Miracle-dz/UniFAR-FTUs huggingface dataset:
Probing macromolecular crowding at the lipid membrane interface with genetically‐encoded sensors

Biochemical processes within the living cell occur in a highly crowded environment. The phenomenon of macromolecular crowding is not an exclusive feature of the cytoplasm and can be observed in the densely protein-packed, nonhomogeneous cellular membranes and at the membrane interfaces. Crowding affects diffusional and conformational dynamics of proteins within the lipid bilayer, and modulates the membrane organization. However, the non-invasive quantification of the membrane crowding is not trivial. Here, we developed the genetically- encoded fluorescence-based sensor for probing the macromolecular crowding at the membrane interfaces. Two sensor variants, both composed of fluorescent proteins and a membrane anchor, but differing by the flexible linker domains were characterized in vitro, and the procedures for the membrane reconstitution were established. Lateral pressure induced by membrane-tethered synthetic and protein crowders altered the sensors’ conformation, causing increase in the intramolecular Förster’s resonance energy transfer. The effect of protein crowders only weakly correlated with their molecular weight, suggesting that other factors, such as shape and charge play role in the quinary interactions. Upon their expression, the designed sensors were localized to the inner membrane of E. coli, and measurements performed in extracted membrane vesicles revealed low level of interfacial crowding. The sensors offer broad opportunities to study interfacial crowding in a complex environment of native membranes, and thus add to the toolbox of methods for studying membrane dynamics and proteostasis.
The adaptive stochasticity hypothesis: Modeling equifinality, multifinality, and adaptation to adversity

Neural phenotypes are the result of probabilistic developmental processes. This means that stochasticity is an intrinsic aspect of the brain as it self-organizes over a protracted period. In other words, while both genomic and environmental factors shape the developing nervous system, another significant—though often neglected—contributor is the randomness introduced by probability distributions. Using generative modelling of brain networks, we provide a framework for probing the contribution of stochasticity to neurodevelopmental diversity. To mimic the prenatal scaffold of brain structure set by activity-independent mechanisms, we start our simulations from the medio-posterior neonatal rich-club (Developing Human Connectome Project; dHCP, n = 630). From this initial starting point, models implementing Hebbian-like wiring processes generate variable yet consistently plausible brain network topologies. By analyzing repeated runs of the generative process (> 107 simulations), we identify critical determinants and effects of stochasticity. Namely, we find that stochastic variation has a greater impact on brain organization when networks develop under weaker constraints. This heightened stochasticity makes brain networks more robust to random and targeted attacks, but more often results in non-normative phenotypic outcomes. To test our framework empirically, we evaluated whether stochasticity varies according to the experience of early-life deprivation using a cohort of neurodiverse children (Centre for Attention, Learning and Memory; CALM n = 357). We show that low socioeconomic status predicts more stochastic brain wiring. We conclude that stochasticity may be an unappreciated contributor to relevant developmental outcomes, and make specific predictions for future research.
Hindbrain boundaries as niches of neural progenitor/stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate

The interplay between neural progenitor/stem cells (NPSC) and their extracellular matrix (ECM), is a crucial regulatory mechanism that determines their behavior. Nonetheless, how the ECM dictates internal processes remains elusive. The hindbrain is valuable to examine this relationship, as cells in the hindbrain boundaries (HB), which arise between any two neighboring rhombomeres, express the NPSC-marker Sox2 while being surrounded with the ECM molecule chondroitin sulphate proteoglycan (CSPG), in chick and mouse embryos. CSPG expression was used to isolate HB/Sox2+ cells for RNA-sequencing, revealing their distinguished molecular properties as typical NPSCs, which express known and newly-identified genes relating to stem cells, cancer, matrisome and cell-cycle. In contrast, the CSPG-/non-HB cells, displayed clear neural-differentiation transcriptome. To address whether CSPG is significant for hindbrain development, its expression was manipulated in vivo and in vitro. CSPG-manipulations shifted the stem versus differentiation state of HB cells, evident by their behavior and altered gene expression. These results provide novel understanding on the uniqueness of hindbrain boundaries as repetitive pools of NPSCs in-between the rapidly-growing rhombomeres, which rely on their microenvironment to maintain undifferentiated during development. SUMMARY: Transcriptomic analysis of hindbrain boundaries revels them to harbor cells with neural progenitor\stem cell properties that rely on local extracellular matrix to maintain their undifferentiated state.
Autonomous development and regeneration of isolated rice egg cells in a fertilization-independent manner

