Miracle-dz/UniFAR-FTUs huggingface dataset:
Codominance of two symbiont genera within the same coral host is associated with elevated symbiont productivity and lower host susceptibility to thermal stress

In recent years, as sea surface temperature increases, many coral species that used to harbor symbionts of the genus Cladocopium have become colonized with the thermally tolerant genus, Durusdinium. Here, we asked how the symbionts of one genus react to the presence of another symbiont genus within the same coral host, and what effect this interaction has on the host. We used previously published transcriptomic data from Acropora hyacinthus corals hosting Cladocopium and/or Durusdinium symbionts and looked at gene expression in all three symbiotic partners depending on the relative proportion of the two symbiont genera within the same host. We find that both Cladocopium and Durusdinium change their expression the most when their proportions within the host are nearly equal (the state that we call “codominance”): both genera elevate expression of photosynthesis and ribosomal genes, suggesting increase in photosynthesis and growth (i.e. higher productivity). At the same time, the coral host also elevates production of ribosomes suggesting faster cellular growth, and, when heated, shows less pronounced stress response. These results can be explained in two alternative ways. One explanation is that increased competition between codominant symbionts switches them to the higher productivity mode, which benefits the host, making it more resilient to stress. Alternatively, the symbionts’ elevated productivity might be not the cause but the consequence of the host being particularly healthy. Under this explanation, rapid growth of the healthy host creates new space, lowering the symbioints’ competition and thus promoting their growth, which allows for codominance to happen where one genus would otherwise outcompete another. The latter explanation is supported by the fact that codominance is associated with lower symbiont densities, assessed as relative proportions of symbiont reads in the data. Irrespective of the causation direction, the presence of mixed symbiont communities could potentially be used as an instant indicator of coral well-being, which would be a useful tool for coral conservation and restoration.
miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to affect muscle contractility upon proteotoxic challenge during ageing

Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also highly plastic, and remodelled in response to stress, growth, neural and metabolic inputs. The evolutionarily conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle biology during development, but whether it plays a role during ageing is unknown. Here we investigated the role of C. elegans miR-1 in muscle function in response to proteostatic stress during adulthood. mir-1 deletion results in improved mid-life muscle motility, pharyngeal pumping, and organismal longevity under conditions of polyglutamine repeat proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunit vha-13/ATP6VIA as a direct target downregulated via its 3’UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. In summary, our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during ageing.
Development of a Semantically Related Emotional and Neutral Stimulus Set

When measuring memory performance for emotional and neutral stimuli many studies are confounded by not controlling for differential semantic relatedness between stimulus sets. This could lead to the misattribution of the cause of an emotional enhancement of memory effect (EEM), because differential semantic relatedness also contributes to the EEM. Participants rated static visual emotional and neutral scenes on measures of arousal, valence, and semantic relatedness. These measures were used to create a novel stimulus set, which – in addition to demonstrating significant differences in measures of valence and arousal – also controlled for within-set semantic relatedness; thus resolving a crucial issue that has not previously been addressed in the use of visual emotional stimuli. As an added advantage, the stimulus set developed here are controlled for measures of objective visual complexity, also implicated as confounding to the investigation of memory. This article introduces a collection of emotional and neutral colour images which can be organised flexibly according to experimental requirements. These stimuli are made freely available for non-commercial use within the scientific community.
Ribosomal DNA revealed an extensive role of allopolyploidy in the radiation of Ulex L

We studied the phylogeny of Ulex L. , a genus of spiny legumes, which its center of diversity in the Iberian Peninsula, using ribosomal DNA markers (rDNA), namely ETS, 5.8S and ITS (45S), and 5S intergenic spacer regions. One of the main findings was the presence of very different haplotypes in 5S-IGS genes and, to a less extent, in ETS and ITS, in seven polyploid taxa. We interpreted these results as an indication of hybrid origins and proposed allopolyploidy for U. argenteus ssp. subsericeus, U. australis ssp. australis, U. australis ssp. welwitschianus, U. densus, U. europaeus ssp. europaeus, U. europaeus ssp. latebracteatus, and U. jussiaei. These results reinforce an early hypothesis which stated that the radiation of Ulex occurred mainly by polyplodization. Phylograms showed two main clades, one grouping the hydrophilic U. gallii, U. breoganii and U. minor, and the other grouping the southern, xerophytic, taxa. The putative allopolyploids showed haplotypes, which grouped in both clades, indicating that allopolyploidy, occurred through hybridization from these hydrophilic and xerophytic lineages. The phylogenetic position of U. micranthus is not certain and it is discussed. The 5S-IGS showed to retain more polymorphisms than ETS gene or ITS markers. This result is compatible with the hypothesis that 5S rDNA region is less vulnerable to inter-loci concerted evolution than 45S, providing a more suitable marker for reconstructing histories of allopolyploid species. We discuss the taxonomic consequences of these results.
A Conserved Machinery Underlies the Synthesis of a Chitosan Layer in the Candida Chlamydospore Cell Wall

