Miracle-dz/UniFAR-FTUs huggingface dataset:
A predicted deleterious allele of the essential meiosis gene MND1, present in ~3% of East Asians, does not disrupt reproduction in mice

Infertility is a major health problem affecting ~15% of couples worldwide. Except for cases involving readily-detectable chromosome aberrations, confident identification of a causative genetic defect is problematic. Despite the advent of genome sequencing for diagnostic purposes, the preponderance of segregating genetic variants complicates identification of culprit genetic alleles or mutations. Many algorithms have been developed to predict the effects of “variants of unknown significance” (VUS), typically SNPs (single nucleotide polymorphisms), but these predictions are not sufficiently accurate for clinical action. As part of a project to identify population variants that impact fertility, we have been generating CRISPR-Cas9 edited mouse models of suspect SNPs in genes that are known to be required for fertility in mice. Here, we present data on a non-synonymous (amino acid altering) SNP (rs140107488) in the meiosis gene Mnd1, which is predicted bioinformatically to be deleterious to protein function. We report that when modeled in mice, this allele (MND1K85M), which is present allele frequency of ~3% in East Asians, has no discernable effect upon fertility, fecundity, or gametogenesis, although it may cause sex skewing of progeny from homozygous males. In sum, this appears to be a benign allele that can be eliminated or de-prioritized in clinical genomic analyses of infertility patients.
Is conversion a syntactic or a lexical process of word formation

Conversion is sometimes described as a syntactic phenomenon by which a lexical item changes its lexical category according to the syntactic environment where it is inserted. This syntactic-ordered approach comes from theoretical fields that conceive the lexicon as the domain of irregularity, whilst regular patterns are treated in syntax (Chomsky 1995). However, Portuguese converted deverbal nouns (remendo ‘event of mending’, curte ‘event of having fun’, trinca ‘event of biting’) manifest a structural behaviour that permits us to situate their formation in the lexicon instead of in the syntax. According to the theoretical allusion we made above, this would characterise converted deverbal nouns as lacking a regular pattern. However, what we mean is that the lexicon is not the field of irregularity. Apart from the irregular material that must be stored in long term memory as to be used by speakers, such as inherited lexemes (e.g. rato ‘mouse’, cao ‘dog’, rir ‘to laugh’, verde ‘green’, etc.), the lexicon is the domain of word formation, which is constraint-based (Rodrigues 2008, 2009). This means the word formation part of the lexicon is constrained by regular patterns that are neither directional in principle, nor syntactic in nature. We follow Jackendoff (2002) conception on the lexicon, conceiving it an interface of syntax, phonology and semantics. Converted deverbal nouns formation seems to agree with this conception, since it depends on phonological, semantic and syntactical constraints (Rodrigues 2004, 2009). Portuguese verb-into-noun conversion is not a simple case of syntactic environment. This is specially visible when we confront this lexical conversion with a purely syntactic type of nominalisation (Kerleroux 1996), such as the one that occurs in O estudar matematica traz-me vantagens. ‘Studying maths brings me advantages’ or O remendar roupa e um recurso nesta epoca. ‘Mending cloths is a good resource nowadays’. Apart from the syntactic constraints that converted deverbal nouns must follow (e.g. as real nouns they cannot directly theta-mark, whilst syntactic nominalisations can), these nouns display phonological constraints in their formation and a semantic variability that is not observable in syntactic nominalisations. This semantic variability is not exclusively explainable by the syntactic environment. Moreover, the formation of converted deverbal nouns obeys to structural constraints that do not act upon syntactic nominalisation. All this means that conversion is not syntactic in nature. Yet it is not irregular either. This evidences that the mainstream generative grammar conception on the lexicon should be abandoned.
Fixed-Wing UAVs Flock Control through Cohesion and Repulsion Behaviours Combined with a Leadership

