Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine

Autophagy is a fundamental catabolic process essential for development, homeostasis and proper immune function 1. During autophagy, a cascade of ATG proteins target intracellular cargoes for lysosomal degradation and recycling 2. This pathway utilises a unique post-translational modification, the conjugation of ATG8 proteins to phosphatidylethanolamine (PE) at autophagosomes, which modulates cargo selection and maturation. ATG8 lipidation also occurs during non-canonical autophagy, a parallel pathway involving Single Membrane ATG8 Conjugation (SMAC) to endolysosomal compartments, which plays a key role in phagocytosis and other processes 3. It has been widely assumed that SMAC involves the same lipidation of ATG8 to PE, but this has yet to be formally tested. Here, we show that ATG8 undergoes alternative lipidation to phosphatidylserine (PS) during non-canonical autophagy/SMAC. Using mass spectrometry, we find that activation of SMAC, by pharmacological agents 4,5, or during non-canonical autophagy processes such as LC3-associated phagocytosis 6,7 and Influenza A virus infection 8, induces the covalent conjugation of ATG8 to PS, as well as PE. This alternative lipidation event is dependent on the ATG16L1 WD40 domain, and occurs at PS enriched endolysosomal membranes. Importantly, we find that the ATG8-PS and ATG8-PE adducts are differentially delipidated by isoforms of the ATG4 family, indicating significant molecular distinctions and mechanisms between these two species. Together, these results provide an important new insight into autophagy signalling, revealing an alternative form of the hallmark ATG8-lipidation event, so widely used to define and assay autophagy. Furthermore, ATG8-PS lipidation provides a specific ‘molecular signature’ for non-canonical autophagy, uncovering a novel means of detecting and monitoring this emerging pathway.
A framework for designing miRNA-based distributed cell classifier circuits

Motivation Cell classifiers are synthetic bio-devices performing type-specific in vivo classification. The circuits identify a cell state based on its molecular fingerprint. In particular, the classifiers may be designed to recognize cancerous cells and trigger their apoptosis, shaping a novel therapy for cancer patients. Recently, we introduced a new theoretical design of such devices employing distributed classifiers. Here, a group of single-circuit classifiers decides collectively according to a pre-defined threshold function whether a cell is cancerous. The multi-circuit architecture has shown the potential to predict the cell condition with high accuracy. However, lack of far-reaching machinery to design and evaluate distributed cell classifiers, in particular, assessing their robustness to noise and novel information, makes their application limited. Results In this study, we present a comprehensive framework for designing and evaluating miRNA-based distributed cell classifiers comprising data simulation, pre-processing, and an extensive testing scheme. We develop optimization criteria that allow increasing the accuracy and robustness of classifiers to noise and novel information as shown in simulated and real-world data studies. The evaluation performed on cancer data demonstrates that distributed classifiers outperform single-circuit designs in terms of prediction accuracy. Our classifiers include relevant miRNAs previously described in the literature, as well as more complex regulation patterns included in the data. Availability The code and data are available at: https://github.com/MelaniaNowicka/RAccoon. Contact m.nowicka@fu-berlin.de
CCR4-NOT complex nuclease Caf1 is a novel shuttle factor involved in the degradation of ubiquitin-modified proteins by 26S proteasome

Protein degradation by ubiquitin proteasome system (UPS) is the major selective proteolytic pathway responsible for the degradation of short lived proteins ranging from regulatory proteins to abnormal proteins. Many diseases are associated with abnormal protein degradation; occasionally such dysregulated protein degradation is compensated by various transcriptional and translational control mechanisms in the cell. Among those pathways CCR4-NOT protein complex is responsible for transcriptional and transitional control of various gene expressions. Furthermore, CCR4-NOT complex also has a RING type ubiquitin ligase (E3) which is required for the degradation of several proteins. Here we report a novel function that the CCR4-NOT complex 3’-5’ exonuclease Caf1 is involved in ubiquitindependent degradation of short lived proteins by the 26S proteasome in yeast Saccharomyces cerevisiae. caf1 deletion results in stabilization of R-Ura3 (N-end rule) and Ub-V76-Ura3 (Ubiquitin fusion degradation) substrates from proteasomal degradation. Additionally, caf1 deletion accumulates ubiquitin-modified Ub-V76-Ura3 proteins and Caf1 binds to poly-ubiquitin conjugates and linear tetra ubiquitin chains. Surprisingly, Caf1 interacts with 19S regulatory particle complex of the 26S proteasome. Therefore, we conclude that Caf1 has an exciting novel function as an ubiquitin shuttle factor in which Caf1 targets ubiquitin-modified proteins to 26S proteasome for efficient degradation.
Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms

The recent proliferation of published TRP channel structures provides a foundation for understanding the diverse functional properties of this important family of ion channel proteins. To facilitate mechanistic investigations, we constructed a structure-based alignment of the transmembrane domains of 120 TRP channel structures. Comparison of structures determined in the absence or presence of activating stimuli reveals similar constrictions in the central ion permeation pathway near the intracellular end of the S6 helices, pointing to a conserved cytoplasmic gate and suggesting that most available structures represent non-conducting states. Comparison of the ion selectivity filters towards the extracellular end of the pore supports existing hypotheses for mechanisms of ion selectivity. Also conserved to varying extents are hot spots for interactions with hydrophobic ligands, lipids and ions, as well as discrete alterations in helix conformations. This analysis therefore provides a framework for investigating the structural basis of TRP channel gating mechanisms and pharmacology, and, despite the large number of structures included, reveals the need for additional structural data and for more functional studies to establish the mechanistic basis of TRP channel function.
Phylogeny, classification and species delimitation in the liverwort genus Odontoschisma (Cephaloziaceae)

A species-level phylogeny of Odontoschisma (Jungermanniidae: Cephaloziaceae) was produced to revisit the infrageneric classification and delimit the species within the genus. New methods of species delimitation have been used to explicitly contrast taxonomic hypotheses and test the relevance of the morphological traits traditionally used in this group. The results confirm previous evidence suggesting that the circumscription of Odontoschisma needs to be enlarged to include Iwatsukia and Cladopodiella, and further indicate that a third genus, Anomoclada, is nested within it. Twentythree molecular entities were recognized based the results of generalized mixed Yule-coalescent (GMYC) analyses. These entities partly conflicted with traditionally defined species that were shown to belong to different, not necessarily closely related entities, adding to the growing body of evidence calling for an extensive revision of species delimitations in taxa with reduced morphologies like leafy liverworts, using an integrative taxonomic approach. A fully revised classification of Odontoschisma into five sections, twenty species, and three subspecies is presented. While the species reported from Europe, Asia and North America were of polyphyletic origins, all Neotropical species were resolved as monophyletic, which could result from a combination of fast speciation rates and reduced dispersal in the Neotropics, and potential extinction in other areas, especially sub-Saharan Africa.
Analytical and Clinical Comparison of Three Nucleic Acid Amplification Tests for SARS-CoV-2 Detection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 and has quickly become a worldwide pandemic. In response, many diagnostic manufacturers have developed molecular assays for SARS-CoV-2 under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) pathway. This study compared three of these assays, the Hologic Panther Fusion SARS-CoV-2 assay (Fusion), the Hologic Aptima SARS-CoV-2 assay (Aptima), and the BioFire Defense COVID-19 test (BioFire), to determine analytical and clinical performance as well as workflow. ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 and has quickly become a worldwide pandemic. In response, many diagnostic manufacturers have developed molecular assays for SARS-CoV-2 under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) pathway. This study compared three of these assays, the Hologic Panther Fusion SARS-CoV-2 assay (Fusion), the Hologic Aptima SARS-CoV-2 assay (Aptima), and the BioFire Defense COVID-19 test (BioFire), to determine analytical and clinical performance as well as workflow. All three assays showed similar limits of detection (LODs) using inactivated virus, with 100% detection, ranging from 500 to 1,000 genome equivalents/ml, whereas use of a quantified RNA transcript standard showed the same trend but had values ranging from 62.5 to 125 copies/ml, confirming variability in absolute quantification of reference standards. The clinical correlation found that the Fusion and BioFire assays had a positive percent agreement (PPA) of 98.7%, followed by the Aptima assay at 94.7%, compared to the consensus result. All three assays exhibited 100% negative percent agreement (NPA). Analysis of discordant results revealed that all four samples missed by the Aptima assay had cycle threshold (Ct) values of >37 by the Fusion assay. In conclusion, while all three assays showed similar relative LODs, we showed differences in absolute LODs depending on which standard was employed. In addition, the Fusion and BioFire assays showed better clinical performance, while the Aptima assay showed a modest decrease in overall PPA. These findings should be kept in mind when making platform testing decisions.
Production and Harvest of Anadromous Striped Bass Stocks along the Atlantic Coast

