Non-random spatial organization of telomeres varies during the cell cycle and requires LAP2 and BAF.

Spatial genome organization within the nucleus influences major biological processes and is impacted by the configuration of linear chromosomes. Here, we applied 3D spatial statistics and modeling on high-resolution telomere and centromere 3D-structured illumination microscopy images in cancer cells. We found a multi-scale organization of telomeres that dynamically evolved from a mixed clustered-and-regular distribution in early G1 to a purely regular distribution as cells progressed through the cell cycle. In parallel, our analysis revealed two pools of peripheral and internal telomeres, the proportions of which were inverted during the cell cycle. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope observed in early G1. Lamina-associated polypeptide (LAP) proteins were found transiently localized to telomeres in anaphase, a stage where LAP2α initiates the reformation of the nuclear envelope, and impacted telomere redistribution in the next interphase together with their partner barrier-to-autointegration factor (BAF).

Paraspinal muscle oxygenation and mechanical efficiency are reduced in individuals with chronic low back pain.

This study aimed to compare the systemic and local metabolic responses during a 5-min trunk extension exercise in individuals with chronic low back pain (CLBP) and in healthy individuals. Thirteen active participants with CLBP paired with 13 healthy participants performed a standardised 5-min trunk extension exercise on an isokinetic dynamometer set in continuous passive motion mode. During exercise, we used near-infrared spectroscopy to measure tissue oxygenation (TOI) and total haemoglobin-myoglobin (THb). We used a gas exchange analyser to measure breath-by-breath oxygen consumption (V̇O2) and carbon dioxide produced (V̇CO2). We also calculated mechanical efficiency. We assessed the intensity of low back pain sensation before and after exercise by using a visual analogue scale. In participants with CLBP, low back pain increased following exercise (+ 1.5 units; p < 0.001) and THb decreased during exercise (- 4.0 units; p = 0.043). Paraspinal muscle oxygenation (65.0 and 71.0%, respectively; p = 0.009) and mechanical efficiency (4.7 and 5.3%, respectively; p = 0.034) were both lower in participants with CLBP compared with healthy participants. The increase in pain sensation was related to the decrease in tissue oxygenation (R2 = - 0.420; p = 0.036). Decreases in total haemoglobin-myoglobin and mechanical efficiency could involve fatigability in exercise-soliciting paraspinal muscles and, therefore, exacerbate inabilities in daily life. Given the positive correlation between tissue oxygenation and exercise-induced pain exacerbation, muscle oxygenation may be related to persisting and crippling low back pain.

Power Is More Relevant Than Ascensional Speed to Determine Metabolic Demand at Different Gradient Slopes During Running.

ABSTRACT: Hingrand, C, Olivier, N, Combes, A, Bensaid, S, and Daussin, FN. Power is more relevant than ascensional speed to determine metabolic demand at different gradient slopes during running. J Strength Cond Res 37(11): 2298-2301, 2023-Trail running is characterized by successive uphill and downhill running sessions. To prescribe training intensity, an assessment of maximal running capacity is required. This study compared 2 uphill incremental tests using the same ascensional speed increment to identify the influence of the slope gradient on performance. Ten subjects (8 men and 2 women) performed 3 incremental exercises on various slope (1%: IT01, 10%: IT10, and 25%: IT25), and the ascensional speed increment was similar between IT10 and IT25 (100 m·h-1 every minute). Gas exchanges, heart rate, and power were monitored continuously during the tests. Similar V̇o2max levels were observed in the 3 conditions: 68.7 ± 6.2 for IT01, 70.1 ± 7.3 for IT10, and 67.6 ± 7.0 for IT25. A greater maximal ascensional speed was reached in the IT25 (1760 ± 190 vs. 1,330 ± 106 for IT25 and IT10, respectively, p < 0.01). A significant relationship was observed between relative V̇o2 levels and relative power without any effect of slope. Power should be the parameter used for prescribing training intensity compared with ascensional speed in trail.

Third harmonic imaging contrast from tubular structures in the presence of index discontinuity.

