Miracle-dz/UniFAR-FTUs huggingface dataset:
MBP-fusion protein of transducin-alpha residues 327-350

Resistance to inhibitors of cholinesterase 8A (Ric8A) is an essential regulator of G protein α-subunits (Gα), acting as a guanine nucleotide exchange factor and a chaperone. We report two crystal structures of Ric8A, one in the apo form and the other in complex with a tagged C-terminal fragment of Gα. These structures reveal two principal domains of Ric8A: an armadillo-fold core and a flexible C-terminal tail. Additionally, they show that the Gα C-terminus binds to a highly-conserved patch on the concave surface of the Ric8A armadillo-domain, with selectivity determinants residing in the Gα sequence. Biochemical analysis shows that the Ric8A C-terminal tail is critical for its stability and function. A model of the Ric8A/Gα complex derived from crosslinking mass spectrometry and molecular dynamics simulations suggests that the Ric8A C-terminal tail helps organize the GTP-binding site of Gα. This study lays the groundwork for understanding Ric8A function at the molecular level. Ric8A regulates G protein α-subunits (Gα) by acting as a guanine nucleotide exchange factor (GEF) and a Gα chaperone. Here, the authors solve the crystal structures of free and Gα fragment bound Ric8A, and provide insights into the structural basis for Ric8A’s GEF and chaperone functions.
Uncoating of COPII from ER exit site membranes precedes cargo accumulation and membrane fission

COPII and COPI are considered to be analogous sets of vesicle coat protein heterocomplexes. Coupled to cargo selection, they mediate the formation of membrane vesicles translocating in opposite directions to differ rent destinations within the secretory pathway. Here, live cell and electron microscopy provided evidence for a different localization and mode of function of the COPII coat during protein export from the endoplasmic reticulum (ER). Pharmaceutical and genetic perturbations of ER-Golgi transport were used to demonstrate that COPII is recruited to membranes defining the boundary of ER-ER Exit Sites (ERES) where it facilitates selective cargo concentration. Uncoating of COPII membranes precedes cargo accumulation and fission of Golgi-bound carriers. Moreover, we report what may be direct transfer of cargo to the Golgi apparatus from Golgi-associated BFA sensitive ERESs. Finally, in ldlF cells the stably expressed functional ε-COPI-EYFP labeled both ERESs and anterograde carriers. These findings change our understanding of the role of coat proteins in ER to Golgi transport.
Recognition of Human Hand Activities Based on a Single Wrist IMU Using Recurrent Neural Networks

Recognition of hand activities could provide new information towards daily human activity logging and gesture interface applications. However, there is a technical challenge due to delicate hand motions and complex movement contexts. In this work, we proposed hand activity recognition (HAR) based on a single inertial measurement unit (IMU) sensor at one wrist via deep learning recurrent neural network. The proposed HAR works directly with signals from a tri-axial accelerometer, gyroscope, and magnetometer sensors within one IMU. We evaluated the performance of our HAR with a public human hand activity database for six hand activities including Open Door, Close Door, Open Fridge, Close Fridge, Clean Table and Drink from Cup. Our results show an overall recognition accuracy of 80.09% with discrete standard epochs and 74.92% with noise-added epochs. With continuous time series epochs, the accuracy of 71.75% was obtained. 
Epigenetic Reprogramming, Apoptosis, and Developmental Competence in Cloned Embryos