The aim of this paper is to present a novel approach to swarm control of small fixed-wing UAVs, which combines only two flocking behaviours with a leadership feature. In the presented approach, two fundamental rules of Reynolds flocking are applied, i.e., cohesion and repulsion, as the base of a decentralized control of self-organization of the flock. These rules are combined with a leadership feature, which is responsible for a global behaviour of guidance, as in the case of animals. Such a bio-inspired combination allows the achievement of a coherent collective flight of a flock of fixed-wing UAVs without applying formal behaviours of migration and alignment. This highly simplifies an implementation of the algorithm. The presented results include both numerical simulations and experimental flights, which validate the hardware implementation of the approach.
Improving Sensitivity of the Digits-In-Noise Test Using Antiphasic Stimuli

Objective The digits-in-noise test (DIN) has become increasingly popular as a consumer-based method to screen for hearing loss. Current versions of all DINs either test ears monaurally or present identical stimuli binaurally (i.e., diotic noise and speech, NoSo). Unfortunately, presentation of identical stimuli to each ear inhibits detection of unilateral sensorineural hearing loss (SNHL), and neither diotic nor monaural presentation sensitively detects conductive hearing loss (CHL). Following an earlier finding of enhanced sensitivity in normally hearing listeners, this study tested the hypothesis that interaural antiphasic digit presentation (NoSπ) would improve sensitivity to hearing loss caused by unilateral or asymmetric SNHL, symmetric SNHL, or CHL. Design This cross-sectional study, recruited adults (18-84 years) with various levels of hearing, based on a four-frequency pure tone average (PTA) at 0.5, 1, 2 and 4kHz. The study sample was comprised of listeners with normal hearing (n=41; PTA ≤ 25 dB HL in both ears), symmetric SNHL (n=57; PTA > 25 dB HL), unilateral or asymmetric SNHL (n=24; PTA > 25 dB HL in the poorer ear) and CHL (n=23; PTA > 25 dB HL and PTA air-bone gap ≥ 20 dB HL in the poorer ear). Antiphasic and diotic speech reception thresholds (SRTs) were compared using a repeated-measures design. Results Antiphasic DIN was significantly more sensitive to all three forms of hearing loss than the diotic DIN. SRT test-retest reliability was high for all tests (ICC r > 0.89). Area under the receiver operating characteristics (ROC) curve for detection of hearing loss (> 25 dB HL) was higher for antiphasic DIN (0.94) than for diotic DIN (0.77) presentation. After correcting for age, PTA of listeners with normal hearing or symmetric SNHL was more strongly correlated with antiphasic (rpartial[96]=0.69) than diotic (rpartial=0.54) SRTs. Slope of fitted regression lines predicting SRT from PTA was significantly steeper for antiphasic than diotic DIN. For listeners with normal hearing or CHL, antiphasic SRTs were more strongly correlated with PTA (rpartial[62]=0.92) than diotic SRTs (rpartial[62]=0.64). Slope of regression line with PTA was also significantly steeper for antiphasic than diotic DIN. Severity of asymmetric hearing loss (poorer ear PTA) was unrelated to SRT. No effect of self-reported English competence on either antiphasic or diotic DIN among the mixed first-language participants was observed Conclusions Antiphasic digit presentation markedly improved the sensitivity of the DIN test to detect SNHL, either symmetric or asymmetric, while keeping test duration to a minimum by testing binaurally. In addition, the antiphasic DIN was able to detect CHL, a shortcoming of previous monaural or binaurally diotic DIN versions. The antiphasic DIN is thus a powerful tool for population-based screening. This enhanced functionality combined with smartphone delivery could make the antiphasic DIN suitable as a primary screen that is accessible to a large global audience.
Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro and In Vivo Studies.

