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Pathogenic variants in CHRNE encoding the epsilon subunit of acetyl choline receptor (AChR) result in impaired neuromuscular transmission and congenital myasthenic syndromes (CMS). Clinical manifestations include facial, ocular and limb fatigability and weakness, whereby severity of symptoms may vary in patients harboring the same pathogenic variant. Although the underlying pathophysiology is well-known, blood biomarkers enabling a patient-stratification are lacking. Previous studies revealed CHRNE protein in white blood cells (WBC) rendering these cells suitable for the study of cellular and minimal-invasive marker proteins. This retrospective two center-study includes 19 patients carrying biallelic pathogenic variants in CHRNE identified by molecular genetic testing. The patients were clinically characterized according to clinical severity (grade 1-4). Biomarker discovery was carried out on blood samples: proteomic profiling was performed on WBC (n =12) and on extracellular vesicles (EVs) purified from serum samples (n =7) in addition to amino acid profiling (n = 9) and miRNA screening (n = 18) on sera. In 19 patients (mean age 14.8 years) from 13 families seven known pathogenic variants in CHRNE were identified in addition to one variant previously not reported (c.1032+2_1032+3delTAinsGT). Whereas 15 patients were classified as mildly affected (group A: grade 1 and 2), 4 patients were classified as moderate or severely affected (group B: grade 3 and 4). Proteomics unveiled a significant increase of 7 and a decrease of 36 proteins in WBC in comparison to normal, age matched controls. GO-term based in silico studies of these dysregulated proteins indicated affection of secretory granules and the extracellular space. When comparing proteomic signatures of CHRNE-patients with a mild (A) versus moderate to severe phenotypes (B), 2 proteins (SCAMP2 and SNX2) were significantly increased in second group (B). These two proteins are involved in vesical transport. Prompted by this finding, proteomic profiling of EVs was initiated revealing a significant dysregulation of 20 proteins (7 are increased and 13 decreased). Three of these proteins (TARSH, ATRN & PLEC) are known to be important for synaptogenesis and synaptic function. Metabolic profiling of sera showed a decrease of 7 amino acids/ amino acid metabolites (aspartic and glutamic acids, phosphoserine, amino adipate, citrulline, ornithine & 1-methyhistidine) in terms of a metabolic fingerprint in CHRNE-related CMS patients. Moreover, miRNA screening unveiled increase of miR−365b−3p and miR−483−3p and decrease of miR-4433b-3p when comparing sera of CHRNE patients versus healthy controls. Moreover, a comparison of CHRNE patients versus other CMS-subtypes showed increase of miR−205−5p, miR−10b−5p, and miR−483−5 and decrease of miR−1290. Our combined data introduce a panel of minimal-invasive biomarkers on protein, metabolic and miRNA level with some of those play different roles along the neuromuscular axis. In the latter regard, impaired EV homeostasis impacting on synaptic function seems to be a molecular disease driver and two proteins in WBC correlate with disease severity. Our miRNA profiles introduce four miRNAs which may open new avenues in CMS patient stratification. [ABSTRACT FROM AUTHOR]

The 97-residue influenza A matrix 2 (ΑM2) protein, a prototype for viroporins, transports protons through water molecules and His37. We discuss structural biology and molecular biophysics experiments and some functional assays that have transformed over 40 years our understanding of the structure and function of AM2. The structural studies on ΑM2 have been performed with different conditions (pH, temperature, lipid, constructs) and using various protein constructs, e.g., AM2 transmembrane (AM2TM) domain, AM2 conductance domain (AM2CD), ectodomain-containing or ectodomain-truncated, AM2 full length (AM2FL) and aimed to describe the different conformations and structural details that are necessary for the stability and function of AM2. However, the conclusions from these experiments appeared sometimes ambiguous and caused exciting debates. This was not due to inaccurate measurements, but instead because of the different membrane mimetic environment used, e.g., detergent, micelles or phospholipid bilayer, the method (e.g., X-ray crystallography, solid state NMR, solution NMR, native mass spectrometry), the used protein construct (e.g., AM2TM or AM2CD), or the amino acids residues to follow observables (e.g., NMR chemical shifts). We present these results according to the different used biophysical methods, the research groups and often by keeping a chronological order for presenting the progress in the research. We discuss ideas for additional research on structural details of AM2 and how the present findings can be useful to explore new routes of influenza A inhibition. The AM2 research can provide inspiration to study other viroporins as drug targets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Antonios Kolocouris reports financial support was provided by Chiesi Hellas SA. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All the figures were created in BioRender. Georgiou, K. (2024)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling., (© 2024. The Author(s).)