Parthenogenesis is suppressed in rice egg cells to avoid precocious development before fertilization. We found that cold treatment released cell cycle arrest in egg cells and triggered mitosis. Egg cells isolated from japonica (Nipponbare; NB) and aus (Kasalath; KS) subspecies divided and regenerated into mature plants after cold treatment. The egg-derived plants showed variety of ploidy levels, including haploid (n), diploid (2n), and tetraploid (4n). Nuclear DNA quantification showed that genome duplication occurred during early parthenogenetic development. Owing to the presence of single nucleotide polymorphisms (SNPs) between NB and KS, inter-subspecific hybrid plants (NB-KS hybrids) were created via electrofusion. Egg cells from the NB-KS hybrid developed parthenogenetically into polyploid plants. 2n and 4n plants originating from the same NB-KS egg cell displayed the same homozygous SNP patterns throughout the genome, indicating that these plants were doubled and quadrupled haploids. Transcriptome analyses of cold-treated egg cells demonstrated that parthenogenesis-related candidate genes, including OsBBML1, were upregulated.
The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB/PDIA1 contributing to liver damage and fibrosis

Collagen is one the most abundant proteins and the main cargo of the secretory pathway, contributing to hepatic fibrosis and cirrhosis due to excessive deposition of extracellular matrix. Here we investigated the possible contribution of the unfolded protein response, the main adaptive pathway that monitors and adjusts the protein production capacity at the endoplasmic reticulum, to collagen biogenesis and liver disease. Genetic ablation of the ER stress sensor IRE1 reduced liver damage and diminished collagen deposition in models of liver fibrosis triggered by carbon tetrachloride (CCl4) administration or by high fat diet. Proteomic and transcriptomic profiling identified the prolyl 4-hydroxylase (P4HB, also known as PDIA1), which is known to be critical for collagen maturation, as a major IRE1-induced gene. Cell culture studies demonstrated that IRE1 deficiency results in collagen retention at the ER and altered secretion, a phenotype rescued by P4HB overexpression. Taken together, our results collectively establish a role of the IRE1/P4HB axis in the regulation of collagen production and its significance in the pathogenesis of various disease states.
Variance Analysis of LC-MS Experimental Factors and Their Impact on Machine Learning

Background Machine learning (ML) technologies, especially deep learning (DL), have gained increasing attention in predictive mass spectrometry (MS) for enhancing the data processing pipeline from raw data analysis to end-user predictions and re-scoring. ML models need large-scale datasets for training and re-purposing, which can be obtained from a range of public data repositories. However, applying ML to public MS datasets on larger scales is challenging, as they vary widely in terms of data acquisition methods, biological systems, and experimental designs. Results We aim to facilitate ML efforts in MS data by conducting a systematic analysis of the potential sources of variance in public MS repositories. We also examine how these factors affect ML performance and perform a comprehensive transfer learning to evaluate the benefits of current best practice methods in the field for transfer learning. Conclusions Our findings show significantly higher levels of homogeneity within a project than between projects, which indicates that it’s important to construct datasets most closely resembling future test cases, as transferability is severely limited for unseen datasets. We also found that transfer learning, although it did increase model performance, did not increase model performance compared to a non-pre-trained model.
Pseudomonas sivasensis 2RO45 inoculation alters the taxonomic structure and functioning of the canola rhizosphere microbial community

