Miracle-dz/UniFAR-FTUs huggingface dataset:
A global phylogenetic regionalization of vascular plants reveals a deep split between Gondwanan and Laurasian biotas

Existing global regionalisation schemes for plants consider the compositional affinities among biotas, but these have not considered phylogenetic information explicitly. Incorporating phylogenetic information may substantially advance our understanding of the relationships among regions and the synopsis of biogeographical schemes, because phylogeny captures information on the evolutionary history of taxa. Here, we present the first phytogeographical delineation of the global vascular flora based on the evolutionary relationships of species. We analysed 8,738,520 geographical occurrence records for vascular plant species together with a time-calibrated phylogenetic tree including 67,420 species. We estimated species composition within 200 × 200 km grid cells across the world, and used a metric of phylogenetic beta diversity to generate a phylogenetic delineation of floristic regions. We contrasted these results with a regionalisation generated using a taxonomic beta diversity metric. We identified 16 phylogenetically distinct phytogeographical units, deeply split into two main clusters that broadly correspond to the Laurasia-Gondwana separation. Our regionalisation broadly matches currently recognized phytogeographical classifications, but also highlights that the Gondwanan area is split into a large Holotropical cluster and an Australian-NeoZelandic-Patagonian cluster. In turn, we found that the northernmost and southernmost units have the most evolutionarily distinct vascular plant assemblages. In contrast, taxonomic dissimilarity returned a regionalisation composed of 23 units with a high degree of shared taxa between Laurasian and Gondwanan areas, with no clear split among their biotas. The integration of phylogenetic information provided new insights into the historical relationships among phytogeographical units, enabling the identification of three large, clearly differentiated biotas, here referred to as kingdoms: Holarctic, Holotropical, and Austral. Our regionalization scheme provides further evidence for delineating transition zones between the Holarctic and Holotropical kingdoms. The latitudinal patterns of evolutionary distinctiveness of vascular plant assemblages are consistent with recent evidence of higher and more recent diversification of flowering plants outside tropical regions.
Correlated evolution of parental care with dichromatism, colour, and patterns in anurans

Parental care is widespread among vertebrates, with clear fitness benefits. Caring parents however incur costs that include higher predation risk. Anurans have among the most diverse forms of parental care, and we test whether the occurrence of care is associated with morphology that minimizes predation risk. We first examine whether parental care co-occurs with sexual dichromatism, testing the hypothesis that when one sex is conspicuous, the other is cryptically patterned and cares for the young. From our phylogenetic comparative analyses of 988 anurans distributed globally, we find that parental care is less likely to co-occur with dichromatism, irrespective of the caring sex. We then examine whether colour gradients and patterns that enhance crypticity are associated with the occurrence of parental care. We found that species with male-only care were more likely to have Bars-Bands, but contrary to our expectation, other colours (Green-Brown, Red-Blue-Black, Yellow) and patterns (Plain, Spots, Mottled-Patches) were not associated with caregiving behaviours. The lack of strong correlations between dorsal morphology and parental care suggests that crypticity is not the dominant strategy to minimise predation risk for care-giving anurans, and that the evolution of body colour and parental care are driven by independent selection pressures.
A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity

Background Cardiovascular toxicities still remain one of the most undesirable side effects in cancer patients receiving chemotherapy, and cardiotoxicity has been detected associated with many therapeutic regimens. A number of mechanisms are reported for these effects, some of which are related to inflammation, oxygen radical generation, mitochondrial damage. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, antioxidant activities which could exert protective effects on the heart cells. One very interesting derivative of EVOO preparation is represented by purified extract form waste waters. Here, we investigated the anti-cancer activity when combined with chemotherapeutics as well as potential cardioprotective activities of a polyphenol-rich extract from waste product of the EVOO, named A009. Methods and Results Mice bearing prostate cancer (PCa) xenografts were treated with cisplatin with and without A009. Tumor cell growth was reduced by cis and by A009 and further hindered by the combination. The effects of the A009 extract on cardiovascular toxicities was investigated in vivo. Hearts of mice were analyzed, and the mitochondria were studied by transmission electron microscopy. A protection activity by A009 was observed. To confirm the in vivo data obtained with cisplatin therapy, tumor cell lines and rat cardiomyocytes were treated with cisplatin in vitro with and without A009. A009 enhanced cisplatin and 5FU reduced cancer cell growth while did not further affect co-treated rat cardiomyocytes. Another frequently used chemotherapeutic agent 5-fluorouracil (5FU), was also tested in this assay a similar effects were observed. The cardioprotective effects of the A009 extract towards 5 FU chemotherapy were further investigated in a second system of in vitro cultures, on cardiomyocytes freshly isolated from mice pups. These cells were treated with 5-fluorouracil and A009. Wastewater extract mitigated toxicity of the fluorpyrimidine. Conclusions In vivo, we found synergisms of A009 and cisplatin in prostate cancer treatment. Hearts of mice xenografted with PCa cell lines and receiving co-treatments of A009 extracts along with cisplatin had reduced mitochondria damage compared to chemotherapy alone, indicating a cardioprotective role. A009 in vitro was additive to cisplatin and 5FU to reduce cancer cell growth while did not further affect rat cardiomyocytes cell cultures treated with cisplatin and 5FU. The A009 extract also rescued the proliferation rate of neonatal murine cardiomyocytes treated with 5-Fluorouracil. Our study demonstrates that the polyphenol rich purified A009 extracts enhances the effect of chemotherapy in vitro and in vivo but mitigates effects on heart and heart cells. It could therefore represent a potential candidate for cardiovascular prevention in patients undergoing cancer chemotherapy.
Millisecond mix-and-quench crystallography (MMQX) enables time-resolved studies of PEPCK with remote data collection

Time-resolved crystallography of biomolecules in action has advanced rapidly as methods for serial crystallography have improved, but the large number of crystals and complex experimental infrastructure required remain serious obstacles to widespread application. We have developed Millisecond Mix-and-Quench crystallography (MMQX), which yields millisecond time-resolved data using far fewer crystals and routine remote synchrotron data collection. To demonstrate the capabilities of MMQX, the conversion of oxaloacetic acid to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase is observed with a time resolution of 40 ms. MMQX, by lowering the entry barrier to time-resolved crystallography, should enable broad expansion in structural studies of protein dynamics.
CD95 expression in triple negative breast cancer blocks induction of an inflammatory state through differential regulation of NF-κB Signaling

CD95L is expressed by tumor-infiltrating lymphocytes to eliminate CD95-expressing tumor cells and thereby CD95 loss by tumor cells is often considered as a consequence of an immunoediting process. Nonetheless CD95 expression is maintained in most triple negative breast cancers (TNBCs), and we recently reported that CD95 loss in TNBC cells triggers the induction of a pro-inflammatory program promoting the recruitment of cytotoxic NK and CD8+ T-cells and impairing tumor growth. Using a comprehensive proteomic approach, we have identified two yet unknown CD95 interaction partners, Kip1 ubiquitination-promoting complex protein 2 (KPC2) and p65. KPC2 contributes to the partial degradation of p105 (NFκB1) and the subsequent generation of p50 homodimers, which transcriptionally represses pro-inflammatory NF-κB-driven gene expression. Mechanistically, KPC2 directly interacts with the C-terminal region of CD95 and links the receptor to RelA (p65) and KPC1, the catalytic subunit of the KPC complex that acts as E3 ubiquitin-protein ligase promoting the partial degradation of p105 into p50. Loss of CD95 in TNBC cells releases KPC2, limiting the formation of the NF-κB inhibitory homodimer complex (p50/p50), promoting NF-κB activation and the production of pro-inflammatory cytokines including CSF1, CSF2, CXCL1 and IL1 members, known to promote recruitment and differentiation of certain adaptive and innate immune effector cells.
The neural correlates of semantic and grammatical encoding during sentence production in a second language: evidence from an fMRI study using syntactic priming

