Hematopoietic potential of neural stem cells

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Unsuspected role of the brain morphogenetic gene Otx1 in hematopoiesis

Otx1 belongs to the paired class of homeobox genes and plays a pivotal role in brain development. Here, we show that Otx1 is expressed in hematopoietic pluripotent and erythroid progenitor cells. Moreover, bone marrow cells from mice lacking Otx1 exhibit a cell-autonomous impairment of the erythroid compartment. In agreement with these results, molecular analysis revealed decreased levels of erythroid genes that include the SCL and GATA-1 transcription factors. Accordingly, a gain of function of SCL rescues the erythroid deficiency in Otx1-/- mice. Taken together, our findings indicate a function for Otx1 in the regulation of blood cell production. There is growing evidence suggesting that common cellular and molecular mechanisms orchestrate differentiation in various tissues. Homeobox-containing genes seem to be strong candidate genes to regulate a number of developmental processes, including neurogenesis and hematopoiesis. Members of the Otx family (Otx1, Otx2, Otx3, and Crx) are the vertebrate homologues of the Drosophila head gap gene orthodenticle and encode transcription factors containing a bicoid-like homeodomain. They are temporally and spatially regulated during development and seem to be required for proper head and sense organ patterning. Otx1, Otx2, and Otx3 show partially overlapping, but distinct expression patterns, and Otx2, the first to be activated during development, plays a major role in gastrulation and in the early specification of the anterior neural plate. In contrast, Otx1 shows a later onset and is involved in corticogenesis, sense organ development, and pituitary function. Mice bearing targeted deletion of Otx1 are affected by a permanent epileptic phenotype and show multiple brain abnormalities and morphological defects of the acoustic and visual sense organs. In addition, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism because of low levels of pituitary hormones. In the present study, we have investigated whether Otx1 also plays a role in blood cell production, as several homeobox genes of different families are involved in normal and/or malignant hematopoiesis

Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencingin aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas

ESHRE good practice recommendations for add- ons in reproductive medicine

The draft of the paper “ESHRE Good practice recommendations for add-ons in reproductive medicine” was published for public review for 4 weeks, between 1 November and 1 December 2022. This report summarizes all reviewers, their comments and the reply of the working group and is published on the ESHRE website as supporting documentation to the paper. During the stakeholder review, a total of 274 comments (including 24 duplicates) were received from 46 reviewers. Reviewers included professionals and representatives of donor-conceived offspring organisations. The comments were focussed on the content of the guideline (209 comments), language and style (31 comments), or were remarks that did not require a reply (10 comments). All comments to the language and format were checked and corrected where relevant. The comments to the content of the paper (n=209) were assessed by the working group and where relevant, adaptations were made in the paper (n=94; 45%). Adaptations included revisions and/or clarifications of the text, and amendments to the recommendations. For a number of comments, the working group considered them outside the scope of the paper or not appropriate/relevant (n=115; 55%).peer-reviewe

Chinese Cities as Sacred Landscapes: The Case of the Capitals of the Ming Dynasty

The advent of the Ming dynasty marks a break through in the history of Chinese architecture. The first Ming rulers Hongwu and Yongle were indeed engaged in a huge building effort, aimed at showing symbolically their divine rights to power—the “Mandate of Heaven”. This resulted in as much as three projected capitals in the course of a few decades: first, a re-planning of Nanjing; second, a completely new capital in Fengyang, which remained unfinished; and finally, of course, the planning and building of Ming Beijing. In the present paper, we explore and compare cognitive and symbolic aspects of these three “sacred landscapes of power” using the methods of modern Archaeoastronomy and Archaeotopography. In this way, we are able to highlight astronomical alignments but also topographical and magnetic orientations, which appear to be related to the feng shui tradition in both its “form” and “compass” schools. These results help in placing the architecture of the Ming capitals within the original perception of the landscape at the time of their planning, also with the aim of contributing to the preservation and fruition of this important Chinese cultural heritage

Case study: Lesions due to forced ritual scarification in Cameroon – A warning from cultural anthropology to forensic medicine

International audienceAsylum seekers and refugees are constantly increasing worldwide because of human rights' violations and political-related abuses. As a result, some of them show scars due to torture and other forms of maltreatments. In addition, they may also present scars due to ethnical practices, namely ritual scarifications. This case study presents a victim who did not give consent to perform such ethnical practices on her body. The authors aim to enlighten the difficulty to understand the origin and the purpose of these specific injuries and the importance to know how to distinguish them from other forms of abuse. Indeed, it appears that such lesions follow a cultural path, meaning that the lesions are performed methodically and may show macroscopic differences compared to others. The story narrated by the victim can be helpful for the experts' assessment, regardless, they may present memory-loss issues. This represents the value of a correct injuries' diagnosis and the importance of cultural anthropology-related analyses. The cultural and social background are relevant since the injuries have their own signification because of their symbolism. Therefore, a multidisciplinary approach with a cultural anthropologist may have the possibility to help the forensic experts in understanding and interpreting such stories fostering their ability to better assess asylum seekers stories and their reliability

LH Pretreatment as a Novel Strategy for Poor Responders

Introduction. Poor response to ovarian stimulation is still a major problem in IVF. The study presents a new stimulation protocol evaluated in a suppopulation of very difficult young poor ovarian responders. Material and Methods. The study consists in two sections. The first includes data from a randomized controlled study involving forty-three young patients with a poor ovarian response in at least two previous cycles (intended as cycle cancellation or with ≤3 collected oocytes). Patients were randomized in two groups: group A (control) received FSH (400 IU/day), while group B received the new stimulation protocol consisting in a sequential association of 150 IU r-LH for 4 days followed by 400 IU r-FSH/after downregulation with daily GnRh agonist. The second includes data from the overall results in 65 patients treated with the new protocol compared to their previous performance with conventional cycles (historical control). Results. Both in the RCT and in the historical control study, LH pretreatment was able to decrease the cancellation rate, to improve the in vitro performance, and to significantly increase the live birth rates. Conclusions. LH pretreatment improved oocyte quantity and quality in young repeated poor responders selected in accordance with the Bologna criteria