Isl1Cre reveals a common Bmp pathway in heart and limb development.

A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo

Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling

Background/Aim: Reduction in serum placental growth factor (PLGF) frequently co-occurs with preeclampsia (PE) and gestational diabetes mellitus (GDM). Recently, we reported that impairment in gestational beta-cell mass growth may result from PE-associated reduction in PLGF and lead to development of GDM. Here, we studied the underlying mechanisms. Methods: We co-cultured primary mouse beta cells with mouse islet endothelial cells (MS1), with or without PLGF. We also cultured beta cells in conditioned media from PLGF-treated MS1. Specific signal-pathway inhibitors were applied to cultured beta cells in conditioned media from PLGF-treated MS1. We analysed beta-cell proliferation by BrdU incorporation. We analysed changes in cell number by a MTT assay. We analysed protein levels of cell-cycle regulators in beta cells by Western blot. Results: PLGF itself failed to induce beta-cell proliferation, but significantly augmented proliferation of beta cells co-cultured with MS1, which resulted in significant increases in cell number. Conditioned media from the PLGF-treated MS1 cells similarly induced beta-cell proliferation, which was abolished by inhibition of PI3k/Akt signalling, but not by inhibition of either ERK/MAPK or JNK signalling. The induction of beta-cell proliferation by PLGF-treated MS1 cells appeared to involve decreases in cell-cycle inhibitors p21 and p27, and increases in cell-cycle activators CDK4 and CyclinD1. Conclusion: Gestational PLGF may target islet endothelial cells to release growth factors that activate PI3k/Akt signalling in beta cells to increase their proliferation. PE-associated reduction in PLGF impairs these processes to result in GDM

Clinical characteristics and prognosis of cystic degeneration in retroperitoneal schwannoma: A retrospective study of 79 patients

Abstract Background and Purpose Diagnosis of retroperitoneal schwannoma (RS), especially cystic RS, is frequently missed or delayed owing to its rarity, location, nonspecific symptoms, and similarities with other tumors on various imaging modalities. This study aimed to determine associations between clinical, radiological, and histopathologic features and outcome. Materials and Methods Seventy‐nine patients with pathologically confirmed RS who underwent tumor resection between June 2010 and June 2020 were retrospectively reviewed and analyzed. Patients were stratified into three groups according to degree of tumoral cystic degeneration. Results Cystic degeneration was significantly associated with multiple foci (p = 0.025), calcification (p = 0.012), and hemorrhage (p = 0.000), but not size (p = 0.08), high Ki‐67 (p = 0.094), malignancy (p = 0.115; prevalence of cystic degeneration in the benign and malignant groups were 53.9% vs 100%), rough margin (p = 0.162), or irregular shape (p = 0.369). Malignant RS was significantly associated with multiple lymph nodes enlargement (p = 0.034). Tumor size, margins, shape, or/and multiplicity did not significantly differ between benign and malignant tumors. No recurrence occurred in patients with benign RS (mean follow‐up, 45 months). All malignant tumors recurred; mean time to recurrence was 11.4 months (mean follow‐up, 33 months). Conclusion Since RS is misdiagnosed mostly as malignancy and diagnosis is often delayed, a suspicion is necessary for diagnosis when atypical features are present. In RS, cystic degeneration was not associated with tumor size, Ki‐67, or malignancy; however, it was significantly associated with multiple foci, calcification, and hemorrhage. Cystic degeneration and related factors are useful for the diagnosis of RS. Malignant RS should be considered when a mass involves multiple lymph nodes. Margins, morphology, and size are not associated with malignancy. Pathological tumor type, tumor location, and adjacent anatomic structures are associated with outcome

Ultrafast and energy-efficient spin–orbit torque switching in compensated ferrimagnets

Spin–orbit torque can be used to manipulate magnetization in spintronic devices. However, conventional ferromagnetic spin–orbit torque systems have intrinsic limitations in terms of operation speed due to their inherent magnetization dynamics. Antiferromagnets and ferrimagnets with antiparallel exchange coupling exhibit faster spin dynamics and could potentially overcome these limitations. Here, we report ultrafast spin–orbit torque-induced magnetization switching in ferrimagnetic cobalt-gadolinium (CoGd) alloy devices. Using a stroboscopic pump–probe technique to perform time-resolved measurements, we show that the switching time in the ferrimagnets can be reduced to the subnanosecond regime and a domain wall velocity of 5.7 km s‒1 can be achieved, which is in agreement with analytical modelling and atomistic spin simulations. We also find that the switching energy efficiency in the ferrimagnets is one to two orders of magnitude higher than that of ferromagnets

Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells

AbstractIslet1 (Isl1) is a LIM homedomain protein that plays a pivotal role in cardiac progenitors of the second heart field. Here, lineage studies with an inducible isl1-cre demonstrated that most Isl1 progenitors have migrated into the heart by E9. Although Isl1 expression is downregulated in most cardiac progenitors as they differentiate, analysis of an isl1-nlacZ mouse and coimmunostaining for Isl1 and lineage markers demonstrated that Isl1 is expressed in distinct subdomains of the heart, and in diverse cardiovascular lineages. Isl1 expression was observed in myocardial lineages of the distal outflow tract, atrial septum, and in sinoatrial and atrioventricular node. The myocardialized septum of the outflow tract was found to derive from Isl1 expressing cells. Isl1 expressing cells also contribute to endothelial and vascular smooth muscle lineages including smooth muscle of the coronary vessels. Our data indicate that Isl1 is a specific marker for a subset of pacemaker cells at developmental stages examined, and suggest genetic heterogeneity within the central conduction system and coronary smooth muscle. Our studies suggest a role for Isl1 in these distinct domains of expression within the heart

Water Passivation of Perovskite Nanocrystals Enables Air-Stable Intrinsically Stretchable Color-Conversion Layers for Stretchable Displays

Conventional organic light-emitting devices without an encapsulation layer are susceptible to degradation when exposed to air, so realization of air-stable intrinsically-stretchable display is a great challenge because the protection of the devices against penetration of moisture and oxygen is even more difficult under stretching. An air-stable intrinsically-stretchable display that is composed of an intrinsically-stretchable electroluminescent device (SELD) integrated with a stretchable color-conversion layer (SCCL) that contains perovskite nanocrystals (PeNCs) is proposed. PeNCs normally decay when exposed to air, but they become resistant to this decay when dispersed in a stretchable elastomer matrix; this change is a result of a compatibility between capping ligands and the elastomer matrix. Counterintuitively, the moisture can efficiently passivate surface defects of PeNCs, to yield significant increases in both photoluminescence intensity and lifetime. A display that can be stretched up to 180% is demonstrated; it is composed of an air-stable SCCL that down-converts the SELD's blue emission and reemits it as green. The work elucidates the basis of moisture-assisted surface passivation of PeNCs and provides a promising strategy to improve the quantum efficiency of PeNCs with the aid of moisture, which allows PeNCs to be applied for air-stable stretchable displays.