Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of breast fibroepithelial tumor associated retinoic acid receptor alpha ligand binding domain mutations on receptor function and retinoid signaling

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) have been implicated in breast fibroepithelial tumors development. However, their role in the tumorigenesis of solid tumors is currently unknown. In this study, using a combination of biochemical and cellular assays, we evaluated the functional consequences of known tumor associated RARα mutations on retinoic acid signaling. All of the clinically associated mutants tested showed diminished transcriptional activities compared to wild type RARα. These mutants also exhibited a dominant negative effect, an activity which has previously been linked to developmental defects and tumor formation in mice. X-ray crystallography showed that mutants remain relatively intact structurally and the loss of transcriptional activity is due to altered co-activator recruitment. In agreement with our biochemical analyses, transcriptomics and cell growth analysis showed that the mutant RARα proteins confer resistance to growth inhibition in the presence of its ligand in phyllodes tumor cells. Although the mutations impair the receptor responses to retinoic acid, certain mutant RARα are partially reactivatable with alternative synthetic agonists. Our data provide insights into the mechanisms by which RARα mutations impact tumorigenesis.
Cytokinin synthesis and export from symbiotic root nodules coordinates shoot growth with nitrogen fixation

Development of symbiotic root nodules is a cytokinin-dependent process that is critical to nitrogen acquisition in legumes. The extent and manner in which root nodules contribute to whole-plant cytokinin and nitrogen supply signalling is unknown. Using a combination of genetic, biochemical and physiological approaches, we characterised the role of cytokinin synthesis, export and perception in coordination of symbiotic nodule development and shoot growth in the legume Lotus japonicus. LjPup1 encodes a plasma membrane localised cytokinin exporter with isopentenyladenine (iP) and trans-Zeatin (tZ) export capacity. LjPup1 shows a distinct nodule-specific expression pattern with greatest transcript levels detected in mature nodules. Mutants accumulate more isopentenyladenine riboside (iPR) in nodule tissues and demonstrate hallmarks of reduced cytokinin signalling. Despite normal nodule numbers and function, shoot growth is markedly reduced in Ljpup1 mutants, as well as in mutants impaired in tZ biosynthesis. We found symbiotic root nodules contribute to shoot growth via export of active cytokinins. A cytokinin exporter in the purine permease family thus contributes to long-distance cytokinin homeostasis regulating plant development.
Ovule cell wall composition is a maternal determinant of grain size in barley

Summary In cereal species, seed and grain size is influenced by growth of the ovule integuments (seed coat), the spikelet hull (lemma and palea) and the filial endosperm. It has remained unclear whether a highly conserved ovule tissue, the nucellus, has any impact on grain size. Immunolabelling revealed that the barley nucellus comprises two distinct cell types that differ in terms of cell wall homogalacturonan (HG) accumulation. Transcriptional profiling of the nucellus identified two pectin methylesterase genes, OVULE PECTIN MODIFIER 1 (OPM1) and OPM2, which are expressed in the ovule but absent from the seed. Ovules from an opm1 opm2 mutant, and plants expressing an ovule-specific pectin methylesterase inhibitor (PMEI), exhibit reduced HG accumulation. This results in changes to ovule cell size and shape, and ovules that are longer than wild-type controls. At grain maturity, this is manifested as significantly longer grain. These findings indicate that cell wall composition during ovule development acts to limit ovule and seed growth. The investigation of ovule PME and PMEI activity reveals an unexpected role of maternal tissues in controlling grain growth prior to fertilisation, one that has been lacking from models exploring improvements in grain size.
Teaching as evolutionary precursor to language

The central thesis of this article is that the evolution of teaching is one of the main factors that lead to increasingly complex communicative systems in the hominin species. Following earlier analyses of the evolution of teaching, the following steps are identified: (i) evaluative feedback, (ii) drawing attention, (iii) demonstration and pantomime, (iv) communicating concepts, (v) explaining relations between concepts, and (vi) narrating. For each of these step the communicative and cognitive demands will be analyzed. The focus will be on demonstration and pantomime, since these seem to be the evolutionarily earliest unique human capacities. An important step is the transition from pantomime for teaching to pantomime for informing and how this in turn leads to communicating concepts. As regards explaining relations between concepts, the focus will be of the role of generics in teaching and communication. Analyzing these topics involves combining cognitive science with evolutionary theory, archaeology and theories of communication. Two factors are important as a background: (i) the evolution of prospective planning, that is, planning for future goals, and (ii) the evolution of a theory mind. These capacities are central in explaining how more advanced forms of teaching, communication and cooperation emerged along the hominin line.
Effects of homocysteine on nonalcoholic fatty liver related disease: A mendelian randomization study

Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study. Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above. Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method. Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis. Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.
Drivers of population divergence and genetic variation in Elymus breviaristatus (Keng) Keng f. (Poaceae: Triticeae), an endemic perennial herb of the Qinghai-Tibet plateau

Elymus breviaristatus, a rare grass species with excellent resistance and ecological importance, is narrowly distributed on the Qinghai-Tibet plateau. Populations of E. breviaristatus are declining due to habitat fragmentation, and thus far, characteristics of genetic differentiation and adaptive responses to climate change remain poorly understood in this species. Here, we explored the genetic structure of 18 natural populations (269 individuals) in the transition zone between Tibet and the Hengduan Mountains using 15 expressed sequence tag (EST)-SSR primer pairs and identified possible barriers to gene flow that might have caused genetic discontinuities. Additional analyses were performed to identify the environmental factors affecting genetic diversity and to test whether the patterns of genetic variation among populations were more consistent with the isolation by distance (IBD) or isolation by environment (IBE) model. Multiple measures of genetic diversity revealed that intra-population genetic variation was low, while inter-population genetic variation was high. Clustering, structure, and principal coordinate analyses identified three genetic groups: (a) Eastern Qamdo, (b) Nagqu and Western Qamdo, and (c) Lhasa and Nyingchi. A clear physical barrier to gene flow was formed by the Yarlung Zangbo Grand Canyon and the Tanggula Mountains. We found that both IBD and IBE contributed to the observed patterns of genetic variation, and the IBE model played a leading role. In addition, precipitation-related variables, soil phosphorus content and soil K:P ratio significantly affected population genetic variation. Overall, our results emphasized the genetic fragility of E. breviaristatus populations and showed that this species requires attention, as future climate changes and human activities may further threaten its survival. In addition, the genetic differences among E. breviaristatus populations should be considered when formulating conservation measures for E. breviaristatus populations in the study area.
Remote reef cryptobenthic diversity: Integrating autonomous reef monitoring structures and in situ environmental parameters

Coral reef sessile organisms inhabiting cryptic spaces and cavities of the reef matrix perform vital and varied functional roles but are often understudied in comparison to those on exposed surfaces. Here, we assess the composition of cryptobenthic taxa from three remote tropical reef sites (Central Indian Ocean) alongside a suite of in situ environmental parameters to determine if, or how, significant patterns of diversity are shaped by local abiotic factors. To achieve this, we carried out a point-count analysis of autonomous reef monitoring structure (ARMS) plate images and employed in situ instrumentation to recover long-term (12 months) profiles of flow velocity, wave heights, temperature, dissolved oxygen, and salinity, and short-term (3 weeks) profiles of light and pH. We recovered distinct environmental profiles between sampling sites and observed that ocean-facing reefs experienced frequent but short-lived cooling internal wave events and that these were key in shaping in situ temperature variability. By comparing temperature and wave height profiles recovered using in situ loggers with ex situ models, we discovered that global satellite products either failed to recover site-specific profiles or both over- and underestimated actual in situ conditions. We found that site choice and recruitment plate face (top or bottom) significantly impacted the percentage cover of bryozoans, gastropods, soft and calcified tube worms, as well as crustose coralline algae (CCA) and fleshy red, brown, and green encrusting macroalgae on ARMS. We observed significant correlations between the abundance of bryozoans, CCA, and colonial tunicates with lower mean temperature and higher mean dissolved oxygen profiles observed across sites. Red and brown encrusting macroalgae abundance correlated significantly with medium-to-high flow velocities and wave height profiles, as well as higher pH and dissolved oxygen. This study provides the first insight into cryptobenthic communities in the Chagos Archipelago marine-protected area and adds to our limited understanding of tropical reef sessile communities and their associations with environmental parameters in this region. With climate change accelerating the decline of reef ecosystems, integrating analyses of cryptobenthic organisms and in situ physicochemical factors are needed to understand how reef communities, if any, may withstand the impacts of climate change.
Perceived overall injustice and organizational deviance—Mediating effect of anger and moderating effect of moral disengagement