Accurate interpretation of third harmonic generation (THG) microscopy images in terms of sample optical properties and microstructure is generally hampered by the presence of excitation field distortions resulting from sample heterogeneity. Numerical methods that account for these artifacts need to be established. In this work, we experimentally and numerically analyze the THG contrast obtained from stretched hollow glass pipettes embedded in different liquids. We also characterize the nonlinear optical properties of 2,2[Formula: see text]-thiodiethanol (TDE), a water-soluble index-matching medium. We find that index discontinuity not only changes the level and modulation amplitude of polarization-resolved THG signals, but can even change the polarization direction producing maximum THG near interfaces. We then show that a finite-difference time-domain (FDTD) modeling strategy can accurately account for contrast observed in optically heterogeneous samples, whereas reference Fourier-based numerical approaches are accurate only in the absence of index mismatch. This work opens perspectives for interpreting THG microscopy images of tubular objects and other geometries.

Evaluation of Slowfade Diamond as a buffer for STORM microscopy.

We study the potential of the commercial mounting medium Slowfade diamond as a buffer for STORM microscopy. We show that although it does not work with the popular far-red dyes typically used for STORM imaging, such as Alexa Fluor 647, it performs really well with a wide variety of green-excited dyes such as Alexa Fluor 532, Alexa Fluor 555 or CF 568. Moreover, imaging can be performed several months after the samples are mounted in this environment and kept in the fridge, providing a convenient way to preserve samples for STORM imaging, as well as to keep calibration samples, for example for metrology or teaching in particular in imaging facilities.

Subjective assessment of a lumbar exoskeleton's impact on lower back pain in a real work situation.

This study evaluated the impact of a lumbar exoskeleton on low back pain perception, in a real work situation. For three weeks, 30 subjects with and without specific low back pain assessed daily their lumbar pain on their work activities at the beginning and end of the workday by a visual analogue scale. The first and the third week, participants worked normally. The second week, participants wore the exoskeleton to work. For subjects with specific low back pain, our results showed a significant decrease in low back pain perception at the end of the week two when wearing the exoskeleton Our result showed that the exoskeleton studied had a positive impact on the pain index perception of workers with mechanical lumbar pathology.

BrdU Incorporation and Labeling of Nascent DNA to Investigate Archaeal Replication Using Super-Resolution Imaging.

The labeling and specific detection of nascent DNA by the incorporation of thymidine analogs provide crucial information about DNA replication dynamics without requiring the intracellular expression of fluorescent proteins. After cell fixation and permeabilization, specific detection of thymidine analogs by antibodies can be performed using super-resolution imaging techniques. Here we describe a protocol to label nascent DNA using 5'-bromo-2'-deoxyuridine (BrdU) in Haloferax volcanii cells and generate super-resolved images of neo-synthesized DNA foci either by 3D Structured illumination microscopy (3D-SIM) or Stochastic Optical Reconstruction Microscopy (STORM).

Identification of von Willebrand factor D4 domain mutations in patients of Afro-Caribbean descent: In vitro characterization.

Background: Von Willebrand disease was diagnosed in two Afro-Caribbean patients and sequencing of the VWF gene (VWF) revealed the presence of multiple variants located throughout the gene, including variants located in the D4 domain of VWF: p.(Pro2145Thrfs*5) in one patient and p.(Cys2216Phefs*9) in the other patient. Interestingly, D4 variants have not been studied often. Objectives: Our goal was to characterize how the D4 variants p.(Pro2145Thrfs*5) and p.(Cys2216Phefs*9) influenced VWF biosynthesis/secretion and functions using in vitro assays. Methods: Recombinant VWF (rVWF), mutant or wild-type, was produced via transient transfection of the human embryonic kidney cell line 293T. The use of different tags for the wild-type and the mutant allele allowed us to distinguish between the two forms when measuring VWF antigen in medium and cell lysates. Binding of rVWF to its ligands, collagen, factor VIII, ADAMTS13, and platelet receptors was also investigated. Results: Homozygous expression of the p.(Cys2216Phefs*9)-rVWF mutation resulted in an almost complete intracellular retention of the protein. Heterozygous expression led to secretion of almost exclusively wild-type-rVWF, logically capable of normal interaction with the different ligands. In contrast, the p.(Pro2145Thrfs*5)-rVWF exhibited reduced binding to type III collagen and αIIbß3 integrin compared to wild-type-rVWF. Conclusions: We report two mutations of the D4 domains that induced combined qualitative and quantitative defects.