Abstract Production indices for juvenile striped bass Morone saxatilis in the Chesapeake Bay and Roanoke River-Albemarle Sound regions have declined in recent years. A concurrent decline in harvest of striped bass along the Atlantic coast also has been observed. Lack of the occurrence of a dominant year class in the Chesapeake Bay since 1970 has affected the coastal harvest and the abundance of the spawning populations. Occurrence of another dominant year class will depend on two factors: Relatively good survival between the egg and juvenile life stages; and a sufficient amount of egg deposition to take advantage of the good survival conditions.
Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila

The final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.
Loss of FSTL1-expressing adipocyte progenitors drives the age-related involution of brown adipose tissue

In humans, brown adipose tissue (BAT) undergoes progressive involution or atrophy with increasing age, as manifested by decreased prevalence and mass, transformation to white adipose tissue (WAT), and reduction in thermogenic activity. This involution process cannot be fully recapitulated in rodent models and thus underlying cellular mechanisms are poorly understood. Here, we show that the interscapular BAT (iBAT) in rabbits involutes rapidly in early life, similarly to that in humans. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied with the loss of brown adipogenic competence of their precursor cells. Through single-cell RNA sequencing, we surveyed the heterogenous populations of mesenchymal cells within the stromal vascular fraction of rabbit and human iBAT. An analogous FSTL1high population of brown adipocyte progenitors exists in both species while gradually disappear during iBAT involution in rabbits. In mice, FSTL1 is highly expressed by adipocyte progenitors in iBAT and genetic deletion of FSTL1 causes defective WNT signaling and iBAT atrophy in neonates. Our results underscore the BAT-intrinsic contribution from FSTL1high progenitors to age-related tissue involution and point to a potential therapeutic approach for obesity and its comorbidities. HIGHLIGHTS Rabbit BAT irreversibly transforms to WAT before puberty. iBAT adipocyte progenitors reprogram transcriptome and lose brown adipogenic ability. Comparable FSTL1high brown adipocyte progenitors exist in rabbit and human iBAT. Loss of FSTL1 in brown adipocyte progenitors causes iBAT atrophy in mice.
BrainGNN: Interpretable Brain Graph Neural Network for fMRI Analysis

Understanding how certain brain regions relate to a specific neurological disorder or cognitive stimuli has been an important area of neuroimaging research. We propose BrainGNN, a graph neural network (GNN) framework to analyze functional magnetic resonance images (fMRI) and discover neurological biomarkers. Considering the special property of brain graphs, we design novel ROI-aware graph convolutional (Ra-GConv) layers that leverage the topological and functional information of fMRI. Motivated by the need for transparency in medical image analysis, our BrainGNN contains ROI-selection pooling layers (R-pool) that highlight salient ROIs (nodes in the graph), so that we can infer which ROIs are important for prediction. Furthermore, we propose regularization terms - unit loss, topK pooling (TPK) loss and group-level consistency (GLC) loss - on pooling results to encourage reasonable ROI-selection and provide flexibility to preserve either individual- or group-level patterns. We apply the BrainGNN framework on two independent fMRI datasets: Autism Spectral Disorder (ASD) fMRI dataset and Human Connectome Project (HCP) 900 Subject Release. We investigate different choices of the hyperparameters and show that BrainGNN outperforms the alternative fMRI image analysis methods in terms of four different evaluation metrics. The obtained community clustering and salient ROI detection results show high correspondence with the previous neuroimaging-derived evidence of biomarkers for ASD and specific task states decoded for HCP.
Changes in ascorbic acid, beta‐carotene and sensory properties in Sundried and stored Amaranthus hybridus vegetables

Amaranthus hybridus was grown as a leafy vegetable in Dar‐Es‐Salaam, Tanzania. Freshly harvested leaves were analyzed for moisture content, beta‐carotene and reduced ascorbic acid. The leaves from the four sites were bulked, blanched and sundried with shade provision drier. The dried samples were stored in polythene bags at 22°C, 28°C and room temperature (30°C to 32°C). At the beginning and thereafter every month during storage, the vegetables were analyzed for beta‐carotene and ascorbic acid and subjected to sensory evaluation in comparison with fresh cooked leaves. Sundrying of the amaranth leaves resulted in significant reductions (P < 0.05) in the levels of ascorbic acid and beta‐carotene, of 87.4% and 16.3% respectively. After storage of the dried vegetables for three months, the retention at 22 ° C, 28 ° C and room temperature of ascorbic acid and beta‐carotene were 42, 40 and 36 mg/100g and 32.4, 29.5 and 27.4 mg/100 g dwb respectively. Sensoric quality evaluation of amaranth leaves showed that significant differences (P < 0.05) existed in appearance and colour, flavour, texture and overall acceptability, although the dried vegetables were still acceptable in all the sensory characteristics tested. The study established that the vegetables could be dried to produce an acceptable product which maintained its eating quality for up to three months in storage.
Perioperative outcomes of the patients treated using laparoscopic cholecystectomy after emergent endoscopic retrograde cholangiopancreatography for bile duct stones: Does timing matter?

