Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopamine in the medial amygdala network mediates human bonding

Significance Early life bonding in humans has critical long-term implications for health, productivity, and well-being in society. Nonetheless, neural mechanisms of bonding are typically studied in rodents, and no studies to date had examined the neurochemistry of human social affiliation. This study utilizes a state-of-the-art technology to demonstrate that human maternal bonding is associated with striatal dopamine function and the recruitment of a cortico–striatal–amygdala brain network that supports affiliation. The simultaneous probing of neurochemical responses and whole-brain network function in mothers watching their infants provides a unique observation into an “affiliating brain. ” These results advance the mechanistic understanding of human social bonding and promote basic and clinical research in social neuroscience, development, and psychopathology. Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers’ dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the “medial amygdala network”) that supports social functioning. We also measured the mothers’ behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother’s infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.
Efficient synthesis and comparative studies of the arginine and Nω,Nω‐dimethylarginine forms of the human nucleolin glycine/arginine rich domain

The Gly‐ and Arg‐rich C‐terminal region of human nucleolin is a 61‐residue long domain involved in a number of protein–protein and protein–nucleic acid interactions. This domain contains 10 aDma residues in the form of aDma‐GG repeats interspersed with Phe residues. The exact role of Arg dimethylation is not known, partly because of the lack of efficient synthetic methods. This work describes an effective synthetic strategy, generally applicable to long RGG peptides, based on side‐chain protected aDma and backbone protected dipeptide Fmoc‐Gly‐(Dmob)Gly‐OH. This strategy allowed us to synthesize both the unmodified (N61Arg) and the dimethylated (N61aDma) peptides with high yield (∼26%) and purity. As detected by NMR spectroscopy, N61Arg does not possess any stable secondary or tertiary structure in solution and Nω,Nω‐dimethylation of the guanidino group does not alter the overall conformational propensity of this peptide. While both peptides bind single‐stranded nucleic acids with similar affinities (Kd = 1.5 × 10−7 M), they exhibit a different behaviour in ssDNA affinity chromatography consistent with the difference in pKa values. It has been previously shown that N61Arg inhibits HIV infection at the stage of HIV attachment to cells. This study demonstrates that Arg‐dimethylated C‐terminal domain lacks any inhibition activity, raising the question of whether nucleolin expressed on the cell‐surface is indeed dimethylated. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Interpreter-mediated Cognitive Assessments: Who Wins and Who Loses?

ABSTRACT Objectives: The number of people with dementia from culturally and linguistically diverse (CALD) backgrounds is increasing dramatically in Australia. Accurate cognitive assessments of people from CALD backgrounds can be achieved with the use of skilled interpreters. This study aimed to explore the experience of interpreter-mediated assessments from the perspectives of clinicians, interpreters and carers. Methods: Consultations with interpreters, clinicians and carers were conducted through individual interviews and focus groups. The consultations explored participants’ experiences of interpreter-mediated assessments, including perception of the interpreting process, roles of interpreters, and challenges associated with interpreter-mediated assessments. Results: Four themes emerged across groups: (1) the importance of having professional interpreters, (2) different perceptions of the roles of interpreters, (3) clinicians’ feelings of having less control over assessments, and (4) particular challenges associated with cognitive assessments. Conclusions: Finding from this study highlight the important role that interpreters play in cognitive assessments with immigrants. However, there appears to be different perceptions of the role between clinicians and interpreters. When these different understandings are not resolved, they will lead to tension between clinicians and interpreters. These findings highlight the importance of relational aspects in interpreter-mediated assessment and suggest that the negotiation of the relationships between clinicians and interpreters is an important factor that determines the effectiveness and accuracy of these assessments. Clinical Implications: This study highlights the need for clinicians and interpreters education of roles of all parties in interpreter-mediated cognitive assessment. Areas to be covered in education could include: common misunderstandings of interpreters roles, and practice tips on how to improve communications in assessments, such as briefing before and after the assessment. Such education will enable more accurate assessment and less stress for patients and their families.
Local and Remote Impacts of Atmospheric Cloud Radiative Effects Onto the Eddy‐Driven Jet

