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The state-of-the-art ammonothermal method for the growth of nitrides is reviewed here, with an emphasis on binary and ternary nitrides beyond GaN. A wide range of relevant aspects are covered, from fundamental autoclave technology, to reactivity and solubility of elements, to synthesized crystalline nitride materials and their properties. Initially, the potential of emerging and novel nitrides is discussed, motivating their synthesis in single crystal form. This is followed by a summary of our current understanding of the reactivity/solubility of species and the state-of-the-art single crystal synthesis for GaN, AlN, AlGaN, BN, InN, and, more generally, ternary and higher order nitrides. Investigation of the synthesized materials is presented, with a focus on point defects (impurities, native defects including hydrogenated vacancies) based on GaN and potential pathways for their mitigation or circumvention for achieving a wide range of controllable functional and structural material properties. Lastly, recent developments in autoclave technology are reviewed, based on GaN, with a focus on advances in development of in situ technologies, including in situ temperature measurements, optical absorption via UV/Vis spectroscopy, imaging of the solution and crystals via optical (visible, X-ray), along with use of X-ray computed tomography and diffraction. While time intensive to develop, these technologies are now capable of offering unprecedented insight into the autoclave and, hence, facilitating the rapid exploration of novel nitride synthesis using the ammonothermal method.

Background: The members of the transforming growth factor-B superfamily, as the bone morphogenetic proteins (BMPs) subfamily and anti-Müllerian hormone (AMH), play a role during follicular development, and the bone morphogenetic protein-2 (BMP2), AMH, and THY1 are expressed in ovaries. Aim: This study was designed to define whether or not the expressions of these proteins in human cumulus cells (CCs) can be used as predictors of the oocyte and embryo competence. Settings and Design: The study included nine female patients who were diagnosed as idiopathic infertility, aged 25-33 years (median 30 years) and underwent Assisted Reproductive Technologies. Materials and Methods: The CCs from 60 oocyte-cumulus complexes obtained from the nine patients were evaluated with immunofluorescence staining in respect of BMPs, AMH and THY1 markers. The CCs surrounding the same oocytes were evaluated separately according to the oocyte and embryo quality. Statistical Analysis: Quantitative data were statistically analyzed for differences using the two-sided Mann-Whitney U test (P < 0.05). Results and Conclusions: Significant differences in immunofluorescence staining were observed in oocyte quality and embryo quality for the BMP2 only (P < 0.05). No significant differences were observed for AMH or CD90/THY1. Conclusion: These results demonstrated that there is a significant difference in the expression of BMP2 in the CCs of good quality oocytes and subsequently a good embryo. [ABSTRACT FROM AUTHOR]

Objective(s): To compare fertilization rates, quality of embryos, pregnancy rates (PRs) and outcome of pregnancies in intracytoplasmic sperm injection (ICSI) using sperm from ejaculates of normal and abnormal semen and testicular sperm of non-obstructive azoospermia. Study design: Four hundred fifty-four patients who underwent 454 ICSI cycles were evaluated retrospectively. Patients were divided into three groups according to the quality and source of sperm. Patients in group 1 underwent 133 cycles of ICSI using ejaculated normal semen, group 2 underwent 235 cycles using ejaculated abnormal semen, and group 3 underwent 86 cycles using testicular sperm. Results: The parameters were compared among the groups with respect to cycles induced by long (n=160) and short (n=294) protocol. In group 3, the fertilization and PRs were significantly lower than in all other groups (51.3 and 10.6% in the long protocol cycles, 53.3 and 5.1% in the short protocol cycles, respectively). There was no significant difference in the outcome of pregnancies in respect to abortion rates between different groups. Conclusion(s): The fertilizing ability of sperm in ICSI is highest with ejaculated sperm and lowest with sperm extracted by testicular biopsy. Also, the clinical PRs are significantly lower in ICSI with sperm from testicular biopsy. However, the outcomes of pregnancies are not affected by using surgically retrieved sperm from ejaculated semen. [Copyright &y& Elsevier]

A letter to the editor is presented which discusses ligneous inflammation diagnosis in a 27-year-old female patient suffering infertility, dysmenorrhea, and heavy vaginal discharge.

