Miracle-dz/UniFAR-FTUs huggingface dataset:
cpSRP54 and FtsH cooperate thylakoid membrane associated proteostasis during de-etiolation in Arabidopsis thaliana

The thylakoid membrane protein quality control, which requires the coordination of membrane protein translocation and degradation of unassembled proteins, determines the chloroplast development during de-etiolation. Despite numerous efforts, the regulation of this progress in land plants is largely unknown. Here, we reported the isolation and characterization of pga4 mutants with defects in chloroplast development during de-etiolation. Map-based cloning and complementation assay confirmed that PGA4 encodes the chloroplast signal recognition particle 54 kDa protein (cpSRP54). A heterogeneous LhcB2-GFP was generated as an indicative substrate for cpSRP54-mediated thylakoid translocation. LhcB2-GFP were not assembled into functional complexes, and degraded to a short form dLhcB2-GFP during de-etiolation, through an N-terminal degradation initiated on thylakoid membranes. Further biochemical and genetic evidences demonstrated that the degradation of LhcB2-GFP to dLhcB2-GFP was disrupted in pga4, and var2 mutants caused by mutations in the VAR2/AtFtsH2 subunit of thylakoid FtsH. The yeast two-hybrid assay showed that the N-terminus of LhcB2-GFP which was degraded consequently, interacts with the protease domain of VAR2/AtFtsH2 in yeasts. Moreover, the over-accumulated LhcB2-GFP in pga4 and var2, formed protein aggregates, which were insoluble in mild nonionic detergents. Genetically, cpSRP54 is a new suppressor locus for the leaf variegation phenotype of var2. Those together demonstrated the coordination of cpSRP54 and thylakoid FtsH in maintenance of thylakoid membrane protein quality control during the assembly of photosynthetic complexes, and provided a trackable substrate and product for monitoring the cpSRP54-dependent protein translocation and the FtsH-dependent protein degradation. One Sentence Summary We revealed the coordination of cpSRP54 and FtsH in thylakoid membrane protein quality control, and provided a trackable marker for monitoring the activity of cpSRP54 and thylakoid FtsH protease.
Anemonefish have finer color discrimination in the ultraviolet

In many animals, ultraviolet (UV) vision guides navigation, foraging, and communication, but few studies have addressed the contribution of UV vision to color discrimination, or behaviorally assessed UV discrimination thresholds. Here, we tested UV-color vision in an anemonefish (Amphiprion ocellaris) using a novel five-channel (RGB-V-UV) LED display designed to test UV perception. We first determined that the maximal sensitivity of the A. ocellaris UV cone was at ∼386 nm using microspectrophotometry. Three additional cone spectral sensitivities had maxima at ∼497, 515, and ∼535 nm, which together informed the modelling of the fish’s color vision. Anemonefish behavioral discrimination thresholds for nine sets of colors were determined from their ability to distinguish a colored target pixel from grey distractor pixels of varying intensity. We found that A. ocellaris used all four cones to process color information and is therefore tetrachromatic, and fish were better at discriminating colors (i.e., color discrimination thresholds were lower, or more acute) when targets had UV chromatic contrast elicited by greater stimulation of the UV cone relative to other cone types. These findings imply that a UV component of color signals and cues improves their detectability, that likely increases the salience of anemonefish body patterns used in communication and the silhouette of zooplankton prey.
Blochmannia endosymbionts reduce brood rearing success in a carpenter ant (Camponotus sp.)