Japanese English learners have difficulty speaking Double Object (DO; give B A) than Prepositional Object (PO; give A to B) structures which neural underpinning is unknown. In speaking, syntactic and phonological processing follow semantic encoding, conversion of non-verbal mental representation into a structure suitable for expression. To test whether DO difficulty lies in linguistic or prelinguistic process, we conducted functional magnetic resonance imaging. Thirty participants described cartoons using DO or PO, or simply named them. Greater reaction times and error rates indicated DO difficulty. DO compared with PO showed parieto-frontal activation including left inferior frontal gyrus, reflecting linguistic process. Psychological priming in PO produced immediately after DO and vice versa compared to after control, indicated shared process between PO and DO. Cross-structural neural repetition suppression was observed in occipito-parietal regions, overlapping the linguistic system in pre-SMA. Thus DO and PO share prelinguistic process, whereas linguistic process imposes overload in DO.
Proteomic analysis of the role of the quality control protease LONP1 in mitochondrial protein aggregation

The mitochondrial matrix protease LONP1 is an essential part of the organellar protein quality control system. LONP1 has been shown to be involved in respiration control and apoptosis. Furthermore, a reduction in LONP1 level correlates with ageing processes. Up to now, the effects of a LONP1 defect were mostly studied by utilizing transient, siRNA-mediated knockdown approaches. We generated a new cellular model system for studying the impact of LONP1 on mitochondrial protein homeostasis by a CRISPR/Cas-mediated genetic knockdown (gKD). These cells show a stable reduction of LONP1 along with a mild phenotype characterized by absent morphological differences and only small negative effects on mitochondrial functions under normal culture conditions. To assess the consequences of a permanent LONP1 depletion on the mitochondrial proteome, we analyzed the alterations of protein levels by quantitative mass spectrometry, demonstrating small adaptive changes, in particular concerning mitochondrial protein biogenesis. In an additional proteomic analysis, we determined the temperature-dependent aggregation behavior of mitochondrial proteins and its dependence on a reduction of LONP1 activity, demonstrating the important role of the protease for mitochondrial protein homeostasis in mammalian cells. We identified a significant number of mitochondrial proteins that are affected by LONP1 activity concerning their stress-induced solubility. Taken together, our results suggest a very good applicability of the LONP1 gKD cell line as a model system for human ageing processes.
Factors That Influence Career Choice among Different Populations of Neuroscience Trainees

Abstract Specific groups have historically been, and continue to be, underrepresented in the biomedical research workforce, especially academia. Career choice is a multifactorial process that evolves over time; among all trainees, expressed interest in faculty research careers decreases over time in graduate school, but that trend is amplified in women and members of historically underrepresented racial and ethnic groups (Golde and Dore, 2004; Fuhrmann et al., 2011; Sauermann and Roach, 2012; Gibbs et al., 2014; Roach and Sauermann, 2017). This work was designed to investigate how career interest changes over time among recent neuroscience PhD graduates, and whether differences in career interests are associated with social identity, experiences in graduate school and postdoctoral training, and personal characteristics. We report results from a survey of 1479 PhD neuroscientists (including 16% underrepresented scientists and 54% women scientists). We saw repeated evidence that individual preferences about careers in general, and academic careers specifically, predict current career interest. These findings were moderated by social identity and experiences in graduate school and postdoctoral training. Our findings highlight the important influence of the advisor in shaping a trainee’s career path, and the ways in which academic culture is perceived as unwelcoming or incongruent with the values or priorities of certain groups. They suggest several areas for positive growth, ways to change how we think about the impact of mentorship, and policy and programmatic interventions that extend beyond trying to change or “fix” the individual and instead recognize the systemic structures that influence career choices.
Cortical Tracking of a Background Speaker Modulates the Comprehension of a Foreground Speech Signal

