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Background In recent years, researchers have made significant strides in understanding the heterogeneity of breast cancer and its various subtypes. However, the wealth of genomic and proteomic data available today necessitates efficient frameworks, instruments, and computational tools for meaningful analysis. Despite its success as a prognostic tool, the PAM50 gene signature’s reliance on many genes presents challenges in terms of cost and complexity. Consequently, there is a need for more efficient methods to classify breast cancer subtypes using a reduced gene set accurately. Results This study explores the potential of achieving precise breast cancer subtype categorization using a reduced gene set derived from the PAM50 gene signature. By employing a “Few-Shot Genes Selection” method, we randomly select smaller subsets from PAM50 and evaluate their performance using metrics and a linear model, specifically the Support Vector Machine (SVM) classifier. In addition, we aim to assess whether a more compact gene set can maintain performance while simplifying the classification process. Our findings demonstrate that certain reduced gene subsets can perform comparable or superior to the full PAM50 gene signature. Conclusions The identified gene subsets, with 36 genes, have the potential to contribute to the development of more cost-effective and streamlined diagnostic tools in breast cancer research and clinical settings.

Mechanosensing by the actin cytoskeleton Living cells need to respond to mechanical forces for many essential biological functions. This mechanosensing activity is thought to be a property of the actin cytoskeleton, but no specific mechanisms have yet been identified. In this study, Ehrlicher et al . identify the actin-binding protein filamin A (FLNa) as a central mechanotransduction element. In a minimal reconstituted system, ligand binding to filamin is affected by mechanical forces, causing certain binding partners to dissociate and others to adhere more strongly. This selectivity may provide a direct molecular link between physical forces and biological activity. Mechanical stresses elicit cellular reactions mediated by chemical signals. Defective responses to forces underlie human medical disorders 1 , 2 , 3 , 4 such as cardiac failure 5 and pulmonary injury 6 . The actin cytoskeleton’s connectivity enables it to transmit forces rapidly over large distances 7 , implicating it in these physiological and pathological responses. Despite detailed knowledge of the cytoskeletal structure, the specific molecular switches that convert mechanical stimuli into chemical signals have remained elusive. Here we identify the actin-binding protein filamin A (FLNA) 8 , 9 as a central mechanotransduction element of the cytoskeleton. We reconstituted a minimal system consisting of actin filaments, FLNA and two FLNA-binding partners: the cytoplasmic tail of β-integrin, and FilGAP. Integrins form an essential mechanical linkage between extracellular and intracellular environments, with β-integrin tails connecting to the actin cytoskeleton by binding directly to filamin 4 . FilGAP is an FLNA-binding GTPase-activating protein specific for RAC, which in vivo regulates cell spreading and bleb formation 10 . Using fluorescence loss after photoconversion, a novel, high-speed alternative to fluorescence recovery after photobleaching 11 , we demonstrate that both externally imposed bulk shear and myosin-II-driven forces differentially regulate the binding of these partners to FLNA. Consistent with structural predictions, strain increases β-integrin binding to FLNA, whereas it causes FilGAP to dissociate from FLNA, providing a direct and specific molecular basis for cellular mechanotransduction. These results identify a molecular mechanotransduction element within the actin cytoskeleton, revealing that mechanical strain of key proteins regulates the binding of signalling molecules.

We show that actin filaments, shortened to physiological lengths by gelsolin and cross-linked with recombinant human filamins (FLNs), exhibit dynamic elastic properties similar to those reported for live cells. To achieve elasticity values of comparable magnitude to those of cells, the in vitro network must be subjected to external prestress, which directly controls network elasticity. A molecular requirement for the strain-related behavior at physiological conditions is a flexible hinge found in FLNa and some FLNb molecules. Basic physical properties of the in vitro filamin-F-actin network replicate the essential mechanical properties of living cells. This physical behavior could accommodate passive deformation and internal organelle trafficking at low strains yet resist externally or internally generated high shear forces.

Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases, however, little information is available on their clinical effect on allergy in humans. Thus, we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 (L-92) on perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled clinical trial, 49 patients with perennial allergic rhinitis were randomized to receive either 100mL of heat-treated fermented milk containing L-92 (n=25) or acidified milk without lactic acid bacteria (placebo; n=24) for 8 wk. The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms. Oral administration of milk fermented with L-92 resulted in a statistically significant improvement of nasal symptom-medication scores. Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group. In addition, clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk. There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1/T helper type 2 ratio between the 2 groups. These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis, however, statistically significant changes were not shown in blood parameters.