All ants of the species rich genus Camponotus (‘carpenter ants’) possess the obligate intracellular bacterial mutualist Blochmannia. We tested the relevance of the endosymbiont Blochmannia for offspring rearing using cross-fostering experiments between Camponotus sp. colonies and subcolonies (worker groups), which were either treated with antibiotics to remove Blochmannia or untreated. Our antibiotic treatment reduced the level of Blochmannia endosymbionts in eggs, larvae and workers significantly. Corroborating previous results, we found that eggs from treated colonies had a significantly reduced probability to develop into larvae and almost zero probability to become adults. Surprisingly, subcolonies treated with antibiotics had a significantly higher success in raising their own and foreign eggs from treated and untreated colonies than untreated subcolonies. This might indicate that the Blochmannia symbiosis entails significant costs for the host in terms of brood rearing, i.e., symbiont-free workers are more successful in brood rearing than untreated workers. If confirmed, this would be a rare case where the costs of a symbiosis can be empirically measured and quantified. Alternatively, the antibiotic treatment increased as a side effect the brood rearing effort of workers leading to the differences in brood rearing success of treated workers. But even if that would be the case, it still indicates that workers that have either lost or have a significantly reduced number of endosymbionts can still raise brood from antibiotic-treated and untreated colonies better than untreated workers. Thus Blochmannia, although crucial for brood development, may reduce the amount of brood a colony can raise.
Impacts of ocean acidification and warming on post-larval growth and metabolism in two populations of the great scallop (Pecten maximus L.)

Ocean acidification and warming are key stressors for many marine organisms. Some organisms display physiological acclimatisation or plasticity, but this may vary across species ranges, especially if populations are adapted to local climatic conditions. Understanding how acclimatisation potential varies among populations is therefore important in predicting species responses to climate change. We carried out a common garden experiment to investigate how different populations of the economically important great scallop (Pecten maximus) from France and Norway responded to variation in temperature and pCO2 concentration. After acclimation, post-larval scallops (spat) were reared for 31 days at one of two temperatures (13°C and 19°C) under either ambient or elevated pCO2 (pH 8.0 and pH 7.7). We combined measures of proteomic, metabolic, and phenotypic traits to produce an integrative picture of how physiological plasticity varies between the populations. The proteome of French spat showed significant sensitivity to environmental variation, with 12 metabolic, structural and stress-response proteins responding to temperature and/or pCO2. Principal component analysis revealed seven energy metabolism proteins in French spat that were consistent with countering ROS stress under elevated temperature. Oxygen uptake in French spat did not change under elevated temperature, but increased under elevated pCO2. In contrast, Norwegian spat reduced oxygen uptake under both elevated temperature and pCO2. Metabolic plasticity seemingly allowed French scallops to maintain greater energy availability for growth than Norwegian spat. However, increased physiological plasticity and growth in French spat may come at a cost, as French (but not Norwegian) spat showed reduced survival under elevated temperature. Summary Statement Juvenile scallops from France and Norway differ in their response to warming and acidification. French scallops show more physiological plasticity, adjusting their proteome and metabolism in order to maintain growth.
MC1R reduces scarring and rescues stalled healing in a novel preclinical chronic wound model

Cutaneous wound repair typically proceeds uneventfully, resulting in scar formation; however, chronic non-healing wounds (CWs) represent a global and escalating health burden causing substantial morbidity and mortality. Estimated to cost Medicare up to $96.8 billion pa and with a profound paucity of effective therapeutics, novel interventions to rescue the stalled healing response of CWs are urgently needed. In this study, we assess the impact of melanocortin 1 receptor (MC1R) agonism on acute wound healing using a selective agonist, BMS-470539 (MC1R-Ag). MC1R-Ag accelerated wound closure and reepithelialisation in wildtype but not MC1Re/e mice, which harbour a non-functional receptor. MC1R-Ag improved wound perfusion and lymphatic drainage by promoting angiogenesis and lymphangiogenesis, reducing local oxidative stress and inflammation with a knock-on effect of reduced scarring. To assess whether manipulating MC1R would be of benefit in pathological healing, we developed a novel murine model of CWs. By combining advanced age and locally elevated oxidative stress, factors shown to be present in most human CWs regardless of category, resultant wounds expand into the surrounding tissue, generate exudate and slough. Histological comparisons to human CWs demonstrate robust recapitulation of the hallmarks of human disease, including hyperproliferative epidermis and fibrinous exudate. Leveraging this model, we demonstrate that topical administration of MC1R-Ag, following ulcer debridement, rescues the stalled healing response, whereas abrogation of MC1R signalling in MC1Re/e mice exacerbates CWs. Collectively, we highlight MC1R agonism as a candidate therapeutic approach for acute and CWs and remove a critical barrier in CW research by providing a novel preclinical model.
Hardness Evolution of Solution-Annealed LPBFed Inconel 625 Alloy under Prolonged Thermal Exposure