The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies. ABSTRACT The polysaccharide chitosan is found in the cell wall of specific cell types in a variety of fungal species where it contributes to stress resistance, or in pathogenic fungi, virulence. Under certain growth conditions, the pathogenic yeast Candida dubliniensis forms a cell type termed a chlamydospore, which has an additional internal layer in its cell wall compared to hyphal or yeast cell types. We report that this internal layer of the chlamydospore wall is rich in chitosan. The ascospore wall of Saccharomyces cerevisiae also has a distinct chitosan layer. As in S. cerevisiae, formation of the chitosan layer in the C. dubliniensis wall requires the chitin synthase CHS3 and the chitin deacetylase CDA2. In addition, three lipid droplet-localized proteins—Rrt8, Srt1, and Mum3—identified in S. cerevisiae as important for chitosan layer assembly in the ascospore wall are required for the formation of the chitosan layer of the chlamydospore wall in C. dubliniensis. These results reveal that a conserved machinery is required for the synthesis of a distinct chitosan layer in the walls of these two yeasts and may be generally important for incorporation of chitosan into fungal walls. IMPORTANCE The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies. This study shows that a set of genes required for the assembly of a chitosan layer in the cell wall of S. cerevisiae is also necessary for chitosan formation in a different cell type in a different yeast, C. dubliniensis. Because chitosan incorporation into the cell wall can be important for virulence, the conservation of this pathway suggests possible new targets for antifungals aimed at disrupting cell wall function.
“Push and Pull”: Biomechanics of the Pollination Apparatus of Oncidium spp.

Comprising ca. 28,000, species the Orchidaceae constitute one of the most species-rich plant families. Orchids differ from other monocotyledons i.a. , in the formation of so-called pollinaria, which are entities consisting of pollen grains aggregated into compact pollinia and accessory structures, a viscidium and mostly also a pollinium stalk. The viscidium releases an adhesive material that attaches the pollinarium to a pollinator. Pollinaria are part of a complex pollination apparatus that enables the orchids to colonize niches in which only a few individuals of the respective pollinator occur infrequently. Because the aggregated pollen grains are removed from the flower at once, the development of a mechanical barrier ensuring that only suitable pollinators are able to access the flowers and more importantly to remove the pollen are important selective traits. In this paper we describe the functional morphology of the pollination apparatus in two orchid species, Oncidium wentworthianum and O. otogaya, by experimentally mimicking the pollination process. Furthermore, we analyzed the mechanical resistance of this apparatus by means of force measurements and showed that it most probably constitutes a hierarchical two-stage barrier. The first stage consists of the presence of the anther cap that not only protects the pollinia, but also serves to prevent premature removal of young and unripe pollinaria from the flower. As soon as the pollinaria are ripe, the anther cap sheds and the second stage of the mechanical barrier takes effect, a severable bond between pollinarium and rostellum. This bond can be overcome by a potential pollinator, applying a load of at least 10.8 mN (O. otogaya) or 12.6 mN (O. wentworthianum), respectively, on the viscidium which at the same time disengages the pollinarium from its anchorage. The adhesive material produced by the viscidium creates sufficient adhesive contact between pollinarium and pollinator. Potential pollinators, such as Centris spp. or Trigona spp. bees, should be well able to exert such forces by pushing their head/forebody into the orchid flowers. Thus, whether a pollinator is able to detach the pollinarium depends on both how forcefully it can push and how strongly it can pull the orchid pollination apparatus.
Interaction Between Phosphoinositide 3-Kinase and the VDAC2 Channel Tethers Endosomes to Mitochondria and Promotes Endosome Maturation