Introduction This study is dedicated to exploring the influence of perceived overall injustice on employee anger and deviant behavior. Based on fairness heuristic theory and cognitive appraisal theory of emotion, a model was developed to investigate the relationship between perceived overall injustice, anger and organizational deviance. Based on social cognitive theory, the moderating role of moral disengagement was proposed. Methods The data were collected from three Chinese manufacturing corporations with a total effective sample size of 264. SPSS 26 and Mplus 8.3 were adopted to analyze data. Confirmatory factor analysis, descriptive statistics analysis and correlation results were illustrated. Hierarchical regression was used to test the model. Results Statistical results showed that there is a significant positive relationship among perceived overall injustice, anger and organizational deviance. The moderating effect of moral disengagement on the relationship between perceived overall injustice and organizational deviance is significant, while that on the relationship between anger and organizational deviance is insignificant. Discussion This study built a model to discuss the emotional and behavioral influences of perceived overall injustice. The findings suggest that individuals feel more anger as the level of perceived overall injustice increases, which thus lead to higher level of organizational deviance. Morally disengaged employees are more likely to engage in organizational deviance after being treated unfairly. However, the moderating effect of moral disengagement on the relationship of anger and organizational deviance was insignificant. The reason might be because anger is an aggressive emotion and individual experiencing anger may lead to impulsive behavior regardless of moral rules. Implications and limitations have been discussed.
Systemic immune-inflammation index is associated with diabetic kidney disease in Type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018

Objective Diabetic kidney disease (DKD) is the most common chronic kidney disease (CKD) and has the highest prevalence of end-stage kidney disease (ESKD) globally, owing mostly to the rise in Type 2 diabetes mellitus (T2DM) correlated with obesity. Current research suggested that the immune response and inflammation may play a role in the pathophysiology of T2DM. The systemic immune-inflammation index (SII) is a novel and integrated inflammatory biomarker that has not yet been linked to DKD. We aimed to identify the potential relationship between SII and DKD. Methods In the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018, the current cross-sectional study was conducted among adults with T2DM. SII was calculated as the platelet count × neutrophil count/lymphocyte count. DKD was diagnosed with impaired glomerular filtration rate (< 60 mL/min/1.73 m2 assessed by using the Chronic Kidney Disease Epidemiology Collaboration algorithm), albuminuria (urine albumin to creatinine ratio ≥ 30 mg/g), or both in T2DM patients. To investigate the independent association between SII and DKD, weighted univariate and multivariable logistic regression analyses and subgroup analyses were performed. Results The study involved 3937 patients in total, of whom 1510 (38.4%) had DKD for the diagnosis. After adjustment for covariates, multivariable logistic regression revealed that a high SII level was associated with increased likelihood of DKD (OR = 1.42, 95% CI: 1.10-1.83, P = 0.01). Subgroup analyses and interaction tests revealed that age, gender, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), body mass index (BMI), hypertension, hyperlipidemia, anti-inflammation therapy (yes or no), metformin use (yes or no), and insulin use (yes or no) had no significant dependence on this positive relationship (all p for interaction >0.05). Conclusions Our results indicate that the higher SII level is associated with DKD in T2DM patients. The SII could be a cost-effective and straightforward approach to detecting DKD. This needs to be verified in further prospective investigations.
Role of casein kinase 1 in the amoeboid migration of B-cell leukemic and lymphoma cells: A quantitative live imaging in the confined environment

The migratory properties of leukemic cells are commonly associated with their pathological potential and can significantly affect the disease progression. While the research in immunopathology mostly employed powerful indirect methods such as flow cytometry, these cells were rarely observed directly using live imaging microscopy. This is especially true for the malignant cells of the B-cell lineage, such as those originating from chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In this study, we employed open-source image analysis tools to automatically and quantitatively describe the amoeboid migration of four B-cell leukemic and lymphoma cell lines and primary CLL cells. To avoid the effect of the shear stress of the medium on these usually non-adherent cells, we have confined the cells using a modified under-agarose assay. Surprisingly, the behavior of tested cell lines differed substantially in terms of basal motility or response to chemokines and VCAM1 stimulation. Since casein kinase 1 (CK1) was reported as a regulator of B-cell migration and a promoter of CLL, we looked at the effects of CK1 inhibition in more detail. Migration analysis revealed that CK1 inhibition induced rapid negative effects on the migratory polarity of these cells, which was quantitatively and morphologically distinct from the effect of ROCK inhibition. We have set up an assay that visualizes endocytic vesicles in the uropod and facilitates morphological analysis. This assay hints that the effect of CK1 inhibition might be connected to defects in polarized intracellular transport. In summary, 1) we introduce and validate a pipeline for the imaging and quantitative assessment of the amoeboid migration of CLL/MCL cells, 2) we provide evidence that the assay is sensitive enough to mechanistically study migration defects identified by the transwell assay, and 3) we describe the polarity defects induced by inhibition or deletion of CK1ε.
Endplate volumetric bone mineral density biomechanically matched interbody cage

