Miracle-dz/UniFAR-FTUs huggingface dataset:
TBBPA targets converging key events of human oligodendrocyte development resulting in two novel AOPs.

Myelinating oligodendrocytes (OLs) establish saltatory nerve conduction during white matter development. Thus, interference with oligodendrogenesis leads to an adverse outcome on brain performance in the child due to aberrant myelination. An intertwined network of hormonal, transcriptional and biosynthetic processes regulates OLs development, thereby simultaneously creating various routes of interference for environmental toxicants. The flame retardant tetrabromobisphenol A (TBBPA) is debated as an endocrine disruptor, especially of the thyroid hormone (TH) system. We identified two independent modes-of-action (MoA) how TBBPA interferes with the establishment of a population of maturing OLs, dependent and independent of TH signaling. Combining the previously published oligodendrocyte maturation assay (NPC6) with large-scale transcriptomics, we describe TBBPA as a TH disruptor impairing human OL maturation in vitro by dysregulation of oligodendrogenesis-associated genes (i.e. MBP, KLF9 and EGR1). Furthermore, TBBPA disrupts a gene expression network regulating cholesterol homeostasis, reducing OL numbers independently of TH signaling. These two MoA converge in a novel putative Adverse Outcome Pathway (AOP) network on the key event (KE) hypomyelination. Comparative analyses of human and rat neural progenitor cells (NPCs) revealed that human oligodendrogenesis is more sensitive to endocrine disruption by TBBPA. Therefore, we emphasize that ethical, cost-efficient and species-overarching in vitro assays are needed for DNT hazard assessment. By incorporation of large-scale transcriptomic analyses, we brought the NPC6 assay to a higher readiness level for future applications in a regulatory context. The combination of phenotypic and transcriptomic analyses helps to study MoA to eventually build AOPs for a better understanding of neurodevelopmental toxicity.
Immunodiagnosis of Fasciolosis by Detection of Coproantigen.

A monoclonal antibody (MAb)-based western blot analysis (WB) was developed for detection o f a 26-28 kD coproantigen in Fasciola. hepatica infected cattle. Using WB the coproantigen was detected in feces from experimentally infected calves with 22 flukes or more. Using the biotin-streptavidin modification of WB, antigen was detected in the feces from experimentally-infected calves with 10 flukes or more as early as 6 weeks post­ infection. The MAbs did not react with the ES of Paramphistomum sp. or Moniezia sp, but showed slight cross-reactivity with ES from F. gigantica, and there was moderate cross-reactivity with Fascioloides magna ES. Differential staining o f purified 26-28 kD coproantigen on SDS-PAGE, under reducing and non-reducing conditions, indicated that the coproantigen was a monomeric, highly glycosylated glycoprotein. Alkaline treatment of the purified coproantigen resulted in an 8 KD protein core which still contains the epitope recognized by the MAbs. No protease activity was associated with the 26-28 kD coproantigen. The coproantigen was cleaved by trypsin without altering the reactive epitope, but was resistant to pepsin treatment. The coproantigen was stable under several different storage conditions. Indirect immunofluorescence on tissue sections of adult flukes indicated that coproantigen was present on gut cells and tegument. A capture enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the 26-28 kD coproantigen. Monoclonal antibody M2 DS/DSF10 was used to capture the antigen from the feces and hyper-immune rabbit ant-26-28 kD glycoprotein followed by peroxidase labeled goat anti-rabbit immunoglobulin was used for detection. The assay was able to detect down to 300 pg coproantigen /ml. Feces from 27 experimentally-infected calves with known numbers o f flukes were used to evaluate the test. Pre-infection feces from the same animals were used as negative controls. Coproantigen was detected in feces of calves with more than 10 flukes. In conclusion, both the coproantigen capture ELISA and WB were both more sensitive than microscopic examination for the diagnosis of Fasciola infection and both could detect pre-patent infections. Moreover, the ELISA for the detection o f coproantigen was easier to perform.
Orthogonal Representations of Reward Magnitude, Certainty, and Volatility in the Macaque Orbitofrontal Cortex