Intracellular organelles of mammalian cells communicate with each other during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identified voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 was found to tether endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and to promote clathrin-independent endocytosis as well as endosome maturation at membrane contact sites. With a newly developed optogenetics system to induce mitochondrion-endosome association, we found that, in addition to its structural role in such association, the pore function of VDAC2 is also required for the promotion of endosome maturation. Our findings thus uncover a previously unappreciated role of mitochondrion-endosome association in the regulation of endocytosis and endosome maturation. Highlights The mitochondrial protein VDAC2 binds PI3K and tethers endosomes to mitochondria VDAC2 promotes clathrin-independent endocytosis VDAC2-PI3K interaction induces acidification of endosomes associated with mitochondria The pore function of VDAC2 also contributes to endosome maturation at contact sites
Evaluation of the effects of SARS-CoV-2 genetic mutations on diagnostic RT-PCR assays

Several mutant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are emerging. Mismatch(es) in primer/probe binding regions would decrease the detection sensitivity of the PCR test, thereby affecting the results of clinical testing. In this study, we conducted an in silico survey on SARS-CoV-2 sequence variability within the binding regions of primer/probe published by the Japan National Institute of Infectious Diseases (NIID) and Centers for Disease Control and Prevention (CDC). In silico analysis revealed the presence of mutations in the primer/probe binding regions. We performed RT-PCR assays using synthetic RNAs containing the mutations and showed that some mutations significantly decreased the detection sensitivity of the RT-PCR assays. Our results highlight the importance of genomic monitoring of SARS-CoV-2 and evaluating the effects of mismatches on PCR testing sensitivity.
Homoepitaxy and Photoluminescence Properties of (0001) AlN

AlN layers are homoepitaxially grown on (0001) AlN substrates. The surfaces are atomically smooth, and the X-ray diffraction rocking curves for the symmetric and asymmetric planes indicate narrow line widths in the range of 10–30 arcsec. The oxygen, silicon, and carbon concentrations are below the detection limits of secondary ion mass spectroscopy. Due to these superior structural properties and low impurity concentrations, sharp free and donor-bound excitons dominate the photoluminescence spectra at low temperatures, while free excitons dominate at elevated temperatures.
Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance

The myeloma cell surface proteome (“surfaceome”) not only determines tumor interaction with the microenvironment but serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to first define surface markers most-enriched on myeloma when compared to B-cell malignancy models, revealing unexpected biological signatures unique to malignant plasma cells. We next integrate our proteomic dataset with existing transcriptome databases, nominating CCR10 and TXNDC11 as possible monotherapeutic targets and CD48 as a promising co-target for increasing avidity of BCMA-directed cellular therapies. We further identify potential biomarkers of resistance to both proteasome inhibitors and lenalidomide including changes in CD53, EVI2B, CD10, and CD33. Comparison of short-term treatment with chronic resistance delineates large differences in surface proteome profile under each type of drug exposure. Finally, we develop a miniaturized version of the surface proteomics protocol and present the first surface proteomic profile of a primary myeloma patient plasma cell sample. Our dataset provides a unique resource to advance the biological, therapeutic, and diagnostic understanding of myeloma.
Mutants libraries reveal negative design shielding proteins from mis-assembly and re-localization in cells

Understanding the molecular consequences of mutations in proteins is essential to map genotypes to phenotypes and interpret the increasing wealth of genomic data. While mutations are known to disrupt protein structure and function, their potential to create new structures and localization phenotypes has not yet been mapped to a sequence space. To map this relationship, we employed two homo-oligomeric protein complexes where the internal symmetry exacerbates the impact of mutations. We mutagenized three surface residues of each complex and monitored the mutations’ effect on localization and assembly phenotypes in yeast cells. While surface mutations are classically viewed as benign, our analysis of several hundred mutants revealed they often trigger three main phenotypes in these proteins: nuclear localization, the formation of puncta, and fibers. Strikingly, more than 50% of random mutants induced one of these phenotypes in both complexes. Analyzing the mutant’s sequences showed that surface stickiness and net charge are two key physicochemical properties associated with these changes. In one complex, more than 60% of mutants self-assembled into fibers. Such a high frequency is explained by negative design: charged residues shield the complex from misassembly, and the sole removal of the charges induces its assembly. A subsequent analysis of several other complexes targeted with alanine mutations suggested that negative design against mis-assembly and mislocalization is common. These results highlight that minimal perturbations in protein surfaces’ physicochemical properties can frequently drive assembly and localization changes in a cellular context.
Is This Within Reach? Left but Not Right Brain Damage Affects Affordance Judgment Tendencies

