bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding meaning in chaos: a selection signature for functional interactions and its use in molecular biology
Authors: Weiner Lorin , Brissette Janice L.
Published: June 2022

A primary goal of biomedical research is to elucidate molecular mechanisms, particularly those responsible for human traits, either normal or pathological. Yet achieving this goal is difficult if not impossible when the traits of interest lack tractable models and so cannot be dissected through time‐honoured approaches like forward genetics or reconstitution. Arguably, no biological problem has hindered scientific progress more than this: the inability to dissect a trait's mechanism without a tractable likeness of the trait. At root, forward genetics and reconstitution are powerful approaches because they assay for specific molecular functions. Here, we discuss an alternative way to uncover important mechanistic interactions, namely, to assay for positive natural selection. If an interaction has been selected for, then it must perform an important function, a function that significantly promotes reproductive success. Accordingly, selection is a consequence and indicator of function, and uncovering multimolecular selection will reveal important functional interactions. We propose a selection signature for interactions and review recent selection‐based approaches through which to dissect traits that are not inherently tractable. The review includes proof‐of‐principle studies in which important interactions were uncovered by screening for selection. In sum, screens for selection appear feasible when screens for specific functions are not. Selection screens thus constitute a novel tool through which to reveal the mechanisms that shape the fates of organisms.
Anti‐tumour effects of a macrolide analog F806 in oesophageal squamous cell carcinoma cells by targeting and promoting GLUT1 autolysosomal degradation
Authors: Li Xiang , Li Liyan , Wu Xiaodong , Wen Bing , Lin Wan , Cao Yufei , Xie Lei , Zhang Hefeng , Dong Geng , Li Enmin , Xu Liyan , Cheng Yinwei
Published: June 2022

Cancer cells are characterized by altered energetic metabolism with increasing glucose uptake. F806, a 16‐membered macrodiolide analogue, has anti‐tumour effects on oesophageal squamous cell carcinoma (ESCC) cells. However, its precise anti‐tumour mechanism remains unclear. Here, metascape analysis of our previous quantitative proteomics data showed that F806 induced glucose starvation response and inhibited energy production in ESCC cells. The reduced glucose uptake and ATP production were further validated by the fluorescent methods, using glucose‐conjugated bioprobe Glu‐1‐O‐DCSN, and the bioluminescent methods, respectively. Consistently, under F806 treatment the AMP‐activated protein kinase signalling was activated, and autophagy flux was promoted and more autophagosomes were formed. Moreover, live‐cell imaging and immunofluorescence analysis showed that F806 induced GLUT1 plasma membrane dissociation and promoted its internalization and autolysosome accumulation and lysosome degradation. Furthermore, molecular docking studies demonstrated that F806 bound to GLUT1 with a comparable binding energy to that of GLUT1’s direct interacting inhibitor cytochalasin B. Amino acid mutation was used to test which residues of GLUT1 may participate in F806 mediated‐GLUT1 internalization and degradation, and results showed that Thr137, Asn411 and Trp388 were required for GLUT1 internalization and degradation, respectively. Taken together, these findings shed light on a novel anti‐tumour mechanism of F806 by targeting and promoting GLUT1 internalization and further autolysosomal degradation.
Railway wheelset fatigue life estimation based on field tests
Authors: Maglio Michele , Kabo Elena , Ekberg Anders
Published: June 2022

Field tests using an instrumented powered wheelset were performed to investigate fatigue damage accumulation in railway axles. Axle bending strains were measured and post‐processed to obtain axle stress spectra. Statistical analyses were used to investigate the variations of axle stress spectra due to changes in railway operation parameters. The study indicates that measured axle stress spectra can be modeled using truncated normal distributions, where the large majority of measured stress amplitudes are lower than 50 MPa. Stress cycles at higher amplitudes are affected by operation parameters such as track design, number of switches and crossings, and whether the wheelset is in a leading or trailing position. Variations in the obtained statistical distributions of axle stresses have been used as input for fatigue life analyses. It was concluded that fatigue damage can potentially initiate on axles suffering from corrosion or small surface cracks/scratches.
Effects of pairing on color change and central gene expression in lined seahorses
Authors: Mederos Sabrina L. , Duarte Rafael C. , Mastoras Mira , Dennis Megan Y. , Settles Matthew L. , Lau Allison R. , Scott Alexandria , Woodward Kacie , Johnson Colby , Seelke Adele M. H. , Bales Karen L.
Published: June 2022

Social monogamy is a reproductive strategy characterized by pair living and defense of a common territory. Pair bonding, sometimes displayed by monogamous species, is an affective construct that includes preference for a specific partner, distress upon separation, and the ability of the partner to buffer against stress. Many seahorse species show a monogamous social structure in the wild, but their pair bond has not been well studied. We examined the gene expression of lined seahorses (Hippocampus erectus) during and after the process of pairing in the laboratory as well as color change (luminance), a potential form of social communication and behavioral synchrony between pair mates. When a seahorse of either sex was interacting with its pair mate, their changes in luminance (“brightness”) were correlated and larger than when interacting with an opposite‐sex stranger. At the conclusion of testing, subjects were euthanized, RNA was extracted from whole brains and analyzed via RNA sequencing. Changes in gene expression in paired males versus those that were unpaired included processes governing metabolic activity, hormones and cilia. Perhaps most interesting is the overlap in gene expression change induced by pairing in both male seahorses and male prairie voles, including components of hormone systems regulating reproduction. Because of our limited sample size, we consider our results and interpretations to be preliminary, and prompts for further exploration. Future studies will expand upon these findings and investigate the neuroendocrine and genetic basis of these behaviors.
Tree growth is connected with distribution and warming‐induced degradation of permafrost in southern Siberia
Authors: Peng Ruonan , Liu Hongyan , Anenkhonov Oleg A. , Sandanov Denis V. , Korolyuk Andrey Yu. , Shi Liang , Xu Chongyang , Dai Jingyu , Wang Lu
Published: June 2022