Epigenetic Reprogramming, Apoptosis, and Developmental Competence in Cloned Embryos by Laura A. Moley, Doctor of Philosophy Utah State University, 2019 Major Professor: Dr. S. Clay Isom Department: Animal, Dairy, and Veterinary Sciences Cloning through somatic cell nuclear transfer (SCNT) remains highly inefficient twenty years after the first demonstration of the technology. The technology could be more routinely utilized to enhance animal agriculture production by increasing efficiency and decreasing cost through the selection of embryos that are most likely to succeed following transfer. We proposed the use of a non-toxic, non-invasive caspase activity reporter, SR-FLICA, to quantitatively assess embryo competency prior to transfer. We hypothesized that following SCNT, a majority of embryos undergo altered epigenetic reprogramming compared to in vivo embryos, resulting in aberrant gene expression and incidentally increased levels of apoptosis. Conversely, a fraction of the embryos undergo proper genome reprogramming, resulting in correct gene expression and low levels of apoptosis. Using porcine embryos, the non-toxic nature of SR-FLICA was validated on oocytes and embryos. No correlation between relative level of apoptosis and cell number was found in blastocysts. DNA methylation and gene expression patterns were analyzed through reduced-representation bisulfite sequencing and RNA-seq to provide global
ELFT-EFS Evaluation of Latent Fingerprint Technologies: Extended Feature Sets [Evaluation #2]

The National Institute of Standards and Technology (NIST) Evaluation of Latent Fingerprint Technologies Extended Feature Sets (ELFT-EFS) consists of multiple ongoing latent algorithm evaluations. This report describes the results and conclusions of ELFT-EFS Evaluation #2; an accuracy test of latent fingerprint searches using features marked by experienced human latent fingerprint examiners, in addition to automatic feature extraction and matching (AFEM). ELFT-EFS Evaluation #1 was the first evaluation of latent fingerprint matchers in which systems from different vendors used a common, standardized feature set. ELFT-EFS Evaluation #2 repeats the same tests using updated matchers. The results show that in most cases there were measureable improvements in the ability of matchers to use images plus manually marked Extended Features (EFS) as an effective and interoperable feature set over the Evaluation #1 results. The accuracy when searching with EFS features is promising considering the results are derived from earlydevelopment matchers. Further studies using next-generation matchers are warranted to determine the performance gains possible with EFS. ELFT-EFS Evaluation #2 Final Report
Non‐cyanobacterial diazotrophs dominate nitrogen‐fixing communities in permafrost thaw ponds

There is a growing concern about the implications of accelerated thawing of permafrost for regional biogeochemical cycling of carbon and other bioreactive elements. One such element of concern is nitrogen, and in this study, we investigated the diversity and biogeography of potential diazotrophs within a series of thaw ponds representing different ontogenetic stages in pond development. Using metagenomic sequence data from subarctic thaw ponds, we identified an array of nitrogenase genes across the ponds. The iron‐only nitrogenase gene (anfH) was positively correlated with sulfate, while there was no correlation with methane despite previous findings that organisms carrying anfH can simultaneously participate in nitrogen fixation and methanogenesis. Sulfate is known to inhibit microbial uptake of molybdate, an element essential for the activity of the nifH (molybdenum‐iron) nitrogenase and this may explain the high potential for nitrogen fixation utilizing anfH in sulfate‐rich ponds. NifH was particularly abundant in the hypolimnion of the deeper and older ponds, with Deltaproteobacteria and Chlorobi as the putative dominant diazotrophs. In the epilimnetic waters, nifH composition was more variable, with various Gammaproteobacteria as abundant representatives, while cyanobacterial diazotrophs were scarce. Interestingly, nifH gene abundance was significantly positively correlated with in situ methane concentration. Based on genome‐resolved metagenomics, we hypothesize that diazotrophs and methanogens engage in syntrophic interactions in anoxic waters, possibly via propionate oxidation or (in Geobacter) by interspecies electron transfer. Our results also suggest that nitrogen fixers may supply bioreactive nitrogen compounds to the thaw pond communities, thereby enhancing growth and activity of methanogens.
Molecular cloning and characterization of genes encoding chitinase and N-acetyl-β-glucosaminidase in Dolerocypris sinensis.

