Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults.

BACKGROUND Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (Abeta). Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network. OBJECTIVES To determine the effects of induced hyperinsulinemia with euglycemia on Abeta, transthyretin, and inflammatory markers and modulators in plasma and cerebrospinal fluid (CSF). DESIGN Randomized crossover trial. SETTING Veterans Affairs hospital clinical research unit. PARTICIPANTS Sixteen healthy adults ranging from 55 to 81 years of age (mean age, 68.2 years). INTERVENTIONS On separate mornings, fasting participants received randomized infusions of saline or insulin (1.0 mU.kg(-1). min(-1)) with variable dextrose levels to maintain euglycemia, achieving plasma insulin levels typical of insulin resistance. Plasma and CSF were collected after an approximately 105-minute infusion. MAIN OUTCOME MEASURES Plasma and CSF levels of interleukin 1alpha, interleukin 1beta, interleukin 6, tumor necrosis factor alpha, F2-isoprostane (CSF only), Abeta, norepinephrine, transthyretin, and apolipoprotein E. RESULTS Insulin increased CSF levels of F2-isoprostane and cytokines (both P<.01), as well as plasma and CSF levels of Abeta42 (both P<.05). The changes in CSF levels of Abeta42 were predicted by increased F2-isoprostane and cytokine levels (both P<.01) and reduced transthyretin levels (P = .02). Increased inflammation was modulated by insulin-induced changes in CSF levels of norepinephrine and apolipoprotein E (both P<.05). CONCLUSION Moderate hyperinsulinemia can elevate inflammatory markers and Abeta42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease.
Dps/Dpr ferritin‐like protein: insights into the mechanism of iron incorporation and evidence for a central role in cellular iron homeostasis in Streptococcus suis

The Dps family members constitute a distinct group of multimeric and ferritin‐like iron binding proteins (up to 500 iron atoms/12‐mer) that are widespread in eubacteria and archaea and implicated in oxidative stress resistance and virulence. Despite the wealth of structural knowledge, the mechanism of iron incorporation has remained elusive. Here, we provide evidence on Dpr of the swine and human pathogen Streptococcus suis that: (i) iron incorporation proceeds by Fe(II) binding, Fe(II) oxidation and subsequent storage as Fe(III); (ii) Fe(II) atoms enter the 12‐mer cavity through four hydrophilic pores; and (iii) Fe(II) atoms are oxidized inside the 12‐mer cavity at 12 identical inter‐subunit sites, which are structurally different but functionally equivalent to the ferroxidase centres of classical ferritins. We also provide evidence, by deleting and ectopically overexpressing Dpr, that Dpr affects cellular iron homeostasis. The key residues responsible for iron incorporation in S. suis Dpr are well conserved throughout the Dps family. A model for the iron incorporation mechanism of the Dps/Dpr ferritin‐like protein is proposed.
Clinical and functional outcomes in patients with major depressive disorder and painful physical symptoms switched to treatment with duloxetine

This post hoc analysis of a multicenter, single‐arm, open‐label trial (the Attributes of Response in Depressed Patients Switched to Treatment with Duloxetine [ARDENT] study) assessed the relationship between functional improvement in the Sheehan Disability Scale (SDS) and clinical outcomes of mood, pain, and anxiety over 8 weeks after switching treatment to duloxetine in patients with major depressive disorder.
New polarized light microscope with precision universal compensator

A new type of polarized light microscope (‘new pol‐scope’) for fast and orientation‐independent measurement of birefringent fine structure has been developed. The design of the new pol‐scope incorporates a precision universal compensator made from two liquid crystal variable retarders. A video camera and digital image processing system provide fast measurements of specimen anisotropy (retardance magnitude and azimuth) at all points of the image forming the field of view. The images document fine structural and molecular organization within a thin optical section of the specimen. The sensitivity of the current instrument is 0·1 nm of specimen retardance, measured with data gathered in 0·43 s at all 640 × 480 image points. Examples of birefringence measurements in biological (microtubule arrays) and industrial (magneto‐optical disc substrate) specimens are presented.
Topological and geometrical disorders correlate robustly in two-dimensional foams