Hemiboreal and boreal forests growing at the southern margin of the permafrost distribution are vulnerable to climate warming. However, how climate warming threatens the growth of dominant tree species that are distributed on permafrost remains to be determined, particularly in synchrony with warming‐induced permafrost degradation. Tree growth in the permafrost region of southern Siberia was hypothesized to be highly sensitive to temperature increasing and warming‐induced permafrost degradation. To test this hypothesis, we sampled the tree ring width of 535 trees of dominant species, larch (including Larix gmelinii and L. sibirica) and white birch (Betula platyphylla), in ten hemiboreal to boreal forest plots within different permafrost zones. The relationships between the tree ring basal area index (BAI) and temperature, precipitation, and the Palmer drought severity index (PDSI) were compared among plots located in two permafrost zones. In the isolated permafrost zone, white birch grows better than larch and is not drought‐stressed (p < .05). We suggest that the deep‐rooted white birch benefits from the water from thawing permafrost, while the growth of the shallow‐rooted larch is stressed by drought. In the sporadic discontinuous permafrost zone, both white birch and larch benefited from permafrost melting, but the sensitivity of larch growth to PDSI is still significant (p < .05), indicating drought is still an important climatic factor limiting the growth of larch. Our results imply that the permafrost degradation caused by climate warming affects tree growth by creating the root layer additional water source. In the future, it is necessary to focus on monitoring permafrost degradation to better predict forest dynamics at the southern margin of the permafrost distribution.
Observation‐based global soil heterotrophic respiration indicates underestimated turnover and sequestration of soil carbon by terrestrial ecosystem models
Authors: He Yue , Ding Jinzhi , Dorji Tsechoe , Wang Tao , Li Juan , Smith Pete
Published: June 2022

Soil heterotrophic respiration (Rh) refers to the flux of CO2 released from soil to atmosphere as a result of organic matter decomposition by soil microbes and fauna. As one of the major fluxes in the global carbon cycle, large uncertainties still exist in the estimation of global Rh, which further limits our current understanding of carbon accumulation in soils. Here, we applied a Random Forest algorithm to create a global data set of soil Rh, by linking 761 field observations with both abiotic and biotic predictors. We estimated that global Rh was 48.8 ± 0.9 Pg C year−1 for 1982–2018, which was 16% less than the ensemble mean (58.6 ± 9.9 Pg C year−1) of 16 terrestrial ecosystem models. By integrating our observational Rh with independent soil carbon stock data sets, we obtained a global mean soil carbon turnover time of 38.3 ± 11 year. Using observation‐based turnover times as a constraint, we found that terrestrial ecosystem models simulated faster carbon turnovers, leading to a 30% (74 Pg C) underestimation of terrestrial ecosystem carbon accumulation for the past century, which was especially pronounced at high latitudes. This underestimation is equivalent to 45% of the total carbon emissions (164 Pg C) caused by global land‐use change at the same time. Our analyses highlight the need to constrain ecosystem models using observation‐based and locally adapted Rh values to obtain reliable projections of the carbon sink capacity of terrestrial ecosystems.
Spatial patterns and driving factors of carbon stocks in mangrove forests on Hainan Island, China
Authors: Meng Yuchen , Gou Ruikun , Bai Jiankun , Moreno‐Mateos David , Davis Charles C. , Wan Luoma , Song Shanshan , Zhang Hongsheng , Zhu Xiaoshan , Lin Guanghui
Published: June 2022

Aim

Mangrove forests are important coastal wetlands for the blue carbon budget and play a significant role in mitigating global climate change. However, spatial patterns of carbon stocks in mangrove forests on an island scale have not been quantified owing to methodological limitations and lack of understanding of controlling factors. We took the entire Hainan Island as a case study and aimed to carry out a comprehensive investigation of the spatial patterns and driving factors of carbon stocks in mangrove forests.

Location

Southern China.

Time period

2017–2020.

Major taxa studied

Mangrove forest.

Methods

The upscaling method combined with field surveys and Sentinel‐2 imagery analysis were used to compare different models for optimization of mangrove ecosystem carbon stock estimations. We also used structural equation modelling (SEM) to evaluate the factors driving the distributional patterns of mangrove carbon stocks on an island scale.

Results

The current total mangrove carbon stock of the entire Hainan Island was estimated to be 703,181 Mg C (with a mean density of 192 Mg C/ha), with the above‐ and below‐ground carbon stocks averaging at 44.7 and 147.3 Mg C/ha, respectively. The mangrove carbon storage in the north‐eastern region of the island was the highest and in the west region the lowest. Sediment nitrogen content and plant species diversity had the most positive driving effects on the distribution of total carbon stock for Hainan Island mangroves.

