Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging Omics Approaches in Aging Research.

SIGNIFICANCE Aging is a complex trait that is influenced by a combination of genetic and environmental factors. Although many cellular and physiological changes have been described to occur with aging, the precise molecular causes of aging remain unknown. Given the biological complexity and heterogeneity of the aging process, understanding the mechanisms that underlie aging requires integration of data about age-dependent changes that occur at the molecular, cellular, tissue, and organismal levels. Recent Advances: The development of high-throughput technologies such as next-generation sequencing, proteomics, metabolomics, and automated imaging techniques provides researchers with new opportunities to understand the mechanisms of aging. Using these methods, millions of biological molecules can be simultaneously monitored during the aging process with high accuracy and specificity. CRITICAL ISSUES Although the ability to produce big data has drastically increased over the years, integration and interpreting of high-throughput data to infer regulatory relationships between biological factors and identify causes of aging remain the major challenges. In this review, we describe recent advances and survey emerging omics approaches in aging research. We then discuss their limitations and emphasize the need for the further development of methods for the integration of different types of data. FUTURE DIRECTIONS Combining omics approaches and novel methods for single-cell analysis with systems biology tools would allow building interaction networks and investigate how these networks are perturbed with aging and disease states. Together, these studies are expected to provide a better understanding of the aging process and could provide insights into the pathophysiology of many age-associated human diseases. Antioxid. Redox Signal. 29, 985-1002.
Inflammatory natalizumab-associated PML: baseline characteristics, lesion evolution and relation with PML-IRIS

Background and objective Natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of inflammation at diagnosis (‘inflammatory PML’), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRIS). We investigated the imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping features. Methods We scored the presence, localisation and pattern of imaging characteristics of inflammation on brain MRI scans of inflammatory NTZ-PML patients. The imaging characteristics were followed up until the occurrence of PML-IRIS. Results Ten out of the 44 NTZ-PML patients included showed signs suggestive of inflammation at the time of diagnosis. The inflammation pattern at diagnosis was similar to the pattern seen at PML-IRIS, with contrast enhancement representing the most frequent sign of inflammation (90% at diagnosis, 100% at PML-IRIS). However, the severity of inflammation differed, with absence of swelling and low frequency of perilesional oedema (10%) at diagnosis, as compared with the PML-IRIS stage (40%). Conclusion Patterns of inflammation at the time of PML diagnosis and at the PML-IRIS stage overlap but differ in their severity of inflammation. This supports histopathological evidence that the inflammation seen at both stages of the same disease shares a similar underlying pathophysiology, representing the immune response to the JC virus to a variable extend.
Impact of Surgeon Specialty on Perioperative Outcomes of Surgery for Benign Esophageal Diseases: A NSQIP Analysis.

BACKGROUND Surgery for benign esophageal disease is mostly performed either by general surgeons (GS) or cardiothoracic surgeons (CTS) in the United States. The purpose of this study was to evaluate the effect of surgeon specialty on perioperative outcomes of surgery for benign esophageal diseases. MATERIALS AND METHODS We have conducted a retrospective analysis using the ACS-NSQIP during the period of 2006-2013. Patients who underwent paraesophageal hernia (PEH) repair, gastric fundoplication, or Heller esophagomyotomy were divided into two groups according to the specialty of the surgeon (GS or CTS). Outcomes compared between the two groups using multivariable logistic regression included 30-day mortality, overall morbidity, discharge destination, hospital length of stay (LOS), and readmission rates. RESULTS Most of the surgeries were performed by general surgeons (PEH: 97.1%; fundoplication: 97.6%; Heller: 91.6%). Patients had lower comorbidities, better physical condition, and underwent a laparoscopic approach more frequently in the GS group. Regression analysis showed that GS group had a lower mortality rate (operating room, 0.44; 95% confidence interval [CI]: 0.23-0.86; P = .017), shorter LOS, and more home discharge for patients undergoing PEH repair. Mortality, morbidity, readmission, LOS, and home discharge were comparable between GS and CTS in fundoplication and Heller esophagomyotomy. CONCLUSION GS perform most of esophageal surgeries for benign diseases. GS group has better outcomes in PEH repair compared with CTS, whereas there is no difference in the overall outcomes between GS and CTS in fundoplication and Heller esophagomyotomy. These results show that specialization is not always the answer to better outcomes. Difference in outcomes, however, might be related to disease severity, approach needed, or case volume.
Emerging infectious diseases: A proactive approach

