Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Na+-Translocating NADH:Quinone Oxidoreductase on Iron Uptake and nqrM Expression in Vibrio cholerae

Investigating strategies of iron acquisition, storage, and delivery in Vibrio cholerae is a prerequisite to understand how this pathogen thrives in hostile, iron-limited environments such as the human host. In addition to highlighting the maturation of the respiratory complex NQR, this study points out the influence of NQR on iron metabolism, thereby making it a potential drug target for antibiotics. ABSTRACT The Na+ ion-translocating NADH:quinone oxidoreductase (NQR) from Vibrio cholerae is a membrane-bound respiratory enzyme which harbors flavins and Fe-S clusters as redox centers. The NQR is the main producer of the sodium motive force (SMF) and drives energy-dissipating processes such as flagellar rotation, substrate uptake, ATP synthesis, and cation-proton antiport. The NQR requires for its maturation, in addition to the six structural genes nqrABCDEF, a flavin attachment gene, apbE, and the nqrM gene, presumably encoding a Fe delivery protein. We here describe growth studies and quantitative real-time PCR for the V. cholerae O395N1 wild-type (wt) strain and its mutant Δnqr and ΔubiC strains, impaired in respiration. In a comparative proteome analysis, FeoB, the membrane subunit of the uptake system for Fe2+ (Feo), was increased in V. cholerae Δnqr. In this study, the upregulation was confirmed on the mRNA level and resulted in improved growth rates of V. cholerae Δnqr with Fe2+ as an iron source. We studied the expression of feoB on other respiratory enzyme deletion mutants such as the ΔubiC mutant to determine whether iron transport is specific to the absence of NQR resulting from impaired respiration. We show that the nqr operon comprises, in addition to the structural nqrABCDEF genes, the downstream apbE and nqrM genes on the same operon and demonstrate induction of the nqr operon by iron in V. cholerae wt. In contrast, expression of the nqrM gene in V. cholerae Δnqr is repressed by iron. The lack of functional NQR has a strong impact on iron homeostasis in V. cholerae and demonstrates that central respiratory metabolism is interwoven with iron uptake and regulation. IMPORTANCE Investigating strategies of iron acquisition, storage, and delivery in Vibrio cholerae is a prerequisite to understand how this pathogen thrives in hostile, iron-limited environments such as the human host. In addition to highlighting the maturation of the respiratory complex NQR, this study points out the influence of NQR on iron metabolism, thereby making it a potential drug target for antibiotics.
Photosynthetic cyclic electron transport provides ATP for homeostasis during trap closure in Dionaea muscipula.

BACKGROUND AND AIMS The processes connected with prey capture and the early consumption of prey by carnivorous Dionaea muscipula require high amounts of energy. The aim of the present study was to identify processes involved in flytrap energy provision and ATP homeostasis under these conditions. METHODS We determined photosynthetic CO2 uptake and chlorophyll fluorescence as well as the dynamics of ATP contents in the snap traps upon closure with and without prey. KEY RESULTS The results indicate that upon prey capture, a transient switch from linear to cyclic electron transport mediates a support of ATP homeostasis. Beyond 4 hours after prey capture, prey resources contribute to the traps' ATP pool and 24 h after prey capture, export of prey-derived resources to other plant organs may become preferential and causes a decline in ATP contents. CONCLUSIONS Apparently, the energy demand of the flytrap for prey digestion and nutrient mining builds on both internal and prey-derived resources.
Hybrid BP-EP Based Iterative Receiver for Faster-Than-Nyquist with Index Modulation

Faster-than-Nyquist (FTN) signaling with index modulation (IM) is an attractive non-orthogonal transmission scheme characterized by high spectral efficiency and energy efficiency. In this paper, we develop a hybrid belief propagation (BP) and expectation propagation (EP) based iterative receiver for FTN-IM systems. To approach the optimal maximum a posteriori (MAP) receiver, we derive the factorization of marginal posterior probability and construct the corresponding factor graph by ignoring trivial interferences. To address the inherent colored noise imposed by FTN signaling, we employ autoregressive (AR) model to approximate the correlated noise samples. To further design low-complexity parametric message passing receiver, we resort to expectation propagation (EP) to derive Gaussian approximation of discrete transmitted symbols containing specific inactivated zeros. As a result, the overall complexity grows linearly with the number of transmitted symbols. Simulation results show that the coded FTN-IM system relying on the proposed iterative receiver can improve the spectral efficiency up to 43% without performance loss. For identical spectral efficiency with the Nyquist counterpart, FTN-IM signaling achieves 0.80 dB performance gain with proper packing factor and coding rate.
Multimodality medical imaging for radiotherapy treatment planning