Main conclusions

The combination of field surveys and Sentinel‐2 imagery analysis can be applied to regional‐scale estimations of carbon stocks for mangrove forests. Spatial pattens of mangrove carbon stocks vary among locations on Hainan Island, and soil nutrient (especially nitrogen) availability is the dominant factor regulating carbon stock variations along the land‐to‐sea gradient. Our findings have significant implications for better understanding the distribution of mangrove carbon stocks and quantification of the global blue carbon budget.
Bringing political science back into public administration research
Authors: Peters B. Guy , Pierre Jon , Sørensen Eva , Torfing Jacob
Published: June 2022

The paper critically reviews the consequences of a bifurcation of Political Science and Public Administration. This divorce of two closely related academic fields has removed political explanations to key developments in the public service from Public Administration research and thus it tends to provide a partial view of the reality that it seeks to capture. There are several developments underway in the public sector, which underscore the political nature of public administration. These developments include the rise of administration politics; a growing emphasis on strategic management; governance‐driven democratization and administrative micro‐politics; the increasing significance of interactive and collaborative forms of governance; the rise of multilevel governance; and the development toward a more active citizenship. We find that in all of these areas, public administration research would benefit from incorporating a political science understanding of power, democracy, governance and citizenship.
Social exclusion and consumer responses: A comprehensive review and theoretical framework
Authors: Rawat Gargi , Dewani Prem Prakash , Kulashri Aditya
Published: June 2022

While social exclusion in the consumption context has gained significant interest recently, its literature remains fragmented and underexplored due to restricted categorization and limited conceptual lenses. This systematic review attempts to broaden social exclusion literature by including multiple possible aspects of social exclusion, and providing a nuanced approach to identifying changes in the consumption response of excluded individuals. Using the ‘Scientific Procedures and Rationales for Systematic Literature Review’ (SPAR‐4‐SLR) protocol to assemble, arrange and assess studies published between 2010 and 2021, we selected 83 studies as the basis of this review. With the objective of providing a synthesized view of the existing literature and presenting possible explanations for inconsistencies, this article (a) undertakes a systematic review of the existing research in the domain, (b) introduces a conceptual framework and (c) provides a taxonomy to categorize diverse strands of consumption responses. Identifying gaps, this study also provides directions for future research using the Theory, Characteristics, Context and Methodology (TCCM) framework. This study can thus enable marketers, advertisers and public policymakers to understand the needs of socially excluded individuals, and subsequently make more inclusive decisions.
Magnetic resonance imaging of in vitro urine flow in single and tandem stented ureters subject to extrinsic ureteral obstruction
Authors: Dror Ishai , Harris Talia , Kalchenko Vyacheslav , Shilo Yaniv , Berkowitz Brian
Published: June 2022

Objective

To quantify the relative volumetric flows in stent and ureter lumina, as a function of stent size and configuration, in both unobstructed and externally obstructed stented ureters.

Methods

Magnetic resonance imaging was used to measure flow in stented ureters using a phantom kidney model. Volumetric flow in the stent and ureter lumina were determined along the stented ureters, for each of four single stent sizes (4.8F, 6F, 7F, and 8F), and for tandem (6F and 7F) configurations. Measurements were made in the presence of a fully encircling extrinsic ureteral obstruction as well as in benchmark cases with no extrinsic ureteral obstruction.

Results

Under no obstruction, the relative contribution of urine flow in single stents is 1–10%, while the relative contributions to flow are ~6 and ~28% for tandem 6F and 7F, respectively. In the presence of an extrinsic ureteral obstruction and single stents, all urine passes within the stent lumen near the extrinsic ureteral obstruction. For tandem 6F and 7F stents under extrinsic ureteral obstruction, relative volumetric flows in the two stent lumina are ~73% and ~81%, respectively, with the remainder passing through the ureter lumen.

Conclusions

Magnetic resonance imaging demonstrates that with no extrinsic ureteral obstruction, minimal urine flow occurs within a stent. Stent lumen flow is significant in the presence of extrinsic ureteral obstruction, in the vicinity of the extrinsic ureteral obstruction. For tandem stents subjected to extrinsic ureteral obstruction, urine flow also occurs in the ureter lumen between the stents, which can reduce the likelihood of kidney failure even in the case of both stent lumina being occluded.
Nursing policy and practice in Mongolia: Issues and the way forward
Authors: Dovdon Baigalmaa , Park Claire Su‐Yeon , McCarley Nigel
Published: June 2022

Global inequality exists in the availability of a nursing workforce, supported evidentially by the ratio, in low‐income countries, of only 9.1 nurses per 10 000 people versus 107.7 nurses per 10 000 people in high‐income countries. Mongolia is no exception with 42.14 nurses per 10 000 people and a nursing shortage severe enough to endanger patient safety and well‐being. This paper details both a policy analysis and contextually well‐designed recommendations to strengthen Mongolia's nursing science and practice systems. Obstacles that significantly affect the successful development of nursing and midwifery professions in Mongolia include (1) a lack of strategic planning and regulation; (2) low status of nurses and midwives; (3) absence of professional representation for nurses and midwives; and (4) a dearth of strategic programs for postgraduate training of nurses and midwives. The suggested recommendations include the appointment of a chief nursing office within the government and a cohort of nurse leaders to work to establish a nursing and midwifery board as an independent, professional regulatory body in Mongolia to develop and implement standards to ensure best practice, higher standards of nurse education, and regulate the profession.
Blood pressure trajectories during pregnancy and preterm delivery: A prospective cohort study in China
Authors: Chan Fanfan , Shen Songying , Huang Peiyuan , He Jianrong , Wei Xueling , Lu Jinhua , Zhang Lifang , Xia Xiaoyan , Xia Huimin , Cheng Kar Keung , Thangaratinam Shakila , Mol Ben Willem , Qiu Xiu
Published: June 2022