Categorical knowledge about the probabilistic and volatile nature of resource availability can improve foraging strategies, yet we have little understanding of how the brain represents such knowledge. Neurons in the orbitofrontal cortex (OFC) of macaques encode several decision variables (e.g., reward magnitude, probability) that could influence choice behavior. Here we investigated whether OFC neurons also represent two aspects of reward predictability: certainty and volatility. Rhesus monkeys performed a visual stimulus-reward association task in which a set of simple shapes preceded the delivery of reward, and they learned the nature of each shape’s reward association along two dimensions. One involved the certainty of a reward outcome; rewards can be either deterministic (and therefore certain) or probabilistic (uncertain). A second dimension reflected the volatility of an outcome; reward schedules can be either stable over time or volatile. During stimulus presentation, the activity of OFC neurons reflected both categorical certainty and categorical volatility, in addition to reward magnitude. These three characteristics were represented orthogonally by three distinct neural populations of similar size. These findings point to a more general role for OFC in processing reward information than one restricted to encoding parametric valuations such as reward magnitude and probability.
Endogenous brassinosteroids in microalgae exposed to salt and low temperature stress

ABSTRACT Brassinosteroids are part of the hormonal network that regulates growth processes and stress responses in plants. There is evidence for a similar hormonal network in microalgae. In the present study, six microalgae (Chlorococcum ellipsoideum, Gyoerffyana humicola, Nautococcus mamillatus, Acutodesmus acuminatus, Protococcus viridis and Chlorella vulgaris) were subjected to salt and low temperature stress with the addition of 36 g l–1 NaCl and transfer from 25°C to 15°C. There was a rapid response to salt stress with the brassinosteroid content (mainly castasterone with lower amounts of brassinolide, homocastasterone and typhasterol) increasing within 30 min of the salt treatment and remaining at these elevated levels after 7 h. The decrease in temperature had little effect on the brassinosteroid content. This was the first study to show that endogenous brassinosteroids increase in response to abiotic stress in a number of microalgae species.
Late Jurassic radiolarians from mudstone near the U–Pb-dated sandstone ofthe North Kitakami Belt in the northeastern Shimokita Peninsula, Tohoku, Japan

In the northeastern Shimokita Peninsula, Aomori Prefecture, a Jurassic accretionary complex (AC) belonging to the North Kitakami Belt is distributed in three hilly areas of the Kuwabatayama, Katasakiyama and Omori. Although the AC in the Kuwabatayama area has been extensively studied and subdivided into the Late Jurassic Iwaya Unit and the Early Cretaceous Shitsukari Unit, those in the other areas are not fully understood except for a recent report of the detrital zircon U–Pb age from sandstone in the Omori area. We extracted radiolarian fossils such as Eucyrtidiellum cf. pyramis indicating the Late Jurassic (probably Kimmeridgian) from mudstone near the U–Pb-dated sandstone in the Omori area. Because this radiolarian age is close to the zircon U–Pb age, and the horizons of the mudstone and sandstone are close without any recognizable distinctive tectonic discontinuity between them, the clastic rocks in the Omori area may be stratigraphically continuous or contemporaneous sequences deposited around the Kimmeridgian. The ACs in the Katasakiyama and Omori areas are correlative to the Iwaya Unit in the Kuwabatayama area based on the lithology, geologic structure and clastic rock age. Therefore, the ACs in the northeastern Shimokita Peninsula can be divided into the Late Jurassic and the Early Cretaceous units; the former is the Iwaya Unit in the Kuwabatayama area and the unnamed ACs in the Omori and Katasakiyama areas, while the latter is the Shitsukari Unit in the Kuwabatayama area.
Latitudinal gradients in population growth do not reflect demographic responses to climate