Radiation therapy is a treatment modality which seeks to deliver radiation energy to a localized site within a patient in order to destroy a malignant tumor. One of the most important aspects of radiation dose treatment planning is the accurate localization of tumor masses. An improved methodology is proposed for the delineation of tumors. Tumor localization is performed using a regularization approach which incorporates data fusion techniques. The contour information, derived from magnetic resonance and X-ray computed tomography, is used to enhance the delineation of tumor boundaries. Directional controlled continuity stabilizers are utilized to perform the fusion task. <<ETX>>
EEG Machine

Electroencephalography (EEG) is the analysis of electrical fields of brain recorded by amplifying the voltage difference between electrodes placed on the scalp, cortex or brain. EEG machine receives these electrical fields from the brain and the signal is run through the electrode wires to various amplifiers, filters and finally to the writing units to obtain a graph representing brain activity. One must understand the basic function of each of these subunits of the machine and especially the special precautions one needs to observe during use in neonates to get a meaningful record. This paper will focus on the technical aspects of EEG. The basic arrangement of the machine is shown in Figure 1.
Imaging of deafness and tinnitus

Acquired deafness and tinnitus are common problems and patients should be carefully selected for imaging.Conductive deafness is best imaged with high resolution CT and sensorineural deafness with T2 weighted 3D MRI. Additional MRI sequences including contrast are used for indeterminate and abnormal cases.Radiologists should be familiar with the common causes of conductive deafness; cholesteatoma, ossicular fixation, ossicular erosion, traumatic subluxations and dislocations and otospongiosis which can cause mixed deafness when the pericochlear region is involved.Investigation of acquired sensorineural deafness mainly revolves around excluding vestibular schwannoma and differentiating this from other causes of CP angle masses, particularly meningiomas, epidermoids and metastases. Rarely post traumatic labyrinthitis ossificans or in children, widened vestibular aqueduct syndrome can be the causes of acquired deafness.Pulsatile tinnitus is best investigated using contrast enhanced CT, looking for venous and .
Sol-Gel Silicon Alkoxides-Polyethylene Glycol Derived Hybrids for Drug Delivery Systems

Purpose: the potential application of hybrid systems based on silicon alkoxides and polyethylene glycol 400 as drug delivery systems was studied. Methods: they were synthesized using the sol-gel technique, using ketoprofen as a model drug. the preparation of the materials and their characterization by X-ray diffraction, infrared spectroscopy, thermogravimetric analysis are reported. drug loading was performed during the gelation of the sols. drug release studies were performed at pH 1.2 and 7.5 mimicking gastrointestinal environments. Results: drug release was affected by the presence of polyethylene glycol in the formulation: a faster release was observed for polyethylene glycol hybrids. Conclusions:the results suggest that these devices should guarantee long durability after implantation and could be suitable for sustained release: after a first period of release by diffusion, complete release will be reached by bioerosion of the matrix. (Journal of Applied Biomaterials & Biomechanics 2010; 10: 14-9)
The Effect of Vaginal Sildenafil on The Outcome of Assisted Reproductive Technology Cycles in Patients with Repeated Implantation Failures: A Randomized Placebo-Controlled Trial

