Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute Negative Allosteric Modulation of M5 Muscarinic Acetylcholine Receptors Inhibits Oxycodone Self-Administration and Cue-Induced Reactivity with no effect on Antinociception.

Opioid Use Disorder (OUD) is a debilitating neuropsychiatric condition characterized by compulsive opioid use, dependence, and repeated relapse after periods of abstinence. Given the high risk of developing OUD following prescription opioid use, the continued need for opioid-induced analgesia, and the limitations of current treatments, it is necessary to develop novel, non-opioid based treatments for OUD and decrease abuse potential of prescription opioids. Recent evidence suggests that negative allosteric modulation (NAM) of the M5 muscarinic acetylcholine receptor (M5 mAChR) may provide an alternative therapeutic approach for the treatment of OUD. Previous studies demonstrated localization of M5 mAChR expression within the mesocorticolimbic reward circuitry and that the selective M5 NAM ML375 attenuates both cocaine and alcohol self-administration in rats. In the present study, the effects of ML375 were evaluated in rats self-administering the µ-opioid agonist oxycodone or remifentanil on a progressive ratio (PR) schedule or on cue-reactivity (a rodent model of relapse) in the absence of oxycodone following 72 hours of abstinence. ML375 reduced the PR break point for oxycodone and remifentanil self-administration and attenuated cue-elicited responding. Importantly, ML375 did not affect sucrose pellet-maintained responding on a PR schedule or opioid-induced analgesia using the hot-plate and tail-flick assays. We also confirm expression of M5 mAChR mRNA in the ventral tegmental area and show that this is primarily on dopamine (tyrosine hydroxylase mRNA-positive) neurons. Taken together, these findings suggest that selective functional antagonism of the M5 mAChR may represent a novel, non-opioid based treatment for OUD.
Regulation of Bacterial Gene Expression by Transcription Attenuation

A wide variety of mechanisms that control gene expression in bacteria are based on conditional transcription termination. Generally, in these mechanisms, a transcription terminator is located between a promoter and a downstream gene(s), and the efficiency of the terminator is controlled by a regulatory effector that can be a metabolite, protein, or RNA. SUMMARY A wide variety of mechanisms that control gene expression in bacteria are based on conditional transcription termination. Generally, in these mechanisms, a transcription terminator is located between a promoter and a downstream gene(s), and the efficiency of the terminator is controlled by a regulatory effector that can be a metabolite, protein, or RNA. The most common type of regulation involving conditional termination is transcription attenuation, in which the primary regulatory target is an essential element of a single terminator. The terminator can be either intrinsic or Rho dependent, with each presenting unique regulatory targets. Transcription attenuation mechanisms can be divided into five classes based primarily on the manner in which transcription termination is rendered conditional. This review summarizes each class of control mechanisms from a historical perspective, describes important examples in a physiological context and the current state of knowledge, highlights major advances, and discusses expectations of future discoveries.
Hyperspectral imaging in the spatial frequency domain with a supercontinuum source

Abstract. We introduce a method for quantitative hyperspectral optical imaging in the spatial frequency domain (hs-SFDI) to image tissue absorption (μa) and reduced scattering (μs′) parameters over a broad spectral range. The hs-SFDI utilizes principles of spatial scanning of the spectrally dispersed output of a supercontinuum laser that is sinusoidally projected onto the tissue using a digital micromirror device. A scientific complementary metal–oxide–semiconductor camera is used for capturing images that are demodulated and analyzed using SFDI computational models. The hs-SFDI performance is validated using tissue-simulating phantoms over a range of μa and μs′ values. Quantitative hs-SFDI images are obtained from an ex-vivo beef sample to spatially resolve concentrations of oxy-, deoxy-, and met-hemoglobin, as well as water and fat fractions. Our results demonstrate that the hs-SFDI can quantitatively image tissue optical properties with 1000 spectral bins in the 580- to 950-nm range over a wide, scalable field of view. With an average accuracy of 6.7% and 12.3% in μa and μs′, respectively, compared to conventional methods, hs-SFDI offers a promising approach for quantitative hyperspectral tissue optical imaging.
[Medium-chain acyl-CoA dehydrogenase enhances invasion and metastasis ability of breast cancer cells].