AIMS Evofosfamide (TH-302) is a hypoxia-activated prodrug (HAP) that releases the DNA-damaging bromo-isophosphoramide mustard (Br-IPM) moiety selectively under hypoxic conditions. Since solid tumors are known to have hypoxic regions, HAPs in combination with chemotherapy or radiotherapy (XRT) will be beneficial. We tested the oxygen dependence of release kinetics of Br-IPM using electron paramagnetic resonance (EPR) with spin trapping by monitoring redox cycling of the nitroimidazole moiety of TH-302, and oxygen dependence of TH-302 on in vitro cytotoxicity at different levels of hypoxia was also examined. Two tumor implants (SCCVII and HT29) in mice were studied. RESULTS TH-302 fragmentation to release Br-IPM was noticed at oxygen levels <76 mmHg, which increased with higher levels of hypoxia. Enhanced cellular cytotoxicity was also observed at oxygen levels <76 mmHg. In vivo pO2 imaging in the two tumor implants showed that the SCCVII tumor implant had higher level of hypoxia compared with the HT29 xenograft. TH-302 as a monotherapy in vivo showed modest effects in SCCVII implants and minimal effects in HT29 xenografts, whereas TH-302 in combination with ionizing radiation showed significant benefit in both tumor models. INNOVATION We examined the kinetics of redox cycling versus fragmentation of TH-302. The combination of oxygen-dependent XRT with TH-302 is effective even in tumors with significant hypoxia. CONCLUSIONS Imaging studies identifying the magnitude of hypoxia in tumors indicated that the responsiveness to TH-302 and the antitumor effect of TH-302 were enhanced by combining with XRT in both the TH-302-sensitive SCCVII tumor and -resistant HT29 tumor. Antioxid. Redox Signal. 28, 131-140.
Improving Students’ Speaking Skill through Pyramid Discussion: A Classroom Action Research at the Tenth Grade Students of the Senior High School in Kendawangan

The purpose of the classroom action research was to find out the improvement of the students’ speaking skill after applying pyramid discussion at the tenth grade students of the senior high school in Kendawangan. The participants were 24 students at the tenth grade students of a senior high school in Kendawangan. Observation and measurement were used as the techniques for data collection.
A bacterial surface layer protein exploits multistep crystallization for rapid self-assembly

Significance Many microbes assemble a crystalline protein layer on their outer surface as an additional barrier and communication platform between the cell and its environment. Surface layer proteins efficiently crystallize to continuously coat the cell, and this trait has been utilized to design functional macromolecular nanomaterials. Here, we report that rapid crystallization of a bacterial surface layer protein occurs through a multistep pathway involving a crystalline intermediate. Upon calcium binding, sequential changes occur in the structure and arrangement of the protein, which are captured by time-resolved small angle X-ray scattering and transmission electron cryo-microscopy. We demonstrate that a specific domain is responsible for enhancing the rate of self-assembly, unveiling possible evolutionary mechanisms to enhance the kinetics of 2D protein crystallization. Surface layers (S-layers) are crystalline protein coats surrounding microbial cells. S-layer proteins (SLPs) regulate their extracellular self-assembly by crystallizing when exposed to an environmental trigger. However, molecular mechanisms governing rapid protein crystallization in vivo or in vitro are largely unknown. Here, we demonstrate that the Caulobacter crescentus SLP readily crystallizes into sheets in vitro via a calcium-triggered multistep assembly pathway. This pathway involves 2 domains serving distinct functions in assembly. The C-terminal crystallization domain forms the physiological 2-dimensional (2D) crystal lattice, but full-length protein crystallizes multiple orders of magnitude faster due to the N-terminal nucleation domain. Observing crystallization using a time course of electron cryo-microscopy (Cryo-EM) imaging reveals a crystalline intermediate wherein N-terminal nucleation domains exhibit motional dynamics with respect to rigid lattice-forming crystallization domains. Dynamic flexibility between the 2 domains rationalizes efficient S-layer crystal nucleation on the curved cellular surface. Rate enhancement of protein crystallization by a discrete nucleation domain may enable engineering of kinetically controllable self-assembling 2D macromolecular nanomaterials.
Role of Neuroimaging Modality in the Assessment of Oxidative Stress in Brain: A Comprehensive Review.