Background The aim of this study was to investigate the effects of vaginal sildenafil on the outcome of patients with at least two unsuccessful in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) attempts. Materials and Methods In this randomized placebo-controlled trial study, a total of 66 infertile women aged ≤38 years, with a history of normal ovarian reserve, two prior consecutive failed IVF/ICSI attempts, human chorionic gonadotropin (hCG) day endometrial thickness <7 mm in all prior IVF/ICSI cycles, normal endometrial appear- ance by either hysteroscopy, hysterosonography, or hysterosalpingography enrolled in this study. The conventional gonadotropin-releasing hormone (GnRH) protocol was used for ovarian stimulation. The patients were randomly divided into three groups: vaginal sildenafil (suppository-100 mg/daily), vaginal placebo/sildenafil (suppository-100 mg/daily), and vaginal placebo (suppository). Each patient underwent colour Doppler ultrasound on day 14 of their previous cycle to investigate any abnormalities in the uterus and adnexa. Endometrial thickness, echo pattern, uterine artery resistance, and pulsatility indices were recorded pre- and post-treatment. The primary outcome measures were implantation, chemical and clinical pregnancy rates. For data analysis, SPSS version 20 software was used. In all tests, the significance level was considered less than 0.05. Results There was no significant difference between three groups in endometrial thickness on the hCG injection day. The chemical pregnancy in women who received sildenafil (alone or in combination with placebo) showed a two-fold increase in comparison to the placebo group. This increase was clinically meaningful, but according to sample size, it was statistically non-significant. The results of our study showed that the implantation was higher in women who received placebo/sildenafil compared to the other groups. The abortion rate was not statistically significant among the groups. Conclusion Vaginal sildenafil may conceivably improve chemical pregnancy rates in repeated IVF failure patients. Further randomized clinical trials using oral or vaginal sildenafil with higher sample size are recommended (Registra- tion number: NCT03192709).
A non-parametric analytic framework for within-host viral phylogenies and a test for HIV-1 founder multiplicity

Abstract Phylogenetics is a powerful tool for understanding the diversification dynamics of viral pathogens. Here we present an extension of the spectral density profile of the modified graph Laplacian, which facilitates the characterization of within-host molecular evolution of viruses and the direct comparison of diversification dynamics between hosts. This approach is non-parametric and therefore fast and model-free. We used simulations of within-host evolutionary scenarios to evaluate the efficiency of our approach and to demonstrate the significance of interpreting a viral phylogeny by its spectral density profile in terms of diversification dynamics. The key features that are captured by the profile are positive selection on the viral gene (or genome), temporal changes in substitution rates, mutational fitness, and time between sampling. Using sequences from individuals infected with HIV-1, we showed the utility of this approach for characterizing within-host diversification dynamics, for comparing dynamics between hosts, and for charting disease progression in infected individuals sampled over multiple years. We furthermore propose a heuristic test for assessing founder heterogeneity, which allows us to classify infections with single and multiple HIV-1 founder viruses. This non-parametric approach can be a valuable complement to existing parametric approaches.
Left-Hemispheric Asymmetry for Object-Based Attention: an ERP Study

It has been shown that selective attention enhances the activity in visual regions associated with stimulus processing. The left hemisphere seems to have a prominent role when non-spatial attention is directed towards specific stimulus features (e.g., color, spatial frequency). The present electrophysiological study investigated the time course and neural correlates of object-based attention, under the assumption of left-hemispheric asymmetry. Twenty-nine right-handed participants were presented with 3D graphic images representing the shapes of different object categories (wooden dummies, chairs, structures of cubes) which lacked detail. They were instructed to press a button in response to a target stimulus indicated at the beginning of each run. The perception of non-target stimuli elicited a larger anterior N2 component, which was likely associated with motor inhibition. Conversely, target selection resulted in an enhanced selection negativity (SN) response lateralized over the left occipito-temporal regions, followed by a larger centro-parietal P300 response. These potentials were interpreted as indexing attentional selection and categorization processes, respectively. The standardized weighted low-resolution electromagnetic tomography (swLORETA) source reconstruction showed the engagement of a fronto-temporo-limbic network underlying object-based visual attention. Overall, the SN scalp distribution and relative neural generators hinted at a left-hemispheric advantage for non-spatial object-based visual attention.
Distinct functional alterations in SCN8A epilepsy mutant channels