A two-dimensional (2D) foam can be characterised by its distributions of bubble area and number of sides. Both distributions have an average and a width (standard deviation). There are therefore at least two very different ways to characterise the disorder. The former is a geometrical measurement, while the latter is purely topological. We discuss the common points and differences between both quantities. We measure them in a foam which is sheared, so that bubbles move past each other and the foam is ‘shuffled’ (a notion we discuss). Both quantities are strongly correlated; in this case (only) it thus becomes sufficient to use either one or the other to characterise the foam disorder. We suggest applications in the analysis of other systems.
Ancestry informative markers for fine-scale individual assignment to worldwide populations

Background and aims The analysis of large-scale genetic data from thousands of individuals has revealed the fact that subtle population genetic structure can be detected at levels that were previously unimaginable. Using the Human Genome Diversity Panel as reference (51 populations - 650,000 SNPs), this works describes a systematic evaluation of the resolution that can be achieved for the inference of genetic ancestry, even when small panels of genetic markers are used. Methods and results A comprehensive investigation of human population structure around the world is undertaken by leveraging the power of Principal Components Analysis (PCA). The problem is dissected into hierarchical steps and a decision tree for the prediction of individual ancestry is proposed. A complete leave-one-out validation experiment demonstrates that, using all available SNPs, assignment of individuals to their self-reported populations of origin is essentially perfect. Ancestry informative genetic markers are selected using two different metrics (In and correlation with PCA scores). A thorough cross-validation experiment indicates that, in most cases here, the number of SNPs needed for ancestry inference can be successfully reduced to less than 0.1% of the original 650,000 while retaining close to 100% accuracy. This reduction can be achieved using a novel clustering-based redundancy removal algorithm that is also introduced here. Finally, the applicability of our suggested SNP panels is tested on HapMap Phase 3 populations. Conclusion The proposed methods and ancestry informative marker panels, in combination with the increasingly more comprehensive databases of human genetic variation, open new horizons in a variety of fields, ranging from the study of human evolution and population history, to medical genetics and forensics.
Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives.

OBJECTIVE Schizophrenia and psychotic bipolar disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. The authors used region-of-interest morphometry to volumetrically assess brain structures frequently implicated in psychotic illness in families affected with schizophrenia or psychotic bipolar disorder. METHOD Magnetic resonance imaging brain scans were obtained from 243 subjects, comprising 42 patients with schizophrenia or schizoaffective disorder, 57 of their unaffected first-degree relatives, 38 patients with psychotic bipolar disorder, 52 of their unaffected first-degree relatives, and 54 healthy comparison subjects. Most of the families affected with schizophrenia and all of the families affected with bipolar disorder were multiply affected with the illness. Volumetric measurements of the cerebrum, lateral ventricles, third ventricle, and hippocampus were completed with stereological methods. RESULTS Patients with schizophrenia had increased volume of the lateral and third ventricles and reduced hippocampal volume. None of these volumetric abnormalities was present in psychotic bipolar disorder. Unaffected relatives of patients with schizophrenia from multiply affected families had enlarged lateral ventricles but no other volumetric deviations. Unaffected relatives of patients with bipolar disorder showed preservation of ventricular and hippocampal volume. CONCLUSIONS Schizophrenia and psychotic bipolar disorder are characterized by morphometric distinctions in ventricular and hippocampal regions. Lateral ventricular enlargement represents a potential morphometric endophenotype for schizophrenia.
Gene function correlates with potential for G4 DNA formation in the human genome

G-rich genomic regions can form G4 DNA upon transcription or replication. We have quantified the potential for G4 DNA formation (G4P) of the 16 654 genes in the human RefSeq database, and then correlated gene function with G4P. We have found that very low and very high G4P correlates with specific functional classes of genes. Notably, tumor suppressor genes have very low G4P and proto-oncogenes have very high G4P. G4P of these genes is evenly distributed between exons and introns, and it does not reflect enrichment for CpG islands or local chromosomal environment. These results show that genomic structure undergoes selection based on gene function. Selection based on G4P could promote genomic stability (or instability) of specific classes of genes; or reflect mechanisms for global regulation of gene expression.
Fish remains from the Santa Marta Formation (Late Cretaceous) of James Ross Island, Antarctica