Abstract Spatial gradients in population growth, such as across latitudinal or elevational gradients, are often assumed to primarily be driven by variation in climate, and are frequently used to infer species’ responses to climate change. Here, we use a novel demographic, mixed‐model approach to dissect the contributions of climate variables vs. other latitudinal or local site effects on spatiotemporal variation in population performance in three perennial bunchgrasses. For all three species, we find that performance of local populations decreases with warmer and drier conditions, despite latitudinal trends of decreasing population growth toward the cooler and wetter northern portion of each species’ range. Thus, latitudinal gradients in performance are not predictive of either local or species‐wide responses to climate. This pattern could be common, as many environmental drivers, such as habitat quality or species’ interactions, are likely to vary with latitude or elevation, and thus influence or oppose climate responses.
Structures of ABC transporters: handle with care

In the past two decades, the ATP‐binding cassette (ABC) transporters' field has undergone a structural revolution. The importance of structural biology to the development of the field of ABC transporters cannot be overstated, as the ensemble of structures not only revealed the architecture of ABC transporters but also shaped our mechanistic view of these remarkable molecular machines. Nevertheless, we advocate that the mechanistic interpretation of the structures is not trivial and should be carried out with prudence. Herein, we bring several examples of structures of ABC transporters that merit re‐interpretation via careful comparison to experimental data. We propose that it is of the upmost importance to place new structures within the context of the available experimental data.
Frenemy at the gate: invasion by Pheidole megacephala facilitates a competitively subordinate plant ant in Kenya.

Biological invasions can lead to the reassembly of communities, and understanding and predicting the impacts of exotic species on community structure and functioning is a key challenge in ecology. We investigated the impact of a predatory species of invasive ant, Pheidole megacephala, on the structure and function of a foundational mutualism between Acacia drepanolobium and its associated acacia-ant community in an East African savanna. Invasion by P. megacephala was associated with the extirpation of three extrafloral nectar-dependent Crematogaster acacia ant species and strong increases in the abundance of a competitively subordinate and locally rare acacia ant species, Tetraponera penzigi, which does not depend on host plant nectar. Using a combination of long-term monitoring of invasion dynamics, observations and experiments, we demonstrate that P. megacephala directly and indirectly facilitates T. penzigi by reducing the abundance of T. penzigi's competitors (Crematogaster spp), imposing recruitment limitation on these competitors, and generating a landscape of low-reward host plants that favor colonization and establishment by the strongly dispersing T. penzigi. Seasonal variation in use of host plants by P. megacephala may further increase the persistence of T. penzigi colonies in invaded habitat. The persistence of the T. penzigi-A. drepanolobium symbiosis in invaded areas afforded host plants some protection against herbivory by elephants (Loxodonta africana), a key browser that reduces tree cover. However, elephant damage on T. penzigi-occupied trees was higher in invaded than in uninvaded areas, likely owing to reduced T. penzigi colony size in invaded habitats. Our results reveal the mechanisms underlying the disruption of this mutualism and suggest that P. megacephala invasion may drive long-term declines in tree cover, despite the partial persistence of the ant-acacia symbiosis in invaded areas.
Remodeling of root morphology by CuO and ZnO nanoparticles: effects on drought tolerance for plants colonized by a beneficial pseudomonad.

Formulations that include nanoparticles of CuO and ZnO are being considered for agricultural applications as fertilizers because they act as sources of Cu or Zn. Currently, few studies of the effects of these nanoparticles (NPs) consider the three-way interactions of NPs with the plant plus its microbiome. At doses that produced root shortening by both nanoparticles (NPs), CuO NPs induced the proliferation of elongated root hairs close to the root tip, and ZnO NPs increased lateral root formation in wheat seedlings (Triticum aestivum L.). These responses occurred with roots colonized by a beneficial bacterium, Pseudomonas chlororaphis O6 (PcO6), originally isolated from roots of wheat grown under dryland farming in calcareous soils. The PcO6-induced tolerance to drought stress in wheat seedlings was not impaired by the NPs. Rather, growth of the PcO6-colonized plants with NPs resulted in systemic increases in the expression of genes associated with tolerance to water stress. Increased expression in the sh.
A practice-based evidence investigation of God representations in spiritually integrated psychotherapies.