Mutations in the SCN8A gene cause early infantile epileptic encephalopathy. We characterize a new epilepsy‐related SCN8A mutation, R850Q, in the human SCN8A channel and present gain‐of‐function properties of the mutant channel. Systematic comparison of R850Q with three other SCN8A epilepsy mutations, T761I, R1617Q and R1872Q, identifies one common dysfunction in resurgent current, although these mutations alter distinct properties of the channel. Computational simulations in two different neuron models predict an increased excitability of neurons carrying these mutations, which explains the over‐excitation that underlies seizure activities in patients. These data provide further insight into the mechanism of SCN8A‐related epilepsy and reveal subtle but potentially important distinction of functional characterization performed in the human vs. rodent channels.
Roadmap of germline development and in vitro gametogenesis from pluripotent stem cells

The germ cell lineage is a fundamental component of the metazoan life cycle, ensuring the perpetuation and substantial diversification of genetic information across generations. Recent advances in the understanding of mouse germ cell development have culminated in the ability to reconstitute gametogenesis in vitro, thereby enabling the biochemical and molecular analyses of germ cell specification and subsequent development in mice. Similar advances in reconstituting human germ cells in vitro would provide critical insight into the etiology of various reproductive conditions and disorders, including infertility.
ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior guidelines.
Convergent evolution of claw shape in a transcontinental lizard radiation.

Species occupying similar selective environments often share similar phenotypes as the result of natural selection. Recent discoveries, however, have led to the understanding that phenotypes may also converge for other reasons than recurring selection. We argue that the vertebrate claw system constitute a promising but understudied model system for testing the adaptive nature of phenotypic, functional, and genetic convergence. In this study, we combine basic morphometrics and advanced techniques in form analysis to examine claw shape divergence in a transcontinental lizard radiation (Lacertidae). We find substantial interspecific variation in claw morphology and phylogenetic comparative statistics reveal a strong correlation with structural habitat use: ground-dwelling species living in open areas are equipped with long, thick, weakly curved, slender-bodied claws, whereas climbing species carry high, short, strongly curved, full-bodied claws. Species occupying densely vegetated habitats tend to carry intermediately shaped claws. Evolutionary models suggest that claw shape evolves towards multiple adaptive peaks, with structural habitat use pulling species towards a specific selective optimum. Contrary to findings in several other vertebrate taxa, our analyses indicate that environmental pressures, not phylogenetic relatedness, drive convergent evolution of similarly shaped claws in lacertids. Overall, our study suggests that lacertids independently evolved similarly shaped claws as an adaptation to similar structural environments in order to cope with the specific locomotory challenges posed by the habitat. Future biomechanical studies that link form and function in combination with genomic and development research will prove valuable in better understanding the adaptive significance of claw shape divergence.
Development and Mechanistic Insight into the Enhanced Cytotoxic Potential of Parvifloron D Albumin Nanoparticles in EGFR-Overexpressing Pancreatic Cancer Cells

Pancreatic cancer is one of the most lethal cancers, with an extremely poor prognosis. The development of more effective therapies is thus imperative. Natural origin compounds isolated from Plectranthus genus, such as parvifloron D (PvD), have cytotoxic and antiproliferative activity against human tumour cells. However, PvD is a very low water-soluble compound, being nanotechnology a promising alternative strategy to solve this problem. Therefore, the aim of this study was to optimize a nanosystem for preferential delivery of PvD to pancreatic tumour cells. Albumin nanoparticles (BSA NPs) were produced through a desolvation method. Glucose cross-linking and bioactive functionalization profiles of BSA platform were elucidated and analysed using static lattice atomistic simulations in vacuum. Using the optimized methodology, PvD was encapsulated (yield higher than 80%) while NPs were characterized in terms of size (100–400 nm) and morphology. Importantly, to achieve a preferential targeting to pancreatic cancer cells, erlotinib and cetuximab were attached to the PvD-loaded nanoparticle surface, and their antiproliferative effects were evaluated in BxPC3 and Panc-1 cell lines. Erlotinib conjugated NPs presented the highest antiproliferative effect toward pancreatic tumour cells. Accordingly, cell cycle analysis of the BxPC3 cell line showed marked accumulation of tumour cells in G1-phase and cell cycle arrest promoted by NPs. As a result, erlotinib conjugated PvD-loaded BSA NPs must be considered a suitable and promising carrier to deliver PvD at the tumour site, improving the treatment of pancreatic cancer.
The activation mechanism of plant S6 kinase (S6K), a substrate of TOR kinase, is different from that of mammalian S6K

