Technique based on LED multispectral imaging and multivariate analysis for monitoring the conservation state of the Dead Sea Scrolls

The aim of this project is the development of a noninvasive technique based on LED multispectral imaging (MSI) for monitoring the conservation state of the Dead Sea Scrolls (DSS) collection. It is well-known that changes in the parchment reflectance drive the transition of the scrolls from legible to illegible. Capitalizing on this fact, we will use spectral imaging to detect changes in the reflectance before they become visible to the human eye. The technique uses multivariate analysis and statistical process control theory. The present study was carried out on a "sample" parchment of calfskin. The monitoring of the surface of a commercial modern parchment aged consecutively for 2 h and 6 h at 80 °C and 50% relative humidity (ASTM) was performed at the Imaging Lab of the Library of Congress (Washington, DC, U.S.A.). MSI is here carried out in the vis-NIR range limited to 1 μm, with a number of bands of 13 and bandwidths that range from about 10 nm in UV to 40 nm in IR. Results showed that we could detect and locate changing pixels, on the basis of reflectance changes, after only a few "hours" of aging.     

Improved CO2 Capture from Flue Gas by Basic Sites,Charge Gradients,and Missing Linker Defects on Nickel Face Cubic Centered MOFs

The adsorptive properties of the isoreticular series [Ni₈(OH)₄(H₂O)₂(BDP_X)₆] (H₂BDP_X = 1,4‐bis(pyrazol‐4‐yl)benzene‐4‐X with X = H (1), OH (2), NH₂ (3)) can be enhanced by postsynthetic treatment with an excess of KOH in ethanol. In the case of X = H, NH₂, this treatment leads to partial removal of the organic linkers, deprotonation of coordinated water molecules and introduction of extraframework cations, giving rise to materials of K[Ni₈(OH)₅(EtO)‐(H₂O)₂(BDP_X)_5.5] (1@KOH, 3@KOH) formulation, in which the original framework topology is maintained. By contrast, the same treatment with KOH in the [Ni₈(OH)₄(H₂O)₂(BDP_OH)₆] (2) system, enclosing the more acidic phenol residues, leads to a new material containing a larger fraction of missing linker defects and extra‐framework cations as well as phenolate residues, giving rise to the material K₃[Ni₈(OH)₃(EtO)(H₂O)₆(BDP_O)₅] (2@KOH), which also conserves the original face cubic centered (fcu) topology. It is noteworthy that the introduction of missing linker defects leads to a higher accessible pore volume with a concomitant increased adsorption capacity. Moreover, the creation of coordinatively unsaturated metal centers, charge gradients, and phenolate nucleophilic sites in 2@KOH gives rise to a boosting of CO₂ capture features with increased adsorption heat and adsorption capacity, as proven by the measurement of pulse gas chromatography and breakthrough curve measurements of simulated flue gas.     

Single-Cell RNA Sequencing for the Detection of Clonotypic V(D)J Rearrangements in Multiple Myeloma

Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient’s malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq). To this end we analyzed CD138⁺ cells purified from bone marrow aspirates of 19 samples with PC dyscrasias by both a standard method based on bulk DNA and by an implementation of the standard 10x Genomics protocol to detect expressed V(D)J sequences. A dominant clonotype was easily identified in each sample, accounting on average for 83.65% of V(D)J-rearranged cells. Compared with standard methods, scRNA-seq analysis proved highly concordant and even more effective in identifying clonal productive rearrangements, by-passing limitations related to the misannealing of consensus primers in hypermutated regions. We next validated its accuracy to track 5 clonal cells with absolute sensitivity in a virtual sample containing 3180 polyclonal cells. This shows that single-cell V(D)J analysis may be used to find rare clonal cells, laying the foundations for functional single-cell dissection of minimal residual disease.     

Influence of Metal Salts Addition on Physical and Electrochemical Properties of Ethyl and Propylammonium Nitrate

In this work, we deepen in the characterization of two protic ionic liquids (PILs), ethylammonium nitrate (EAN) and propylammonium nitrate (PAN). With this aim, we determined the influence of inorganic nitrate salts addition on their physical properties and their electrochemical potential window (EPW). Thus, experimental measurements of electrical conductivity, density, viscosity, refractive index and surface tension of mixtures of {EAN or PAN + LiNO₃, Ca(NO₃)₂, Mg(NO₃)₂ or Al(NO₃)₃} at a temperature range between 5 and 95 °C are presented first, except for the last two properties which were measured at 25 °C. In the second part, the corresponding EPWs were determined at 25 °C by linear sweep voltammetry using three different electrochemical cells. Effect of the salt addition was associated mainly with the metal cation characteristics, so, generally, LiNO₃ showed the lower influence, followed by Ca(NO₃)₂, Mg(NO₃)₂ or Al(NO₃)₃. The results obtained for the EAN + LiNO₃ mixtures, along with those from a previous work, allowed us to develop novel predictive equations for most of the presented physical properties as functions of the lithium salt concentration, the temperature and the water content. Electrochemical results showed that a general order of EPW can be established for both PILs, although exceptions related to measurement conditions and the properties of the mixtures were found.     