OBJECTIVE To investigate the effect of medium-chain acyl-CoA dehydrogenase (ACADM) on invasion and metastasis of breast cancer cells and explore the underlying mechanism. METHODS A large cancer genome database was used to analyze the expression of ACADM in breast cancer tissues and normal tissues. The proliferation, migration and invasion of cultured breast cancer MCF-7 and T47D cells with ACADM overexpression or ACADM silencing were evaluated using MTT proliferation assay, EdU assay, Transwell chamber assay, and Boyden invasion assay; Western blotting was used to detect the protein expressions of the related pathway in the cells. In nude mouse models of tail vein metastasis of MCF-7 cells with or without ACADM overexpression, the tumor growth and tumor histopathology were observed using HE staining. RESULTS Analysis of the Oncomine sample set showed a significantly higher expression level of ACADM in breast cancer tissues than in normal breast tissues (P < 0.05). Overexpression of ACADM obviously enhanced the migration and invasion abilities and promoted the epithelial-mesenchymal transition (EMT) of cultured MCF-7 and T47D cells; conversely, silencing of ACADM significantly suppressed the migration and invasion of the breast cancer cells. In the nude mouse models, ACADM overexpression in MCF-7 cells significantly enhanced their in vivo migration and invasion abilities. CONCLUSIONS ACADM can promote the EMT process of breast cancer cells and improve the migration and invasion ability. ACADM is an oncogene in breast cancer.
A Short Survey of Intrusion Detection Systems

As the cost of information processing and Internet accessibility falls, organizations are becoming increasingly vulnerable to potential cyber threats such as network intrusions. So, there exists a need to provide secure and safe transactions through the use of firewalls, Intrusion Detection Systems (IDSs), encryption, authentication, and other hardware and software solutions. Many IDS variants exist which allow security managers and engineers to identify attack network packets primarily through the use of signature detection; i.e., the IDS “recognizes” attack packets due to their well-known “fingerprints” or signatures as those packets cross the network’s gateway threshold. On the other hand, anomaly based ID systems determine what is normal traffic within a network and reports abnormal traffic behaviour. IDS are made so they can reliably detect Probe, DoS, U2R, R2L and data attacks against Solaris, Sun OS, Linux and Windows NT operating systems with low false alarm rates. However, for most systems, complete attack prevention is not realistically attainable due to system complexity, configuration and administration errors, and abuse by authorized users. For this reason, attack detection has been an important aspect of recent computer security efforts [2, 5] .
Sequential Recovery of Heavy and Noble Metals by Mussel-Inspired Polydopamine-Polyethyleneimine Conjugated Polyurethane Composite Bearing Dithiocarbamate Moieties

Dithiocarbamate-grafted polyurethane (PU) composites were synthesized by anchoring dithiocarbamate (DTC) as a chelating agent to the polyethyleneimine-polydopamine (PE-DA)-functionalized graphene-based PU matrix (PE-DA@GB@PU), as a new adsorbent material for the recovery of Cu2+, Pb2+, and Cd2+ from industrial effluents. After leaching with acidic media to recover Cu2+, Pb2+, and Cd2+, dithiocarbamate-grafted PE-DA@GB@PU (DTC-g-PE-DA@GB@PU) was decomposed and PE-DA@GP was regenerated. The latter was used to recover Pd2+, Pt4+, and Au3+ from the copper leaching residue and anode slime. The present DTC-g-PE-DA@GB@PU and PE-DA@GB@PU composites show high adsorption performance, effective separation, and quick adsorption of the target ions. The morphologies of the composites were studied by scanning electron microscopy and their structures were investigated by Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy. The effects of pH values, contact time, and initial metal ion concentration conditions were also studied. An adsorption mechanism was proposed and discussed in terms of the FT-IR results.
Antibodies to Borrelia turicatae in Experimentally Infected Dogs Cross-React with Borrelia burgdorferi Serologic Assays