Inoculation with plant growth-promoting rhizobacteria (PGPR) is an eco-friendly sustainable strategy for improving crop productivity in diverse environments under different conditions. Our earlier study demonstrated that Pseudomonas sivasensis 2RO45 significantly stimulated canola (Brassica napus L. var. napus) growth. The aim of the present study was to investigate the structural and functional dynamics in the canola rhizosphere microbiome after inoculation with PGPR P. sivasensis 2RO45. The results based on alpha diversity metrics showed that P. sivasensis 2RO45 did not significantly alter the diversity of the native soil microbiota. However, the introduced strain modified the taxonomic structure of microbial communities, increasing the abundance of plant beneficial microorganisms, e.g., bacteria affiliated with families Comamonadaceae, Vicinamibacteraceae, genus Streptomyces, and fungi assigned to Nectriaceae, Didymellaceae, Exophiala, Cyphellophora vermispora, and Mortierella minutissima. The analysis of community level physiological profiling (CLPP) revealed that microbial communities in the P. sivasensis 2RO45 treated canola rhizospheres were more metabolically active than those in the non-treated canola rhizosphere. Four carbon sources (phenols, polymers, carboxylic acids, and amino acids) were better metabolized by the microbial communities from the rhizosphere of plants inoculated with the P. sivasensis 2RO45 than non-inoculated canola rhizospheres. Based on the community-level physiological profiles, the functional diversity of the rhizosphere microbiome was altered by the P. sivasensis 2RO45 inoculation. Substrate utilization Shannon diversity (H) index and evenness (E) index were significantly increased in the treated canola plants. The study provides new insight into PGPR-canola interactions for sustainable agriculture development.
Odor exploration behavior of the domestic pig (Sus scrofa) as indicator of enriching properties of odors

Introduction and aim Although the sense of smell in pigs is widely recognized as being highly developed, surprisingly little is known about their sensory ability. This study aimed to (a) identify which non-social odors pigs were able to detect and distinguish between, (b) investigate the types of behavior expressed when exploring odors and, (c) compare pigs’ responses to the different odors to evaluate their interest in the odors. Methods Growing pigs (N = 192) of crossbred commercial breeds were enrolled in the experiment (32–110 days of age, weighing 64.9 ± 10.1kg). Littermate pairs of opposite sex were tested in test pens with two odor insertion points in the pen wall, 55 cm apart. All pigs were habituated to the test pens and experimenters. Twelve odors were tested (eight essential oils and four synthetic perfumes) in groups of three odors, with each pig pair tested once with one set of three odors (all possible orders of the three odors were tested on 24 pairs in total), always against a non-odor control (demineralized water). In a test, each of the three odors were presented during three trials in a row (a total of 9 trials per test; trial duration: 1 min; inter-trial breaks: 2 min; total test duration: 25 min). Response variables included: duration of sniffing, feeding-related behavior (licking, biting and rooting), agonistic behavior (biting, displacement and pushing) and no approach of the odor or control, recorded throughout each 1-min odor presentation. Results All pigs sniffed an odor less when repeatedly presented (LMM: all odors P < 0.05), and significantly longer at the subsequent presentation of a new odor [LMM (3rd vs. 1st presentations): P < 0.001]. Specific odor and odor type (essential oil vs. synthetic perfume) had no significant effect on sniffing duration. Overall, feeding-related behavior and agonistic behavior were expressed significantly more when pigs explored the odor compared with the control insertion point (Paired t-tests: P < 0.001), and specific odor only affected the expression of feeding-related behavior. Conclusion Collectively, pigs express sniffing, agonistic, and feeding-related behavior when exploring odors, which suggests that pigs perceive odors of non-social origin as a resource. Odors may thus constitute relevant enrichment material for pigs.
Toward consistent reporting of sample characteristics in studies investigating the biological mechanisms of romantic love