Women's blood pressure (BP) changes throughout pregnancy. The effect of BP trajectories on preterm delivery is not clear. The authors aim to evaluate the association between maternal BP trajectories during pregnancy and preterm delivery. The authors studied pregnant women included in the Born in Guangzhou Cohort Study in China between February 2012 and June 2016. Maternal BP was measured at antenatal visits between 13 and 40 gestational weeks, and gestational age of delivery data was collected. The authors used linear mixed models to capture the BP trajectories of women with term, and spontaneous and iatrogenic preterm delivery. BP trajectories of women with various gestational lengths (34, 35, 36, 37, 38, 39, 40 weeks) were compared. Of the 17 426 women included in the analysis, 618 (3.55%) had spontaneous preterm delivery; 158 (.91%) had iatrogenic preterm delivery; and 16 650 (95.55%) women delivered at term. The BP trajectories were all J‐shaped curves for different delivery types. Women with iatrogenic preterm delivery had the highest mean BP from 13 weeks till delivery, followed by those with spontaneous preterm delivery and term delivery (p < .001). Trajectory analysis stratified by maternal parity showed similar results for nulliparous and multiparous women. Excluding women with pre‐eclampsia and gestational hypertension (GH) significantly attenuated the aforementioned association. Also, women with shorter gestational length tend to have higher BP trajectories during pregnancy. In conclusion, Women with spontaneous preterm delivery have a higher BP from 13 weeks till delivery than women with term delivery, while women with iatrogenic preterm delivery have the highest BP.
The effect of mountaineering on the association between blood pressure and physical activity: A new multi‐sensor ambulatory blood‐pressure monitoring device. The Mount Fuji Study
Authors: Komori Takahiro , Hoshide Satoshi , Kanazawa Hidenori , Taki Mizuri , Suzuki Noriyasu , Kotruchin Praew , Kario Kazuomi
Published: June 2022

It has not been fully investigated whether the response of blood pressure (BP) to activity at high altitudes differs from that at low altitudes or how temperature is involved in these differences. The author compared BP response to accelerometer measurements during mountaineering and daily living. In 15 healthy people (mean age 33 ± 6 years), a new multi‐sensor ambulatory BP monitoring (ABPM) device equipped with barometer, thermometer, and accelerometer was used to measure BP responses to activity during a trip to Mt. Fuji and during daily living. Associations between physical activity (log‐transformed 5‐min average values of accelerometer just before each ambulatory BP) and the corresponding BP were obtained from 843 and 676 readings during the Mt. Fuji trip and daily living, respectively. All ambulatory systolic BP (SBP) parameters were significantly higher during the Mt. Fuji trip than during daily living (all p < .01). There were significant positive correlations between physical activity and corresponding BPs in both mountaineering and daily living (all p < .01), and there was an interaction between BPs and physical activity according to the two conditions (p < .01). On Mt. Fuji, multivariate regression analysis showed increased physical activity and lower temperature were associated with increased 24‐h SBP and diastolic BP (DBP) (all p < .05). The goodness‐of‐fit values of the association between activity and 24‐h SBP or DBP were improved by adding temperature to the model of both 24‐h SBP and DBP. However, these associations were not found in the daily living model. BP response to activity was more pronounced during mountaineering than daily living.
Evaluation of application protocol of the 4% hydrogen peroxide for at‐home bleaching: A randomized clinical trial
Authors: de Paula Alexandra M. , Hanzen Taíse Alessandra , de Andrade Heloísa Forville , Grokoski Eduardo , Loguercio Alessandro D. , Reis Alessandra
Published: June 2022

Objective

Few studies evaluated low concentrations of hydrogen peroxide protocols. The aim of this paper was evaluated two application protocols using 4% hydrogen peroxide in at‐home bleaching.

Materials and Methods

Eighty‐six patients with upper canines' shade A2 or darker were randomly allocated under two experimental conditions: two daily applications of 1 h each or a 2‐h single application. Color change was evaluated using Vita Classical, Vita Bleachedguide, and digital spectrophotometer weekly and 1 month after the bleaching procedure through one‐way ANOVA. The risk and intensity of tooth sensitivity (TS) was assessed through visual and numeric rating scale and measured by Fisher's exact test, Mann–Whitney test and one‐way ANOVA respectively.

Results

After 3 weeks, the mean difference for the ΔSGU Vita Classical (1.0; 95% CI −0.1 to 2.0), ΔEab (0.7; 95% CI −1.4 to 2.8), ΔE00 (0.1; 95% CI −1.4 to 1.6) and Wi (1.8; 95% CI ‐1.9 to 5.5) presented no difference (p > 0.08). The relative risk for TS was 0.91 (0.72 to 1.14) without significant difference neither in the risk (p = 0.6) nor in the TS intensity for both pain scales (p > 0.65).