Infectious diseases are now emerging or reemerging almost every year. This trend will continue because a number of factors, including the increased global population, aging, travel, urbanization, and climate change, favor the emergence, evolution, and spread of new pathogens. The approach used so far for emerging infectious diseases (EIDs) does not work from the technical point of view, and it is not sustainable. However, the advent of platform technologies offers vaccine manufacturers an opportunity to develop new vaccines faster and to reduce the investment to build manufacturing facilities, in addition to allowing for the possible streamlining of regulatory processes. The new technologies also make possible the rapid development of human monoclonal antibodies that could become a potent immediate response to an emergency. So far, several proposals to approach EIDs have been made independently by scientists, the private sector, national governments, and international organizations such as the World Health Organization (WHO). While each of them has merit, there is a need for a global governance that is capable of taking a strong leadership role and making it attractive to all partners to come to the same table and to coordinate the global approach.
A Statistical Physics Perspective to Understand Social Visual Attention in Autism Spectrum Disorder

This study investigated social visual attention in children with Autism Spectrum Disorder (ASD) and with typical development (TD) in the light of Brockmann and Geisel’s model of visual attention. The probability distribution of gaze movements and clustering of gaze points, registered with eye-tracking technology, was studied during a free visual exploration of a gaze stimulus. A data-driven analysis of the distribution of eye movements was chosen to overcome any possible methodological problems related to the subjective expectations of the experimenters about the informative contents of the image in addition to a computational model to simulate group differences. Analysis of the eye-tracking data indicated that the scanpaths of children with TD and ASD were characterized by eye movements geometrically equivalent to Lévy flights. Children with ASD showed a higher frequency of long saccadic amplitudes compared with controls. A clustering analysis revealed a greater dispersion of eye movements for these children. Modeling of the results indicated higher values of the model parameter modulating the dispersion of eye movements for children with ASD. Together, the experimental results and the model point to a greater dispersion of gaze points in ASD.
TIE2 Associates with Caveolae and Regulates Caveolin-1 To Promote Their Nuclear Translocation

ABSTRACT DNA repair pathways are aberrant in cancer, enabling tumor cells to survive standard therapies—chemotherapy and radiotherapy. Our group previously reported that, upon irradiation, the membrane-bound tyrosine kinase receptor TIE2 translocates into the nucleus and phosphorylates histone H4 at Tyr51, recruiting ABL1 to the DNA repair complexes that participate in the nonhomologous end-joining pathway. However, no specific molecular mechanisms of TIE2 endocytosis have been reported. Here, we show that irradiation or ligand-induced TIE2 trafficking is dependent on caveolin-1, the main component of caveolae. Subcellular fractionation and confocal microscopy demonstrated TIE2/caveolin-1 complexes in the nucleus, and using inhibitor or small interfering RNAs (siRNAs) against caveolin-1 or Tie2 inhibited their trafficking. TIE2 was found in caveolae and directly phosphorylated caveolin-1 at Tyr14 in vitro and in vivo. This modification regulated the generation of TIE2/caveolin-1 complexes and was essential for TIE2/caveolin-1 nuclear translocation. Our data further demonstrate that the combination of TIE2 and caveolin-1 inhibitors resulted in significant radiosensitization of malignant glioma cells, which will guide the development of combinatorial treatment with radiotherapy for patients with glioblastoma.
Longitudinal Effects of Teriparatide or Zoledronic Acid on Bone Modeling‐ and Remodeling‐Based Formation in the SHOTZ Study