OBJECTIVE This practice-based evidence study examined trajectories of God representations and psychological distress among Christians participating in spiritually integrated psychotherapies (SIPs). METHODS In total, 17 clinicians practicing SIPs in a mid-sized city on the US Gulf Coast implemented session-to-session assessments of these outcomes with 158 clients over a 4-month period and also reported their use of specific spiritual interventions after each session (e.g., affirmed client's divine worth). RESULTS Multivariate growth modeling revealed clients' psychological distress decreased over the study period whereas authoritarian God representations increased and benevolent God representations remained stable. In addition, clients who increased in benevolent representations of God had a greater likelihood of experiencing alleviation of psychological distress. CONCLUSION These findings affirm the potential efficacy of SIPs and cultural importance of belief in a benevolent deity as a source of strength, identity, and potential healing among Christians clients who prefer a spiritually integrated approach in psychotherapy.
Sphincter‐saving surgery for ultra‐low rectal carcinoma initially indicated for abdominoperineal resection: Is it safe on a long‐term follow‐up?

Rate of abdominoperineal resection (APR) varies from countries and surgeons. Surgical impact of preoperative treatment for ultra‐low rectal carcinoma (ULRC) initially indicated for APR is debated. We report the 10‐year oncological results from a prospective controlled trial (GRECCAR 1) which evaluate the sphincter saving surgery (SSR).
Canola meal in nursery pig diets: growth performance and gut health

Abstract An experiment was conducted to determine the effects of including canola meal (CM) in nursery pig diets on growth performance, immune response, fecal microbial composition, and gut integrity. A total of 200 nursery pigs (initial body weight = 7.00 kg) were obtained in two batches of 100 pigs each. Pigs in each batch were housed in 25 pens (four pigs per pen) and fed five diets in a randomized complete block design. The five diets were corn–soybean meal (SBM)-based basal diets with 0%, 10%, 20%, 30%, or 40% of CM. The diets were fed in three phases: phase 1: day 0 to 7, phase 2: day 7 to 21, and phase 3: day 21 to 42. Diets in each phase were formulated to similar net energy, Ca, and digestible P and amino acid contents. Feed intake and body weight were measured by phase. Immune response and gut integrity parameters were measured at the end of phases 1 and 2. Fecal microbial composition for diets with 0% or 20% CM was determined at the end of phase 2. Overall average daily gain (ADG) responded quadratically (P < 0.05) to increasing dietary level of CM such that ADG was increased by 17% due to an increase in the dietary level of CM from 0% to 20% and was reduced by 16% due to an increase in the dietary level of CM from 20% to 40%. Pigs fed diets with 0% or 40% CM did not differ in overall ADG. Dietary CM tended to quadratically decrease (P = 0.09) serum immunoglobulin A (IgA) level at the end of phase 2 such that serum IgA level tended to reduce with an increase in dietary CM from 0% to 20% and to increase with an increase in dietary CM from 20% to 40%. Dietary CM at 20% decreased (P < 0.05) the relative abundance of Bacteroidetes phylum and tended to increase (P = 0.07) the relative abundance of Firmicutes phylum. Dietary CM linearly increased (P < 0.05) the lactulose to mannitol ratio in the urine by 47% and 49% at the end of phases 1 and 2, respectively, and tended to linearly decrease (P < 0.10) ileal transepithelial electrical resistance at the end of phase 1 by 64%. In conclusion, CM fed in the current study could be included in corn–SBM-based diets for nursery pigs 20% to improve the growth performance and gut microbial composition and reduce immune response. Also, the CM used in the current study could be included in corn–SBM-based diets for nursery pigs at 30% or 40% without compromising growth performance. Dietary CM increased gut permeability, implying that dietary CM at 20% improves the growth performance of weaned pigs through mechanisms other than reducing gut permeability.
Biological fluid levels of iron and iron‐related proteins in Parkinson’s disease: Review and meta‐analysis

Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD. However, the results on cerebrospinal (CSF) and serum/plasma iron levels in PD patients have been controversial. The aim of this systematic review and meta‐analysis was to establish the CSF and serum/plasma levels of iron and iron‐related proteins (ferritin, transferrin, lactoferrin, haptoglobin, and hepcidine) levels, and the urine levels of iron, in patients with PD.
Use of critically important antimicrobial classes early in life may adversely impact bacterial resistance profiles during adult years: potential co‐selection for plasmid‐borne fluoroquinolone and macrolide resistance via extended‐spectrum beta‐lactam use in dairy cattle

The transfer of antimicrobial resistance genes commonly occurs via vertical and horizontal gene transfer, as such genes are often found on the same mobile genetic element. This occurrence can lead to the co‐selection of resistance to antimicrobials without their application. Dairy cattle located in the south‐western United States were enrolled in a matched‐pair longitudinal study to evaluate the effects of a two‐dose ceftiofur treatment for metritis on levels of third‐generation cephalosporin resistance among faecal Escherichia coli temporally. Escherichia coli chosen for further investigation were isolated on selective media, harboured extended‐spectrum beta‐lactam, fluoroquinolone and macrolide resistance genes. This combination has previously been unreported; importantly, it included genes encoding for resistance to antibiotics that can only be used in dairy cattle less than 20 months of age. Fluoroquinolones, macrolides and third and higher generation cephalosporins are considered critically important and highest priority for human medicine by the World Health Organization.
Intranuclear inclusions consistent with a Nucleospora sp. in a lymphoid lesion in a laboratory zebrafish, Danio rerio (Hamilton 1822).

Michael L. Kent1,2, Katrina N. Murray3, Maurine R. Hobbs4, Louis M. Weiss5, Sean T. Spagnoli2, Justin L. Sanders2 1Department of Microbiology, Oregon State University, Corvallis, OR, USA 2Department of Biomedical Sciences, Oregon State University, Corvallis, OR, USA 3Zebrafish International Resource Center, Eugene, OR, USA 4Centralized Zebrafish Animal Resource, University of Utah, Salt Lake City, UT, USA 5Albert Einstein College of Medicine, Bronx, NY, USA
'We realised we needed a new approach': Government and law enforcement perspectives on the implementation and future of the drug decriminalisation policy in vietnam.

In 2009, Vietnam officially decriminalised drug use through amendments to the criminal law. The amendments outlined explicitly that illicit drug use would be seen as an administrative violation, but not a criminal offence. This legal transition has not been without implementation challenges, and police particularly have struggled to find a balance between drug law enforcement and decriminalisation. Despite being a health-orientated drug policy amendment, in practice it allows police to send suspected drug users to compulsory treatment centres without judicial oversight and people who use drugs continue to face challenges in their interface with law enforcement which can negatively impact access to harm reduction and community-based treatment programs. Using policy desk research combined with indepth interviews with 14 key informants from people representing a range of relevant Vietnamese government (n = 10) and non-government agencies (n = 4), this paper explores some insights and considerations into how decriminalisation of drug use in the amended law was implemented. We explore key informant perspectives into how the decriminalisation amendment could be implemented more effectively in order to improve health outcomes for people who use drugs in Vietnam through re-envisioned police protocols and practices. Findings show that while decriminalising drug use in Vietnam was designed as a progressive and health-orientated drug policy, the ongoing disconnect between the health intent of the policy and the police-led oversight of its implementation in the community persists. Part of this disconnect is explained by the lack of training and clear protocols that would enhance the police in their ability to contribute to the health intent of the policy rather than continue to view drug use through a drug law enforcement only lens. The paper calls for further collaboration across policing and the health and community-based organisations delivering services for people who use drugs. We suggest that through developing a deeper understanding of the interplay between policing and the implementation of harm reduction policy and programs, decriminalisation can co-exist within a broader and deeply entrenched drug control strategy in Vietnam.