BACKGROUND & OBJECTIVE Oxidative stress (OS) is the secondary source of an injury in consequence to the earlier caused primary injury; it is the condition of an imbalance between oxidants and antioxidants within the physiological system. OS causes alterations in proteins and DNA structure, leading to inflammation, apoptotic cell death, and tissue damage. Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, Glioma-induced neurodegeneration and the normal aging-related neuro-degeneration are primarily associated with the increased OS. The present review article is committed to delivering a comprehensive overview of the current neuroimaging modalities which estimates an indirect correlate of OS in the brain. OS-induced changes in white matter tracts and the gray matter volumes are reviewed assessing the role of diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) respectively. Further, the role of magnetic resonance spectroscopy (MRS) to assess the OS-induced alterations of chemical moieties, and thus the resultant structural implications in the neurological disorders are also briefly as well as precisely reviewed. CONCLUSION In the present review article we present an overview of the role of neuroimaging modalities in the diagnosis, and longitudinal assessment during treatment of the OS induced changes.
Construction of synthetic microbiota for reproducible flavor metabolism in Chinese light aroma type liquor produced by solid-state fermentation

Natural microbiota plays an essential role in flavor compounds producing for traditional food fermentation. Whereas, the fluctuation of natural microbiota results in the inconstancy of food quality. Thus, it is critical to reveal the core microbiota for flavor compounds producing and construct a synthetic core microbiota for constant food fermentation. Here, we revealed the core microbiota based on their flavor-producing and co-occurrence performance, using Chinese light aroma type liquor as a model system. Five genera were identified to be the core microbiota, including Lactobacillus, Saccharomyces, Pichia, Geotrichum, and Candida. The synthetic core microbiota of these five genera presented a reproducible dynamic profile with that in the natural microbiota. Monte Carlo test showed that the interpretation of five environmental factors (lactic acid, ethanol and acetic acid contents, moisture and pH) on the synthetic microbiota distribution were highly significant (P < 0.01), which was similar with that in the natural fermentation system. In addition, 77.27% of the flavor compounds produced by the synthetic core microbiota showed a similar dynamic profile (ρ > 0) with that in the natural liquor fermentation process, and the flavor profile presented a similar composition. It indicated that the synthetic core microbiota is efficient for reproducible flavor metabolism. This work established a method for identifying core microbiota and constructing a synthetic microbiota for reproducible flavor compounds. It is of great significance for the tractable and constant production of various fermented foods. IMPORTANCE The transformation from natural fermentation to synthetic fermentation is essential to construct a constant food fermentation process, which is the premise for stably making high-quality food. According to the functions of flavor-producing and co-occurring in dominant microbes, we provided a system-level approach to identify the core microbiota in Chinese light aroma type liquor fermentation. In addition, we successfully constructed a synthetic core microbiota to simulate the microbial community succession and flavor compounds production in the in vitro system. The constructed synthetic core microbiota could not only facilitate a mechanistic understanding of the structure and function of the microbiota, but also be beneficial for constructing a tractable and reproducible food fermentation process.
A Transferable Model For Chromosome Architecture

In vivo, the human genome folds into a characteristic ensemble of three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model for chromatin (Minimal Chromatin Model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. First, we trained our energy function using the Hi-C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then we used the model to perform molecular dynamics simulations producing an ensemble of 3D structures for all GM12878 autosomes. Finally, we used these 3D structures to generate contact maps. We found that simulated contact maps closely agree with experimental results for all GM12878 autosomes. The ensemble of structures resulting from these simulations exhibited unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories. One Sentence Summary: We report a model for chromatin that explains and accurately reproduces the three-dimensional structure of chromosomes in interphase.
Body and Pectoral Fin Kinematics During Routine Yaw Turning in Bonnethead Sharks (Sphyrna tiburo)