The state-of-the-art ammonothermal method for the growth of nitrides is reviewed here, with an emphasis on binary and ternary nitrides beyond GaN. A wide range of relevant aspects are covered, from fundamental autoclave technology, to reactivity and solubility of elements, to synthesized crystalline nitride materials and their properties. Initially, the potential of emerging and novel nitrides is discussed, motivating their synthesis in single crystal form. This is followed by a summary of our current understanding of the reactivity/solubility of species and the state-of-the-art single crystal synthesis for GaN, AlN, AlGaN, BN, InN, and, more generally, ternary and higher order nitrides. Investigation of the synthesized materials is presented, with a focus on point defects (impurities, native defects including hydrogenated vacancies) based on GaN and potential pathways for their mitigation or circumvention for achieving a wide range of controllable functional and structural material properties. Lastly, recent developments in autoclave technology are reviewed, based on GaN, with a focus on advances in development of in situ technologies, including in situ temperature measurements, optical absorption via UV/Vis spectroscopy, imaging of the solution and crystals via optical (visible, X-ray), along with use of X-ray computed tomography and diffraction. While time intensive to develop, these technologies are now capable of offering unprecedented insight into the autoclave and, hence, facilitating the rapid exploration of novel nitride synthesis using the ammonothermal method.

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization. Tissue stiffness increases during vascular morphogenesis resulting from emergent interactions between endothelial cells, fibroblasts, and ECM and correlates with enhanced vascular function. Contractile cellular forces are key to emergent tissue stiffening and synergize with ECM mechanical properties to modulate the mechanics of vascularization. Emergent tissue stiffening and vascular function rely on mechanotransduction signaling within fibroblasts, mediated by YAP1. Mouse embryos lacking YAP1 in fibroblasts exhibit both reduced tissue stiffness and develop lethal vascular defects. Translating our findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine.

High-content image-based cell phenotyping provides fundamental insights into a broad variety of life science disciplines. Striving for accurate conclusions and meaningful impact demands high reproducibility standards, with particular relevance for high-quality open-access data sharing and meta-analysis. However, the sources and degree of biological and technical variability, and thus the reproducibility and usefulness of meta-analysis of results from live-cell microscopy, have not been systematically investigated. Here, using high-content data describing features of cell migration and morphology, we determine the sources of variability across different scales, including between laboratories, persons, experiments, technical repeats, cells, and time points. Significant technical variability occurred between laboratories and, to lesser extent, between persons, providing low value to direct meta-analysis on the data from different laboratories. However, batch effect removal markedly improved the possibility to combine image-based datasets of perturbation experiments. Thus, reproducible quantitative high-content cell image analysis of perturbation effects and meta-analysis depend on standardized procedures combined with batch correction., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

A parametric approach based on parametric analysis of the acoustical properties of a layered media is proposed to derive a reduced layered Green's function. The approach relies on the smallness of one of the problem parameters and allows a simpler form of Green's function by disregarding the smaller parametric terms. Several illustrative examples comparing the amplitudes of exact and reduced Green's function for small parameter of density ratio in various source and observation location setups are presented. It is demonstrated that the CPU times calculated at different points decrease considerably for the reduced Green's function, further justifying the presented method.