[Cutaneous malakoplakia: A rare pseudo-tumor to know in immunocompromised patients]. / Malakoplakie cutanée : une pseudo-tumeur rare à ne pas méconnaître chez l'immunodéprimé.

Cutaneous malakoplakia is a rare pseudo-tumor that occurs in immunocompromised patients. It is a reaction to an infection caused by Gram negative bacteria. The clinical presentation is nonspecific and the diagnosis is histological. The evolution is recurrent and the combination of a surgical treatment, antibiotics and adaptation of immunosuppressive therapy is necessary to cure the disease. The emergence of antibiotic resistance in bacteria responsible for the pathology can complicate the treatment and require additional microbial sampling. We report a case that occurred in a renal transplant patient with a complex diagnostic and therapeutic management.

Structural Rearrangements of a Dodecameric Ketol-Acid Reductoisomerase Isolated from a Marine Thermophilic Methanogen.

Ketol-acid reductoisomerase (KARI) orchestrates the biosynthesis of branched-chain amino acids, an elementary reaction in prototrophic organisms as well as a valuable process in biotechnology. Bacterial KARIs belonging to class I organise as dimers or dodecamers and were intensively studied to understand their remarkable specificity towards NADH or NADPH, but also to develop antibiotics. Here, we present the first structural study on a KARI natively isolated from a methanogenic archaea. The dodecameric structure of 0.44-MDa was obtained in two different conformations, an open and close state refined to a resolution of 2.2-Å and 2.1-Å, respectively. These structures illustrate the conformational movement required for substrate and coenzyme binding. While the close state presents the complete NADP bound in front of a partially occupied Mg2+-site, the Mg2+-free open state contains a tartrate at the nicotinamide location and a bound NADP with the adenine-nicotinamide protruding out of the active site. Structural comparisons show a very high conservation of the active site environment and detailed analyses point towards few specific residues required for the dodecamerisation. These residues are not conserved in other dodecameric KARIs that stabilise their trimeric interface differently, suggesting that dodecamerisation, the cellular role of which is still unknown, might have occurred several times in the evolution of KARIs.

Enhanced light-extraction efficiency and emission directivity in compact photonic-crystal based AlGaInP thin-films for color conversion applications.

We investigated the use of photonic crystals with different opto-geometrical parameters for light extraction from AlGaInP/InGaP MQW color converters. Blue-to-red and green-to-red color conversions were demonstrated using room-temperature photoluminescence with excitation wavelengths at 405nm and 514nm. Complete, compact and highly directional light extraction was demonstrated. 3D-FDTD and a herein-developed phenomenological model derived from the standard coupled-mode theory were used to analyze the results. The highest light extraction gains were ∼8 times better than unpatterned reference structures, which were paired with short extraction lengths (between 2µm and 6µm depending on the acceptance angle) and directional light emission for square lattice of nanopillars with a lattice period of 400nm. The design guidelines set in this work could pave the way for the use of inorganic MQW epi-layer color converters to achieve full color microdisplays on a single wafer.

Exceptional fossil assemblages confirm the existence of complex Early Triassic ecosystems during the early Spathian.