Synopsis Maneuvering is a crucial locomotor strategy among aquatic vertebrates, common in routine swimming, feeding, and escape responses. Combinations of whole body and fin movements generate an imbalance of forces resulting in deviation from an initial path. Sharks have elongate bodies that bend substantially and, in combination with pectoral fin rotation, play a role in yaw (horizontal) turning, but previous studies focus primarily on maximal turning performance rather than routine maneuvers. Routine maneuvering is largely understudied in fish swimming, despite observations that moderate maneuvering is much more common than the extreme behaviors commonly described in the literature. In this study, we target routine maneuvering in the bonnethead shark, Sphyrna tiburo. We use video reconstruction of moving morphology to describe three-dimensional pectoral fin rotation about three axes to compare to those previously described on yaw turning by the Pacific spiny dogfish. We quantify kinematic variables to understand the impacts of body and fin movements on routine turning performance. We also describe the anatomy of bonnethead pectoral fins and use muscle stimulation to confirm functional hypotheses about their role in actuating the fin. The turning performance metrics we describe for bonnethead sharks are comparable to other routine maneuvers described for the Pacific spiny dogfish and manta rays. These turns were substantially less agile and maneuverable than previously documented for other sharks, which we hypothesize results from the comparison of routine turning to maneuvering under stimulated conditions. We suggest that these results highlight the importance of considering routine maneuvering in future studies. Cinemática del Cuerpo y de las Aletas Pectorales Durante el giro en el eje Vertical en la Cabeza del Tiburón Pala (Sphyrna tiburo) (Body and Pectoral Fin Kinematics During Routine Yaw Turning in Bonnethead Sharks [Sphyrna tiburo])
Untapped microbial composition along a horizontal oxygen gradient in a Costa Rican volcanic influenced acid rock drainage system

Based on the analysis of 16S rRNA gene metabarcoding, here we report the shift in the microbial community structure along a horizontal oxygen gradient (0.40-6.06 mg L−1) in a volcanic influenced acid rock drainage (VARD) environment, known as San Cayetano (Cartago, Costa Rica; pH =2.94-3.06, sulfate ~0.87-1.19 g L−1, iron ~35-61 mg L−1). This VARD is dominated by microorganisms involved in the geochemical cycling of iron, sulfur and nitrogen; however, the identity of the species changes with the oxygen gradient along the river course. The anoxic spring of San Cayetano is dominated by a putative anaerobic sulfate-reducing Deltaproteobacterium as well as sulfur-oxidizing bacteria (such as Acidithiobacillus or Sulfobacillus), which favor the process of dissolution of sulfide minerals and oxidation of H2S. In oxic conditions, aerobic iron-oxidizers (Leptospirillum, Acidithrix, Ferritrophicum, Ferrovum) and heterotrophic bacteria (Burkholderiaceae Betaproteobacterium, Trichococcus, Acidocella) were identified among others. Thermoplasmatales archaea closely related to environmental phylotypes found in other ARD/AMD niches were also found throughout the entire ecosystem. This work describes the changes in bacterial diversity, and possible metabolic activities occurring along a horizontal oxygen gradient in a volcanic influenced acid rock drainage system.
La suplementación con DL-ácido málico mejora las características de la canal de borregos Pelibuey en finalización

The aim of the present study was to evaluate the effect of DL-malic acid addition in Pelibuey finishing diet on average daily gain, carcass characteristics and non-carcass components. Sixteen (16) male lambs with a mean body weight of 27 ± 1.92 kg, were used in a 48-d feeding experiment. Animals were fed a high-energy diet containing corn stover, as the only forage source, with and without the DL-malic acid (MA) addition. Animals were assigned randomly in two treatments with eight lambs each: 1) Addition of 4 g of DL-malic acid per kg of feed and 2) Control (diet 1 without MA). Four male lambs of each treatment were harvested after feeding experiment to measure carcass characteristics and non-carcass components. Lambs fed with MA presented a larger (P 0.05) of MA on daily average weight gain and non-carcass components weight. In conclusion, addition of 4 g DL-malic acid to a high-energy feed enhances muscle accretion, which improves carcass quality of finishing lambs.