Miracle-dz/UniFAR-FTUs huggingface dataset:
Conformational plasticity of molecular chaperones involved in periplasmic and outer membrane protein folding

How proteins reach their native conformation and location has been a major question of biology during the last 50 years. To counterbalance protein misfolding and the accumulation of aggregation products, a complex network of chaperones and proteases takes care of protein quality control in the cell. Such a chaperone network is in place in the periplasm of Gram-negative bacteria, where it is necessary for the survival of the bacteria as well as for outer membrane biogenesis. First mechanistic insights into the periplasmic chaperones that comprise this system came from crystal structures of their apo states. While these crystal structures represent stable conformations of the proteins, they typically lack the information to understand the conformational changes that regulate the functional cycle and the mechanisms coordinating the dynamic adaptation of the chaperones to client proteins. During the past few years, the main actors of periplasmic and outer membrane protein folding have been extensively studied by a combination of experimental techniques. This review aims to give an overview of how recent structural biology developments have helped to achieve a better understanding of the functional cycles of the molecular chaperones Skp, SurA and BamA and how these cycles are regulated by dynamic conformational rearrangements.
Régir, gouverner et mettre en oeuvre

Examinant les cadres institutionnels distincts des regimes d'Etats-Providence francais et etatsuniens ainsi que les modes differents de gouvernance des programmes de transformation des quartiers populaires des villes de Paris et de Chicago, cet article distingue les notions de « gouvernance » et de « mise en œuvre ». Gouverner correspond a la maniere dont on souhaite mettre en œuvre et se refere davantage a des programmes d'action publique. Mettre en œuvre signifie concretiser et accomplir une activite dans le cadre d'une politique sectorielle specifique. En outre, ce papier demontre qu'un regime d'investissement social strategique est relaye par le programme national pour la renovation urbaine francais alors qu'un regime d'Enabling State semble s'imposer aux Etats-Unis. Il rend finalement compte de l'entrecroisement des echelles de realisation nationales, municipales et locales des programmes publics et temoigne de la force explicative des demarches de recherche comparatives.
Sulfide production kinetics and model of stormwater retention ponds.

Stormwater retention ponds can play a critical role in mitigating the detrimental effects of urbanization on receiving waters that result from increases in polluted runoff. However, the benthic oxygen demand of stormwater facilities may cause significant hypoxia and trigger the production of hydrogen sulfide (H2S). This process is not well-documented and further research is needed to characterize benthic processes in stormwater retention ponds in order to improve their design and operation. In this study, sediment oxygen demand (SOD), sediment ammonia release (SAR) and sediment sulfide production (SSP) kinetics were characterized in situ and in the laboratory. In situ SOD and SSP data were utilized to develop a stormwater retention pond water sulfide concentration model which demonstrates strong correlation with sulfide concentrations observed in situ (r = 0.724, N = 91, p < 0.001) and in laboratory experiments (r = 0.691, N = 38, p < 0.001). At 4 °C, in situ rates of SOD, SAR and SSP were higher than those measured in laboratory. Sulfate-reducing bacteria (SRB) represented 4.99% of the bacteria present in the top 30 cm of the pond sediment, with Desulfobulbaceae spp. , Desulfobacteraceae spp. and Desulfococcus spp. being the dominant SRB taxa identified.
Mechanisms of precipitate formation during the purification of an Fc‐fusion protein

