Miracle-dz/UniFAR-FTUs huggingface dataset:
Attenuation law of normal disc galaxies with clumpy distributions of stars and dust

We investigate the attenuation law seen through an interstellar medium (ISM) with clumpy spatial distributions of stars and dust. The clumpiness of the dust distribution is introduced by a multiphase ISM model. We solve a set of radiative transfer equations with multiple anisotropic scatterings through the clumpy ISM in a one-dimensional plane-parallel geometry by using the mega-grain approximation, in which dusty clumps are regarded as very large particles (i.e. mega-grains). The clumpiness of the stellar distribution is introduced by the youngest stars embedded in the clumps. We assume a smooth spatial distribution for older stars. The youngest stars are surrounded by denser dusty gas and suffer stronger attenuation than diffuse older stars (i.e. age-selective attenuation). The apparent attenuation law is a composite of the attenuation laws for the clumpy younger stars and for the diffuse older stars with a luminosity weight. In general, the stellar population dominating the luminosity changes from older stars to younger stars as the wavelength decreases. This makes the attenuation law steep; the composite attenuation rapidly increases from small attenuation for older stars at a long wavelength to large attenuation for younger stars at a short wavelength. The resultant attenuation law of normal disc galaxies is expected to be much steeper than that of starburst galaxies observed by Calzetti et al. Finally, the Calzetti attenuation law is regarded as a special case with a large density in our framework.
Postlexical Prosodic Structure and Vowel Devoicing in Japanese (2009)

The thesis explores the nature of postlexical representation, as compared to lexical representation. In particular, focusing on prosodic representations, the question is asked as to whether the representation really alters when it appears to do so. I investigate this question through a study of the postlexical process of High Vowel Devoicing/Deletion (HVD) in Japanese. In this process, apparent consonant clusters are created, with the apparent deletion of the vowel, and of the syllable and mora units projected from the vowel in the lexical domain. Two questions are raised. First, is the prosodic unit deleted in HVD? Second, does the prosodic inventory change in the postlexical domain; do these apparent consonant clusters actually form clusters linearly with the deletion of the vowel in the postlexical representation? The literature on HVD shows disagreement. Some researchers argue that the syllable unit is maintained (e.g., Beckman 1996) while others argue for desyllabification (e.g., Kondo 1997). Some researchers argue for the deletion of the vowel (e.g., Beckman & Shoji 1984) while others argue that the vowel is not deleted but rather devoiced (e.g., McCawley 1968, Tsuchida 1997). The thesis presents the following claims. First, the syllable unit and the mora unit are maintained in the postlexical domain in Japanese. By showing that the lexical accent contrasts are maintained in pitch contours in HVD, I conclude that the syllable unit remains present in HVD. With respect to the mora, by examining places where the mora is important (e.g., poetry), I show that there is no evidence for demoraification with HVD. Second, the syllable and mora inventories do not change in the postlexical domain in Japanese. I specifically test the hypothesis that HVD derives syllabic/moraic voiceless consonants. Considering the consequences of this hypothesis for segmental processes and the learning process along with the perception of Japanese speakers, I conclude that the apparent consonant clusters are best analyzed not as clusters postlexically, and that the prosodic inventory does not alter. Rather, segments and prosodic units are all kept intact as in the lexical representation, with the vowel undergoing HVD remaining present in the representation.
Molecular Determinants of Fibrillation in a Viral Amyloidogenic Domain from Combined Biochemical and Biophysical Studies