Chitinases and N-acetyl-β-glucosaminidase (NAG) are important in molting and growth of crustaceans. In ostracods, the genes encoding these enzymes have not been characterized. The aim of the present study was to clone the genes encoding chitinase (DsChi) and NAG (DsNAG) from the ostracod, Dolerocypris sinensis, elucidate the phylogenetic relationships between the cloned genes and known chitinolytic enzymes, and determine the expression patterns of these genes at different stages of growth in the presence of an environmental pollutant. The genes were amplified from the genomic DNA of the organism using polymerase chain reaction (PCR). The products from PCR were cloned and characterized with bioinformatics tools, and their expression patterns at different growth stages were determined using real-time quantitative PCR (qRT-PCR). Nine and five introns were identified in DsChi and DsNAG genes, respectively. When compared with protein sequences available in GenBank, chitinase from D. sinensis was most closely related to that of Macrobrachium nipponense (61 % homology). The NAG of D. sinensis was most closely related to that of Limulus polyphemus (55.6 % homology). Based on phylogenetic analysis of known chitinases from crustaceans and insects, the D. sinensis chitinase tightly clustered in the same branch with chitinases from species within the Malacostraca class. In contrast, NAG of D. sinensis was clustered with NAG from F. candida.The level of expression of DsChi mRNA was significantly higher than that of DsNAG throughout the period of growth (p < 0.05). Treatment of D. sinensis cells with fenoxycarb significantly downregulated the expressions of DsChi and DsNAG throughout the period of growth (p < 0.05). These results show that the protein products of DsChi and DsNAG possess remarkable biochemical properties characteristic of a chitinase and NAG, respectively.
Control of Daily Locomotor Activity Patterns in Drosophila suzukii by the Circadian Clock, Light, Temperature and Social Interactions

Understanding behavioral rhythms in a pest species can contribute to improving the efficacy of control methods targeting that pest. However, in some species, the behavioral patterns recorded in artificial conditions contrast greatly with observed wild-type behavioral rhythms. In this study, we identify the determinants of daily activity rhythms of the soft and stone fruit pest Drosophila suzukii. The impact of gender, space, social housing, temperature, light, fly morph, and the circadian clock on D. suzukii locomotor rhythms was investigated. Assays were performed under artificial laboratory conditions or more natural semifield conditions to identify how these factors affected daily locomotor behavior. Daily locomotor activity patterns collected under semifield conditions varied very little between the various sex and social condition combinations. However, in lab-based assays, individual and group-housed males often exhibited divergent activity patterns, with more prominent hyperactivity at light/dark transitions. In contrast, hyperactivity responses were suppressed under lab protocols mimicking summer conditions for groups of females and mixed-sex groups. Moreover, when environmental cues were removed, flies held in groups displayed stronger rhythmicity than individual flies. Thus, social interactions can reinforce circadian behavior and resist hyperactivity responses in D. suzukii. Fly morph appeared to have little impact on behavioral pattern, with winter and summer morph flies displaying similar activity profiles under April semifield and laboratory mimic environmental conditions. In conclusion, separate and combined effects of light, temperature, circadian clock function, and social interactions were apparent in the daily activity profiles of D. suzukii. When groups of female or mixed-sex flies were used, implementation of matching photoperiods and realistic daily temperature gradients in the lab was sufficient to re-create behavioral patterns observed in summer semifield settings. The ability to leverage lab assays to predict D. suzukii field behavior promises to be a valuable asset in improving control measures for this pest.
Towards Evolving More Brain-Like Artificial Neural Networks

An ambitious long-term goal for neuroevolution, which studies how artificial evolutionary processes can be driven to produce brain-like structures, is to evolve neurocontrollers with a high density of neurons and connections that can adapt and learn from past experience. Yet while neuroevolution has produced successful results in a variety of domains, the scale of natural brains remains far beyond reach. In this dissertation two extensions to the recently introduced Hypercube-based NeuroEvolution of Augmenting Topologies (HyperNEAT) approach are presented that are a step towards more brain-like artificial neural networks (ANNs). First, HyperNEAT is extended to evolve plastic ANNs that can learn from past experience. This new approach, called adaptive HyperNEAT, allows not only patterns of weights across the connectivity of an ANN to be generated by a function of its geometry, but also patterns of arbitrary local learning rules. Second, evolvable-substrate HyperNEAT (ES-HyperNEAT) is introduced, which relieves the user from deciding where the hidden nodes should be placed in a geometry that is potentially infinitely dense. This approach not only can evolve the location of every neuron in the network, but also can represent regions of varying density, which means resolution can increase holistically over evolution. The combined approach, adaptive ES-HyperNEAT, unifies for the first time in neuroevolution the abilities to indirectly encode connectivity through geometry, generate patterns of heterogeneous plasticity, and simultaneously encode the density and placement of nodes in space. The dissertation
Hook Breathing Facilitates SaO2 Recovery After Deep Dives in Freedivers With Slow Recovery