Understanding speech in background noise is a difficult task. The tracking of speech rhythms such as the rate of syllables and words by cortical activity has emerged as a key neural mechanism for speech-in-noise comprehension. In particular, recent investigations have used transcranial alternating current stimulation (tACS) with the envelope of a speech signal to influence the cortical speech tracking, demonstrating that this type of stimulation modulates comprehension and therefore providing evidence of a functional role of the cortical tracking in speech processing. Cortical activity has been found to track the rhythms of a background speaker as well, but the functional significance of this neural response remains unclear. Here we use a speech-comprehension task with a target speaker in the presence of a distractor voice to show that tACS with the speech envelope of the target voice as well as tACS with the envelope of the distractor speaker both modulate the comprehension of the target speech. Because the envelope of the distractor speech does not carry information about the target speech stream, the modulation of speech comprehension through tACS with this envelope provides evidence that the cortical tracking of the background speaker affects the comprehension of the foreground speech signal. The phase dependency of the resulting modulation of speech comprehension is, however, opposite to that obtained from tACS with the envelope of the target speech signal. This suggests that the cortical tracking of the ignored speech stream and that of the attended speech stream may compete for neural resources. SIGNIFICANCE STATEMENT Loud environments such as busy pubs or restaurants can make conversation difficult. However, they also allow us to eavesdrop into other conversations that occur in the background. In particular, we often notice when somebody else mentions our name, even if we have not been listening to that person. However, the neural mechanisms by which background speech is processed remain poorly understood. Here we use transcranial alternating current stimulation, a technique through which neural activity in the cerebral cortex can be influenced, to show that cortical responses to rhythms in the distractor speech modulate the comprehension of the target speaker. Our results provide evidence that the cortical tracking of background speech rhythms plays a functional role in speech processing.
Normalisr: normalization and association testing for single-cell CRISPR screen and co-expression

Single-cell RNA sequencing (scRNA-seq) provides unprecedented technical and statistical potential to study gene regulation but is subject to technical variations and sparsity. Here we present Normalisr, a linear-model-based normalization and statistical hypothesis testing framework that unifies single-cell differential expression, co-expression, and CRISPR scRNA-seq screen analyses. By systematically detecting and removing nonlinear confounding from library size, Normalisr achieves high sensitivity, specificity, speed, and generalizability across multiple scRNA-seq protocols and experimental conditions with unbiased P-value estimation. We use Normalisr to reconstruct robust gene regulatory networks from trans-effects of gRNAs in large-scale CRISPRi scRNA-seq screens and gene-level co-expression networks from conventional scRNA-seq.
Discovery and characterization of Hv1-type proton channels in reef-building corals

Voltage-dependent proton-permeable channels are membrane proteins mediating a number of important physiological functions. Here we report the presence of a gene encoding for Hv1 voltage-dependent, proton-permeable channels in two species of reef-building corals. We performed a characterization of their biophysical properties and found that these channels are fast-activating and modulated by the pH gradient in a distinct manner. The biophysical properties of these novel channels make them interesting model systems. We have also developed an allosteric gating model that provides mechanistic insight into the modulation of voltage-dependence by protons. This work also represents the first functional characterization of any ion channel in scleractinian corals. We discuss the implications of the presence of these channels in the membranes of coral cells in the calcification and pH regulation processes and possible consequences of ocean acidification related to the function of these channels.
Predicting population genetic change in an experimental stochastic environment

