evaluations of HNF1A variants in precision medicine.
Chemical cues involved in the host foraging behavior of Psyttalia concolor wasps to locate the olive fruit fly Bactrocera oleae
Authors: Bogka Giannoula , Anastasaki Eirini , Milonas Panagiotis G. , Psoma Aikaterini , Kabourakis Emmanouil M. , Zwaan Bas J. , Pannebakker Bart A. , Fatouros Nina E.
Published: June 2023

Foraging parasitoids rely on infochemicals, derived from the habitat, host plant and/or host insect itself. Here, we studied the olive fruit fly Bactrocera oleae (Rossi) (Diptera: Tephritidae), a major pest in olive agroecosystem and its larval parasitoid, Psyttalia concolor (Szépligeti) (Hymenoptera: Braconidae), a well-established and abundant wasp in Crete. To improve parasitoid’s efficiency as biological control agent, more knowledge on its host location behavior is required. The aim of this study was to investigate the role of oviposition- (OIPVs) and herbivore-induced plant volatiles (HIPVs) emitted by olive trees upon infestation by B. oleae as well as cues emitted by B. oleae, e.g., pheromones, therein. We conducted two-choice bioassays to test the preference of P. concolor to different olfactory stimuli. Moreover, we collected headspace volatiles from olive fruits and branches to investigate whether egg or larval infestation changes volatile emissions locally or/and systemically. We found that P. concolor wasps showed a strong preference to volatiles of B. oleae larval-infested fruits (HIPVs) compared to clean air, non-infested, egg-infested, and mechanical-damaged fruits. But they were not able to discriminate between volatiles of non-infested and larval-infested branches. In addition, the wasps were attracted to cues emitted from the virgin and mated B. oleae females. They were neither attracted to cues emitted by the virgin and mated males nor to the olive fruits with or without the cues of the oviposition marking of the B. oleae. We found important qualitative differences in volatile profiles of egg- and larval-infested fruits: nineteen volatile compounds were only detected in infested fruits, such as the terpenoids (E)-β-ocimene and (E,E)-α-farnesene. Moreover, volatile analysis showed that olives change volatile emissions locally and systemically in response to larval infestation. Our results suggest that both HIPVs and host cues play an important role to P. concolor during host location. Further knowledge on the chemical compounds utilized by the parasitoid to locate infested fruits could help application in olive orchards and to improve the control of the olive fruit fly by natural enemies.
The ecological nature of whole river macrosystems: new perspectives from the riverine ecosystem synthesis
Authors: Thorp James H. , Thoms Martin C. , Delong Michael D. , Maasri Alain
Published: June 2023

Opportunities to understand and protect natural aquatic diversity in both relatively pristine and managed rivers can be enhanced with a comprehensive, system-wide understanding of a river’s hydrogeomorpholgy and its effects on ecological structure and functioning from the river’s headwaters to its terminus in an ocean, lake, or natural endorheic basin. While a moderate number of macrosystem ecology studies have been undertaken recently in headwaters, comparable ecological approaches to studying whole rivers or at least their larger components from upstream to downstream are relatively rare. This is partially correlated with the paucity of applicable river ecosystem models developed over the last half century which could otherwise provide diverse, testable tenets (hypotheses). This manuscript focuses on a 15+ year updated, system-wide analysis of the applicability of the 17 tenets included in our previously published, lotic model - the Riverine Ecosystem Synthesis, or RES. We also propose here four new tenets and analyze the system-wide applicability of the revised RES. Those new tenets hypothesize that: (H-18) “The range and degree of impacts of a Functional Process Zone on biodiversity and ecological processes differ among several factors, including types of FPZs, total river area covered, and dependent variables examined, even in the same river network position”; (H-19) “The degree of ecological differences among types of FPZs vary seasonally with the process being examined while also differing among types of life history characteristics - especially when contrasting responses among seasonal periods of either maximum or minimum growth and reproduction”; (H-20) “The relative importance of in-stream versus watershed drivers of ecological processes in streams can vary within macrosystems and among ecoregions and partially depends on elevation, terrestrial characteristics (natural or human modified), and FPZ type and extent”; and (H-21) “The provision of ecosystem services varies significantly with FPZ type, river size, and location vis-à-vis human populations”. Where appropriate, we also evaluate aspects of several other models published by colleagues that pertain to river ecology.
Biomineralization technology for solidification/stabilization of heavy metals in ecosystem: status and perspective
Authors: Li Shuang , Wu Xiang , Xie Jiamin
Published: June 2023