Isolated fish remains including a tooth of the oldest described frilled shark, Chlamydoselachus thomsoni sp. nov. are described and figured from the Santa Marta Formation (Santonian–Campanian, Late Cretaceous) of James Ross Island, Antarctic Peninsula. Their geological and palaeoecological context is considered in the light of recent geological studies.
Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.
Improved certificateless signature scheme provably secure in the standard model

Certificateless cryptography shares many features of identity-based cryptography and partially solves the problem of key escrow. Three certificateless signature schemes without random oracles were found in the literature. However, all the schemes suffer from some common drawbacks. First, by obtaining a signature on a message and replacing the public key of a signer, an adversary can forge valid signatures on the same message under the replaced public key. Secondly, all the schemes require a relatively large size of public parameters. The authors propose a new certificateless signature scheme, which exhibits an improvement on the existing schemes. Compared with the previous schemes, the proposed scheme offers stronger security, shorter system parameters and higher computational efficiency.
Footwear Exchange Has No Influence on the Incidence of Febrile Neutropenia in Patients Undergoing Chemotherapy for Hematologic Malignancies

Abstract Objective: To determine whether footwear exchange affects the incidence of febrile neutropenia among patients undergoing chemotherapy for hematologic malignancies. Design: Open trial with historical comparison. Setting: The 12-bed high-efficiency particulate air-fil-tered hematology unit at Osaka University Hospital, Suita, Japan. Patients: Those with hematologic malignancies who underwent chemotherapy from January 1997 through January 2003. Footwear exchange was discontinued in January 2000. Methods: The surveillance system was based on the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention. Rates of febrile neutropenia were calculated for neutropenic patient-days (ie, days with neutropenia < 500/μL). Results: From January 1997 through December 1999 and from February 2000 through January 2003, 58 and 54 patients endured 237 and 184 neutropenic periods following chemotherapy, and their total neutropenic days were 3,123 and 2,503, respectively. They showed episodes of febrile neutropenia 89 and 68 times, respectively. Infection rates were 28.5 and 27.2 per 1,000 neutropenic patient-days (P = .83), respectively. Conclusion: The incidence of febrile neutropenia was not affected by footwear exchange. In hematology units, changing shoes does not appear to affect the rate of infections during neutropenic periods.
Pillars and globules at the edges of H ii regions - Confronting Herschel observations and numerical simulations

Context. Herschel far-infrared imaging observations have revealed the density structure of the interface between H ii regions and molecular clouds in great detail. In particular, pillars and globules are present in many high-mass star-forming regions, such as the Eagle nebula (M 16) and the Rosette molecular cloud, and understanding their origin will help characterize triggered star formation. Aims. The formation mechanisms of these structures are still being debated. The initial morphology of the molecular cloud and its turbulent state are key parameters since they generate deformations and curvatures of the shell during the expansion of the H ii region. Recent numerical simulations have shown how pillars can arise from the collapse of the shell in on itself and how globules can be formed from the interplay of the turbulent molecular cloud and the ionization from massive stars. The goal here is to test this scenario through recent observations of two massive star-forming regions, M 16 and the Rosette molecular cloud. Methods. First, the column density structure of the interface between molecular clouds and associated H ii regions was characterized using column density maps obtained from far-infrared imaging of the Herschel HOBYS key programme. Then, the DisPerSe algorithm was used on these maps to detect the compressed layers around the ionized gas and pillars in different evolutionary states. Column density profiles were constructed. Finally, their velocity structure was investigated using CO data, and all observational signatures were tested against some distinct diagnostics established from simulations. Results. The column density profiles have revealed the importance of compression at the edge of the ionized gas. The velocity properties of the structures, i.e. pillars and globules, are very close to what we predict from the numerical simulations. We have identified a good candidate of a nascent pillar in the Rosette molecular cloud that presents the velocity pattern of the shell collapsing on itself, induced by a high local curvature. Globules have a bulk velocity dispersion that indicates the importance of the initial turbulence in their formation, as proposed from numerical simulations. Altogether, this study re-enforces the picture of pillar formation by shell collapse and globule formation by the ionization of highly turbulent clouds.
Selective Blockade of P/Q-Type Calcium Channels by the Metabotropic Glutamate Receptor Type 7 Involves a Phospholipase C Pathway in Neurons