In this non-systematic review, we consider the sample reporting practices of 42 studies up to and including 2021 investigating the biological mechanisms of romantic love (i.e., 31 neuroimaging studies, nine endocrinological studies, one genetics study, and one combined neuroimaging and genetics study). We searched scientific databases using key terms and drew on our and other authors’ knowledge to identify studies that investigated the mechanisms associated with romantic love using neuroimaging, endocrinological, and genetic methods. Only studies with a group or entire sample experiencing romantic love were included. The aim was to collate all relevant studies and determine the comparability of studies and ability to assess the generalizability of findings. We summarize how these studies report sex/gender, age, romantic love, relationship duration/time in love, and sample descriptors. We then outline the case for promoting comparability and the ability to determine generalizability in future studies. The findings indicate a limited ability to compare studies’ samples or make an assessment of the generalizability of findings. Existing studies are not representative of the general population in a particular country or globally. We conclude by presenting ideas about how best to report sex, age, romantic love characteristics, relationship status, time in love, relationship duration, relationship satisfaction, type of unrequited love, sexual activity, cultural characteristics, socio-economic status, student status, and method-relevant descriptors. If our ideas are adopted, in part or in whole, we expect the comparability of studies to increase. Adopting our ideas will also make it easier to make an assessment of the generalizability of findings.
Global research trends and focus on the link between colorectal cancer and gut flora: a bibliometric analysis from 2001 to 2021

Background Colorectal cancer (CRC) is a highly prevalent cancer, and the global healthcare system bears a significant burden due to its incidence. Modulating the gut microbiota is a promising approach to enhance the efficacy of CRC treatment and reduce its adverse effects. The causal relationship between specific microorganisms’ presence and CRC development has been widely validated. However, few studies have investigated this relationship using bibliometric methods. Therefore, this study analyzed the research hotspots and trends in human gut microbiology and CRC over the last two decades from a bibliometric perspective. The study aims to provide novel insights into basic and clinical research in this field. Methods The articles and reviews on gut microbiota in CRC were obtained from the Web of Science Core Collection (WOSCC) on November 2, 2022. CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge-map analysis. Results A total of 2,707 publications were obtained, with a rapid increase in the number of publications since 2015. The United States and China are the main contributors in this field and have established a network of partnerships in several countries. 414 academic journals have published articles on this topic. The author with the highest number of publications is Jun Yu from the Chinese University of Hong Kong. In addition to “intestinal flora” and “colorectal cancer,” high frequency terms in the keyword co-occurrence network analysis included inflammatory bowel disease, Fusobacterium nucleatum, inflammation, long-chain fatty acids, ulcerative colitis, bile acids, and resistant starch. Analysis of keyword trends using burst testing revealed that biomarkers, abnormal crypt foci, bifidobacteria, β-glucuronidase, short-chain fatty acids, bile acids, and DNA methylation are at the forefront of research in this area. Conclusion The findings of this study provide a bibliometric analysis and visualization of the key research areas in gut microbiota and CRC over the past 20 years. The results suggest that the role of gut microbiota in CRC and its underlying mechanisms should be closely monitored, particularly in the areas of biomarkers, metabolic pathways, and DNA methylation, which may emerge as hot topics in this field.
The molecular mechanism of Gorham syndrome: an update

Gorham syndrome, also known as “vanishing osteopathy” and “invasive hemangiomatosis,” is a rare clinical syndrome whose etiology is unknown and can invade the whole-body skeleton. At present, more than 300 cases have been reported at home and abroad, usually manifesting as spontaneous chronic osteolysis with no periosteal reaction at the lysis site and occult onset, often with fractures, scoliosis, chylothorax, etc. When waiting for medical treatment, the condition is serious, and the prognosis is poor. At present, there is no effective treatment. The main pathological manifestations of Gorham syndrome are the non-neoplastic abnormal proliferation of lymphatic vessels or blood vessels and osteolysis caused by osteoclast proliferation or increased activity. At present, there is no unified conclusion regarding Gorham syndrome’s pathogenesis. This paper starts with the two most studied osteolysis methods at present, osteoclast osteolysis and osteolysis caused by vascular and lymphatic proliferation and summarizes the corresponding most possible molecular mechanisms in recent years to provide more ideas for Gorham syndrome treatment.
Iguratimod as an alternative therapy for systemic sclerosis and prevention of the occurrence of ischemic digital ulcer