: Thanks to its high weldability, Inconel 625 (IN625) can be easily processed by laser powder bed fusion (LPBF). After production, this alloy is typically subjected to speciﬁc heat treatments to design speciﬁc microstructure features and mechanical performance suitable for various industrial applications, including aeronautical, aerospace, petrochemical, and nuclear ﬁelds. When employed in structural applications, IN625 can be used up to around 650 ◦ C. This limitation is mainly caused by the transformation of metastable γ ” phases into stable δ phases occurring under prolonged thermal exposure, which results in drastically reduced ductility and toughness of the alloy. Because the microstructure and mechanical properties change during thermal exposure, it is essential to study the material simulating possible service temperatures. In the current study, LPBFed IN625 samples were solution-annealed and then subjected to thermal exposure at 650 ◦ C for different times up to 2000 h. The characterization focused on the evolution of the main phases, γ ” and δ phases, and their inﬂuence on the hardness evolution. The microstructure and hardness of the heat-treated LPBFed IN625 samples were compared with data related to the traditionally processed IN625 alloy (e.g., wrought state) reported in the literature.
Cálculo de grupos de homotopia dos grupos clássicos

The main purpose of this work is to calculate homotopy groups of some classical groups as the rotation groups of the euclidean space R, SO(n), the unitary group U(n), your special unitary subgroup SU(n) and the symplectic group Sp(n). For these calculus we will use exact sequences and properties relacionated to the fibre bundle.
Current Themes and Controversies in the Alzheimer’s Disease Field: Looking Ahead to the CTAD Meeting in San Francisco, November 29–December 2 2022

During the 23 years since Dale Schenk demonstrated that injection of amyloid beta into mice generated antiamyloid antibodies which removed amyloid plaques (1), there have been many efforts to demonstrate the effectiveness of this approach in humans. There have been numerous negative trials, often associated with serious adverse effects, leading many to say that this approach is doomed to failure and that the “amyloid hypothesis” (2) has little merit. The experience with Biogen’s Aducanumab (Aduhelm), a mAb that significantly lowered amyloid plaques in humans (3) was mixed for several reasons. First, they halted their two Phase 3 trials early (apparently because of futility) only then to show that one (but not both) of the trials demonstrated significant slowing of progression. Additionally there were significant side effects, mostly ARIA. Second, the FDA advisory panel strongly recommended not to approve Aducanumab, but the FDA granted accelerated approval based on amyloid plaque removal. Finally, the Center for Medicare Services (CMS) declined to reimburse for Aduhelm, leading to extremely little clinical use. Then, a press release from Eisai last month reported that their single Phase 3 study of Lecanemab, another plaque clearing mAb, met its primary and secondary endpoints, with a significant 27% slowing of the decline in CDR sum of boxes. We have few details of this study, but Eisai is scheduled to present at CTAD and we eagerly await the data. Furthermore, Roche has completed its Phase 3 study of Gantenerumab, and they have informed the CTAD that they also wish to present their results. As of this writing these have not been announced. The Eisai and Roche presentations alone will make this CTAD meeting very informative and exciting. There will be panel discussions of the data, and there will be opportunities for panelists and speakers from the audience to voice their enthusiasm, questions, and concerns about these studies. There are some (including myself) who believe that the cognitive decline associated with plaque clearing mAbs has clinical significance and affirms the amyloid hypothesis, but others disagree and all voices will be heard.
Austral summer of 1998: Observations on El Niño and the North Patagonian Icefield