BACKGROUND There is no consensus on the optimal timing for laparoscopic cholecystectomy (LC) after emergent endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis. Although certain data suggest that an early interval or single-stage treatment by LC, together with laparoscopic bile duct exploration, has more favorable outcomes, delayed LC is most often preferred as the standard treatment of patients with gallstones and choledocholithiasis following ERCP due to lack of experience, necessary instrumentation, or organizational restrictions. This study aims to compare the effects of different time intervals between ERCP and LC on perioperative outcomes. METHODS In this paper, preoperative and postoperative data from consecutive patients who were treated for common bile duct stones with emergent ERCP and then underwent LC were reviewed retrospectively. To evaluate the impacts of different time intervals on outcomes, patients were classified into three groups according to the duration from the last ERCP to LC: within two weeks (Group 1), between 2-6 weeks (Group 2), and over six weeks (Group 3). RESULTS This study involved an analysis of 67 patients with a mean age of 52.8 years. Overall conversion rate was 20.0% in Group 1, 25.0% in Group 2, and 13.6% in Group 3 (p=0.646). The rate of conversion to open surgery was 25.0% in male patients and 14.2% in females. In addition, no significant difference was found between the groups concerning gender, comorbidities, laboratory and gallbladder features, operation time, and length of the hospital stay. The perioperative complication rate was found to be 17.9%; however, there was no significant difference between the three groups. CONCLUSION Our results support that LC after ERCP is more complex and has higher conversion rates than LC for uncomplicated cholelithiasis. Although no significant effect of different time intervals between ERCP and LC on perioperative outcomes was demonstrated in patients with common bile duct stones concomitant with cholelithiasis, the 2-6 weeks after ERCP is a critical period for conversion to open surgery. It is recommended that LC after ERCP should be performed in the early period, considering that serious complications may occur in the late period and recurrent biliary attacks may occur.
Prostaglandin F2α Receptors on Enzyme-Dissociated Pig Luteal Cells throughout the Estrous Cycle*

A deficiency of luteal cell prostaglandin F2α (PGF2α) receptors might help explain the well documented refractoriness of pig corpora lutea to the luteolytic effects of PGF2α administered in vivo before day 12 of the estrous cycle. Accordingly, experiments were conducted to measure the levels of [3H] PGF2α-binding sites/receptors on collagenase-dispersed pig luteal cells taken at different stages of the estrous cycle. Pig corpora lutea were obtained surgically at various stages of the estrous cycle and dissociated with collagenase in medium 199. Dissociated mixed luteal cells (-5-15 X 104 large luteal cells/ tube) were assayed for [3H]PGF2a-binding activity by saturation (Scatchard) analysis. In preliminary experiments it was determined that PGF2o binding was maximal after incubation for 45 min at 30 C in assay buffer of pH 5.75. Additionally, it was determined that [3H]PGF2α binding was displaceable by PGF2α = PGD2 > PGE2 > 13,14-dihydro-15-keto-PGF2α. Other eicosanoids did not inhibit [3H]PGF2α binding.
DNA, Phylogeny, and the Flowering of Plant SystematicsMolecular technology now produces data easily, but its analysis is fraught with theoretical and technical problems

hese are challenging and exciting times for systematics, the field that George Gaylord Simpson defined in his classic 1961 book as "the scientific study of the kinds and diversity of organisms and of any and all relationships among them. " Challenging times, because it is clear that the single scientific discipline fundamentally concerned with identifying, cataloging, naming, and reconstructing the history of biological diversity must assume a central role in the worldwide struggle to preserve the threatened biota. Exciting times, because over the past few decades there has been considerable progress in systematics, and the field is now equipped with the theoretical and empirical tools needed to meet such a challenge. Three important developments together have amounted to a revolution in systematics. First and most important has been the rigorous theory of phylogenetic reconstruction based on the principles of Hennig (1966), which has provided a conceptual foundation for the field. Second, advances in computer technology have enabled the objective analysis required by phylogenetic theory to progress beyond the original crude manual methods for constructing evolutionary trees. Finally, and most recently, the molecular biological revolution has generated an explosion of data from which