Conclusions

The application protocols evaluated (two daily applications of 1 h each or a 2‐h single application) for at‐home bleaching with 4% hydrogen peroxide did not showed differences in color change and tooth sensitivity.

Clinical Relevance

Higher amount of active hydrogen peroxide in two daily applications for at‐home bleaching neither accelerate bleaching nor increase the risk or intensity of tooth sensibility.
Overlapping functions of YDA and MAPKKK3/MAPKKK5 upstream of MPK3/MPK6 in plant immunity and growth/development
Authors: Liu Yidong , Leary Emma , Saffaf Obai , Frank Baker R. , Zhang Shuqun
Published: June 2022

Arabidopsis MITOGEN‐ACTIVATED PROTEIN KINASE3 (MAPK3 or MPK3) and MPK6 play important signaling roles in plant immunity and growth/development. MAPK KINASE4 (MKK4) and MKK5 function redundantly upstream of MPK3 and MPK6 in these processes. YODA (YDA), also known as MAPK KINASE KINASE4 (MAPKKK4), is upstream of MKK4/MKK5 and forms a complete MAPK cascade (YDA–MKK4/MKK5–MPK3/MPK6) in regulating plant growth and development. In plant immunity, MAPKKK3 and MAPKKK5 function redundantly upstream of the same MKK4/MKK5–MPK3/MPK6 module. However, the residual activation of MPK3/MPK6 in the mapkkk3 mapkkk5 double mutant in response to flg22 pathogen‐associated molecular pattern (PAMP) treatment suggests the presence of additional MAPKKK(s) in this MAPK cascade in signaling plant immunity. To investigate whether YDA is also involved in plant immunity, we attempted to generate mapkkk3 mapkkk5 yda triple mutants. However, it was not possible to recover one of the double mutant combinations (mapkkk5 yda) or the triple mutant (mapkkk3 mapkkk5 yda) due to a failure of embryogenesis. Using the clustered regularly interspaced short palindromic repeats (CRISPR) – CRISPR‐associated protein 9 (Cas9) approach, we generated weak, N‐terminal deletion alleles of YDA, yda‐del, in a mapkkk3 mapkkk5 background. PAMP‐triggered MPK3/MPK6 activation was further reduced in the mapkkk3 mapkkk5 yda‐del mutant, and the triple mutant was more susceptible to pathogen infection, suggesting YDA also plays an important role in plant immune signaling. In addition, MAPKKK5 and, to a lesser extent, MAPKKK3 were found to contribute to gamete function and embryogenesis, together with YDA. While the double homozygous mapkkk3 yda mutant showed the same growth and development defects as the yda single mutant, mapkkk5 yda double mutant and mapkkk3 mapkkk5 yda triple mutants were embryo lethal, similar to the mpk3 mpk6 double mutants. These results demonstrate that YDA, MAPKKK3, and MAPKKK5 have overlapping functions upstream of the MKK4/MKK5–MPK3/MPK6 module in both plant immunity and growth/development.
Melatonin use and the risk of 30‐day mortality among US veterans with sepsis: A retrospective study
Authors: Sutton S. Scott , Magagnoli Joseph , Cummings Tammy H. , Hardin James W.
Published: June 2022

Prior research suggests melatonin has beneficial effects that could improve survival among sepsis patients. This exploratory analysis sought to compare 30‐day survival among melatonin treated and untreated patients with sepsis. A retrospective cohort study was conducted among patients with a primary inpatient admission diagnosis for sepsis utilizing the International Classification of Diseases, versions 9 and 10, Clinical Modification (ICD‐9‐CM and ICD‐10‐CM) diagnosis codes between 2000 and 2021. Propensity score weighting was utilized, accounting for demographic, clinical, and laboratory factors. Weighted Cox models were estimated for 30‐day in‐hospital and 30‐day overall survival. A total of 9386 patients were included in the study with 593 exposed to melatonin within the first day of hospitalization. Propensity score weighted Cox models reveal melatonin was associated with a 37.9% decreased risk of 30‐day in‐hospital mortality (HR = 0.621; 95% CI = [0.415–0.931]) and a 33.5% decreased risk of 30‐day overall mortality (HR = 0.665; 95% CI = [0.493–0.897]). Factors associated with higher risk of both in‐hospital and overall mortality include male sex, white race, age, higher Charlson comorbidity burden, sodium and potassium levels, intensive care unit stay, invasive ventilation, and vasopressor use. Higher serum albumin levels are associated with lower mortality risks. Among patients diagnosed with sepsis, exposure to melatonin was associated with a lower in‐hospital and 30‐day mortality. Additional research is warranted to fully understand the role of melatonin in sepsis.
Melatonin mitigates aflatoxin B1‐induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice
Authors: Liu Shuiping , Kang Weili , Mao Xinru , Ge Lei , Du Heng , Li Jinyan , Hou Lili , Liu Dandan , Yin Yulong , Liu Yunhuan , Huang Kehe
Published: June 2022

Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1‐induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO‐1, Occludin, and Claudin‐1), decreased intestinal permeability, reduced production of gut‐derived Lipopolysaccharide (LPS) and remodeled gut microbiota, ultimately alleviated AFB1‐induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic‐treated mice. Meanwhile, MT pretreatment significantly increased the farnesoid X receptor (FXR) protein expression of ileum, and decreased the TLR4/NF‐κB signaling pathway‐related messenger RNA (mRNA) and proteins (TLR4, MyD88, p‐p65, and p‐IκBα) expression in livers of AFB1‐exposed mice. Subsequently, pretreatment by Gly‐β‐MCA, an intestine‐selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver‐specific expression of TLR4/NF‐κB signaling pathway‐related mRNA and proteins (TLR4, MyD88, p‐p65, and p‐IκBα). In conclusion, MT pretreatment ameliorated AFB1‐induced liver injury and the potential mechanism may be related to regulate gut microbiota/intestinal FXR/liver TLR4 signaling axis, which provides a strong evidence for the protection of gut‐derived liver inflammation.
MZB1 targeted by miR‐185‐5p inhibits the migration of human periodontal ligament cells through NF‐κB signaling and promotes alveolar bone loss
Authors: Li Dingyi , Zhu Yiting , Zhang Lu , Shi Luyao , Deng Li , Ding Zhiqiang , Ai Rongshuang , Zhang Xiaonan , He Yujuan
Published: June 2022

Objective

To explore the role of Marginal Zone B and B‐1 Cell‐Specific Protein (MZB1), a novel molecule associated with periodontitis, in migration of human periodontal ligament cells (hPDLCs) and alveolar bone orchestration.

Background

MZB1 is an ER‐localized protein and its upregulation has been found to be associated with a variety of human diseases. However, few studies have investigated the effect and mechanism of MZB1 on hPDLCs in periodontitis.

Methods

Gene expression profiles in human gingival tissues were acquired from the Gene Expression Omnibus (GEO) database, and candidate molecules were then selected through bioinformatic analysis. Subsequently, we identified the localization and expression of MZB1 in human gingival tissues, mice, and hPDLCs by immunofluorescence, RT‐qPCR, and Western blot. Dual‐luciferase reporter assay was applied to assess the binding of miR‐185‐5p to MZB1. Furthermore, the effects of MZB1 on cell migration, proliferation, and apoptosis in vitro were investigated by wound‐healing assay, transwell assay, CCK‐8 assay, and flow cytometry analysis. Finally, Micro‐CT analysis and H&E staining were performed to examine the effects of MZB1 on alveolar bone loss in vivo.

Results

Bioinformatic analysis discovered that MZB1 was one of the most significantly increased genes in periodontitis patients. MZB1 was markedly increased in the gingival tissues of periodontitis patients, in the mouse models, and in the hPDLCs treated with lipopolysaccharide of Porphyromonas gingivalis (LPS‐PG). Furthermore, in vitro experiments showed that MZB1, as a target gene of miR‐185‐5p, inhibited migration of hPDLCs. Overexpression of MZB1 specifically upregulated the phosphorylation of p65, while pretreatment of MZB1‐overexpressed hPDLCs with PDTC (NF‐κB inhibitor) notably reduced the p‐p65 level and promoted cell migration. In addition, the mRNA expression levels of alkaline phosphatase (ALP) and Runt‐related transcription factor 2 (Runx2) were inhibited in MZB1‐overexpressed hPDLCs and miR‐185‐5p inhibitor treated hPDLCs, respectively. In vivo experiments showed that knockdown of MZB1 alleviated the loss of alveolar bone.

Conclusion

As a target gene of miR‐185‐5p, MZB1 plays a crucial role in inhibiting the migration of hPDLCs through NF‐κB signaling pathway and deteriorating alveolar bone loss.
The legal protection of new plant varieties in Algerian and American system
Authors: Mousseddek Kheira
Published: June 2022

The importance of plants in almost all fields yields for a continuous international effort to determine the protection of innovations in plants, especially with the tendency of countries to make huge investments in this area. Though, most of the world's countries agreed to set‐up effective protection for new plant varieties, they differ over the type and nature of proper legal protection. This discrepancy in international positions on legal protection frameworks leads the researchers to investigate the most appropriate legal adaptations of innovative new plant varieties; are they inventions or an independent intellectual property right? And what are the suitable ways to protect it? Thereby, a comparative analysis of the national texts with some foreign legislation has been conducted. The study structure is twofold. The first section dealt with the legal protection of plant varieties within an independent legal system: a study in the Algerian law, while the second one presented the possibility of protecting a new plant variety under a patent: a study in the American legislation. The results showed that the adoption of a patent protection system is of great importance. It is, thus, preferable for the legislator to approve the dual protection of new plant varieties.
Recent genetic exchanges and admixture shape the genome and population structure of the zoonotic pathogen Cryptosporidium parvum
Authors: Corsi Giulia I. , Tichkule Swapnil , Sannella Anna Rosa , Vatta Paolo , Asnicar Francesco , Segata Nicola , Jex Aaron R. , van Oosterhout Cock , Cacciò Simone M.
Published: June 2022