The Nipah and Hendra viruses (NiV and HeV) are biosafety level 4 human pathogens classified within the Henipavirus genus of the Paramyxoviridae family. In both NiV and HeV, the gene encoding the Phosphoprotein (P protein), an essential polymerase cofactor, also encodes the V and W proteins. These three proteins, which share an intrinsically disordered N-terminal domain (NTD) and have unique C-terminal domains (CTD), are all known to counteract the host innate immune response, with V and W acting by either counteracting or inhibiting Interferon (IFN) signaling. Recently, using a combination of biophysical and structural approaches, the ability of a short region within the shared NTD (PNT3 region) to form amyloid-like structures was reported. Here, we evaluated the relevance of each of three contiguous tyrosine residues located in a previously identified amyloidogenic motif (EYYY) within HeV PNT3 to the fibrillation process. Our results indicate that removal of a single tyrosine in this motif significantly decreases the ability to form fibrils independently of position, mainly affecting the elongation phase. In addition, we show that the C-terminal half of PNT3 has an inhibitory effect on fibril formation that may act as a molecular shield and could thus be a key domain in the regulation of PNT3 fibrillation. Finally, the kinetics of fibril formation for the two PNT3 variants with highest and lowest fibrillation propensity were studied by Taylor Dispersion Analysis (TDA). The results herein presented shed light onto the molecular mechanisms involved in fibril formation. In addition, the PNT3 variants we generated represent valuable tools to further explore the functional impact of V/W fibrillation in transfected and infected cells.
Druggable Growth Dependencies and Tumor Evolution Analysis in Patient-Derived Organoids of Neuroendocrine Cancer

Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors and poorly-differentiated carcinomas. Treatment options for patients with NENs are limited, in part due to lack of accurate models. To address this need we established the first patient-derived tumor organoids (PDTOs) from pulmonary neuroendocrine tumors and derived PDTOs from an understudied NEN subtype, large cell neuroendocrine carcinoma (LCNEC). PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through drug sensitivity analyses, we uncover therapeutic sensitivities to an inhibitor of NAD salvage biosynthesis and to an inhibitor of BCL-2. Finally, we identify a dependency on EGF in pulmonary neuroendocrine tumor PDTOs. Consistent with these findings, analysis of an independent cohort showed that approximately 50% of pulmonary neuroendocrine tumors expressed EGFR. This study identifies a potentially actionable vulnerability for a subset of NENs, and further highlights the utility of these novel PDTO models for the study of NENs. Graphical abstract Highlights PDTOs of pulmonary NETs and LCNEC were established PDTOs recapitulate intra-tumoral heterogeneity and evolution of parental tumors Drug assays reveal therapeutic vulnerabilities and biomarkers Pulmonary NET PDTOs are dependent on EGF
Optimization of genomewide CRISPR screens using AsCas12a and multi-guide arrays

Genomewide loss-of-function (LOF) screening using CRISPR (clustered regularly interspaced short palindromic repeats) has facilitated the discovery of novel gene functions across diverse physiological and pathophysiological systems. A challenge with conventional genomewide CRISPR/Cas9 libraries is the unwieldy size (60,000 to 120,000 constructs), which is resource intensive and prohibitive in some experimental contexts. One solution to streamlining CRISPR screening is by multiplexing two or more guides per gene on a single construct, which enables functional redundancy to compensate for suboptimal gene knockout by individual guides. In this regard, AsCas12a (Cpf1) and its derivatives, e.g., enhanced AsCas12a (enAsCas12a), have enabled multiplexed guide arrays to be specifically and efficiently processed for genome editing. Prior studies have established that multiplexed CRISPR/Cas12a libraries perform comparably to the larger equivalent CRISPR/Cas9 libraries, yet the most efficient CRISPR/Cas12a library design remains unresolved. Here, we demonstrate that CRISPR/Cas12a genomewide LOF screening performed optimally with three guides arrayed per gene construct and could be adapted to robotic cell culture without noticeable differences in screen performance. Thus, the conclusions from this study provide novel insight to streamlining genomewide LOF screening using CRISPR/Cas12a and robotic cell culture.
Chromosome Fissions and Fusions Act as Barriers to Gene Flow between Brenthis Fritillary Butterflies