This study examines the cause of the spread of extratropical circulation responses to the inclusion of atmospheric cloud radiative effects (ACRE) across atmospheric general circulation models. The ensemble of Clouds On‐Off Klimate Intercomparison Experiment aquaplanet simulations shows that these responses include both equatorward and poleward shifts of the eddy‐driven jet of varying magnitudes. These disparate extratropical responses occur despite the relatively consistent response in the tropics: a heating in the upper troposphere, which leads to a strengthening of the Hadley cell. It is argued that the eddy‐driven jet response is a competition between two effects: the local influence of clouds driving shifts of the jet through meridional gradients in ACRE and the remote impact of a strengthened Hadley cell causing an equatorward shift of the eddy‐driven jet. Simulations in which cloud radiative effects are separately turned on in the tropics and extratropics demonstrate this explicitly.
Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers

Significance Decoupling stiffness, pore size, and cell infiltration is a critical hurdle in biomaterials design. Here, by adding ultrasoft colloidal hydrogels to polymerizing fibrin, the particles are driven into a percolated three-dimensional tunnel-like structure throughout the fibrin network. The colloidal particles remain embedded, in stark contrast to the fate of a sacrificial porogen. Yet, cells use the long-time flow behavior of the colloidal network within the tunnels to migrate. Importantly, the colloidal volume fraction, ϕ, defines the critical physical dimensions of the network, which can thus be tuned. Additionally, the stiffness of the constituent particles affects the viscous flow of the colloidal network, affecting cell migration rates. This simplistic approach makes its potential applicability in clinical settings highly tractable. In regenerative medicine, natural protein-based polymers offer enhanced endogenous bioactivity and potential for seamless integration with tissue, yet form weak hydrogels that lack the physical robustness required for surgical manipulation, making them difficult to apply in practice. The use of higher concentrations of protein, exogenous cross-linkers, and blending synthetic polymers has all been applied to form more mechanically robust networks. Each relies on generating a smaller network mesh size, which increases the elastic modulus and robustness, but critically inhibits cell spreading and migration, hampering tissue regeneration. Here we report two unique observations; first, that colloidal suspensions, at sufficiently high volume fraction (ϕ), dynamically assemble into a fully percolated 3D network within high-concentration protein polymers. Second, cells appear capable of leveraging these unique domains for highly efficient cell migration throughout the composite construct. In contrast to porogens, the particles in our system remain embedded within the bulk polymer, creating a network of particle-filled tunnels. Whereas this would normally physically restrict cell motility, when the particulate network is created using ultralow cross-linked microgels, the colloidal suspension displays viscous behavior on the same timescale as cell spreading and migration and thus enables efficient cell infiltration of the construct through the colloidal-filled tunnels.
Inhibition of Diverse DsbA Enzymes in Multi-DsbA Encoding Pathogens

Abstract Aims: DsbA catalyzes disulfide bond formation in secreted and outer membrane proteins in bacteria. In pathogens, DsbA is a major facilitator of virulence constituting a target for antivirulence antimicrobial development. However, many pathogens encode multiple and diverse DsbA enzymes for virulence factor folding during infection. The aim of this study was to determine whether our recently identified inhibitors of Escherichia coli K-12 DsbA can inhibit the diverse DsbA enzymes found in two important human pathogens and attenuate their virulence. Results: DsbA inhibitors from two chemical classes (phenylthiophene and phenoxyphenyl derivatives) inhibited the virulence of uropathogenic E. coli and Salmonella enterica serovar Typhimurium, encoding two and three diverse DsbA homologues, respectively. Inhibitors blocked the virulence of dsbA null mutants complemented with structurally diverse DsbL and SrgA, suggesting that they were not selective for prototypical DsbA. Structural characterization of DsbA-inhibitor complexes showed that compounds from each class bind in a similar region of the hydrophobic groove adjacent to the Cys30-Pro31-His32-Cys33 (CPHC) active site. Modeling of DsbL- and SrgA-inhibitor interactions showed that these accessory enzymes could accommodate the inhibitors in their different hydrophobic grooves, supporting our in vivo findings. Further, we identified highly conserved residues surrounding the active site for 20 diverse bacterial DsbA enzymes, which could be exploited in developing inhibitors with a broad spectrum of activity. Innovation and Conclusion: We have developed tools to analyze the specificity of DsbA inhibitors in bacterial pathogens encoding multiple DsbA enzymes. This work demonstrates that DsbA inhibitors can be developed to target diverse homologues found in bacteria. Antioxid. Redox Signal. 29, 653–666.
Genes Required for the Fitness of Salmonella enterica Serovar Typhimurium during Infection of Immunodeficient gp91−/− phox Mice