Although presynaptic localization of mGluR7 is well established, the mechanism by which the receptor may control Ca2+channels in neurons is still unknown. We show here that cultured cerebellar granule cells express native metabotropic glutamate receptor type 7 (mGluR7) in neuritic processes, whereas transfected mGluR7 was also expressed in cell bodies. This allowed us to study the effect of the transfected receptor on somatic Ca2+ channels. In transfected neurons, mGuR7 selectively inhibited P/Q-type Ca2+ channels. The effect was mimicked by GTPγS and blocked by pertussis toxin (PTX) or a selective antibody raised against the G-protein αo subunit, indicating the involvement of a Go-like protein. The mGuR7 effect did not display the characteristics of a direct interaction between G-protein βγ subunits and the α1A Ca2+ channel subunit, but was abolished by quenching βγ subunits with specific intracellular peptides. Intracellular dialysis of G-protein βγ subunits did not mimic the action of mGluR7, suggesting that both G-protein βγ and αo subunits were required to mediate the effect. Inhibition of phospholipase C (PLC) blocked the inhibitory action of mGluR7, suggesting that a coincident activation of PLC by the G-protein βγ with αo subunits was required. The Ca2+ chelator BAPTA, as well as inhibition of either the inositol trisphosphate (IP3) receptor or protein kinase C (PKC) abolished the mGluR7 effect. Moreover, activation of native mGluR7 induced a PTX-dependent IP3 formation. These results indicated that IP3-mediated intracellular Ca2+ release was required for PKC-dependent inhibition of the Ca2+ channels. Possible control of synaptic transmission by the present mechanisms is discussed.
The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies

It is well admitted that the link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis. The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis. This family contains three members: ubiquitously expressed COX-1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated. COX-2 was described to modulate cell proliferation and apoptosis mainly in solid tumors, that is, colorectal, breast, and prostate cancers, and, more recently, in hematological malignancies. These findings prompt us to analyze here the effects of a combination of COX-2 inhibitors together with different clinically used therapeutic strategies in order to further improve the efficiency of future anticancer treatments. COX-2 modulation is a promising field investigated by many research groups.
Muscle atrophy and metal-on-metal hip implants

Background and purpose — Muscle atrophy is seen in patients with metal-on-metal (MOM) hip implants, probably because of inflammatory destruction of the musculo-tendon junction. However, like pseudotumors, it is unclear when atrophy occurs and whether it progresses with time. Our objective was to determine whether muscle atrophy associated with MOM hip implants progresses with time. Patients and methods — We retrospectively reviewed 74 hips in 56 patients (32 of them women) using serial MRI. Median age was 59 (23–83) years. The median time post-implantation was 83 (35–142) months, and the median interval between scans was 11 months. Hip muscles were scored using the Pfirrmann system. The mean scores for muscle atrophy were compared between the first and second MRI scans. Blood cobalt and chromium concentrations were determined. Results — The median blood cobalt was 6.84 (0.24–90) ppb and median chromium level was 4.42 (0.20–45) ppb. The median Oxford hip score was 34 (5–48). The change in the gluteus minimus mean atrophy score between first and second MRI was 0.12 (p = 0.002). Mean change in the gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p = 0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean pseudotumor grade increased by 0.18 (p = 0.02). Interpretation — Worsening muscle atrophy and worsening pseudotumor grade occur over a 1-year period in a substantial proportion of patients with MOM hip implants. Serial MRI helps to identify those patients who are at risk of developing worsening soft-tissue pathology. These patients should be considered for revision surgery before irreversible muscle destruction occurs.