Biomineralization technology offers an eco-friendly and efficient method for stabilizing heavy metals (HMs) in ecosystem. This technology comprises two primary methods: microbially induced carbonate precipitation (MICP) and enzyme-induced carbonate precipitation (EICP). Biomineralization provides a superior alternative to stabilize heavy metals due to its low energy consumption, reduced carbon dioxide emissions, and superior biocompatibility. In the process of biomineralization, heavy metal ions precipitate and co-precipitate with calcium carbonate, forming a solidified and stabilized product. Despite its many advantages, little attention has been paid to the impact of biomineralization on mitigation of ammonia nitrogen of bio-treated polluted water and the strength of contaminated soil, limiting its further applications in ecological environment restoration. This paper summarizes recent advancements in biomineralization for solidifying and stabilizing (S/S) heavy metals in contaminated water and soil. Key factors inhibiting this method’s application include the concentration and combinations of heavy metal ions, the concentration of ammonia nitrogen in polluted water, and the properties of contaminated soil. Finally, this paper offers recommendations on the optimization of further research and experimental design of biomineralization on S/S polluted water and contaminated soil.
Case report: Application of targeted NGS for the detection of non-canonical driver variants in MPN
Authors: Zhang Jin , Shen Kefeng , Xiao Min , Huang Jinjin , Wang Jin , Wang Yaqin , Hong Zhenya
Published: June 2023

Background: JAK2, CALR, and MPL gene mutations are recognized as driver mutations of myeloproliferative neoplasms (MPNs). MPNs without these mutations are called triple-negative (TN) MPNs. Recently, novel mutation loci were continuously discovered using next-generation sequencing (NGS), along with continued discussion and modification of the traditional TN MPN.

Case presentation: Novel pathogenic mutations were discovered by targeted NGS in 4 patients who were diagnosed as JAK2 unmutated polycythaemia vera (PV) or TN MPN. Cases 1, 2, and 3 were of patients with PV, essential thrombocythemia (ET), and primary myelofibrosis (PMF); NGS detected JAK2 p.H538_K539delinsQL (uncommon), CALR p.E380Rfs*51 (novel), and MPL p.W515_Q516del (novel) mutations. Case 4 involved a patient with PMF; JAK2, CALR, or MPL mutations were not detected by qPCR or NGS, but a novel mutation SH2B3 p.S337Ffs*3, which is associated with the JAK/STAT signal transduction pathway, was found by NGS.

Conclusion: NGS, a more multidimensional and comprehensive gene mutation detection, is required for patients suspected of having MPN to detect non-canonical driver variants and avoid the misdiagnosis of TN MPN. SH2B3 p.S337Ffs*3 can drive MPN occurrence, and SH2B3 mutation may also be a driver mutation of MPN.
Constructing a novel signature and predicting the immune landscape of colon cancer using N6-methylandenosine-related lncRNAs
Authors: Wang Yongfeng , Zhang Dongzhi , Li Yuxi , Wu Yue , Ma Haizhong , Jiang Xianglai , Fu Liangyin , Zhang Guangming , Wang Haolan , Liu Xingguang , Cai Hui
Published: June 2023

Background: Colon cancer (CC) is a prevalent malignant tumor that affects people all around the world. In this study, N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) in 473 colon cancers and 41 adjacent tissues of CC patients from The Cancer Genome Atlas (TCGA) were investigated.

Method: The Pearson correlation analysis was conducted to examine the m6A-related lncRNAs, and the univariate Cox regression analysis was performed to screen 38 prognostic m6A-related lncRNAs. The least absolute shrinkage and selection operator (LASSO) regression analysis were carried out on 38 prognostic lncRNAs to develop a 14 m6A-related lncRNAs prognostic signature (m6A-LPS) in CC. The availability of the m6A-LPS was evaluated using the Kaplan–Meier and Receiver Operating Characteristic (ROC) curves.