Previously, we reported on bone histomorphometry, biochemical markers, and bone mineral density distribution after 6 and 24 months of treatment with teriparatide (TPTD) or zoledronic acid (ZOL) in the SHOTZ study. The study included a 12‐month primary study period, with treatment (TPTD 20 μg/d by subcutaneous injection or ZOL 5 mg/yr by intravenous infusion) randomized and double‐blind until the month 6 biopsy (TPTD, n = 28; ZOL, n = 30 evaluable), then open‐label, with an optional 12‐month extension receiving the original treatment. A second biopsy (TPTD, n = 10; ZOL, n = 9) was collected from the contralateral side at month 24. Here we present data on remodeling‐based bone formation (RBF), modeling‐based bone formation (MBF), and overflow modeling‐based bone formation (oMBF, modeling overflow adjacent to RBF sites) in the cancellous, endocortical, and periosteal envelopes. RBF was significantly greater after TPTD versus ZOL in all envelopes at 6 and 24 months, except the periosteal envelope at 24 months. MBF was significantly greater with TPTD in all envelopes at 6 months but not at 24 months. oMBF was significantly greater at 6 months in the cancellous and endocortical envelopes with TPTD, with no significant differences at 24 months. At 6 months, total bone formation surface was also significantly greater in each envelope with TPTD treatment (all p < 0.001). For within‐group comparisons from 6 to 24 months, no statistically significant changes were observed in RBF, MBF, or oMBF in any envelope for either the TPTD or ZOL treatment groups. Overall, TPTD treatment was associated with greater bone formation than ZOL. Taken together the data support the view that ZOL is a traditional antiremodeling agent, wheareas TPTD is a proremodeling anabolic agent that increases bone formation, especially that associated with bone remodeling, including related overflow modeling, with substantial modeling‐based bone formation early in the course of treatment. © 2017 American Society for Bone and Mineral Research.
Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish

Significance In vertebrates, proper patterning during appendage regeneration is regulated by positional memory—a cellular property hypothesized to rely on gradients of molecules present in uninjured limbs. Only one gene, exclusive to salamanders, has been shown to regulate positional memory and be expressed in a gradient in the uninjured limb. To identify new candidate effectors of positional memory, we mapped the abundance of RNAs, proteins, and metabolites along the uninjured zebrafish tail fin. We identified hundreds of molecular gradients and generated a high-confidence list of 32 genes and 42 metabolites that are candidate effectors of positional memory in zebrafish. Furthermore, expression patterns discovered here may help to explain how size-homeostasis and patterning are maintained in a complex adult tissue. Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the global abundance of transcripts, proteins, and metabolites along the proximodistal axis of caudal fins of uninjured and regenerating adult zebrafish. Using this approach, we uncovered complex overlapping expression patterns for hundreds of molecules involved in diverse cellular functions, including development, bioelectric signaling, and amino acid and lipid metabolism. Moreover, 32 genes differentially expressed at the RNA level had concomitant differential expression of the encoded proteins. Thus, the identification of proximodistal differences in levels of RNAs, proteins, and metabolites will facilitate future functional studies of positional memory during appendage regeneration.
Evaluation of the Efficacy of Methyl Bromide in the Decontamination of Building and Interior Materials Contaminated with Bacillus anthracis Spores

ABSTRACT The primary goal of this study was to determine the conditions required for the effective inactivation of Bacillus anthracis spores on materials by using methyl bromide (MeBr) gas. Another objective was to obtain comparative decontamination efficacy data with three avirulent microorganisms to assess their potential for use as surrogates for B. anthracis Ames. Decontamination tests were conducted with spores of B. anthracis Ames and Geobacillus stearothermophilus, B. anthracis NNR1Δ1, and B. anthracis Sterne inoculated onto six different materials. Experimental variables included temperature, relative humidity (RH), MeBr concentration, and contact time. MeBr was found to be an effective decontaminant under a number of conditions. This study highlights the important role that RH has when fumigation is performed with MeBr. There were no tests in which a ≥6-log10 reduction (LR) of B. anthracis Ames was achieved on all materials when fumigation was done at 45% RH. At 75% RH, an increase in the temperature, the MeBr concentration, or contact time generally improved the efficacy of fumigation with MeBr. This study provides new information for the effective use of MeBr at temperatures and RH levels lower than those that have been recommended previously. The study also provides data to assist with the selection of an avirulent surrogate for B. anthracis Ames spores when additional tests with MeBr are conducted.
Differences in stress and disease resilience related to emergence time for first feeding in farmed rainbow trout (Oncorhynchus mykiss)