In February 1998 we visited the Nef Glacier (47”07’S, 73’12’W) on the east side of the North Patagonian Icefield, in southern Chile, as part of a long-term project aimed at investigating the links between recent glacier fluctuations around the icefield and climate change. Of particular interest for our study is the effect of strong El Niiio Southern Oscillation (ENSO) events on icefield and glacier ablation in the region. Our expedition took place during one of the strongest ENSO events of this century in a region where weather stations are scarce and many gather precipitation data only (Fig. 1). Although satellite data have, to some extent, remedied the lack of year-round observations over southern Chile and the south-eastern Pacific, detailed ground observations are still scarce and teleconnections with El Niiio are only studied in outline with research mainly focused on the more populated regions of central Chile (e.g. Yarnal 1985; Aceituno 1987; Rutllant and Fuenzalida 199 1). However, generalised outlines can be misleading as, for example, that published in the Climate Diagnostics Bulletin of January and February 1998: “Enhanced westerlies have produced increased storminess and above-normal precipitation across much of the eastern South Pacific and South America”. Although the weather in central Chile in the months preceding and during our expedition was unusually wet and cool, this was not true for latitudes between 40 and 50”s. The weather over the southern Andes during the austral summer of 1998, in the latitudes of the roaring forties, normally among the most stormy and wet in the world, was exceptionally stable, dry and SUMY ideal expedition weather. Background
Biocide-Resistant Escherichia coli ST540 Co-Harboring ESBL, dfrA14 Confers QnrS-Dependent Plasmid-Mediated Quinolone Resistance

Emerging sequence types of pathogenic bacteria have a dual ability to acquire resistance islands/determinants, and remain renitent towards disinfection practices; therefore, they are considered “critical risk factors” that contribute significantly to the global problem of antimicrobial resistance. Multidrug-resistant Escherichia coli was isolated, its genome sequenced, and its susceptibilities characterized, in order to understand the genetic basis of its antimicrobial resistance.The draft genome sequencing of E. coli ECU32, was performed with Illumina NextSeq 500, and annotated using a RAST server. The antibiotic resistome, genomic island, insertion sequences, and prophages were analyzed using bioinformatics tools. Subsequently, analyses including antibiotic susceptibility testing, E-test, bacterial growth, survival, and efflux inhibition assays were performed.The draft genome of E. coli ECU32 was 4.7 Mb in size, the contigs were 107, and the G+C content was 50.8%. The genome comprised 4658 genes, 4543 CDS, 4384 coding genes, 115 RNA genes, 88 tRNAs, and 3 CRISPR arrays. The resistome characterization of ST540 E. coli ECU32 revealed the presence of ESBL, APH(6)-Id, APH(3′)-IIa, dfrA14, and QnrS1, with broad-spectrum multidrug and biocide resistance. Comparative genome sequence analysis revealed the presence of transporter and several virulence genes. Efflux activity and growth inhibition assays, which were performed with efflux substrates in the presence of inhibitor PAβN, exhibited significant reduced growth relative to its control.This study discusses the genotypic and phenotypic characterization of the biocide-tolerant multidrug-resistant E. coli O9:H30 strain, highlighting the contributory role of qnrS-dependent plasmid-mediated quinolone resistance, in addition to innate enzymatic modes of multidrug resistance mechanisms.
Real-world Challenges in Leveraging Electrocardiograms for Coronary Artery Disease Classification

This work investigates coronary artery disease (CAD) prediction from electrocardiogram (ECG) data taking into account different windows with respect to the time of diagnosis. We report that ECG waveform measurements automatically collected during ECG recordings contain sufficient features for good classification of CAD using machine learning models up to five years before diagnosis. On the other hand, convolutional neural networks trained on the ECG signals themselves appear to best extract CAD related features when processing data collected within one year before or after a diagnosis is made. Through this work we demonstrate that the type of ECG data and the time window with respect to diagnosis should guide model selection.
Care burden on family caregivers of patients with dementia and affecting factors in China: A systematic review