The S6 kinases (S6Ks) are known to be activated by the target of rapamycin through phosphorylation of their hydrophobic motif (HM). However, our previous research showed that the HM site of plant S6Ks is not phosphorylated and is not essential for their activity in yeast cells lacking Ypk3, an ortholog of mammalian S6K. Here, we demonstrate that the HM site of mammalian S6Ks is phosphorylated and is indispensable for their activity in yeast ypk3∆ cells. Furthermore, pseudo‐phosphorylation at the HM site of plant S6Ks results in regaining of activity that is lost due to mutation in the conserved phosphorylation sites, namely the T‐loop and Turn motif. These results indicate the activation mechanism of plant S6Ks is different from that of mammals.
Exploring the Molecular Mechanisms Underlying the in vitro Anticancer Effects of Multitarget‐Directed Hydrazone Ruthenium(II)–Arene Complexes

The molecular targets and the modes of action behind the cytotoxicity of two structurally established N,O‐ or N,N‐hydrazone ruthenium(II)–arene complexes were explored in human breast adenocarcinoma cells (MCF‐7) and paralleled in non‐cancerous and cisplatin‐resistant counterparts (MCF‐10A and MCF‐7CR respectively). Both complexes, [Ru(hmb)(L1)Cl] (1, L1=4‐((2‐(2,4‐dinitrophenyl)hydrazono)(phenyl)methyl)‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐olate) and [Ru(cym)(L2)Cl] (2, L2=1‐((3‐methyl‐5‐oxo‐1‐phenyl‐1H‐pyrazol‐4(5H)‐ylidene)(phenyl)methyl)‐2‐(pyridin‐2‐yl)hydrazin‐1‐ide), reversibly interact with moderate‐to‐high affinity with a number of molecular targets in cell‐free assays, namely serum albumin, DNA, the 20S proteasome and hydroxymethylglutaryl‐CoA reductase. Most interestingly, only 2 readily crosses the cell membrane and preserves its binding/modulatory ability toward the targets of interest upon rapid cellular internalization. The resulting action at multiple levels of the cancer cascade is likely the cause for the selective sensitization of tumour cells to p27‐mediated apoptotic death, and for the ability of 2 to overcome the drug resistance problem.
Photic generation of 11-cis-retinal in bovine retinal pigment epithelium

Photoisomerization of the 11-cis-retinal chromophore of rod and cone visual pigments to an all-trans-configuration is the initiating event for vision in vertebrates. The regeneration of 11-cis-retinal, necessary for sustained visual function, is an endergonic process normally conducted by specialized enzyme systems. However, 11-cis-retinal also can be formed through reverse photoisomerization from all-trans-retinal. A nonvisual opsin known as retinal pigment epithelium (RPE)-retinal G-protein–coupled receptor (RGR) was previously shown to mediate visual chromophore regeneration in photic conditions, but conflicting results have cast doubt on its role as a photoisomerase. Here, we describe high-level production of 11-cis-retinal from RPE membranes stimulated by illumination at a narrow band of wavelengths. This activity was associated with RGR and enhanced by cellular retinaldehyde-binding protein (CRALBP), which binds the 11-cis-retinal produced by RGR and prevents its re-isomerization to all-trans-retinal. The activity was recapitulated with cells heterologously expressing RGR and with purified recombinant RGR. Using an RGR variant, K255A, we confirmed that a Schiff base linkage at Lys-255 is critical for substrate binding and isomerization. Single-cell RNA-Seq analysis of the retina and RPE tissue confirmed that RGR is expressed in human and bovine RPE and Müller glia, whereas mouse RGR is expressed in RPE but not in Müller glia. These results provide key insights into the mechanisms of physiological retinoid photoisomerization and suggest a novel mechanism by which RGR, in concert with CRALBP, regenerates the visual chromophore in the RPE under sustained light conditions.