ABSTRACT Salmonella enterica causes systemic diseases (typhoid and paratyphoid fever), nontyphoidal septicemia (NTS), and gastroenteritis in humans and other animals worldwide. An important but underrecognized emerging infectious disease problem in sub-Saharan Africa is NTS in children and immunocompromised adults. A current goal is to identify Salmonella mutants that are not pathogenic in the absence of key components of the immune system such as might be found in immunocompromised hosts. Such attenuated strains have the potential to be used as live vaccines. We have used transposon-directed insertion site sequencing (TraDIS) to screen mutants of Salmonella enterica serovar Typhimurium for their ability to infect and grow in the tissues of wild-type and immunodeficient mice. This was to identify bacterial genes that might be deleted for the development of live attenuated vaccines that would be safer to use in situations and/or geographical areas where immunodeficiencies are prevalent. The relative fitness of each of 9,356 transposon mutants, representing mutations in 3,139 different genes, was determined in gp91 −/− phox mice. Mutations in certain genes led to reduced fitness in both wild-type and mutant mice. To validate these results, these genes were mutated by allelic replacement, and resultant mutants were retested for fitness in the mice. A defined deletion mutant of cysE was attenuated in C57BL/6 wild-type mice and immunodeficient gp91 −/− phox mice and was effective as a live vaccine in wild-type mice.
Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates

The Ebola virus (EBOV) outbreak in West Africa during 2013–2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.
Illumina sequencing‐based analysis of sediment bacteria community in different trophic status freshwater lakes

Sediment bacterial community is the main driving force for nutrient cycling and energy transfer in aquatic ecosystem. A thorough understanding of the community's spatiotemporal variation is critical for us to understand the mechanisms of cycling and transfer. Here, we investigated the sediment bacterial community structures and their relations with environmental factors, using Lake Taihu as a model system to explore the dependence of biodiversity upon trophic level and seasonality. To combat the limitations of conventional techniques, we employed Illumina MiSeq Sequencing and LeFSe cladogram to obtain a more comprehensive view of the bacterial taxonomy and their variations of spatiotemporal distribution. The results uncovered a 1,000‐fold increase in the total amount of sequences harvested and a reverse relationship between trophic level and the bacterial diversity in most seasons of a year. A total of 65 phyla, 221 classes, 436 orders, 624 families, and 864 genera were identified in the study area. Delta‐proteobacteria and gamma‐proteobacteria prevailed in spring/summer and winter, respectively, regardless trophic conditions; meanwhile, the two classes dominated in the eutrophication and mesotrophication lake regions, respectively, but exclusively in the Fall. For LEfSe analysis, bacterial taxon that showed the strongest seasonal or spatial variation, majority had the highest abundance in spring/summer or medium eutrophication region, respectively. Pearson's correlation analysis indicated that 5 major phyla and 18 sub‐phylogenetic groups showed significant correlation with trophic status. Canonical correspondence analysis further revealed that porewater NH4+‐N as well as sediment TOM and NOx‐N are likely the dominant environmental factors affecting bacterial community compositions.
Black carbon or brown carbon? The nature of light-absorbing carbonaceous aerosols