To facilitate recovery from hypoxia, many freedivers use a breathing method called “hook breathing” (HB) after diving, involving an interrupted exhale to build up intrapulmonary pressure. Some divers experience a delay in recovery of arterial oxygen saturation (SaO2) after diving, interpreted as symptoms of mild pulmonary edema, and facilitated recovery may be especially important in this group to avoid hypoxic “blackout. ” We examined the influence of HB on recovery of SaO2 in freedivers with slow recovery (SR) and fast recovery (FR) of SaO2 after deep “free immersion” (FIM) apnea dives to 30 m depth. Twenty-two male freedivers, with a mean (SD) personal best in the discipline FIM of 57(26) m, performed two 30 m deep dives, one followed by HB and one using normal breathing (NB) during recovery, at different days and weighted order. SaO2 and heart rate (HR) were measured via pulse oximetry during recovery. The SR group (n = 5) had a faster SaO2 recovery using HB, while the FR group (n = 17) showed no difference between breathing techniques. At 105 s, the SR group reached a mean (SD) SaO2 of 95(5)% using HB, while using NB, their SaO2 was 87(5)% (p < 0.05), and 105–120 s after surfacing SaO2 was higher with HB (p < 0.05). In SR subjects, the average time needed to reach 95% SaO2 with HB was 60 s, while it was 120 s at NB (p < 0.05). HR was similar in the SR group, while it was initially elevated at HB in the FR group (p < 0.05). We conclude that HB efficiently increases SaO2 recovery in SR individuals, but not in the FR group. The proposed mechanism is that increased pulmonary pressure with HB will reverse any pulmonary edema and facilitate oxygen uptake in divers with delayed recovery.
Simultaneous mRNA and protein quantification at the single-cell level delineates trajectories of CD4+ T-cell differentiation

Abstract The transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed traditionally by two largely exclusive types of technologies: single cell RNA-sequencing (scRNA-seq) technologies and antibody-based cytometry. Here we demonstrate that the simultaneous targeted quantification of mRNA and protein expression in single-cells provides a high-resolution map of human primary CD4+ T cells, and reveals precise trajectories of canonical T-cell lineage differentiation in blood and tissue. We report modest correlation between mRNA and protein in primary CD4+ T cells at the single-cell level, highlighting the importance of including quantitative protein expression data to characterise cell effector function. This approach provides a massively-parallel, cost-effective, solution to dissect the heterogeneity of immune cell populations and is ideally suited for the detailed immunophenotypic characterisation of rare and potentially pathogenic immune subsets. This transcriptomic and proteomic hybrid technology could have important clinical applications to re-define differentiation and activation of tissue-resident and blood human immune cells.
Bcl11b prevents fatal autoimmunity by promoting Treg cell program and constraining innate lineages in Treg cells

Lack of Bcl11b in Treg cells causes fatal autoimmunity and altered Treg cell program and identity. Regulatory T (Treg) cells are essential for peripheral tolerance and rely on the transcription factor (TF) Foxp3 for their generation and function. Several other TFs are critical for the Treg cell program. We found that mice deficient in Bcl11b TF solely in Treg cells developed fatal autoimmunity, and Bcl11b-deficient Treg cells had severely altered function. Bcl11b KO Treg cells showed decreased functional marker levels in homeostatic conditions, inflammation, and tumors. Bcl11b controlled expression of essential Treg program genes at steady state and in inflammation. Bcl11b bound to genomic regulatory regions of Treg program genes in both human and mouse Treg cells, overlapping with Foxp3 binding; these genes showed altered chromatin accessibility in the absence of Bcl11b. Additionally, Bcl11b restrained myeloid and NK cell programs in Treg cells. Our study provides new mechanistic insights on the Treg cell program and identity control, with major implications for therapies in autoimmunity and cancer.
Reducing lesion incidence in pork carcasses by heating foot-and-mouth disease vaccine before injection