Chromosome rearrangements are thought to promote reproductive isolation between incipient species. However, it is unclear how often, and under what conditions, fission and fusion rearrangements act as barriers to gene flow. Here we investigate speciation between two largely sympatric fritillary butterflies, Brenthis daphne and B. ino. We use a composite likelihood approach to infer the demographic history of these species from whole genome sequence data. We then compare chromosome-level genome assemblies of individuals from each species and identify a total of nine chromosome fissions and fusions. Finally, we fit a demographic model where effective population sizes and effective migration rate vary across the genome, allowing us to quantify the effects of chromosome rearrangements on reproductive isolation. We show that chromosomes involved in rearrangements experienced less effective migration since the onset of species divergence and that genomic regions near rearrangement points have a further reduction in effective migration rate. Our results suggest that the evolution of multiple rearrangements in the B. daphne and B. ino populations, including alternative fusions of the same chromosomes, have resulted in a reduction in gene flow. While fission and fusion of chromosomes are unlikely to be the only processes that have led to speciation between these butterflies, this study shows that these rearrangements can directly promote reproductive isolation and may be involved in speciation when karyotypes evolve quickly.
The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification

Iron sulfur clusters (FeS) are ancient and ubiquitous protein cofactors that play fundamental roles in many aspects of cell biology. These cofactors cannot be scavenged or trafficked within a cell and thus must be synthesized in any subcellular compartment where they are required. We examined the FeS synthesis proteins found in the relict plastid organelle, called the apicoplast, of the human malaria parasite Plasmodium falciparum. Using a chemical bypass method, we deleted four of the FeS pathway proteins involved in sulfur acquisition and cluster assembly and demonstrated that they are all essential for parasite survival. However, the effect that these deletions had on the apicoplast organelle differed. Deletion of the cysteine desulfurase SufS led to disruption of the apicoplast organelle and loss of the organellar genome, whereas the other deletions did not affect organelle maintenance. Ultimately, we discovered that the requirement of SufS for organelle maintenance is not driven by its role in FeS biosynthesis, but rather, by its function in generating sulfur for use by MnmA, a tRNA modifying enzyme that we localized to the apicoplast. By complementing the activity of the parasite MnmA and SufS with a bacterial MnmA and its cognate cysteine desulfurase, we showed that the parasite SufS provides sulfur for both FeS biosynthesis and tRNA modification in the apicoplast. The dual role of parasite SufS is likely to be found in other plastid-containing organisms and highlights the central role of this enzyme in plastid biology.
How Black Holes Shape Globular Clusters: Modeling NGC 3201

Numerical simulations have shown that black holes (BHs) can strongly influence the evolution and present-day observational properties of globular clusters (GCs). Using a Monte Carlo code, we construct GC models that match the Milky Way cluster NGC 3201, the first cluster in which a stellar-mass BH was identified through radial velocity measurements. We predict that NGC 3201 contains ≳200 stellar-mass BHs. Furthermore, we explore the dynamical formation of main-sequence–BH binaries and demonstrate that systems similar to the observed BH binary in NGC 3201 are produced naturally. Additionally, our models predict the existence of bright blue straggler–BH binaries that are unique to core-collapsed clusters, which otherwise retain few BHs.
A CRISPRi-based genetic resource to study essential Staphylococcus aureus genes

ABSTRACT We have optimized a clustered regularly interspaced short palindromic repeat (CRISPR) interference system to facilitate gene knockdown in the Gram-positive bacterial pathogen Staphylococcus aureus. Our approach used a CRISPRi system derived from Streptococcus pyogenes, which involves the co-expression of the dcas9 gene encoding a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). In our system, dcas9 is expressed from a single copy in the chromosome of methicillin-resistant S. aureus strains COL or JE2, under the control of a tightly regulated promoter, inducible by anhydrotetracycline. The sgRNAs are expressed from a replicative plasmid under the control of a constitutively active promoter. This system enables efficient, inducible, knockdown of both essential and non-essential genes. Using this approach, we constructed the Lisbon CRISPRi Mutant Library comprising 261 strains, in the JE2 background, containing sgRNAs targeting 200 essential genes/operons. This library facilitates the study of the function of essential S. aureus genes and is complementary to the Nebraska Transposon Mutant Library, which consists of nearly 2,000 strains, each carrying a transposon insertion within a non-essential gene. The availability of these two libraries will facilitate the study of S. aureus pathogenesis and biology. IMPORTANCE Staphylococcus aureus is an important clinical pathogen that causes a high number of antibiotic-resistant infections. The study of S. aureus biology, and particularly of the function of essential proteins, is of particular importance to develop new approaches to combat this pathogen. We have optimized a clustered regularly interspaced short palindromic repeat interference (CRISPRi) system that allows efficient targeting of essential S. aureus genes. Furthermore, we have used that system to construct a library comprising 261 strains, which allows the depletion of essential proteins encoded by 200 genes/operons. This library, which we have named Lisbon CRISPRi Mutant Library, should facilitate the study of S. aureus pathogenesis and biology. Staphylococcus aureus is an important clinical pathogen that causes a high number of antibiotic-resistant infections. The study of S. aureus biology, and particularly of the function of essential proteins, is of particular importance to develop new approaches to combat this pathogen. We have optimized a clustered regularly interspaced short palindromic repeat interference (CRISPRi) system that allows efficient targeting of essential S. aureus genes. Furthermore, we have used that system to construct a library comprising 261 strains, which allows the depletion of essential proteins encoded by 200 genes/operons. This library, which we have named Lisbon CRISPRi Mutant Library, should facilitate the study of S. aureus pathogenesis and biology.
Transcranial magnetic stimulation to frontal but not occipital cortex disrupts endogenous attention