ABSTRACT Salmonid individuals show a relatively high variability in the time required to abandon the gravel nest where they hatch, the so-called ‘emergence time’. Different behavioral and physiological traits have been shown to be associated with emergence time in wild salmonids. In general, early- and late-emerging fish have traits resembling those of proactive and reactive stress coping styles, respectively. Proactive fish are considered to be more resilient to stress and probably to disease, so it was hypothesized that fish with different emergence times have different abilities to resist repeated episodes of stress without suffering deleterious effects on their welfare or health status. In this study, rainbow trout eyed eggs were hatched and larvae were fractionated according to their emergence time (early fraction: first 20% of fish to emerge; intermediate fraction: mid 20%; late fraction: last 20%). When the fish were 4 months old, they were exposed to a daily repeated stress protocol for 15 days. The next day, both naïve and repeatedly stressed fish were exposed to an acute stress challenge. Different plasma (cortisol, glucose, lactate) as well as CNS (serotonergic activity) stress markers were assessed to evaluate the stress resilience of the different groups. Furthermore, an intraperitoneal infection challenge with Flavobacterium psychrophilum was carried out to assess disease resilience. Altogether, the results showed that fish from different fractions displayed differences in activation of the hypothalamus–pituitary–inter-renal axis, indicating a higher stress resilience in the fish with early emergence times. However, those differences were not reflected in the ability of the different fractions to grow and perform well in terms of growth, or in the ability to overcome infection with bacteria, which was similar for all the emergence fractions. This suggests that discriminating fish according to emergence time would probably have little effect in improving the performance and the welfare of farmed fish. Summary: The neuroendocrine response to acute stress and repeated stress of farmed juvenile rainbow trout is related to their individual time of emergence, but has no influence on their performance in captivity.
The acetylcholine signaling network of corneal epithelium and its role in regulation of random and directional migration of corneal epithelial cells.

PURPOSE Because cholinergic drugs are used in ophthalmology and cholinergic stimulation has been shown to facilitate epithelialization of mucocutaneous wounds, we performed a systematic analysis of components of the cholinergic network of human and murine corneal epithelial cells (CECs) and determined the role of autocrine and paracrine acetylcholine (ACh) in regulation of CEC motility. METHODS We investigated the expression of ACh receptors at the mRNA and protein levels in human immortalized CECs, localization of cholinergic molecules in normal and wounded murine cornea, and the effects of cholinergic drugs on CEC directional and random migration in vitro, intercellular adhesion, and expression of integrin αV and E-cadherin. RESULTS We demonstrated that corneal epithelium expresses the ACh-synthesizing enzyme choline acetyltransferase, the ACh-degrading enzyme acetylcholinesterase, two muscarinic ACh receptors (mAChRs), M3 and M4, and several nicotinic ACh receptors (nAChRs), including both α7- and α9-made homomeric nAChRs and predominantly the α3β2±α5 subtype of heteromeric nAChRs. Wounding affected the expression patterns of cholinergic molecules in the murine corneal epithelium. Constant stimulation of CECs through both muscarinic and nicotinic signaling pathways was essential for CEC survival and both directional and random migration in vitro. Both α7 and non-α7 nAChRs elicited chemotaxis, with the α7 signaling exhibiting a stronger chemotactic effect. Cholinergic stimulation of CECs upregulated expression of the integrin and cadherin molecules involved in epithelialization. We found synergy between the proepithelialization signals elicited by different ACh receptors expressed in CECs. CONCLUSIONS Simultaneous stimulation of mAChRs and nAChRs by ACh may be required to synchronize and balance ionic and metabolic events in a single cell. Localization of these cholinergic enzymes and receptors in murine cornea indicated that the concentration of endogenous ACh and the mode of its signaling differ among corneal epithelial layers. Elucidation of the signaling events elicited upon agonist binding to corneal mAChRs and nAChRs will be crucial for understanding the mechanisms of ACh signaling in CECs, which has salient clinical implications.
Archaeological Textiles of Sechín Bajo – a formative Site of the North Coast of Peru: Preliminarily Results