Tick-borne relapsing fever (TBRF) is caused by several Borrelia spp. (including Borrelia turicatae), which are primarily transmitted by Ornithodoros ticks. Relapsing fever group species are found worldwide, except for Antarctica. Approximately 500 human cases were reported between 1990 and 2011 in the United States (likely an underestimate), while cases in domestic and wild dogs were reported from Florida, Texas, and Washington. TBRF spirochetes are related to Borrelia burgdorferi, the agent of Lyme borreliosis. ABSTRACT Tick-borne relapsing fever (TBRF) is caused by several Borrelia spp. (including Borrelia turicatae), which are primarily transmitted by Ornithodoros ticks. Relapsing fever group species are found worldwide, except for Antarctica. Approximately 500 human cases were reported between 1990 and 2011 in the United States (likely an underestimate), while cases in domestic and wild dogs were reported from Florida, Texas, and Washington. TBRF spirochetes are related to Borrelia burgdorferi, the agent of Lyme borreliosis. Dogs are routinely screened for B. burgdorferi, but it is unknown if infection with TBRF agents produces antibodies cross-reactive with B. burgdorferi assays. These data are critical for accurate surveillance of TBRF and Lyme borreliosis in dogs. In this study, B. burgdorferi-negative dogs were inoculated with B. turicatae, and seroconversion was confirmed by the rBipA (recombinant Borrelia immunogenic protein A) Western blot. Seropositive samples were tested with commercial and veterinary diagnostic laboratory B. burgdorferi-based tests. Borrelia turicatae-seroreactive samples cross-reacted with a whole-cell indirect fluorescent antibody (IFA) test and two multiantigen tests, but not with single-antigen tests using C6. Cross-reactivity with TBRF can confound epidemiology and surveillance efforts and confuse recommendations made by veterinarians for prevention and control. These findings demonstrate the need to critically evaluate results from B. burgdorferi diagnostic tests in the context of the assay type and the animal’s geographical location and history of travel, as well as highlighting the need for commercially available specific diagnostic tests for TBRF spirochetes.
Minimum Clinically Important Difference in 30-s Sit-to-Stand Test After Pulmonary Rehabilitation in Subjects With COPD

BACKGROUND: The sit-to-stand (STS) test is a feasible tool for measuring peripheral muscle strength of the lower limbs. There is evidence of increasing use of STS tests in patients with COPD. We sought to evaluate in subjects with COPD the minimum clinically important difference in 30-s STS test after pulmonary rehabilitation. METHODS: Stable COPD subjects undergoing a 30-s STS test and a 6-min walk test (6MWT) before and after pulmonary rehabilitation were included. Responsiveness to pulmonary rehabilitation was determined by the change in 30-s STS test results (Δ 30-s STS) before and after pulmonary rehabilitation. The minimum clinically important difference was evaluated using an anchor-based method. RESULTS: 96 subjects with moderate-to-severe COPD were included. At baseline, 30-s STS test results were significantly related to distance covered in a 6MWT (6MWD) (r = 0.65, P < .001), FVC (r = 0.46, P < .001), PaCO2 (r = −0.42, P < .001), FEV1 (r = 0.39, P < .001), and age (r = −0.31, P = .002). After pulmonary rehabilitation, a significant improvement in 30-s STS test results was observed (mean difference +2 repetitions, P < .001). The Δ30-s STS was positively related to Δ6MWD (r = 0.62, P < .001), transitional dyspnea index (r = 0.67, P < .001), and baseline residual volume (r = 0.27, P = .007). The receiver operating characteristic curves method identified a Δ 30-s STS cut-off of 2 repetitions as the best discriminating value (area under the curve: 0.892, P < .001) to identify the minimum clinically important difference for Δ6MWD (30 m). In a multivariate logistic regression model, baseline 30-s STS (odds ratio 2.63; 95% CI 1.09–6.35, P = .031) and diffusing capacity of the lung for carbon monoxide (< 53% predicted) (odds ratio 2.49, 95% CI 1.04–5.98, P = .041) predict the risk to have a Δ 30-s STS ≥ 2 repetitions. CONCLUSIONS: Our study indicates that in stable subjects with moderate-to-severe COPD, the 30-s STS test was a sensitive tool to assess the efficacy of pulmonary rehabilitation. A Δ 30-s STS of ≥ 2 repetitions represented the minimum clinically important difference, which may be predicted by the baseline ability in the 30-s STS test and lung function in terms of diffusing lung capacity (ClinicalTrials.gov registration NCT03627624).
The Nuclear Export Receptors TbMex67 and TbMtr2 Are Required for Ribosome Biogenesis in Trypanosoma brucei