Lamins A and C are components of the lamina at the nuclear periphery and associate with heterochromatin. A distinct, relatively mobile pool of lamin A/C in the nuclear interior associates with euchromatic regions and with lamin-associated polypeptide 2α (LAP2α). Here we show that phosphorylation-dependent impairment of lamin assembly had no effect on its chromatin association, while LAP2α depletion was sufficient to increase chromatin association of lamins. This suggests that complex interactions between LAP2α, chromatin, and lamins regulate lamin chromatin binding. Both the C terminus of LAP2α and its N-terminal LAP2-Emerin-MAN1 (LEM) domain, mediating interaction with lamin A/C indirectly via barrier-to-autointegration factor (BAF), are required for binding to lamins. The N-terminal LEM-like domain of LAP2α, but not its LEM domain, mediates chromatin association of LAP2α and requires LAP2α dimerization via its C terminus. Our data suggest that formation of several LAP2α-, lamin A/C-, and BAF-containing complexes in the nucleoplasm and on chromatin affects lamin chromatin association., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Molecular vibrations that bear information about intrinsic properties of chemical compounds are challenging to detect at submonolayer densities. Surface-enhanced infrared absorption (SEIRA) spectroscopy has been proven to be a viable approach to enhance and detect weak vibration signals. Here, we report a SEIRA sensor based on mid-infrared surface plasmon resonances supported by single-walled carbon nanotubes (SWCNTs). Due to the 1D nature of SWCNTs, their plasmon modes are highly polarized with the electromagnetic fields spatially confined to nanometer scales. Leveraging these characteristics of SWCNTs, we observe a polarization selective coupling between their surface plasmons and vibrational modes of chemical bonds introduced onto their surfaces. A maximum modulation of ∼15% to the plasmon resonance peak is obtained for a submonolayer chemical group coverage. These findings suggest that SWCNTs may potentially serve as a highly sensitive SEIRA platform for revealing intricate information about molecular compositions and bond orientations.

Rats can condition cephalic-phase insulin responses (CPIRs) to specific sounds or times of the day that predict food availability. The present study asked whether mice can condition a CPIR to the flavor of sapid solutions that produce postoral glucose stimulation. To this end, we subjected C57BL/6 mice to one of six experimental protocols. We varied both the duration of the five training sessions (i.e., 23 h or 1 h) and the nature of the training solution. In Experiment 1, consumption of a 0.61% saccharin solution was paired with IG co-infusion of a 16% glucose solution. In Experiments 2-6, the mice consumed a training solution containing a mixture of 0.61% saccharin + 16% glucose, 32% sucrose, 32% maltodextrin, flavored 32% maltodextrin, or 16% maltodextrin. We subsequently asked whether consumption of any of these fluids conditioned a CPIR to a test solution that produced a similar flavor, but which did not elicit a CPIR in naïve mice. The mice did condition a CPIR, but only to the solutions containing 32% maltodextrin. We attribute this conditioning to postoral actions of the concentrated maltodextrin solutions.

It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies., (© 2024. The Author(s).)

Background: Stress during the early ERCP learning curve may interfere with acquisition of skills during training. The purpose of this study was to compare stress biomarkers in the saliva of trainees before and after familiarisation with ERCP exercises on a virtual simulator., Methods: Altogether 26 endoscopists under training, 14 women and 12 men, completed the three phases of this study: Phase 1. Three different ERCP procedures were performed on the simulator. Saliva for α-amylase (sAA), Chromogranin A (sCgA), and Cortisol (sC) were collected before (baseline), halfway through the exercise (ex.), and 10 min after completion of the exercise (comp.); Phase 2. A three-week familiarisation period where at least 30 different cases were performed on the virtual ERCP simulator; and Phase 3. Identical to Phase 1 where saliva samples were once again collected at baseline, during, and after the exercise. Percentage differences in biomarker levels between baseline and exercise (Diff ex ) and between baseline and completion (Diff comp ) during Phase 1 and Phase 3 were calculated for each stress marker., Results: Mean % changes, Diff ex and Diff comp , were significantly positive ( p  < 0.05) for all markers in both Phase 1 and Phase 3. Diff ex in Phase 1 was significantly greater than Diff ex in Phase 3 ( p  < 0.05) for sAA and sCgA. Diff comp for sAA in Phase 1 was significantly greater than Diff comp in Phase 3 ( p  < 0.05). No significant differences were found in sC concentration between Phases 1 and 3., Conclusion: This study shows that familiarisation with the ERCP simulator greatly reduced stress as measured by the three saliva stress biomarkers used with sAA being the best. It also suggests that familiarisation with an ERCP simulator might reduce stress in the clinical setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Georgiou, Boyanov, Thanasas, Sandblom, Linardoutsos and Enochsson.)