Results: Three m6A modification patterns with significantly different N stages, survival time, and immune landscapes were identified. It has been discovered that the m6A-LPS, which is based on 14 m6A-related lncRNAs (TNFRSF10A-AS1, AC245041.1, AL513550.1, UTAT33, SNHG26, AC092944.1, ITGB1-DT, AL138921.1, AC099850.3, NCBP2-AS1, AL137782.1, AC073896.3, AP006621.2, AC147651.1), may represent a new, promising biomarker with great potential. It was re-evaluated in terms of survival rate, clinical features, tumor infiltration immune cells, biomarkers related to Immune Checkpoint Inhibitors (ICIs), and chemotherapeutic drug efficacy. The m6A-LPS has been revealed to be a novel potential and promising predictor for evaluating the prognosis of CC patients.

Conclusion: This study revealed that the risk signature is a promising predictive indicator that may provide more accurate clinical applications in CC therapeutics and enable effective therapy strategies for clinicians.
Skin immunity in wound healing and cancer
Authors: Jakovija Arnolda , Chtanova Tatyana
Published: June 2023

The skin is the body’s largest organ. It serves as a barrier to pathogen entry and the first site of immune defense. In the event of a skin injury, a cascade of events including inflammation, new tissue formation and tissue remodeling contributes to wound repair. Skin-resident and recruited immune cells work together with non-immune cells to clear invading pathogens and debris, and guide the regeneration of damaged host tissues. Disruption to the wound repair process can lead to chronic inflammation and non-healing wounds. This, in turn, can promote skin tumorigenesis. Tumors appropriate the wound healing response as a way of enhancing their survival and growth. Here we review the role of resident and skin-infiltrating immune cells in wound repair and discuss their functions in regulating both inflammation and development of skin cancers.
Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma
Authors: Digifico Elisabeth , Erreni Marco , Mannarino Laura , Marchini Sergio , Ummarino Aldo , Anfray Clément , Bertola Luca , Recordati Camilla , Pistillo Daniela , Roncalli Massimo , Bossi Paola , Zucali Paolo Andrea , D’Incalci Maurizio , Belgiovine Cristina , Allavena Paola
Published: June 2023

Background

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.

Methods

Expression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model.

Results

In patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene (Spp1) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo.

Conclusion

These results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo. These findings have translational potential to improve the therapeutic response of human MPM.
The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype
Authors: Ortiz Wilczyñski Juan Manuel , Mena Hebe Agustina , Ledesma Martin Manuel , Olexen Cinthia Mariel , Podaza Enrique , Schattner Mirta , Negrotto Soledad , Errasti Andrea Emilse , Carrera Silva Eugenio Antonio
Published: June 2023

Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14+ monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage.
The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease
Authors: Jackson Jacob T. , Nutt Stephen L. , McCormack Matthew P.
Published: June 2023

The Haematopoietically expressed homeobox transcription factor (Hhex) is a transcriptional repressor that is of fundamental importance across species, as evident by its evolutionary conservation spanning fish, amphibians, birds, mice and humans. Indeed, Hhex maintains its vital functions throughout the lifespan of the organism, beginning in the oocyte, through fundamental stages of embryogenesis in the foregut endoderm. The endodermal development driven by Hhex gives rise to endocrine organs such as the pancreas in a process which is likely linked to its role as a risk factor in diabetes and pancreatic disorders. Hhex is also required for the normal development of the bile duct and liver, the latter also importantly being the initial site of haematopoiesis. These haematopoietic origins are governed by Hhex, leading to its crucial later roles in definitive haematopoietic stem cell (HSC) self-renewal, lymphopoiesis and haematological malignancy. Hhex is also necessary for the developing forebrain and thyroid gland, with this reliance on Hhex evident in its role in endocrine disorders later in life including a potential role in Alzheimer’s disease. Thus, the roles of Hhex in embryological development throughout evolution appear to be linked to its later roles in a variety of disease processes.
Immune functions of pattern recognition receptors in Lepidoptera
Authors: Zhao Lin , Niu Jinlan , Feng Disong , Wang Xialu , Zhang Rong
Published: June 2023