Covert endogenous (voluntary) attention improves visual performance. Human neuroimaging studies suggest that the putative human homolog of macaque FEF (FEF+) is critical for this improvement, whereas early visual areas are not. Yet, MRI methods are correlational, as they do not manipulate brain function. Here we investigated whether rFEF+ or V1/V2 play a causal role in endogenous attention. We used transcranial magnetic stimulation (TMS) to alter activity in visual cortex (Exp.1) or rFEF+ (Exp.2) when observers performed an orientation discrimination task while attention was manipulated. On every trial, they received double-pulse TMS at a predetermined site (stimulated region) around the occipital pole or the rFEF+. Two cortically magnified gratings were presented, one in the stimulated region (contralateral to the stimulated cortical area) and another in the symmetric (ipsilateral) non-stimulated region. Grating contrast was varied to measure contrast response functions (CRFs) for all attention and stimulation combinations. In Exp.1, the CRFs were similar at the stimulated and non-stimulated regions, indicating that early visual areas do not modulate endogenous attention during stimulus presentation. In contrast, occipital TMS eliminates exogenous (involuntary) attention effects on performance (1). In Exp.2, rFEF+ stimulation decreased the overall attentional effect; neither benefits at the attended location nor cost at the unattended location were significant. This pattern is mimicked in the frequency and directionality of microsaccades: Whereas occipital stimulation did not affect microsaccades, rFEF+ stimulation caused a higher microsaccade rate selectively directed toward the stimulated hemifield. These results provide causal evidence of the role of this frontal region for endogenous attention. SIGNIFICANCE STATEMENT Human neuroimaging studies have revealed activity in frontal regions (e.g., FEF+) as a neural correlate of endogenous (voluntary) attention, and early visual areas (V1/V2) as neural correlates of both endogenous and exogenous (involuntary) attention. Using a causal manipulation–transcranial magnetic stimulation–we show that briefly disrupting activity in rFEF+ weakens endogenous attention’s benefits at attended and costs at unattended locations. In contrast, V1/V2 stimulation did not alter endogenous attention (although we have previously demonstrated that it eliminates effects of exogenous attention). Correspondingly, whereas stimulation to rFEF+ increased the rate of microsaccades directed toward the stimulated hemifield, occipital stimulation did not. Together, these results provide causal evidence for the role of rFEF+ but not V1/V2 in endogenous attention.
Neural basis of melodic learning explains cross-cultural regularities in musical scales