Protein precipitates that arise during bioprocessing can cause manufacturing challenges, but they can also aid in clearance of host‐cell protein (HCP) and DNA impurities. Such precipitates differ from many protein precipitates that have been studied previously in their heterogeneous composition, particularly in the presence of high concentrations of the product protein. Here, we characterize the precipitates that form after neutralization of protein A purified and viral‐inactivated material of an Fc‐fusion protein produced in Chinese hamster ovary cells. The physical growth of precipitate particles was observed by optical microscopy, transmission electron microscopy, dynamic light scattering, and small‐angle and ultra‐small‐angle X‐ray scattering to characterize the precipitate microstructure and growth mechanism. The precipitate microstructure is well‐described as a mass fractal with fractal dimension approximately 2. The growth is governed by a diffusion‐limited aggregation mechanism as indicated by a power‐law dependence on time of the size of the principal precipitate particles. Optical microscopy shows that these primary particles can further aggregate into larger particles in a manner that appears to be promoted by mixing. Absorbance experiments at varying pH and salt concentrations reveal that the growth is largely driven by attractive electrostatic interactions, as growth is hindered by an increase in ionic strength. The solution conditions that resulted in the most significant particle growth are also correlated with the greatest removal of soluble impurities (DNA and HCPs). Proteomic analysis of the precipitates allows identification of O ( 100 ) unique HCP impurities, depending on the buffer species (acetate or citrate) used for the viral inactivation. Most of these proteins have pI values near the precipitation pH, supporting the likely importance of electrostatic interactions in driving precipitate formation.
Functional Regulation of PPARs through Post-Translational Modifications

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily and they are essential regulators of cell differentiation, tissue development, and energy metabolism. Given their central roles in sensing the cellular metabolic state and controlling metabolic homeostasis, PPARs became important targets of drug development for the management of metabolic disorders. The function of PPARs is mainly regulated through ligand binding, which induces structural changes, further affecting the interactions with co-activators or co-repressors to stimulate or inhibit their functions. In addition, PPAR functions are also regulated by various Post-translational modifications (PTMs). These PTMs include phosphorylation, SUMOylation, ubiquitination, acetylation, and O-GlcNAcylation, which are found at numerous modification sites. The addition of these PTMs has a wide spectrum of consequences on protein stability, transactivation function, and co-factor interaction. Moreover, certain PTMs in PPAR proteins have been associated with the status of metabolic diseases. In this review, we summarize the PTMs found on the three PPAR isoforms PPARα, PPARβ/δ, and PPARγ, and their corresponding modifying enzymes. We also discuss the functional roles of these PTMs in regulating metabolic homeostasis and provide a perspective for future research in this intriguing field.
Swendsen‐Wang dynamics for general graphs in the tree uniqueness region

The Swendsen‐Wang (SW) dynamics is a popular Markov chain for sampling from the Gibbs distribution for the ferromagnetic Ising model on a graph G = (V,E). The dynamics is conjectured to converge to equilibrium in O(|V|1/4) steps at any (inverse) temperature β, yet there are few results providing o(|V|) upper bounds. We prove fast convergence of the SW dynamics on general graphs in the tree uniqueness region. In particular, when β < βc(d) where βc(d) denotes the uniqueness/nonuniqueness threshold on infinite d‐regular trees, we prove that the relaxation time (i.e., the inverse spectral gap) of the SW dynamics is Θ(1) on any graph of maximum degree d ≥ 3. Our proof utilizes a monotone version of the SW dynamics which only updates isolated vertices. We establish that this variant of the SW dynamics has mixing time O(log|V|) and relaxation time Θ(1) on any graph of maximum degree d for all β < βc(d). Our proof technology can be applied to general monotone Markov chains, including for example the heat‐bath block dynamics, for which we obtain new tight mixing time bounds.
Risk Factors and Clinical Course for Liver Steatosis or Nonalcoholic Steatohepatitis After Living Donor Liver Transplantation

Background Posttransplant liver steatosis occurs frequently and can affect patient outcome. Our aim was to clarify the risk factors for steatosis or steatohepatitis after living donor liver transplantation (LT) through a retrospective examination of recent 100 living donor LT recipients and their liver donors. Methods Liver biopsy was performed at 1 year after LT and each year, thereafter, or as needed due to abnormal liver enzyme levels, with a median follow-up of 4 years (2-10 years). Results Liver steatosis (≥5%) was identified in 33 cases, with steatohepatitis identified in 9 of 33 patients with liver steatosis. Recipients with liver steatosis were younger than those without steatosis (53.4 ± 9.5 years vs 57.6 ± 9.9 years, respectively; P = 0.045). Of note, the prevalence of steatosis was significantly higher among LT recipients who received a graft from a donor with steatosis than without (60% vs 23%, respectively; P = 0.001). Donor steatosis was also associated with steatohepatitis in recipients after LT (steatohepatitis/simple steatosis, 88%:50%). On multivariate analysis, younger recipient age (P = 0.023) and donor steatosis (P = 0.005) were independent risk factors of liver steatosis after LT. Among the 33 recipients in our study group, 26 were assessed by serial liver biopsies, with 6 showing progression of the nonalcoholic fatty liver disease activity score. An increase in body weight was predictive of steatosis progression after LT (P = 0.005). Conclusions Age and donor steatosis influence the risk of liver steatosis and steatohepatitis in recipients after LT. The clinical course of steatosis is relatively benign, with only 19% developing nonalcoholic fatty liver disease activity score and 7.6% significant fibrosis.
Postoperative Cognitive Dysfunction and Noncardiac Surgery