Objectives This study aimed to assess the effectiveness of iguratimod (IGU) as an alternative treatment for systemic sclerosis (SSc), especially in the prevention of ischemic digital ulcers (DUs). Methods We constructed two cohorts from the Renji SSc registry. In the first cohort, SSc patients receiving IGU were observed prospectively with effectiveness and safety. In the second cohort, we picked up all the DU patients with at least a 3-month follow-up to investigate the prevention of IGU on ischemic DU. Results From 2017 to 2021, 182 SSc patients were enrolled in our SSc registry. A total of 23 patients received IGU. With a median follow-up of 61 weeks (IQR: 15–82 weeks), the drug persistence was 13/23. In total, 91.3% of the patients (21/23) became free of deterioration in the last visit with IGU. Of note, 10 patients withdrew from the study due to the following reasons: two patients withdrew due to deterioration, three due to incompliance, and five due to mild-to-moderate side effects. All the patients with side effects recovered fully after stopping IGU. Of note, 11 patients had ischemic DU, and 8 out of 11 (72.7%) patients had no new occurrence of DU during the follow-up. In the second cohort of 31 DU patients receiving a combination of vasoactive agents with a median follow-up of 47 weeks (IQR, 16–107 weeks), IGU treatment was protective of new DU occurrence (adjusted risk ratio = 0.25; 95% CI, 0.05–0.94; adjusted odds ratio = 0.07; and 95% CI, 0.01–0.49). Conclusion Our study for the first time describes the potential of IGU possibly as an alternative treatment for SSc. To our surprise, this study provides a hint that IGU treatment can be used for the prevention of the occurrence of ischemic DU and merits further investigation.
Structural changes and carbon reduction due to habitat loss in Atlantic Forest

Habitat loss is a significant threat to biodiversity in tropical forests, leading to changes in composition, structure, and function. In this study, we aimed to evaluate the influence of the forest amount at the landscape scale on the structure and the stored carbon of tree communities. Eleven landscape samples of 36 km2 (6 × 6 km), with different amounts of forest cover at the landscape scale (between 5 and 60%), were randomly selected within a wide latitudinal range of Atlantic Forests in Brazil. We also used a sample design to control and avoid some biases in landscape-scale studies during the landscape selection, such as the rescue effect from the surrounding landscapes, differences in matrix permeability in each landscape, and the control for the same vegetation type or successional stage. In each selected landscape, we surveyed all woody individuals with a diameter at breast height (DBH) ≥ 2.5 cm in eight plots of 250 m2, randomly placed in the landscape’s forested areas. The structural variables evaluated were: total abundance, the abundance of prominent families, the abundance of large trees (DBH ≥ 30 cm), mean DBH, and average height, besides carbon storage. From the set of 8,179 individuals, we observed a positive correlation between forest amount and the total abundance, the abundance of large trees, and carbon stock. The abundance of the prominent hardwood tree families were positively correlated with forest amount. When comparing the two landscapes with the lowest proportion of habitats (5–15%) and the highest proportion (55−60%), almost one thousand trees and more than 150 T of carbon per hectare are lost. This reduction in the overall abundance and carbon indicates no compensatory effects on the tree community due to a turnover in composition or substitution of large trees for smaller ones. The Atlantic Forest is undergoing a process of homogenization and functional collapse, derived directly or indirectly from habitat loss, leading to a possible regime shift.