Strong light-matter interactions have attracted much attention as a means to control the physical/chemical properties of organic semiconducting materials with light-matter hybrids called polaritons. To unveil the processes under strong coupling, studies on the dynamics of polaritons are of particular importance. While highly condensed molecular materials with large dipole density are ideal to achieve strong coupling, the emission properties of such films often become a mixture of monomeric and excimeric components, making the role of excimers unclear. Here, we use amorphous neat films of a new bis(phenylethynyl anthracene) derivative showing only excimer emission and investigate the excited-state dynamics of a series of strongly coupled microcavities, with each cavity being characterised by a different exciton-photon detuning. A time-resolved photoluminescence study shows that the excimer radiatively pumps the lower polariton in the relaxation process and the decay profile reflects the density of states. The delayed emission derived from triplet-triplet annihilation is not sensitive to the cavity environment, possibly due to the rapid excimer formation. Our results highlight the importance of controlling intermolecular interactions towards rational design of organic exciton-polariton devices, whose performance depends on efficient polariton relaxation pathways.

One of the largest uncertainties in the terrestrial carbon cycle is the timing and magnitude of soil organic carbon (SOC) response to climate and vegetation change. This uncertainty prevents models from adequately capturing SOC dynamics and challenges the assessment of management and climate change effects on soils. Reducing these uncertainties requires simultaneous investigation of factors controlling the amount (SOC abundance) and duration (SOC persistence) of stored C. We present a global synthesis of SOC and radiocarbon profiles (n Profile  = 597) to assess the timescales of SOC storage. We use a combination of statistical and depth-resolved compartment models to explore key factors controlling the relationships between SOC abundance and persistence across pedo-climatic regions and with soil depth. This allows us to better understand (i) how SOC abundance and persistence covary across pedo-climatic regions and (ii) how the depth dependence of SOC dynamics relates to climatic and mineralogical controls on SOC abundance and persistence. We show that SOC abundance and persistence are differently related; the controls on these relationships differ substantially between major pedo-climatic regions and soil depth. For example, large amounts of persistent SOC can reflect climatic constraints on soils (e.g., in tundra/polar regions) or mineral absorption, reflected in slower decomposition and vertical transport rates. In contrast, lower SOC abundance can be found with lower SOC persistence (e.g., in highly weathered tropical soils) or higher SOC persistence (e.g., in drier and less productive regions). We relate variable patterns of SOC abundance and persistence to differences in the processes constraining plant C input, microbial decomposition, vertical C transport and mineral SOC stabilization potential. This process-oriented grouping of SOC abundance and persistence provides a valuable benchmark for global C models, highlighting that pedo-climatic boundary conditions are crucial for predicting the effects of climate change and soil management on future C abundance and persistence., (© 2024 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Malnutrition is a major issue in gastrointestinal perioperative situations, as only 40% of malnourished patients are finally treated. This literature review investigates the inconsistencies regarding the diagnostic approach to both preoperative and postoperative patients and the various underlying causes, as well as the efficiency of the various therapeutic regimens. A literature search was conducted until August 2023 in MEDLINE and Scopus. Clinical studies involving perioperative nutritional assessment in adult gastrointestinal surgery patients during the last 10 years were included in the present review. Finally, 19 articles were included in the study. Preoperative nutritional therapy is increasingly recognized as a key component of surgical care. Malnourished patients who are hospitalized and operated on, have significantly worse clinical results. Gastrointestinal postoperative malnutrition coexists with metabolic stress, as patients usually suffer from minor chronic inflammations; therefore, postoperative malnutrition is the result of a combination of the effects of inflammation and a lack of food intake. Postoperative malnutrition leads to prolonged hospitalizations and hospital complications and therefore the need to treat it is essential. There are many recognized tools for detecting malnutrition. However, all tools showed inconsistent results regarding their validity. Per os feeding after surgery, and dietary supplements when necessary, have been recommended. Therefore, it is very important to reduce malnutrition and define clear strategies towards that direction., Competing Interests: Conflict of interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Experimental binding free energies of 27 adamantyl amines against the influenza M2(22-46) WT tetramer, in its closed form at pH 8, were measured by ITC in DPC micelles. The measured K d 's range is ~44 while the antiviral potencies (IC 50 ) range is ~750 with a good correlation between binding free energies computed with K d and IC 50 values (r = 0.76). We explored with MD simulations (ff19sb, CHARMM36m) the binding profile of complexes with strong, moderate and weak binders embedded in DMPC, DPPC, POPC or a viral mimetic membrane and using different experimental starting structures of M2. To predict accurately differences in binding free energy in response to subtle changes in the structure of the ligands, we performed 18 alchemical perturbative single topology FEP/MD NPT simulations (OPLS2005) using the BAR estimator (Desmond software) and 20 dual topology calculations TI/MD NVT simulations (ff19sb) using the MBAR estimator (Amber software) for adamantyl amines in complex with M2(22-46) WT in DMPC, DPPC, POPC. We observed that both methods with all lipids show a very good correlation between the experimental and calculated relative binding free energies (r = 0.77-0.87, mue = 0.36-0.92 kcal mol -1 ) with the highest performance achieved with TI/MBAR and lowest performance with FEP/BAR in DMPC bilayers. When antiviral potencies are used instead of the K d values for computing the experimental binding free energies we obtained also good performance with both FEP/BAR (r = 0.83, mue = 0.75 kcal mol -1 ) and TI/MBAR (r = 0.69, mue = 0.77 kcal mol -1 )., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Full Spectrum Imaging System (FSIS-II) was assessed for the detection of latent fingermarks on a variety of substrates, specifically focusing on UV-C imaging for untreated marks and those that have been treated with cyanoacrylate (CA). The use of UV-C was effective at the detection of latent fingermarks on a variety of substrates and UV-C imaging may be effective when UV-A does not provide any fingermark detections on thermal paper. A Phase 2 and a small Phase 3 trials on aluminium cans were carried out with a detection sequence of UV-C imaging, CA fuming, UV-C imaging, UV-A imaging and BY40. For Phase 2 laboratory trials, the use of initial UV-C reflection was effective at removing the background and was a useful tool for initial screening. The use of UV-C was superior to UV-A after CA fuming and provided the highest overall number of high-quality marks. For phase 3 trials, the results showed that BY40 fluorescence was marginally more effective than UV-C imaging of CA-treated marks. This preliminary study shows that the FSIS-II and UV-C imaging can complement other methods for the detection of latent fingermarks., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kevin Farrugia reports equipment, drugs, or supplies was provided by Arrowhead Forensics and ForenteQ., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tooth autotransplantation is one of the methods used for tooth loss rehabilitation in children. Premolars are usually used as autotransplants requiring esthetic alterations. The purpose of this paper is to present an innovative, alternative and inexpensive way to restore auto-transplanted teeth using the crown of the tooth of the recipient site. A seven-year-old male with a non-contributory medical history presented with an intrusion of his permanent maxillary right central incisor. The tooth underwent orthodontic extrusion using fixed appliances but eventually showed signs of ankylosis. At 10 years old, autotransplantation of a premolar to substitute the ankylosed incisor was undertaken. Six weeks after the autotransplantation, the premolar was restored to an incisor by modifying the extracted ankylosed tooth to a veneer for the transplanted tooth, providing functional and esthetic restoration. The patient has been followed up for two years without any complications. This technique can help clinicians restore autotransplants in an easy and esthetic manner.