Intraoperative Tumor Detection Using Pafolacianine

Cancer is a leading cause of death worldwide, with increasing numbers of new cases each year. For the vast majority of cancer patients, surgery is the most effective procedure for the complete removal of the malignant tissue. However, relapse due to the incomplete resection of the tumor occurs very often, as the surgeon must rely primarily on visual and tactile feedback. Intraoperative near-infrared imaging with pafolacianine is a newly developed technology designed for cancer detection during surgery, which has been proven to show excellent results in terms of safety and efficacy. Therefore, pafolacianine was approved by the U.S. Food and Drug Administration (FDA) on 29 November 2021, as an additional approach that can be used to identify malignant lesions and to ensure the total resection of the tumors in ovarian cancer patients. Currently, various studies have demonstrated the positive effects of pafolacianine’s use in a wide variety of other malignancies, with promising results expected in further research. This review focuses on the applications of the FDA-approved pafolacianine for the accurate intraoperative detection of malignant tissues. The cancer-targeting fluorescent ligands can shift the paradigm of surgical oncology by enabling the visualization of cancer lesions that are difficult to detect by inspection or palpation. The enhanced detection and removal of hard-to-detect cancer tissues during surgery will lead to remarkable outcomes for cancer patients and society, specifically by decreasing the cancer relapse rate, increasing the life expectancy and quality of life, and decreasing future rates of hospitalization, interventions, and costs.     

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.     

Rhus Coriaria L. Extract: Antioxidant Effect and Modulation of Bioenergetic Capacity in Fibroblasts from Parkinson’s Disease Patients and THP-1 Macrophages

Sumac, Rhus coriaria L., is a Mediterranean plant showing several useful properties, such as antioxidant and neuroprotective effects. Currently, there is no evidence about its possible neuroprotective action in Parkinson’s disease (PD). We hypothesized that sumac could modulate mitochondrial functionality in fibroblasts of familial early-onset PD patients showing PARK2 mutations. Sumac extract volatile profile, polyphenolic content and antioxidant activity have been previously characterized. We evaluated ROS and ATP levels on sumac-treated patients’ and healthy control fibroblasts. In PD fibroblasts, all treatments were effective in reducing H₂O₂ levels, while patients’ ATP content was modulated differently, probably due to the varying mutations in the PARK2 gene found in individual patients which are also involved in different mitochondrial phenotypes. We also investigated the effect of sumac extract on THP-1-differentiated macrophages, which show different embryogenic origin with respect to fibroblasts. In THP-1 macrophages, sumac treatment determined a reduction in H₂O₂ levels and an increase in the mitochondrial ATP content in M1, assuming that sumac could polarize the M1 to M2 phenotype, as demonstrated with other food-derived compounds rich in polyphenols. In conclusion, Rhus coriaria L. extracts could represent a potential nutraceutical approach to PD.     

Structural and compositional analysis of (InGa) (AsSb)/GaAs/GaP Stranski–Krastanov quantum dots

We investigated metal-organic vapor phase epitaxy grown (InGa)(AsSb)/GaAs/GaP Stranski–Krastanov quantum dots (QDs) with potential applications in QD-Flash memo...     

The Greatwall–Endosulfine Switch Accelerates Autophagic Flux during the Cell Divisions Leading to G1 Arrest and Entry into Quiescence in Fission Yeast

Entry into quiescence in the fission yeast Schizosaccharomyces pombe is induced by nitrogen starvation. In the absence of nitrogen, proliferating fission yeast cells divide twice without cell growth and undergo cell cycle arrest in G1 before becoming G0 quiescent cells. Under these conditions, autophagy is induced to produce enough nitrogen for the two successive cell divisions that take place before the G1 arrest. In parallel to the induction of autophagy, the Greatwall–Endosulfine switch is activated upon nitrogen starvation to down-regulate protein phosphatase PP2A/B55 activity, which is essential for cell cycle arrest in G1 and implementation of the quiescent program. Here we show that, although inactivation of PP2A/B55 by the Greatwall–Endosulfine switch is not required to promote autophagy initiation, it increases autophagic flux at least in part by upregulating the expression of a number of autophagy-related genes.     

The Adaptability of Chromosomal Instability in Cancer Therapy and Resistance

Variation in chromosome structure is a central source of DNA damage and DNA damage response, together representinga major hallmark of chromosomal instability. Cancer cells under selective pressure of therapy use DNA damage and DNA damage response to produce newfunctional assets as an evolutionary mechanism. Recent efforts to understand DNA damage/chromosomal instability and elucidate its role in initiation or progression of cancer have also disclosed its vulnerabilities represented by inappropriate DNA damage response, chromatin changes, andinflammation. Understanding these vulnerabilities can provide important clues for predicting treatment response and for the development of novel strategies that prevent the emergence of therapy resistant tumors.