The nuclear export of ribosomal subunits (60S and 40S) depends in part on the activity of the essential auxiliary export receptors TbMtr2 and TbMex67. When these proteins are individually depleted from the medically and agriculturally significant parasite Trypanosoma brucei, distinct alterations in the processing of the rRNAs of the large subunit (60S) are observed as well as aberrations in the assembly of functional ribosomes (polysomes). We also established that TbMex67 and TbMtr2 interact directly or indirectly with the protein components of the 5S RNP, including the trypanosome-specific P34/P37. The critical role that TbMex67 and TbMtr2 play in this essential biological process together with their parasite-specific interactions may provide new therapeutic targets against this important parasite. ABSTRACT Ribosomal maturation is a complex and highly conserved biological process involving migration of a continuously changing RNP across multiple cellular compartments. A critical point in this process is the translocation of individual ribosomal subunits (60S and 40S) from the nucleus to the cytoplasm, and a number of export factors participate in this process. In this study, we characterize the functional role of the auxiliary export receptors TbMex67 and TbMtr2 in ribosome biogenesis in the parasite Trypanosoma brucei. We demonstrate that depletion of each of these proteins dramatically impacts the steady-state levels of other proteins involved in ribosome biogenesis, including the trypanosome-specific factors P34 and P37. In addition, we observe that the loss of TbMex67 or TbMtr2 leads to aberrant ribosome formation, rRNA processing, and polysome formation. Although the TbMex67-TbMtr2 heterodimer is structurally distinct from Mex67-Mtr2 complexes previously studied, our data show that they retain a conserved function in ribosome biogenesis. IMPORTANCE The nuclear export of ribosomal subunits (60S and 40S) depends in part on the activity of the essential auxiliary export receptors TbMtr2 and TbMex67. When these proteins are individually depleted from the medically and agriculturally significant parasite Trypanosoma brucei, distinct alterations in the processing of the rRNAs of the large subunit (60S) are observed as well as aberrations in the assembly of functional ribosomes (polysomes). We also established that TbMex67 and TbMtr2 interact directly or indirectly with the protein components of the 5S RNP, including the trypanosome-specific P34/P37. The critical role that TbMex67 and TbMtr2 play in this essential biological process together with their parasite-specific interactions may provide new therapeutic targets against this important parasite.
Case studies in neuroscience: Subcortical origins of the frequency-following response.

The auditory frequency-following response (FFR) reflects synchronized and phase-locked activity along the auditory pathway in response to sound. While historically thought to reflect subcortical activity, recent evidence suggests an auditory cortex contribution as well. Here we present electrophysiological evidence for the FFR's origins from two cases: a patient with bilateral auditory cortex lesions and a patient with auditory neuropathy, a condition of subcortical origin. The patient with auditory cortex lesions had robust and replicable FFRs, but no cortical responses. In contrast, the patient with auditory neuropathy had no FFR despite robust and replicable cortical responses. This double dissociation shows that subcortical synchrony is necessary and sufficient to generate an FFR.
Characterization of a thermostable Deconica castanella Laccase and application toward pentachlorophenol degradation

Abstract Pentachlorophenol (PCP) is an organochlorine pesticide whose toxicity led it to be banned in several countries. In Brazil however, this compound is widely accessible, and its indiscriminate use leads to extensive soil contamination, which requires henceforth, the development of new approaches to manage PCP presence in environment. Considering that PCP is susceptible to undergo enzymatic degradation, this investigation is thence, aimed at the purification, and characterization, of a thermostable fungal enzyme (i.e. Laccase of Deconica castanella (Dc-Lac), and assess its role in PCP in vitro biodegradation. Results evidenced that, molecular mass of the partially purified Dc-Lac was estimated to be of 64 kDa, presenting apparent Km of 0.47 µmol, and Vmax of 11.56 U mg−1. The optimum temperature and pH were 55 °C and 2.5, respectively. The T½ verified at 55, 60, and 80 °C were 19 and 17 hr, and 47 min, respectively. The highest PCP biodegradation was of 23% at pollutant concentration of 100 µg L−1, which evidenced that Dc-Lac is a thermostable enzyme that acted directly in PCP degradation and may be a useful asset to remediate this pollutant.
Peptide‐Based 2‐Aminophenylamide Probes for Targeting Endogenous Class I Histone Deacetylase Complexes