Cryptosporidium parvum is a globally distributed zoonotic pathogen and a major cause of diarrhoeal disease in humans and ruminants. The parasite's life cycle comprises an obligatory sexual phase, during which genetic exchanges can occur between previously isolated lineages. Here, we compare 32 whole genome sequences from human‐ and ruminant‐derived parasite isolates collected across Europe, Egypt and China. We identify three strongly supported clusters that comprise a mix of isolates from different host species, geographic origins, and subtypes. We show that: (1) recombination occurs between ruminant isolates into human isolates; (2) these recombinant regions can be passed on to other human subtypes through gene flow and population admixture; (3) there have been multiple genetic exchanges, and most are probably recent; (4) putative virulence genes are significantly enriched within these genetic exchanges, and (5) this results in an increase in their nucleotide diversity. We carefully dissect the phylogenetic sequence of two genetic exchanges, illustrating the long‐term evolutionary consequences of these events. Our results suggest that increased globalization and close human‐animal contacts increase the opportunity for genetic exchanges between previously isolated parasite lineages, resulting in spillover and spillback events. We discuss how this can provide a novel substrate for natural selection at genes involved in host–parasite interactions, thereby potentially altering the dynamic coevolutionary equilibrium in the Red Queens arms race.
Peripheral endothelial and microvascular damage in liver cirrhosis: A systematic review and meta‐analysis
Authors: Papagiouvanni Ioanna , Theodorakopoulou Marieta P. , Sarafidis Pantelis A. , Sinakos Emmanouil , Goulis Ioannis
Published: June 2022

Objective

This is the first systematic review and meta‐analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non‐cirrhotic individuals.

Methods

Literature search involved PubMed, Web‐of‐Science, and Scopus databases, as well as gray literature sources. We included studies in adult subjects evaluating endothelial function with any semi‐invasive or non‐invasive functional method in patients with and without liver cirrhosis.

Results

From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta‐analysis. In six studies examining endothelial function with flow‐mediated‐dilatation, no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [−2.87, 5.53], I2 = 97%, p < .00001). Among studies assessing differences in endothelial‐dependent or endothelial‐independent vasodilation with venous‐occlusion‐plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[−0.04, 1.63], I2 = 94%, p < .00001).

Conclusions

No differences in peripheral endothelial function assessed with semi‐invasive or non‐invasive functional methods exist between cirrhotic and non‐cirrhotic subjects. The increasing co‐existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.
Tight junction channels claudin‐10b and claudin‐15: Functional mapping of pore‐lining residues
Authors: Hempel Caroline , Rosenthal Rita , Fromm Anja , Krug Susanne M. , Fromm Michael , Günzel Dorothee , Piontek Jörg
Published: June 2022

Although functional and structural models for paracellular channels formed by claudins have been reported, mechanisms regulating charge and size selectivity of these channels are unknown in detail. Here, claudin‐15 and claudin‐10b cation channels showing high‐sequence similarity but differing channel properties were analyzed. Mutants of pore‐lining residues were expressed in MDCK‐C7 cells. In claudin‐15, proposed ion interaction sites (D55 and E64) conserved between both claudins were neutralized. D55N and E64Q substitutions decreased ion permeabilities, and D55N/E64Q had partly additive effects. D55N increased cation dehydration capability and decreased pore diameter. Additionally, residues differing between claudin‐15 and ‐10b close to pore center were analyzed. Claudin‐10b–mimicking W63K affected neither assembly nor function of claudin‐15 channels. In contrast, in claudin‐10b, corresponding (claudin‐15b‐mimicking) K64W and K64M substitutions disturbed integration into tight junction and slightly altered relative permeabilities for differently sized monovalent cations. Removal of claudin‐10b–specific negative charge (D36A substitution) was without effect. The data suggest that a common tetra‐aspartate ring (D55/D56) in pore center of claudin‐15/‐10b channels directly attracts cations, while E64/D65 may be at least partly shielded by W63/K64. Charge at position W63/K64 affects assembly and properties for claudin‐10b but not for claudin‐15 channels. Our findings add to the mechanistic understanding of the determinants of paracellular cation permeability.
Federal budget process reform: An economics perspective, with imperfect, “Human” decision‐makers
Authors: Phaup Marvin
Published: June 2022

This paper develops and supports the thesis that the performance of the federal budget process would be improved by the criteria of efficiency and stability by the addition of an explicit budget constraint with ex ante budgeting for fiscal shocks. Adding a constraint would nudge policymakers to choose more efficient policies, while reducing the risk of a fiscal crisis. Anticipating and provisioning for shocks in advance of occurrence would avoid undermining the constraint ex post. Both changes could be effected by a behaviorally‐informed version of a proposal originally advanced and endorsed by economists in the 1950s.
Delayed vaccination the children up to 2 years of age
Authors: Garcia Érica Marvila , Waldman Eliseu Alves , Toriyama Aurea Tamami Minagawa , Sato Ana Paula Sayuri
Published: June 2022

Objective

To analyze factors associated with vaccination delay in children up to 2 years of age.

Methods

Cross‐sectional study with primary data from a probabilistic sample of 388 children born in 2015. The data were described using absolute and relative frequencies. For the analysis of factors associated with vaccination delay, Cox proportional risk regression was performed, considering the time from birth to the first vaccination delay as a dependent variable and as sociodemographic, economic, behavioral aspects related to health services as independent variables.

Results

The delayed vaccination rate was 88.66%. Variables associated with delayed vaccination were: mother's health problems during delivery or in the first 7 days (HR: 0.68; 95% CI: 0.48–0.96); hospitalization of the child in the first 2 years of life (HR: 1.52; 95% CI: 1.10–2.11); mother's poor bond with health professionals at the health unit (HR: 1.75; 95% CI: 1.01–3.03); purposeful decision to delay or not to vaccinate the child (HR: 1.56; 95% CI: 1.14–2.13).