Heart failure (HF) is characterized by a progressive clinical course marked by frequent exacerbations and repeated hospitalizations, leading to considerably high morbidity and mortality rates. Patients with HF present with a constellation of bothersome symptoms, which range from physical to psychological and mental manifestations. With the transition to more advanced HF stages, symptoms become increasingly more debilitating, interfere with activities of daily living and disrupt multiple domains of life, including physical functioning, psychological status, emotional state, cognitive function, intimate relationships, lifestyle status, usual role activities, social contact and support. By inflicting profuse limitations in numerous aspects of life, HF exerts a profoundly negative impact on health-related quality of life (HRQOL). It is therefore not surprising that patients with HF display lower levels of HRQOL compared not only to the general healthy population but also to patients suffering from other chronic diseases. On top of this, poor HRQOL in patients with HF becomes an even greater concern considering that it has been associated with unfavorable long-term outcomes and poor prognosis. Nevertheless, HRQOL may differ significantly among patients with HF. Indeed, it has consistently been reported that women with HF display poorer HRQOL compared to men, while younger patients with HF tend to exhibit lower levels of HRQOL than their older counterparts. Moreover, patients presenting with higher New York Heart Association (NYHA) functional class (III-IV) have significantly more impaired HRQOL than those in a better NYHA class (I-II). Furthermore, most studies report worse levels of HRQOL in patients suffering from HF with preserved ejection fraction (HFpEF) compared to patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF). Last, but not least, differences in HRQOL have been noted depending on geographic location, with lower HRQOL levels having been recorded in Africa and Eastern Europe and higher in Western Europe in a recent large global study. Based on the observed disparities that have been invariably reported in the literature, this review article aims to provide insight into the underlying differences in HRQOL among patients with HF. Through an overview of currently existing evidence, fundamental differences in HRQOL among patients with HF are analyzed based on sex, age, NYHA functional class, ejection fraction and geographic location or ethnicity.