Postoperative cognitive dysfunction (POCD) is an objectively measured decline in cognition postoperatively compared with preoperative function. POCD has been considered in the anesthetic and surgical literature in isolation of cognitive decline which is common in the elderly within the community and where it is labeled as mild cognitive impairment, neurocognitive disorder, or dementia. This narrative review seeks to place POCD in the broad context of cognitive decline in the general population. Cognitive change after anesthesia and surgery was described over 100 years ago, initially as delirium and dementia. The term POCD was applied in the 1980s to refer to cognitive decline assessed purely on the basis of a change in neuropsychological test results, but the construct has been the subject of great heterogeneity. The cause of POCD remains unknown. Increasing age, baseline cognitive impairment, and fewer years of education are consistently associated with POCD. In geriatric medicine, cognitive disorders defined and classified as mild cognitive impairment, neurocognitive disorder, and dementia have definitive clinical features. To identify the clinical impact of cognitive impairment associated with the perioperative period, POCD has recently been redefined in terms of these geriatric medicine constructs so that the short-, medium-, and long-term clinical and functional impact can be elucidated. As the aging population present in ever increasing numbers for surgery, many individuals with overt or subclinical dementia require anesthesia. Anesthesiologists must be equipped to understand and manage these patients.
Rate of Tobacco Smoking Among Psychiatric Outpatients Attending a Tertiary Care Hospital in Oman:  A Cross-sectional Study.

Objectives Tobacco smoking is the single most avoidable cause of morbidity and mortality around the world. Patients with psychiatric disorders tend to smoke tobacco at a higher rate than the general population, with significant adverse health consequences. This study aimed to determine the rate of tobacco smoking among psychiatric outpatients attending Sultan Qaboos University Hospital, a tertiary care hospital in Muscat, Oman. Methods We conducted a cross-sectional study among psychiatric outpatients attending a psychiatric clinic from 1 January to 1 August 2017. The patients' demographic information, history of smoking, previous hospitalizations, and the number of and specific psychotropics used during treatment was documented. The degree of dependence on tobacco smoking was measured using the Fagerstrom test for nicotine dependence. Results A total of 272 patients were included in this study. The overall rate of smoking among psychiatric patients was 13.6%. Patients with schizophrenia had the highest rate of smoking (22.2%), followed by those with bipolar (13.1%), and anxiety disorders (11.1%). Patients who smoked tobacco were more likely to be admitted to the psychiatric ward than non-smokers (p < 0.050). Conclusions Tobacco smoking is common among psychiatric patients, a finding consistent with similar studies conducted in different parts of the world. Assessment of smoking status and its associated adverse health associations among patients with mental disorders is of paramount importance.
Elevated Pressure Increases Ca2+ Influx Through AMPA Receptors in Select Populations of Retinal Ganglion Cells