Summary Seeking exposure to unfamiliar experiences constitutes an essential aspect of the human condition, and the brain must adapt to the constantly changing environment by learning the evolving statistical patterns emerging from it. Cultures are shaped by norms and conventions and therefore novel exposure to an unfamiliar culture induces a type of learning that is often described as implicit: when exposed to a set of stimuli constrained by unspoken rules, cognitive systems must rapidly build a mental representation of the underlying grammar. Music offers a unique opportunity to investigate this implicit statistical learning, as sequences of tones forming melodies exhibit structural properties learned by listeners during short- and long-term exposure. Understanding which specific structural properties of music enhance learning in naturalistic learning conditions reveals hard-wired properties of cognitive systems while elucidating the prevalence of these features across cultural variations. Here we provide behavioral and neural evidence that the prevalence of non-uniform musical scales may be explained by their facilitating effects on melodic learning. In this study, melodies were generated using an artificial grammar with either a uniform (rare) or non-uniform (prevalent) scale. After a short exposure phase, listeners had to detect ungrammatical new melodies while their EEG responses were recorded. Listeners’ performance on the task suggested that the extent of statistical learning during music listening depended on the musical scale context: non-uniform scales yielded better syntactic learning. This behavioral effect was mirrored by enhanced encoding of musical syntax in the context of non-uniform scales, which further suggests that their prevalence stems from fundamental properties of learning.
Consumer feces impact coral health in guild-specific ways

Microbiota from consumer feces can impact resource species in guild-specific ways. We tested the effect of fresh and heat-killed feces from corallivorous (coral-eating) and grazer/detritivorous fish on coral health and found that fresh grazer/detritivore feces, but not fresh corallivore feces, affected coral health in detrimental ways compared to heat-killed feces, suggesting that microbiota in grazer/detritivore feces were harmful. Bacterial diversity across 10 fish species suggests our experimental findings are generalizable to consumer guild: corallivore feces contained more coral-associated bacteria, and lower abundances of the coral pathogen, Vibrio coralliilyticus. These findings recontextualize the ecological roles of consumers on coral reefs: although herbivores support coral dominance through removal of algal competitors, they also disperse coral pathogens. Corallivore predation can wound corals, yet their feces contain potentially beneficial coral-associated bacteria, supporting the hypothesized role of corallivores in coral symbiont dispersal. Such consumer-mediated microbial dispersal as demonstrated here has broad implications for environmental management.
Mineral phase analysis of various marine-species shells and skeletons collected in Japan: Implications for marine biominerals

Mineral phase analysis was performed, using X-ray diffractometry (XRD), for marine-organism shell/skeleton samples of 146–148 extant species of the following 10 phyla (18 classes) collected in Japan: Rhodophyta (Florideophyceae), Foraminifera (Globothalamea and Tubothalamea), Porifera (Hexactinellida), Cnidaria (Anthozoa and Hydrozoa), Bryozoa (Gymnolaemata), Brachiopoda (Lingulata and Rhynchonellata), Mollusca (Bivalvia, Cephalopoda, Gastropoda and Polyplacophora), Annelida (Polychaeta), Arthropoda (Cirripedia), and Echinodermata (Asteroidea, Crinoidea and Echinoidea). Some of the species were analyzed for each specific part of their shells/skeletons. Almost all the samples exhibited any of calcite, aragonite or their mixed phase, predominantly depending on their taxonomy and shell/skeletal structures. For samples containing significant amounts of calcite, the MgCO3 wt % of calcite has been determined from their XRD data, which ranges from ∼0 to ∼15 wt % and indicates clear inter-taxonomic differences. Low MgCO3 values (∼0–4 wt %) are observed for Rhynchonellata, Bivalvia, Gastropoda and Cirripedia; intermediate values (∼4–8 wt %) for Cephalopoda; high values (∼8–15 wt %) for Florideophyceae, Globothalamea, Tubothalamea, Polychaeta, Asteroidea and Crinoidea; low-to-high values for Gymnolaemata; intermediate-to-high values for Anthozoa and Echinoidea. These MgCO3 data show broad trends mostly consistent with general phylogenetic evolution (i.e. very similar patterns for each phylogenetic group). Distinct within-individual variability of the MgCO3 content is found for regular Echinoidea species (i.e. their teeth and spines have lower MgCO3 values than the other skeletal parts). Correlation of the MgCO3 content with seawater temperature is also examined/discussed for most of the above calcite-containing classes. In order to interpret our XRD-based observations of various marine-species shells/skeletons, detailed discussions are presented by comparing with previous studies and also by using knowledge of taxonomy, shell/skeletal structures, habitats, living modes and so on. The comprehensive dataset and discussions will provide useful implications for biomineralization studies.