Disc degenerative problems affect the aging population, globally, and interbody fusion is a crucial surgical treatment. The interbody cage is the critical implant in interbody fusion surgery; however, its subsidence risk becomes a remarkable clinical complication. Cage subsidence is caused due to a mismatch of material properties between the bone and implant, specifically, the higher elastic modulus of the cage relative to that of the spinal segments, inducing subsidence. Our recent observation has demonstrated that endplate volumetric bone mineral density (EP-vBMD) measured through the greatest cortex-occupied 1.25-mm height region of interest, using automatic phantomless quantitative computed tomography scanning, could be an independent cage subsidence predictor and a tool for cage selection instruction. Porous design on the metallic cage is a trend in interbody fusion devices as it provides a solution to the subsidence problem. Moreover, the superior osseointegration effect of the metallic cage, like the titanium alloy cage, is retained. Patient-specific customization of porous metallic cages based on the greatest subsidence-related EP-vBMD may be a good modification for the cage design as it can achieve biomechanical matching with the contacting bone tissue. We proposed a novel perspective on porous metallic cages by customizing the elastic modulus of porous metallic cages by modifying its porosity according to endplate elastic modulus calculated from EP-vBMD. A three-grade porosity customization strategy was introduced, and direct porosity-modulus customization was also available depending on the patient’s or doctor’s discretion.
Collimated terahertz radiation through a laser irradiating on a T-type target

A scheme, applying a linearly polarized laser irradiating on a T-type target which contains a longitudinal target followed by a transverse target, is proposed to collimate the terahertz radiation. The results show that the interaction between the laser and the longitudinal target can effectively reduce the electron transverse divergence while increasing the electron maximum cut-off energy. In this way, the terahertz radiation can be well collimated while enhancing its intensity. By using two-dimensional particle-in-cell simulations, we show that the pointing angle is about −13.6° and 17.5° when the length and thickness of the longitudianl target are 90.0 μm and 4.0 μm, respectively. In addition, the impact of the laser and target parameters on the collimation of terahertz radiation are also investigated separately. Such a scheme may pave a new way for enhancing and collimating the terahertz radiation via laser-solid interactions.
Natural hazards and earthquake science: Gender matters

Gender equality in Earth Sciences is gradually increasing. Looking back at the past twenty years, positive trends have shown an increase in the number of female full and associate professors, like in Italian Universities, from 9.0% to 18.5% and from 23.6% to 28.9% respectively (e.g. Agnini et al., 2020); the progress seen is steady but slow. In United States universities “the fraction of women in the faculty pool decreases with rank, as women comprise 46% of assistant professors, 34% of associate professors, and 19% of full professors” (Ranganathan et al., 2021); similar patterns are reported in Australasia, with 26:74 ratio female:male researchers (Handley et al., 2020). Like other stakeholders, scientific societies such as the European Geosciences Union through its DEI Group (Jesus-Rydin et al., 2020. Eds., 2020) and the Seismological Society of America–JEDI Task Force (Velasco et al., 2021) are recently championing this topic with noteworthy programs, that represent a relevant trend compared to the past; the intergovernmental partnership Group on Earth Observations–GEO begun to reflect on the diversity of its organizational structure and to promote networking with other initiatives (GEO, 2021). Most of the ongoing work is aimed at balancing the current imbalance in the field. The special issue “Women in Seismology 2022” of Frontiers in Earth Sciences itself gives voice and visibility to those who generally have less, both as authors and editors (e.g., Henriques and Garcia, 2022). However, counting the figures of male/female researchers and implementing actions to rectify the situation do not exhaust gender issues in (Earth) Sciences. Therefore, shall we continue reasoning about the integration of gender in research content, where the scenario appears still challenging. Notions of sex and gender need to be preliminarily clarified. Sex refers to biological characteristics while gender refers to socially and culturally constructed norms and behaviors, and the concept varies over time and in different countries. For example, women and men react differently to toxic chemicals. In general, the female body is more OPEN ACCESS