The mass extinction characterizing the Permian/Triassic boundary (PTB; ~ 252 Ma) corresponds to a major faunal shift between the Palaeozoic and the Modern evolutionary fauna. The temporal, spatial, environmental, and ecological dynamics of the associated biotic recovery remain highly debated, partly due to the scarce, or poorly-known, Early Triassic fossil record. Recently, an exceptionally complex ecosystem dated from immediately after the Smithian/Spathian boundary (~ 3 myr after the PTB) was reported: the Paris Biota (Idaho, USA). However, the spatiotemporal representativeness of this unique assemblage remained questionable as it was hitherto only reported from a single site. Here we describe three new exceptionally diverse assemblages of the same age as the Paris Biota, and a fourth younger one. They are located in Idaho and Nevada, and are taxonomic subsets of the Paris Biota. We show that the latter covered a region-wide area and persisted at least partially throughout the Spathian. The presence of a well-established marine fauna such as the Paris Biota, as soon as the early Spathian, indicates that the post-PTB biotic recovery and the installation of complex ecosystems probably took place earlier than often assumed, at least at a regional scale.

Au(I)-Catalyzed Pictet-Spengler Reactions All around the Indole Ring.

Au(I) complexes catalyze iso-Pictet-Spengler reactions. Ethylamine or methylamine chains were introduced at C2, C4, or the nitrogen atom of the indole ring, and the corresponding substrates were reacted in the presence of aldehydes and catalytic amounts of Au(I) complexes, leading to a variety of polycyclic scaffolds. Selectivity could be achieved in the course of a double iso-Pictet-Spengler reaction involving two successive aldehydes, leading to highly complex molecules.

Benefits of a four-week functional restoration program in chronic low back pain patients and three-month follow-up: focus on paraspinal muscle aerobic metabolism responses to exercise.

BACKGROUND: Chronic low back pain (CLBP) is a major health concern characterized by paraspinal muscle fatigability. This can be improved following a functional restoration program. Muscle fatigability can be related to impairment in aerobic metabolism responses. In this study, we investigated paraspinal muscles aerobic metabolism in CLBP patients before and after a functional restoration program, in order to determine if the enhancement in patients' condition following the program is associated to changes in metabolism responses. METHODS: Twenty-two CLBP patients (11 women, 11 men; 41.6±1.8 years; 73.7±3.1 kg; 1.74±0.02 m) were evaluated before and after a 4-week functional restoration program, with exercise therapy as the main component. Three months later, 12 patients were seen for a follow-up visit. During each testing session, patients performed a five-minute isokinetic trunk extension exercise in measuring pulmonary gas exchanges and paraspinal muscle oxygenation. Mechanical efficiency and onset V̇O2 kinetics were also calculated, in addition to usual questionnaires and exercises designed to evaluate psychosocial and physical factors. RESULTS: At the end of the program, paraspinal muscle oxygenation, mechanical efficiency, and the V̇O2 onset kinetics were improved (P<0.05). All measures remained stable during the three-month follow-up except for paraspinal muscle oxygenation, which deteriorated (P<0.05). Return-to-work was associated with the level of workday physical activities and to a decrease in fear-avoidance beliefs. CONCLUSIONS: At the end of the program, aerobic metabolism responses were improved in paraspinal muscles in patients. These improvements were not associated with return-to-work, which was primarily influenced by socio-psychological factors.

Enantioselective Gold-Catalyzed Pictet-Spengler Reaction.

Cationic chiral Au(I) complexes catalyze asymmetric Pictet-Spengler reactions between tryptamines and arylaldehydes. The resulting tetrahydro-ß-carbolines are obtained with wide functional group tolerance in high yield and with high enantioselectivities (up to 95%). Aldehydes bearing polar or protic functions are well tolerated. The reaction features a hitherto unknown C2-auration of the indole as the key step, supported by density functional theory calculations.

Trunk Muscle Aerobic Metabolism Responses in Endurance Athletes, Combat Athletes and Untrained Men.