The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca2+ (CI-AMPAR). However, some AMPA receptors are permeable to Ca2+ (CP-AMPAR) and play important roles in development, plasticity and disease. In the retina, ganglion cells (RGCs) are targets of disease including glaucoma and diabetic retinopathy, but there are many types of RGCs and not all types are targeted equally. In the present study, we sought to determine if there are differences in expression of AMPARs amongst RGC subtypes, and if these differences might contribute to differential vulnerability in a model of stress. Using cultured RGCs we first show that acute exposure to elevated pressure increased expression of Ca2+-permeable AMPA receptors (CP-AMPARs) in some, but not all classes of RGCs. When RGCs were sampled without regard to subtype, AMPA currents, measured using patch clamp recording, were blocked by the CP-AMPAR blocker PhTX-74 to a greater extent in pressure-treated RGCs vs. control. Furthermore, imaging experiments revealed an increase in Ca2+ influx during AMPA application in pressure-treated RGCs. However, examination of specific RGC subtypes using reporter lines revealed striking differences in both baseline AMPAR composition and modulation of this baseline composition by stress. Notably, ON alpha RGCs identified using the Opn4 mouse line and immunohistochemistry, had low expression of CP-AMPARs. Conversely, an ON-OFF direction selective RGC and putative OFF alpha RGC each expressed high levels of CP-AMPARs. These differences between RGC subtypes were also observed in RGCs from whole retina. Elevated pressure further lowered expression of CP-AMPARs in ON alpha RGCs, but raised expression in ON-OFF and OFF RGCs. Changes in CP-AMPAR expression following challenge with elevated pressure were correlated with RGC survival: ON alpha RGCs were unaffected by application of pressure, while the number of putative OFF alpha RGCs declined by approximately 50% following challenge with pressure. Differences in expression of CP-AMPARs between RGC subtypes may form the underpinnings for subtype-specific synaptic plasticity. Furthermore, the differential responses of these RGC subtypes to elevated pressure may contribute to the reported resistance of ON alpha, and susceptibility of OFF and ON-OFF RGCs to injury in models of glaucoma.
Murine Pancreatic Cancer Alters T Cell Activation and Apoptosis and Worsens Survival After Cecal Ligation and Puncture

ABSTRACT Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. However, pancreatic cancer/pneumonia decreases lymphocyte apoptosis and increases gut apoptosis while lung cancer/CLP increases lymphocyte apoptosis and decreases intestinal proliferation. These results cannot distinguish the individual roles of cancer versus sepsis since different models of each were used. We therefore created a new cancer/sepsis model to standardize each variable. Mice were injected with a pancreatic cancer cell line and 3 weeks later cancer mice and healthy mice were subjected to CLP. Cancer septic mice had a significantly higher 10-day mortality than previously healthy septic mice. Cancer septic mice had increased CD4+ T cells and CD8+ T cells, associated with decreased CD4+ T cell apoptosis 24 h after CLP. Further, splenic CD8+ T cell activation was decreased in cancer septic mice. In contrast, no differences were noted in intestinal apoptosis, proliferation, or permeability, nor were changes noted in local bacterial burden, renal, liver, or pulmonary injury. Cancer septic mice thus have consistently reduced survival compared with previously healthy septic mice, independent of the cancer or sepsis model utilized. Changes in lymphocyte apoptosis are common to cancer model and independent of sepsis model, whereas gut apoptosis is common to sepsis model and independent of cancer model. The host response to the combination of cancer and sepsis is dependent, at least in part, on both chronic comorbidity and acute illness.
(2E,5E)-2,5-Bis(3-hydroxy-4-methoxybenzylidene) cyclopentanone Exerts Anti-Melanogenesis and Anti-Wrinkle Activities in B16F10 Melanoma and Hs27 Fibroblast Cells

Ultraviolet (UV) radiation exposure is the primary cause of extrinsic skin aging, which results in skin hyperpigmentation and wrinkling. In this study, we investigated the whitening effect of (2E,5E)-2,5-bis(3-hydroxy-4-methoxybenzylidene)cyclopentanone (BHCP) on B16F10 melanoma and its anti-wrinkle activity on Hs27 fibroblasts cells. BHCP was found to potently inhibit tyrosinase, with 50% inhibition concentration (IC50) values of 1.10 µM and 8.18 µM for monophenolase (l-tyrosine) and diphenolase (l-DOPA), and the enzyme kinetics study revealed that BHCP is a competitive-type tyrosinase inhibitor. Furthermore, BHCP significantly inhibited melanin content and cellular tyrosinase activity, and downregulated the levels of microphthalmia-associated transcription factor (MITF), phosphorylated levels of cAMP response element-binding (CREB) protein, and tyrosinase in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Moreover, BHCP inhibited the phosphorylation of p65 and expression of matrix metalloproteinases (MMP-1, MMP-9, MMP-12, and MMP-13) in Hs27 fibroblasts stimulated with UV radiation. Therefore, our results demonstrate that BHCP may be a good candidate for the development of therapeutic agents for diseases associated with hyperpigmentation and wrinkling.
Image segmentation and 3D visualization for MRI mammography