Conclusions

The factors associated with health care, such as the mother's health problems, the child's hospitalization in the first 2 years of life, and the bond between the mother and the health professionals affect the timeliness of vaccine doses.
Formation of Stilbene Azo‐Dimer by Direct Irradiation of p‐Azidostilbene†
Authors: Osisioma Onyinye , Patton Leanna J. , Merugu Rajkumar , Govorov Dmitrii , Milbrandt Margaret A. , Jarus Cassandra , Karney William L. , Gudmundsdottir Anna D.
Published: June 2022

Triplet arylnitrenes may provide direct access to aryl azo‐dimers, which have broad commercial applicability. Herein, the photolysis of p‐azidostilbene (1) in argon‐saturated methanol yielded stilbene azo‐dimer (2) through the dimerization of triplet p‐nitrenostilbene (31N). The formation of 31N was verified by electron paramagnetic resonance spectroscopy and absorption spectroscopy (λmax ~ 375 nm) in cryogenic 2‐methyltetrahydrofuran matrices. At ambient temperature, laser flash photolysis of 1 in methanol formed 31N (λmax ~ 370 nm, 2.85 × 107 s−1). On shorter timescales, a transient absorption (λmax ~ 390 nm) that decayed with a similar rate constant (3.11 × 107 s−1) was assigned to a triplet excited state (T) of 1. Density functional theory calculations yielded three configurations for T of 1, with the unpaired electrons on the azido (TA) or stilbene moiety (TTw, twisted and TFl, flat). The transient was assigned to TTw based on its calculated spectrum. CASPT2 calculations gave a singlet–triplet energy gap of 16.6 kcal mol−1 for 1 N; thus, intersystem crossing of 11N to 31N is unlikely at ambient temperature, supporting the formation of 31N from T of 1. Thus, sustainable synthetic methods for aryl azo‐dimers can be developed using the visible‐light irradiation of aryl azides to form triplet arylnitrenes.
Effect of simple calculation and reading aloud on cognitive function and depression in postoperative older adults
Authors: Çetinkaya Funda , Diri Mehmet Akif , Gül Murat
Published: June 2022

Background

This study was conducted to determine the effect of simple calculation and reading aloud on postoperative cognitive function and depression level in older adults.

Method

The study was a randomised controlled experimental study. A personal information form, Mini‐Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) were used for data collection.

Results

In the evaluation of MMSE and GDS scores of the intervention and control groups 4 weeks after the operation, the differences between the two groups were found to be statistically significant.

Conclusion

The results found that simple calculation and reading aloud after surgery had a positive effect on cognitive function and depression level in older people.
Constitutional Norms—Erosion, Sabotage, and Response
Authors: Postema Gerald J.
Published: June 2022

This article explains the nature and constitutional role of norms and explores ways to respond to the challenges they face, which threaten the viability of democracy. Constitutional norms are informal unwritten rules embedded in the normative practices of officials and political leaders. The effect of departures from constitutional norms depends on the seriousness with which participants take responsibility for their practice. The article distinguishes norm infringers, who depart from norms but do not intentionally challenge them; norm entrepreneurs, who challenge the norm in hopes of reforming or replacing it; and norm saboteurs, who seek to deal a deathblow to the norm or the constitutional system of which it is a part. Responses appropriate to each kind of deviation are considered.
Evidence on continuous flow peritoneal dialysis: A review
Authors: de Vries Joost C. , van Gelder Maaike K. , Cappelli Gianni , Bajo Rubio Maria A. , Verhaar Marianne C. , Gerritsen Karin G. F.
Published: June 2022

Clinical application of continuous flow peritoneal dialysis (CFPD) has been explored since the 1960s, but despite anticipated clinical benefits, CFPD has failed to gain a foothold in clinical practice, among others due to the typical use of two catheters (or a dual‐lumen catheter) and large dialysate volumes required per treatment. Novel systems applying CFPD via the existing single‐lumen catheter using rapid dialysate cycling may solve one of these hurdles. Novel on‐demand peritoneal dialysate generation systems and sorbent‐based peritoneal dialysate regeneration systems may considerably reduce the storage space for peritoneal dialysate and/or the required dialysate volume. This review provides an overview of current evidence on CFPD in vivo. The available (pre)clinical evidence on CFPD is limited to case reports/series with inherently nonuniform study procedures, or studies with a small sample size, short follow‐up, and no hard endpoints. Small solute clearance appears to be higher in CFPD compared to conventional PD, in particular at dialysate flows ≥100 mL/min using two single‐lumen catheters or a double‐lumen catheter. Results of CFPD using rapid cycling via a single‐lumen catheter are too preliminary to draw any conclusions. Continuous addition of glucose to dialysate with CFPD appears to be effective in reducing the maximum intraperitoneal glucose concentration while increasing ultrafiltration efficiency (mL/g absorbed glucose). Patient tolerance may be an issue since abdominal discomfort and sterile peritonitis were reported with continuous circulation of the peritoneal dialysate. Thus, well‐designed clinical trials of longer duration and larger sample size, in particular applying CFPD via the existing catheter, are urgently required.