Lysine deacetylases or histone deacetylases (HDACs) remove acetylation markers from numerous cellular proteins, thereby regulating their function and activity. Recently established peptide probes containing the HDAC‐trapping amino acid α‐aminosuberic acid ω‐hydroxamate (AsuHd) have been used to investigate the compositions of HDAC complexes in a site‐specific manner. Here we report the new HDAC‐trapping amino acid 2‐amino‐8‐[(2‐aminophenyl)amino]‐8‐oxooctanoic acid (AsuApa) and the utility of AsuApa‐containing probes for HDAC complex profiling on a proteome‐wide scale. Unlike AsuHd‐containing probes, AsuApa enriched only HDACs 1, 2, and 3 efficiently and was the most potent probe tested for capturing the last of these. These findings indicate that the inherent specificity of reported small‐molecule pimelic diphenylamide HDAC inhibitors is preserved in AsuApa and that this HDAC‐trapping amino acid represents a potent tool for investigating class I HDAC complexes.
Perceived quality of HIV care and client satisfaction across different service providers in Ukraine.

BACKGROUND Prior studies have shown that high client satisfaction and quality of services are important drivers of uptake and retention in human immunodeficiency virus (HIV) care. Study objectives were to assess the perceived quality of HIV services, satisfaction and associated factors across different types of health facilities in Ukraine. METHODS We conducted a cross-sectional study among 649 individuals receiving HIV services across 47 health facilities in three regions of Ukraine. Primary outcomes were satisfaction and perceived quality of services measured along five dimensions: accessibility, user-friendliness, privacy and confidentiality, comprehensiveness (separately for testing and treatment services). Quality dimensions were constructed by confirmatory factor analysis. Links between quality dimensions, satisfaction and related factors were measured by structural equation modelling. RESULTS Median scores for accessibility, user-friendliness, privacy and confidentiality, comprehensiveness of services and overall satisfaction ranged from 0.75 to 1 out of 1. User-friendliness was the main determinant associated with satisfaction (total effect: β = 0.515, P < 0.001). Satisfaction was higher at primary healthcare centres (direct effect: β = 0.145, P < 0.001; indirect effect through accessibility: β = 0.060, P < 0.001), narcological/tuberculosis dispensaries (direct effect: β = 0.105, P = 0.006; indirect effect through accessibility: β = 0.060, P < 0.001) and hospitals (indirect effects through user-friendliness and accessibility: β = 0.180, P < 0.001) when compared to acquired immune deficiency syndrome centres. CONCLUSIONS User-friendliness is a key driver of client satisfaction with HIV services in Ukraine. Decentralization of services, together with improved training and supervision for provider-client interactions may provide important levers to improve client satisfaction with HIV services and enrolment and retention in the cascade of HIV services.
An analog-to-digital conversion based on a moving window deconvolution

A high-performance analog-to-digital conversion technique for nuclear spectroscopy applications with unconventional architecture is described. This technique is planned to be used in Phase III of the European /spl gamma/-ray facility project EUROBALL. The conversion is based on the Moving Window Deconvolution (MWD) method for signal processing in nuclear spectroscopy which has been introduced recently. This method allows the conversion to be represented as a sequence of measurements of the total charge of the event and consequently, by applying for example a simple oversampling scheme to achieve a high accuracy. The proposed MWD-type conversion exhibits very low differential and integral nonlinearities over a 14-bit resolution range with an effective conversion dead-time virtually zero. The last feature combined with an inherent pipeline conversion structure is of great importance for applications in large-scale multi-detector arrays like EUROBALL. The key parameters of the development have been theoretically estimated and measured with a prototype consisting of a free running A/D converter and a digital signal processor. >