In spring 2014, I took part in an archaeological project carried out by a German-Peruvian team of archeologists in the Sechín Valley, next to the Valley of Casma, on the North Coast of Peru. The project started more than ten years ago and has been taking place parallel to some other important archaeological projects on the North Coast. Its aim was to unearth the temple mounds and to reconstruct the parts of the various phases. The earliest layers date back to the Pre-Ceramic Period. During the wall construction of the temple, many textile fabrics such as nets and ropes were used and some very early textile fabrics were found. The site was abandoned after thousands of years and a cemetery was placed on top of it. The cemetery comes from a later time period and contains tombs from different phases of cultures of the north Coast i.e. Moche and Chimú. My task was to examine these archeological textiles. The aim was to classify the textile objects and create an initial source of data. In this article I will present the textiles of the excavation and some particular examples with their typical characteristics. The textile artifacts were excavated in a small but very concrete area and the fabrics reflect a very long period of time.
Effect of cyclooxygenase inhibition on the inspiratory muscle metaboreflex-induced cardiovascular consequences in men.

Inspiratory muscle metaboreflex activation increases mean arterial pressure (MAP) and limb vascular resistance (LVR) and decreases limb blood flow (Q̇L). Cyclooxygenase (COX) inhibition has been found to attenuate limb skeletal muscle metaboreflex-induced increases in muscle sympathetic nerve activity. We hypothesized that compared with placebo (PLA), COX inhibition would attenuate inspiratory muscle metaboreflex-induced 1) increases in MAP and LVR and 2) decreases in Q̇L Seven men (22 ± 1 yr) were recruited and orally consumed ibuprofen (IB; 10 mg/kg) or PLA 90 min before performing the cold pressor test (CPT) for 2 min and inspiratory resistive breathing task (IRBT) for 14.9 ± 2.0 min at 65% of maximal inspiratory pressure. Breathing frequency was 20 breaths/min with a 50% duty cycle during the IRBTs. MAP was measured via automated oscillometry, Q̇L was determined via Doppler ultrasound, and LVR was calculated as MAP divided by Q̇L Electromyography was recorded on the leg to ensure no muscle contraction occurred. The 65% IRBT led to greater increases (P = 0.02) in 6-keto-prostaglandin-F1α with PLA compared with IB. IB, compared with PLA, led to greater (P < 0.01) increases in MAP (IB: 17 ± 7 mmHg vs. PLA: 8 ± 5 mmHg) and LVR (IB: 69 ± 28% vs. PLA: 52 ± 22%) at the final minute of the 65% IRBT. The decrease in Q̇L was not different (P = 0.72) between IB (-28 ± 11%) and PLA (-27 ± 9%) at the final minute. The increase in MAP during the CPT was not different (P = 0.87) between IB (25 ± 11 mmHg) and PLA (24 ± 6 mmHg). Contrary to our hypotheses, COX inhibition led to greater inspiratory muscle metaboreflex-induced increases in MAP and LVR.NEW & NOTEWORTHY Cyclooxygenase (COX) products play a role in activating the muscle metaboreflex. It is not known whether COX products contribute to the inspiratory muscle metaboreflex. Herein, we demonstrate that COX inhibition led to greater increases in blood pressure and limb vascular resistance compared with placebo during inspiratory muscle metaboreflex activation.