MRI mammography has a number of advantages, including the tomographic, and therefore three-dimensional (3-D) nature, of the images. It allows the application of MRI mammography to breasts with dense tissue, post operative scarring, and silicon implants. However, due to the vast quantity of images and subtlety of difference in MR sequence, there is a need for reliable computer diagnosis to reduce the radiologist's workload. The purpose of this work was to develop automatic breast/tissue segmentation and visualization algorithms to aid physicians in detecting and observing abnormalities in breast. Two segmentation algorithms were developed: one for breast segmentation, the other for glandular tissue segmentation. In breast segmentation, the MRI image is first segmented using an adaptive growing clustering method. Two tracing algorithms were then developed to refine the breast air and chest wall boundaries of breast. The glandular tissue segmentation was performed using an adaptive thresholding method, in which the threshold value was spatially adaptive using a sliding window. The 3D visualization of the segmented 2D slices of MRI mammography was implemented under IDL environment. The breast and glandular tissue rendering, slicing and animation were displayed.
Bifurcations and exceptional points in a   -symmetric dipolar Bose–Einstein condensate

We investigate the bifurcation structure of stationary states in a dipolar Bose–Einstein condensate located in an external   -symmetric potential. The imaginary part of this external potential allows for the effective description of in- and outcoupling of particles. To unveil the complete bifurcation structure and the properties of the exceptional points we perform an analytical continuation of the Gross–Pitaevskii equation, which is used to describe the system. We use an elegant and numerically efficient method for the analytical continuation of the Gross–Pitaevskii equation with dipolar interactions containing bicomplex numbers. The Bose–Einstein condensate with dipole interaction shows a much richer bifurcation scenario than a condensate without long-range interactions. The inclusion of analytically continued states can also explain property changes of bifurcation points which were hidden before, and allows for the examination of the properties of the exceptional points associated with the branch points. With the new analytically continued states we are able to prove the existence of an exceptional point of fifth order.
[Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat hippocampal neurons].

OBJECTIVE To investigate the role of caspase-1 activation in bilirubin-induced neuronal injury and the protective effect of VX-765 against bilirubin-induced neurotoxicity in cultured primary rat hippocampal neurons. METHODS Cultured primary rat hippocampal neurons were exposed to DMSO (control group), 50 µmol/L bilirubin, or 50 µmol/L bilirubin 1 h after 50 µmol/L VX-765 treatment. The expressions of NLRP3 and caspase-1 in the neurons were detected by Western blotting, and the relative cell survival and death rates were assessed with a modified MTT assay, lactate dehydrogenase assay and Typan blue staining. Interleukin-18 (IL-18) concentration in the culture supernatant was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS In cultured primary rat hippocampal neurons, bilirubin exposure for 3 and 6 h caused significant increases in the expressions of NLRP3 and activated caspase-1 compared with those in the control group (P<0.05). Pretreatment of the cells with VX-765 obviously suppressed bilirubin-induced activation of caspase-1 (P<0.05). The relative survival rate of the neurons was (84.02∓2.31)% in VX-765 intervention group, significantly higher than that in bilirubin group (P<0.05) but lower than that in the control group (P<0.05); LDH release rate in VX-765 intervention group was (10.78∓1.58)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). The cell death rate in VX-765 intervention group was (5.58∓1.23)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). CONCLUSION In cultured primary rat hippocampal neurons, caspase-1 activation plays a role in bilirubin-induced neurotoxicity, and VX-765 treatment provides protection against bilirubin-induced neuronal injury by inhibiting caspase-1 activation.