Most natural environments exhibit a substantial component of random variation. Such environmental noise is expected to cause random fluctuations in natural selection, affecting the predictability of evolution. But despite a long-standing theoretical interest for understanding the population genetic consequences of stochastic environments, there has been a dearth of empirical validation and estimation of the underlying parameters of this theory. Indeed, tracking the genetics of a large number of replicate lines under a controlled level of environmental stochasticity is particularly challenging. Here, we tackled this problem by resorting to an automated experimental evolution approach. We used a liquid-handling robot to expose over a hundred lines of the micro-alga Dunaliella salina to randomly fluctuating salinity over a continuous range, with controlled mean, variance, and autocorrelation. We then tracked the frequency of one of two competing strains through amplicon sequencing of a nuclear and choloroplastic barcode sequences. We show that the magnitude of environmental fluctuations (variance), but also their predictability (autocorrelation), have large impacts on the average selection coefficient. Furthermore, the stochastic variance in population genetic change is substantially higher in a fluctuating environment. Reaction norms of selection coefficients and growth rates of single strains against the environment captured the mean response accurately, but failed to explain the high variance induced by environmental stochasticity. Overall, our results provide exceptional insights on the prospects for understanding and predicting genetic evolution in randomly fluctuating environments.
Visualization of loop extrusion by DNA nanoscale tracing in single human cells

The spatial organization of the genome is essential for its functions, including gene expression, DNA replication and repair, as well as chromosome segregation1. Biomolecular condensates and loop extrusion have been proposed as the principal driving forces that underlie the formation of non-random structures such as chromatin compartments and topologically associating domains2,3. However, if the actual 3D-folding of DNA in single cells is consistent with these mechanisms has been difficult to address in situ. Here, we present LoopTrace, a workflow for high-resolution reconstruction of 3D genome architecture without DNA denaturation. Classical fluorescence in situ hybridization approaches can link chromatin architecture to DNA sequence but disrupt chromatin structure at the critical nanoscale of individual loops. Our workflow employs non-denaturing enzymatic strand resection4,5, to conserve chromatin structure and can resolve the 3D-fold of chromosomal DNA with better than 5-kb-resolution in single human cells. Our results show that the chromatin fiber behaves as a random coil that can be further structured in a manner consistent with loop formation, explaining the emergence of topologically associated domain-like features in cell population averages. Mining a large amount of single-cell data computationally, we reveal chromatin folding intermediates consistent with progressive loop extrusion and stabilized loops, highlighting the power of our method to visualize the nanoscale features of genome organization in situ.
Integrating spatial, phylogenetic, and threat assessment data from frogs and lizards to identify areas for conservation priorities in Peninsular Malaysia

Malaysia is recognized as a megadiverse country and biodiversity hotspot, which necessitates sufficient levels of habitat protection and effective conservation management. However, conservation planning in Malaysia has hitherto relied largely on species distribution data without taking into account the rich evolutionary history of taxa. This represents the first study that integrates spatial and evolutionary approaches to identify important centers of diversity, endemism, and bioregionalization that can be earmarked for conservation priorities in Peninsular Malaysia. Using georeferenced species occurrences, comprehensive phylogenies, and threat assessments of frogs and lizards, we employed a spatial phylogenetics framework that incorporates various diversity metrics including weighted endemism, phylogenetic diversity, phylogenetic endemism, and evolutionary distinctiveness and global endangerment. Ten areas of high conservation value were identified via the intersection of these metrics—northern Perlis, Langkawi Geopark, southern Bintang range, Cameron Highlands, Fraser’s Hill, Benom-Krau complex, Selangor-Genting complex, Endau-Rompin National Park, Seribuat Archipelago (Tioman and Pemanggil Islands), and southern Johor. Of these, Cameron Highlands requires the highest conservation priority based on severe environmental degradation, inadequately protected areas, and high numbers of endangered and evolutionary distinct species. Other areas, especially in the northwestern (states of Kedah and Penang) and northeastern regions (states of Kelantan) were not only identified as areas of high conservation value but also areas of biogeographic importance. Taken together, frogs and lizards demonstrate distinct east-west and north-south patterns of bioregionalization that are largely modulated by mountain ranges. Article Impact Statement The first study to use a spatial phylogenetic approach to identify areas for conservation priorities in Malaysia