Pattern recognition receptors (PRRs), as the “sensors” in the immune response, play a prominent role in recognizing pathogen-associated molecular patterns (PAMPs) and initiating an effective defense response to pathogens in Lepidoptera. It is becoming increasingly clear that damage-associated molecular patterns (DAMPs) normally play a physiological role within cells; however, when exposed to extracellular, they may become “part-time” critical signals of the immune response. Based on research in recent years, we review herein typical PRRs of Lepidoptera, including peptidoglycan recognition protein (PGRP), gram-negative binding protein (GNBP), β-1,3-glucan recognition protein (βGRP), C-type lectin (CTL), and scavenger receptor (SR). We also outline the ways in which DAMPs participate in the immune response and the correlation between PRRs and immune escape. Taken together, these findings suggest that the role of PRRs in insect innate immunity may be much greater than expected and that it is possible to recognize a broader range of signaling molecules.
Advances in epigenetic modifications of autophagic process in pulmonary hypertension
Authors: Mao Min , Song Shasha , Li Xin , Lu Jiayao , Li Jie , Zhao Weifang , Liu Hanmin , Liu Jingxin , Zeng Bin
Published: June 2023

Pulmonary hypertension is characterized by pulmonary arterial remodeling that results in increased pulmonary vascular resistance, right ventricular failure, and premature death. It is a threat to public health globally. Autophagy, as a highly conserved self-digestion process, plays crucial roles with autophagy-related (ATG) proteins in various diseases. The components of autophagy in the cytoplasm have been studied for decades and multiple studies have provided evidence of the importance of autophagic dysfunction in pulmonary hypertension. The status of autophagy plays a dynamic suppressive or promotive role in different contexts and stages of pulmonary hypertension development. Although the components of autophagy have been well studied, the molecular basis for the epigenetic regulation of autophagy is less understood and has drawn increasing attention in recent years. Epigenetic mechanisms include histone modifications, chromatin modifications, DNA methylation, RNA alternative splicing, and non-coding RNAs, which control gene activity and the development of an organism. In this review, we summarize the current research progress on epigenetic modifications in the autophagic process, which have the potential to be crucial and powerful therapeutic targets against the autophagic process in pulmonary hypertension development.
Goat milk extracellular vesicles: immuno-modulation effects on porcine monocyte-derived macrophages in vitro
Authors: Franzoni Giulia , Mecocci Samanta , De Ciucis Chiara Grazia , Mura Lorena , Dell’Anno Filippo , Zinellu Susanna , Fruscione Floriana , De Paolis Livia , Carta Tania , Anfossi Antonio G. , Dei Guidici Silvia , Chiaradia Elisabetta , Pascucci Luisa , Oggiano Annalisa , Cappelli Katia , Razzuoli Elisabetta
Published: June 2023

Introduction

Extracellular vesicles (EVs) are nanometric-membrane-bound sub-cellular structures, which can be recovered from milk. Milk EVs have drawn increasing interest due to their potential biomedical applications, therefore it is important to investigate their impact on key immune cells, such as macrophages.

Methods

In this work, the immunomodulatory effects of goat milk EVs on untreated (moMФ) and classically activated (moM1) porcine monocyte-derived macrophages were investigated using flow cytometry, ELISA, and gene expression assays.

Results

These particles were efficiently internalized by macrophages and high doses (60 mg protein weight) triggered the upregulation of MHC I and MHC II DR on moMФ, but not on moM1. In moMФ, exposure to low doses (0.6 mg) of mEVs enhanced the gene expression of IL10, EBI3, and IFNB, whereas high doses up-regulated several pro-inflammatory cytokines. These nanosized structures slightly modulated cytokine gene expression on moM1. Accordingly, the cytokine (protein) contents in culture supernatants of moMФ were mildly affected by exposure to low doses of mEVs, whereas high doses promoted the increased release of TNF, IL-8, IL-1a, IL-1b, IL-1Ra, IL-6, IL-10, and IL-12. The cytokines content in moM1 supernatants was not critically affected.

Discussion

Overall, our data support a clinical application of these molecules: they polarized macrophages toward an M1-like phenotype, but this activation seemed to be controlled, to prevent potentially pathological over-reaction to stressors.