The use of phenotypic screening was central to the discovery and development of novel thalidomide analogs, the IMiDs (immunomodulatory drugs) agents. With the discovery that these agents bind the E3 ligase, CRL4 CRBN , and alter its substrate specificity, there has been a great deal of endeavor to discover other small molecules that can modulate alternative E3 ligases. Furthermore, the chemical properties necessary for drug discovery and the rules by which neo-substrates are selected for degradation are being defined in the context of phenotypic alterations in specific cellular systems. This review gives a detailed summary of these recent advances and the methodologies being exploited to understand the mechanism of action of emerging protein degradation therapies., Competing Interests: Declaration of interests The authors declare no competing interests. R.C. is a former employee of Celgene Corporation and previously had commercial interest in IMiDs, and is also a founder of Monte Rosa Therapeutics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The transcriptional regulator YAP1 is critical for the pathological activation of fibroblasts. In normal fibroblasts, YAP1 is located in the cytoplasm, while in activated cancer-associated fibroblasts, it is nuclear and promotes the expression of genes required for pro-tumorigenic functions. Here, we investigate the dynamics of YAP1 shuttling in normal and activated fibroblasts, using EYFP-YAP1, quantitative photobleaching methods, and mathematical modeling. Imaging of migrating fibroblasts reveals the tight temporal coupling of cell shape change and altered YAP1 localization. Both 14-3-3 and TEAD binding modulate YAP1 shuttling, but neither affects nuclear import. Instead, we find that YAP1 nuclear accumulation in activated fibroblasts results from Src and actomyosin-dependent suppression of phosphorylated YAP1 export. Finally, we show that nuclear-constrained YAP1, upon XPO1 depletion, remains sensitive to blockade of actomyosin function. Together, these data place nuclear export at the center of YAP1 regulation and indicate that the cytoskeleton can regulate YAP1 within the nucleus., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed their function and gene expression. These analyses reveal that activation of the YAP transcription factor is a signature feature of CAFs. YAP function is required for CAFs to promote matrix stiffening, cancer cell invasion and angiogenesis. Remodelling of the ECM and promotion of cancer cell invasion requires the actomyosin cytoskeleton. YAP regulates the expression of several cytoskeletal regulators, including ANLN and DIAPH3, and controls the protein levels of MYL9 (also known as MLC2). Matrix stiffening further enhances YAP activation, thus establishing a feed-forward self-reinforcing loop that helps to maintain the CAF phenotype. Actomyosin contractility and Src function are required for YAP activation by stiff matrices. Further, transient ROCK inhibition is able to disrupt the feed-forward loop, leading to a long-lasting reversion of the CAF phenotype.

CD98 H chain (4F2 Ag, Slc3a2) was discovered as a lymphocyte-activation Ag. Deletion of CD98 H chain in B cells leads to complete failure of B cell proliferation, plasma cell formation, and Ab secretion. In this study, we examined the role of T cell CD98 in cell-mediated immunity and autoimmune disease pathogenesis by specifically deleting it in murine T cells. Deletion of T cell CD98 prevented experimental autoimmune diabetes associated with dramatically reduced T cell clonal expansion. Nevertheless, initial T cell homing to pancreatic islets was unimpaired. In sharp contrast to B cells, CD98-null T cells showed only modestly impaired Ag-driven proliferation and nearly normal homeostatic proliferation. Furthermore, these cells were activated by Ag, leading to cytokine production (CD4) and efficient cytolytic killing of targets (CD8). The integrin-binding domain of CD98 was necessary and sufficient for full clonal expansion, pointing to a role for adhesive signaling in T cell proliferation and autoimmune disease. When we expanded CD98-null T cells in vitro, they adoptively transferred diabetes, establishing that impaired clonal expansion was responsible for protection from disease. Thus, the integrin-binding domain of CD98 is required for Ag-driven T cell clonal expansion in the pathogenesis of an autoimmune disease and may represent a useful therapeutic target.

Objective: To examine whether blood estradiol level tendencies during the late follicular and early luteal phases and the 11 days after embryo transfer have any association with the outcome of intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles., Study Design: This prospective study involved 38 assisted reproductive technology cycles in 35 infertile patients treated with assisted reproductive technologies in which blood samples taken on the 4th, 7th, 9th and 11th days following ET were tested for progesterone, estradiol and hCG levels using an enzyme-linked immunoassay. The estradiol blood levels were compared with the maximal follicular phase blood estradiol. The data were analyzed using Microsoft Excel (Redmond, Washington) and SPSS 10.0 (Chicago, Illinois). The chi2, Mann-Whitney U, Wilcoxon and Pearson tests were usedfor statistical analysis., Results: Average maximum estradiol blood level, number of oocytes produced,fertilization rates and cleavage rates did not show any significant difference between pregnant and nonpregnant cycles. The lower the ratios of estradiol levels measured on posttransfer days 4, 7 and 9 to the maximumfollicular phase level, the lower the probability of pregnancy (P < .01, P < .01 and P < .01, respectively)., Conclusion: The steeper the decline in blood estradiol levels (affecting the periimplantation period) following ovum pickup relative to the maximum follicular phase estradiol levels, the lower the chance of pregnancy in ICSI-ET cycles.