Background Dementia is a chronic and progressive illness characterized by severe impairment and high dependencies. Under the influence of Chinese traditional culture, 80% of patients with dementia are watched over at home by family caregivers as primary caregivers. However, long-term care brings formidable burdens to them and reduces the quality of their life. It is necessary to find out the influencing factors of caregivers’ burden. Methods A scoping search was conducted on eight electronic databases from 1 January 2010 to 14 June 2022: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, China VIP Database, China Biomedical Literature Database, and Wanfang Data Knowledge Service Platform. Research articles included in this review discussed the factors affecting Chinese dementia family caregivers’ care burden or stress, and the level of care burden was evaluated by a standardized care burden scale. Results A total of 1,888 related articles were found and 23 cross-sectional studies were eventually included. After quality assessment, 12 were of good quality and 11 were of fair quality. A total of 32 factors were identified that were associated with caregiver burden, and the results were grouped into three categories: patient, caregiver, and society. The severity of disease, poor self-care ability, neuropsychiatric symptoms, care time, number of helpers, poor health status, economic stress, poor psychological status, social support, and age were reported in many previous studies. Conclusion In this review, the factors that affect the caregiver burden for people with dementia were clarified. By identifying these factors, hospitals, decision-makers, and communities can carry out special projects for these populations, provide appropriate assistance, or design corresponding intervention measures to reduce the caregiver burden and improve the quality of care for patients with dementia. Systematic review registration [https://www.crd. york.ac. uk/PROSPERO/], identifier [CRD42022347816].
Accurate classification of lung nodules on CT images using the TransUnet

Background Computed tomography (CT) is an effective way to scan for lung cancer. The classification of lung nodules in CT screening is completely doctor dependent, which has drawbacks, including difficulty classifying tiny nodules, subjectivity, and high false-positive rates. In recent years, deep convolutional neural networks, a deep learning technology, have been shown to be effective in medical imaging diagnosis. Herein, we propose a deep convolutional neural network technique (TransUnet) to automatically classify lung nodules accurately. Methods TransUnet consists of three parts: the transformer, the Unet, and global average pooling (GAP). The transformer encodes discriminative features via global self-attention modeling on CT image patches. The Unet, which collects context by constricting route, enables exact lunge nodule localization. The GAP categorizes CT images, assigning each sample a score. Python was employed to pre-process all CT images in the LIDI-IDRI, and the obtained 8,474 images (3,259 benign and 5,215 lung nodules) were used to evaluate the method's performance. Results The accuracies of TransUnet in the training and testing sets were 87.90 and 84.62%. The sensitivity, specificity, and AUC of the proposed TransUnet on the testing dataset were 70.92, 93.17, and 0.862%, respectively (0.844–0.879). We also compared TransUnet to three well-known methods, which outperformed these methods. Conclusion The experimental results on LIDI-IDRI demonstrated that the proposed TransUnet has a great performance in classifying lung nodules and has a great potential application in diagnosing lung cancer.
PABPC1——mRNA stability, protein translation and tumorigenesis

Mammalian poly A-binding proteins (PABPs) are highly conserved multifunctional RNA-binding proteins primarily involved in the regulation of mRNA translation and stability, of which PABPC1 is considered a central regulator of cytoplasmic mRNA homing and is involved in a wide range of physiological and pathological processes by regulating almost every aspect of RNA metabolism. Alterations in its expression and function disrupt intra-tissue homeostasis and contribute to the development of various tumors. There is increasing evidence that PABPC1 is aberrantly expressed in a variety of tumor tissues and cancers such as lung, gastric, breast, liver, and esophageal cancers, and PABPC1 might be used as a potential biomarker for tumor diagnosis, treatment, and clinical application in the future. In this paper, we review the abnormal expression, functional role, and molecular mechanism of PABPC1 in tumorigenesis and provide directions for further understanding the regulatory role of PABPC1 in tumor cells.
New insights into the interplay between autophagy and cartilage degeneration in osteoarthritis

Autophagy is an intracellular degradation system that maintains the stable state of cell energy metabolism. Some recent findings have indicated that autophagy dysfunction is an important driving factor for the occurrence and development of osteoarthritis (OA). The decrease of autophagy leads to the accumulation of damaged organelles and macromolecules in chondrocytes, which affects the survival of chondrocytes and ultimately leads to OA. An appropriate level of autophagic activation may be a new method to prevent articular cartilage degeneration in OA. This minireview discussed the mechanism of autophagy and OA, key autophagy targets regulating OA progression, and evaluated therapeutic applications of drugs targeting autophagy in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.