Although the definition and measurement techniques for atmospheric "black carbon" ("BC") or "elemental carbon'' ("EC") have long been subjects of scientific controversy, the recent discovery of light-absorbing carbon that is not black ("brown carbon, C brown ") makes it imperative to reassess and redefine the components that make up light-absorbing carbonaceous matter (LAC) in the atmosphere. Evidence for the atmospheric presence of C brown comes from (1) spectral aerosol light absorption measurements near specific combustion sources, (2) observations of spectral properties of water extracts of continental aerosol, (3) laboratory studies indicating the formation of light-absorbing organic matter in the atmosphere, and (4) indirectly from the chemical analogy of aerosol species to colored natural humic substances. We show that brown carbon may severely bias measurements of "BC" and "EC" over vast parts of the troposphere, especially those strongly polluted by biomass burning, where the mass concentration of C brown is high relative to that of soot carbon. Chemical measurements to determine "EC" are biased by the refractory nature of C brown as well as by complex matrix interferences. Optical measurements of "BC" suffer from a number of problems: (1) many of the presently used instruments introduce a substantial bias into the determination of aerosol light absorption, (2) there is no unique conversion factor between light absorption and "EC" or "BC" concentration in ambient aerosols, and (3) the difference in spectral properties between the different types of LAC, as well as the chemical complexity of C brown , lead to several conceptual as well as practical complications. We also suggest that due to the sharply increasing absorption of C brown towards the UV, single-wavelength light absorption measurements may not be adequate for the assessment of absorption of solar radiation in the troposphere. We discuss the possible consequences of these effects for our understanding of tropospheric processes, including their influence on UV-irradiance, atmospheric photochemistry and radiative transfer in clouds.
Joint Monocular 3D Car Shape Estimation and Landmark Localization via Cascaded Regression

Previous works on reconstruction of a three-dimensional (3D) point shape model commonly use a two-step framework. Precisely localizing a series of feature points in an image is performed on the first step. Then the second procedure attempts to fit the 3D data to the observations to get the real 3D shape. Such an approach has high time consumption, and easily gets stuck into local minimum. To address this problem, we propose a method to jointly estimate the global 3D geometric structure of car and localize 2D landmarks from a single viewpoint image. First, we parametrizing the 3D shape by the coefficients of the linear combination of a set of predefined shape bases. Second, we adopt a cascaded regression framework to regress the global shape encoded by the prior bases, by jointly minimizing the appearance and shape fitting differences under a weak projection camera model. The position fitting item can help cope with the description ambiguity of local appearance, and provide more information for 3D reconstruction. Experimental results on a multi-view car dataset demonstrate favourable improvements on pose estimation and shape prediction, compared with some previous methods.
Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a Therapeutic Target in Triple-Negative Breast Cancer

Cancer cells can exhibit altered dependency on specific metabolic pathways and targeting these dependencies is a promising therapeutic strategy. Triple-negative breast cancer (TNBC) is an aggressive and genomically heterogeneous subset of breast cancer that is resistant to existing targeted therapies. To identify metabolic pathway dependencies in TNBC, we first conducted mass spectrometry–based metabolomics of TNBC and control cells. Relative levels of intracellular metabolites distinguished TNBC from nontransformed breast epithelia and revealed two metabolic subtypes within TNBC that correlate with markers of basal-like versus non-basal–like status. Among the distinguishing metabolites, levels of the cellular redox buffer glutathione were lower in TNBC cell lines compared to controls and markedly lower in non-basal–like TNBC. Significantly, these cell lines showed enhanced sensitivity to pharmacologic inhibition of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Consistent with this, patients whose tumors express elevated levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival. We find, further, that agents that limit the availability of glutathione precursors enhance both glutathione depletion and TNBC cell killing by γ-glutamylcysteine ligase inhibitors in vitro. Importantly, we demonstrate the ability to this approach to suppress glutathione levels and TNBC xenograft growth in vivo. Overall, these findings support the potential of targeting the glutathione biosynthetic pathway as a therapeutic strategy in TNBC and identify the non-basal-like subset as most likely to respond. Mol Cancer Ther; 17(1); 264–75. ©2017 AACR.
Polar Coding for the Wiretap Channel With Shared Key

The wiretap channel with shared key (WTC-K) refers to the classic wiretap channel with a secret key of arbitrary rate shared between the transmitter and the legitimate receiver. While the secrecy capacity of WTC-K has been obtained using random coding arguments, in this paper, we propose a low-complexity polar coding scheme achieving the secrecy capacity under the strong secrecy condition. Our construction consists of choosing the sets of information indices and using the shared key properly. Specifically, we utilize the structure of superposition coding in the proposed scheme.