The aim was to investigate the effects of far infrared (FIR) ray emitting clothes on indirect markers of exercise-induced muscle damage and physical performance recovery after a plyometric bout applied to soccer players. Twenty-one male players (18.9±0.6 years; 70.8±5.01 kg; 178.3±0.06 cm) performed 100 drop-jumps. Six hours after the bout, athletes put on FIR clothes (FIR) (density of 225 g·m(-2), 88% far infrared rays emitting polyamide 66 Emana yarn (PA66) fibre, 12% Spandex, emissivity of 0.88 and power emitted of 341 W/m2µm at 37°C in the 5-20 µm wavelength range, patent WO 2009/077834 A2) (N = 10) or placebo clothes (PLA) (N = 11). Mid-thigh circumferences, creatine kinase (CK), and delayed-onset muscle soreness (DOMS) were assessed before, immediately after and 24, 48, and 72 h after the bout. Squat (SJ) and countermovement jump (CMJ) heights were measured before and at 24, 48, and 72 h after, while 1RM leg press (maximum strength) was measured before and at 72 h after the plyometrics. No differences between groups were found in mid-thigh circumferences, SJ, CMJ or 1RM. CK increased significantly 24 h after the plyometrics in comparison to before (p < 0.05) in both groups. PLA showed significant DOMS increases at 24, 48, and 72 h, while FIR showed significant increases at 24 and 48 h (p < 0.05). DOMS effect sizes were greater in FIR (moderate at 48 h, ES = 0.737 and large at 72 h, ES = 0.844), suggesting that FIR clothes may reduce perceived DOMS after an intense plyometric session performed by soccer players.

A collective order of spin and charge degrees of freedom into stripes has been predicted to be a possible ground state of hole-doped CuO 2 planes, which are the building blocks of high-temperature superconductors. In fact, stripe-like spin and charge order has been observed in various layered cuprate systems. For the prototypical high-temperature superconductor La 2− x Sr x CuO 4 , no charge-stripe signal has been found so far, but several indications for a proximity to their formation. Here we report the observation of a pronounced charge-stripe signal in the near surface region of 12-percent doped La 2− x Sr x CuO 4 . We conclude that this compound is sufficiently close to charge stripe formation that small perturbations or reduced dimensionality near the surface can stabilize this order. Our finding of different phases in the bulk and near the surface of La 2− x Sr x CuO 4 should be relevant for the interpretation of data from surface-sensitive probes, which are widely used for La 2− x Sr x CuO 4 and similar systems. Charge stripe order has been predicted to be the ground state for the parent compounds of copper oxide superconductors. Using resonant X-ray diffraction, Schüßler-Lagenheine et al . probe the surface region of 12 percent doped La 2− x Sr x CuO 4 , and observe charge-stripe order.

Math1 , a basic helix-loop-helix transcription factor homolog of the Drosophila atonal gene, is considered to be a key factor for induction of sensory hair cells (HCs) during development of the organ of Corti or cochlea. Although embryonic stem (ES) cells are able to produce HC-like cells, the role of Math1 in induction of those cells has not been thoroughly elucidated. In the present study, we introduced Math1 into ES cells in order to achieve efficient generation of HC-like cells. ES cells carrying Tet-inducible Math1 , Math1-ES cells, were generated using a Tet-On gene expression system. Embryoid bodies (EBs) formed in the absence of doxycycline (Dox) for 4 days were allowed to grow for an additional 14 days in the dishes in the presence of 400  μ g/ml of Dox. At the end of those 14-day cultures, approximately 10% of the cells in EB outgrowths expressed the HC-related markers myosin6 , myosin7a , calretinin , α9AchR , and Brn3c (also known as Pou4f3 ) and showed formation of stereocilia-like structures, whereas few cells in EB outgrowths grown without Dox showed those markers. Reporter assays of Math1-ES cells using a Brn3c-promoter plasmid demonstrated positive regulation of Brn3c by Math1 . Furthermore, such HC-related marker-positive cells derived from Math1-ES cells were found to be incorporated in the developing inner ear after transplantation into chick embryos. Math1-ES cells are considered to be an efficient source of ES-derived HC-like cells, and Math1 may be an important factor for induction of HC-like cells from differentiating ES cells.

We have developed downsizing a piston-cylinder clamp-cell to measure a specific heat under pressure using a commercial Differential Scanning Calorimeter (Shimadzu DSC-60 plus). The downsized cell with a diameter of 6.0 mm and a height of 5.0 mm has been achieved by a simplification of the cell design and using a high-yield-strength alloy of β-titanium (KOBELCO, KS15-5-3). The cell allows us to achieve pressures of 0.7 GPa at room temperature as our designed value. As a demonstration of the cell, we have measured the specific heat anomaly due to the first-order transition at around 357 K in Ca2RuO4. The pressure variation of the transition temperature indicates that our cell allows us to achieve pressure of ~0.3 GPa. Moreover, we have estimated that a heat capacity of ∼0.6 mJ/K is fully possible to measure within β-Titanium cell as absolute accuracy.