Rearrangement of Mouse Immunoglobulin Kappa Deleting Element Recombining Sequence Promotes Immune Tolerance and Lambda B Cell Production

SummaryThe recombining sequence (RS) of mouse and its human equivalent, the immunoglobulin (Ig) kappa deleting element (IGKDE), are sequences found at the 3′ end of the Ig kappa locus (Igk) that rearrange to inactivate Igk in developing B cells. RS recombination correlates with Ig lambda (Igλ) light (L) chain expression and likely plays a role in receptor editing by eliminating Igk genes encoding autoantibodies. A mouse strain was generated in which the recombination signal of RS was removed, blocking RS-mediated Igk inactivation. In RS mutant mice, receptor editing and self-tolerance were impaired, in some cases leading to autoantibody formation. Surprisingly, mutant mice also made fewer B cells expressing lambda chain, whereas λ versus κ isotype exclusion was only modestly affected. These results provide insight into the mechanism of L chain isotype exclusion and indicate that RS has a physiological role in promoting the formation of λ L chain-expressing B cells

Electromechanical characterization of a tissue-engineered myocardial patch derived from extracellular matrix

ObjectiveExtracellular matrix scaffolds have been successfully used for myocardial wall repair. However, regional functional evaluation (ie, contractility, electrical conductivity) of the extracellular matrix scaffold during the course of remodeling has been limited. In the present study, we evaluated the remodeled scaffold for evidence of electrical activation.MethodsThe extracellular matrix patch was implanted into the porcine right ventricular wall (n = 5) to repair an experimentally produced defect. Electromechanical mapping was performed with the NOGA system (Biosense Webster Inc, Diamond Bar, Calif) 60 days after implantation. Linear local shortening was recorded to assess regional contractility. After sacrifice, detailed histologic examinations were performed.ResultsHistologic examinations showed repopulation of the scaffold with cells, including a monolayer of factor VIII–positive cells in the endocardial surface and multilayered α-smooth muscle actin–positive cells beneath the monolayer cells. The α-smooth muscle actin–positive cells tended to be present at the endocardial aspect of the remodeled scaffold and at the border between the remodeled scaffold and the normal myocardium. Electromechanical mapping demonstrated that the patch had low-level electrical activity (0.56 ± 0.37 mV; P < .0001) in most areas and moderate activity (2.20 ± 0.70 mV; P < .0001) in the margin between the patch and the normal myocardium (7.58 ± 2.23 mV).ConclusionsThe extracellular matrix scaffolds were repopulated by α-smooth muscle actin–positive cells 60 days after implantation into the porcine heart. The presence of the cells corresponded to areas of the remodeling scaffold that showed early signs of electrical conductivity

Style-transfer based Speech and Audio-visual Scene Understanding for Robot Action Sequence Acquisition from Videos

To realize human-robot collaboration, robots need to execute actions for new tasks according to human instructions given finite prior knowledge. Human experts can share their knowledge of how to perform a task with a robot through multi-modal instructions in their demonstrations, showing a sequence of short-horizon steps to achieve a long-horizon goal. This paper introduces a method for robot action sequence generation from instruction videos using (1) an audio-visual Transformer that converts audio-visual features and instruction speech to a sequence of robot actions called dynamic movement primitives (DMPs) and (2) style-transfer-based training that employs multi-task learning with video captioning and weakly-supervised learning with a semantic classifier to exploit unpaired video-action data. We built a system that accomplishes various cooking actions, where an arm robot executes a DMP sequence acquired from a cooking video using the audio-visual Transformer. Experiments with Epic-Kitchen-100, YouCookII, QuerYD, and in-house instruction video datasets show that the proposed method improves the quality of DMP sequences by 2.3 times the METEOR score obtained with a baseline video-to-action Transformer. The model achieved 32% of the task success rate with the task knowledge of the object.Comment: Accepted to Interspeech202

Translocation t(11;18)(q21;q21) in gastric B‐cell lymphomas

Translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration reported in gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Intriguingly, this translocation has been reported only rarely in diffuse large B-cell lymphomas; it has been proposed that t(11;18)-positive tumors rarely progress to diffuse large B-cell lymphomas. We examined the frequency of chromosomal translocation t(11;18)(q21;q21) in mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma of the stomach. Paraffin-embedded tissues from patients with gastric B-cell lymphomas were selected retrospectively. The presence of the t(11;18)(q21;q21) was determined using reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. beta-Actin transcript was also determined to evaluate the integrity and efficiency of RNA (cDNA) recovery from paraffin-embedded tissues. We analyzed 53 gastric B-cell lymphomas (33 diffuse large B-cell and 20 mucosa-associated lymphoid tissue) obtained from Italy, the USA, or Japan. Beta-actin transcript was amplified in 50 cases (94%), including 19 mucosa-associated lymphoid tissue and 31 diffuse large B-cell lymphomas (five with mucosa-associated lymphoid tissue components). The t(11;18) translocation was detected in 19% (6 of 31) cases with diffuse large B-cell lymphoma versus 26% (five of 19) with mucosa-associated lymphoid tissue lymphoma (P = 0.72). One of five diffuse large B-cell lymphomas with a mucosa-associated lymphoid tissue component showed the t(11;18)(q21;q21). In conclusion, translocation t(11;18)(q21;q21) was found in both mucosa-associated lymphoid tissue lymphomas and diffuse large B-cell lymphomas of the stomach at approximately equivalent frequencies; its presence does not exclude progression to diffuse large B-cell lymphoma

FAK nuclear export signal sequences

AbstractUbiquitously expressed focal adhesion kinase (FAK), a critical component in transducing signals from sites of cell contacts with extracellular matrix, was named after its typical localization in focal adhesions. A nuclear localization of FAK has been also reported and its scaffolding role in nucleus and requirement for p53 ubiquitination were only recently described. Whereas FAK nuclear localization signal (NLS) was found in F2 lobe of FERM domain, nuclear export signal (NES) sequences have not been yet determined. Here we demonstrate that FAK has two NES sequences, NES1 in F1 lobe of FERM domain and NES2 in kinase domain. Although, both NES1 and NES2 are evolutionary conserved, and present as well in FAK-related protein kinase Pyk2, only NES2 demonstrates full biological nuclear export activity

The Bullet cluster at its best: weighing stars, gas and dark matter

We present a new strong lensing mass reconstruction of the Bullet cluster (1E 0657-56) at z=0.296, based on WFC3 and ACS HST imaging and VLT/FORS2 spectroscopy. The strong lensing constraints underwent substantial revision compared to previously published analysis, there are now 14 (six new and eight previously known) multiply-imaged systems, of which three have spectroscopically confirmed redshifts (including one newly measured from this work). The reconstructed mass distribution explicitly included the combination of three mass components: i) the intra-cluster gas mass derived from X-ray observation, ii) the cluster galaxies modeled by their fundamental plane scaling relations and iii) dark matter. The model that includes the intra-cluster gas is the one with the best Bayesian evidence. This model has a total RMS value of 0.158" between the predicted and measured image positions for the 14 multiple images considered. The proximity of the total RMS to resolution of HST/WFC3 and ACS (0.07-0.15" FWHM) demonstrates the excellent precision of our mass model. The derived mass model confirms the spatial offset between the X-ray gas and dark matter peaks. The fraction of the galaxy halos mass to total mass is found to be f_s=11+/-5% for a total mass of 2.5+/-0.1 x 10^14 solar mass within a 250 kpc radial aperture.Comment: Accepted by A&A 15 pages, 12 figure