Objective This study was conducted to investigate the effect of heating of foot-and-mouth disease (FMD) vaccine before injection, on the incidence of lesions at the injection site (pork butt), amount of discarded meat, and economical benefit. Methods In total, 101,086 piglets raised in 30 farms, were vaccinated in the neck with 2 mL of FMD vaccine at 56 d and 84 d of age using a commercial syringe. The heat treatment group (48,511 pigs) was injected with the FMD vaccine after it had been heated in a water bath at 40°C for 20 min. After slaughter, the incidence of lesions on the pork butt was inspected, and the subsequent amount of discarded meat was recorded. Results Heat treatment of FMD vaccine reduced the incident rate of lesions on the pork butt (p<0.01). Overall, 17.81% of the pigs in the heat treatment group had lesions, while the incident rate in the control group was 21.70%. The amount of discarded meat per head of total pigs and per head of pigs with lesions were significantly lower in the heat treatment group than the control group (p<0.01). Thus, the proportion of discarded meat to dressed carcass was lower in the heat treatment group (0.249%) compared with the control group (0.338%) (p<0.01). Farms that rear 1,000 sows can gain 1,863,289 KRW (1,600 USD) in one year when they adopt heat treatment of FMD vaccine before injection. Conclusion Heat treatment of FMD vaccine using simple heat equipment (water bath) can be effective in reducing lesions caused by FMD vaccination and increase the economic benefits in pig farms.
The Relationship Between Parsing and Generation

Humans use their linguistic knowledge in at least two ways: on the one hand, to convey what they mean to others or to themselves, and on the other hand, to understand what others say or what they themselves say. In either case, they must assemble the syntactic structures of sentences in a systematic fashion, in accordance with the grammar of their language. In this article, we advance the view that a single mechanism for building sentence structure may be sufficient for structure building in comprehension and production. We argue that differing behaviors reduce to differences in the available information in either task. This view has broad implications for the architecture of the human language system and provides a useful framework for integrating largely independent research programs on comprehension and production by both constraining the models and uncovering new questions that can drive further research.
Recent expansions of novel strategies towards the drug targeting into the brain

Abstract The treatment of central nervous system (CNS) disorders always remains a challenge for the researchers. The presence of various physiological barriers, primarily the blood–brain barrier (BBB) limits the accessibility of the brain and hinders the efficacy of various drug therapies. Hence, drug targeting to the brain, particularly to the diseased cells by circumventing the physiological barriers is essential to develop a promising therapy for the treatment of brain disorders. Presently, the investigations emphasize the role of different nanocarrier systems or surface modified target specific novel carrier system to improve the efficiency and reduce the side effects of the brain therapeutics. Such approaches supposed to circumvent the BBB or have the ability to cross the barrier function and thus increases the drug concentration in the brain. Although the efficacy of novel carrier system depends upon various physiological factors like active efflux transport, protein corona of the brain, stability, and toxicity of the nanocarrier, physicochemical properties, patient-related factors and many more. Hence, to develop a promising carrier system, it is essential to understand the physiology of the brain and BBB and also the other associated factors. Along with this, some alternative route like direct nose-to-brain drug delivery can also offer a better means to access the brain without exposure of the BBB. In this review, we have discussed the role of various physiological barriers including the BBB and blood-cerebrospinal fluid barrier (BCSFB) on the drug therapy and the mechanism of drug transport across the BBB. Further, we discussed different novel strategies for brain targeting of drug including, polymeric nanoparticles, lipidic nanoparticles, inorganic nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, quantum dots, etc. along with the intranasal drug delivery to the brain. We have also illustrated various factors affecting the drug targeting efficiency of the developed novel carrier system.