The ability to judge accurately whether or not an action can be accomplished successfully is critical for selecting appropriate response options that enable adaptive behaviors. Such affordance judgments are thought to rely on the perceived fit between environmental properties and knowledge of one's current physical capabilities. Little, however, is currently known about the ability of individuals to judge their own affordances following a stroke, or about the underlying neural mechanisms involved. To address these issues, we employed a signal detection approach to investigate the impact of left or right hemisphere injuries on judgments of whether a visual object was located within reach while remaining still (i.e., reachability). Regarding perceptual sensitivity and accuracy in judging reachability, there were no significant group differences between healthy controls (N = 29), right brain damaged (RBD, N = 17) and left brain damaged stroke patients (LBD, N = 17). However, while healthy controls and RBD patients demonstrated a negative response criterion and thus overestimated their reach capability, LBD patients' average response criterion converged to zero, indicating no judgment tendency. Critically, the LBD group's judgment tendency pattern is consistent with previous findings in this same sample on an affordance judgment task that required estimating whether the hand can fit through apertures (Randerath et al., 2018). Lesion analysis suggests that this loss of judgment tendency may be associated with damage to the left insula, the left parietal and middle temporal lobe. Based on these results, we propose that damage to the left ventro-dorsal stream disrupts the retrieval and processing of a stable criterion, leading to stronger reliance on intact on-line body-perceptive processes computed within the preserved bilateral dorsal network.
Characterization of the nanomechanical properties of the fission yeast (Schizosaccharomyces pombe) cell surface by atomic force microscopy

Variations in cell wall composition and biomechanical properties can contribute to the cellular plasticity required during complex processes such as polarized growth and elongation in microbial cells. This study utilizes atomic force microscopy (AFM) to map the cell surface topography of fission yeast, Schizosaccharomyces pombe, at regions of active polarized growth and to characterize the biophysical properties within these regions under physiological, hydrated conditions. High-resolution images acquired from AFM topographic scanning reveal decreased surface roughness at actively growing cell poles. Force extension curves acquired by nanoindentation probing with AFM cantilever tips under low applied force revealed increased cell wall elasticity and decreased cellular stiffness (cellular spring constant) at cell poles (17 ± 4 mN/m) relative to the main body of the cell that is not undergoing growth and expansion (44 ± 10 mN/m). These findings suggest that the increased elasticity and decreased stiffness at regions undergoing polarized growth at fission yeast cell poles provide the plasticity necessary for cellular extension. This is the first direct biophysical characterization of the S. pombe cell surface by AFM, and it provides a foundation for future investigation of how the surface topography and local nanomechanical properties vary during different cellular processes.
DAP5 enables translation re-initiation on structured messenger RNAs

Half of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is selectively required for re-initiation at the main CDS following uORF translation. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-mediated re-initiation occurs on messenger RNAs (mRNAs) with long, structure-prone 5′ leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates re-initiation by unrecycled post-termination 40S subunits. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors.
Establish a Nomogram to Predict Falls in Spinocerebellar Ataxia Type 3

Purpose: Falls are common and are frequently accompanied by injuries in patients with spinocerebellar ataxias type 3 (SCA3). We explored which factors could predict falls in a cohort of patients with SCA3 and developed a nomogram model to predict the first fall in non-fallen patients with SCA3. Method: We conducted a prospective cohort study. Forty-four non-fallen patients with SCA3 were followed up until the first fall or November 5, 2020, whichever came first. Univariate and multivariate Cox proportional hazard regression analyses were applied to explore the predictive factors of falls in patients with SCA3. A nomogram model predicting the no-fall probabilities at 3, 6, 12, and 24 months was formulated based on the results of the multivariate Cox analysis. Internal validation was conducted to assess the discrimination and calibration of the final model using bootstrapping with 1,000 resamples. Results: Multivariate Cox proportional hazard regression showed that the presence of dystonia, hyperreflexia, urinary incontinence, and hidrosis and the number of abnormal eye movements predicted a more rapid progression to falls in patients with SCA3. The nomogram model showed good discrimination with a concordance index of 0.83 and good calibration. Conclusion: Patients with dystonia, hyperreflexia, urinary incontinence, and hidrosis, and more types of abnormal eye movement had a more rapid progression to falls in SCA3.