This study investigated aerobic metabolism responses in trunk muscles during a prolonged trunk extension exercise in athletes and untrained young men. The aim was to analyze the adaptations induced by 2 types of sports: one involving intensive use of trunk muscles (i. e., judo), and one known to induce high aerobic capacity in the whole body (i. e., cycling). Eleven judokas, 10 cyclists and 9 healthy untrained young men performed trunk extension exercises on an isokinetic dynamometer. During the first session, muscle strength was assessed during maximal trunk extension. During a second session, a 5-min exercise was performed to investigate aerobic responses with regard to trunk muscles. The near infrared spectroscopy technique and a gas exchange analyzer were used continuously to evaluate mechanical efficiency, V̇O2 on-set kinetics, trunk muscle deoxygenation and blood volume. Judokas showed greater trunk strength and mechanical efficiency (p<0.05). Cyclists presented faster V̇O2 on-set kinetics (p<0.05) and greater muscle deoxygenation and blood volume compared to untrained men (p<0.001). These results suggest that practicing judo improves trunk extension efficiency whereas cycling accelerates aerobic pathways and enhances microvascular responses to trunk extension exercise. Sport practice improves aerobic metabolism responses in trunk extensor muscles differently, according to the training specificities.

Relationships Between Isokinetic Shoulder Evaluation and Fitness Characteristics of Elite French Female Water-Polo Players.

Swimming and throwing are involved in water-polo player performance. These movements have a common biomechanical basis in the use of the internal shoulder rotation and adductor muscles. The aim of the study was to evaluate the relationship between shoulder isokinetic evaluation and throwing velocity as well as swimming performance in female water-polo players. Fifteen high level water-polo players completed two isokinetic shoulder evaluations to determine peak torque of shoulder rotators of the dominant shoulder (concentric and eccentric movements at an angular velocity of 60°·s-1 and concentric movements at an angular velocity of 240°·s-1) and shoulder extensors of both arms (concentric movements at an angular velocity of 60°·s-1 and 240°·s-1). Throwing velocity was measured using a radar gun placed 5 m behind the goal post. Front crawl swimming velocity was determined at 25 m, 100 m and 400 m distances. Concentric peak torque at 60°·s-1 and 240°·s-1 of internal rotators and eccentric peak torque at 60°·s-1 of external rotators were predictors of throwing velocity. The best model to explain the relationship between isokinetic evaluations and throwing velocity was obtained with concentric IR peak torque at 60°·s-1 and eccentric ER peak torque at 60°·s-1 (r2 = 0.52, p = 0.012). Relative total work done and peak torque of shoulder extensors were predictors of 25 m swimming velocity. Shoulder isokinetic evaluations correlate significantly with swimming performance and throwing velocity of female water-polo players. The results may help coaches to develop new strategies such as eccentric dry land training programs to increase both shoulder external rotators strength and throwing velocity.

Molecular coordination of Staphylococcus aureus cell division.

The bacterial cell wall is essential for viability, but despite its ability to withstand internal turgor must remain dynamic to permit growth and division. Peptidoglycan is the major cell wall structural polymer, whose synthesis requires multiple interacting components. The human pathogen Staphylococcus aureus is a prolate spheroid that divides in three orthogonal planes. Here, we have integrated cellular morphology during division with molecular level resolution imaging of peptidoglycan synthesis and the components responsible. Synthesis occurs across the developing septal surface in a diffuse pattern, a necessity of the observed septal geometry, that is matched by variegated division component distribution. Synthesis continues after septal annulus completion, where the core division component FtsZ remains. The novel molecular level information requires re-evaluation of the growth and division processes leading to a new conceptual model, whereby the cell cycle is expedited by a set of functionally connected but not regularly distributed components.

Generalization of the optical theorem: experimental proof for radially polarized beams.

The optical theorem, which is a consequence of the energy conservation in scattering processes, directly relates the forward scattering amplitude to the extinction cross-section of the object. Originally derived for planar scalar waves, it neglects the complex structure of the focused beams and the vectorial nature of the electromagnetic field. On the other hand, radially or azimuthally polarized fields and various vortex beams, essential in modern photonic technologies, possess a prominent vectorial field structure. Here, we experimentally demonstrate a complete violation of the commonly used form of the optical theorem for radially polarized beams at both visible and microwave frequencies. We show that a plasmonic particle illuminated by such a beam exhibits strong extinction, while the scattering in the forward direction is zero. The generalized formulation of the optical theorem provides agreement with the observed results. The reported effect is vital for the understanding and design of the interaction of complex vector beams carrying longitudinal field components with subwavelength objects important in imaging, communications, nanoparticle manipulation, and detection, as well as metrology.