A single-cell atlas of pig gastrulation as a resource for comparative embryology.

Cell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc of pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present a single-cell transcriptomic atlas of pig gastrulation, revealing cell-fate emergence dynamics, as well as conserved and divergent gene programs governing early porcine, primate, and murine development.

NANOG controls testicular germ cell tumour stemness through regulation of MIR9-2.

Background: Testicular germ cell tumours (TGCTs) represent a clinical challenge; they are most prevalent in young individuals and are triggered by molecular mechanisms that are not fully understood. The origin of TGCTs can be traced back to primordial germ cells that fail to mature during embryonic development. These cells express high levels of pluripotency factors, including the transcription factor NANOG which is highly expressed in TGCTs.

Review: A barnyard in the lab: prospect of generating animal germ cells for breeding and conservation.

In vitro gametogenesis (IVG) offers broad opportunities for gaining detailed new mechanistic knowledge of germ cell biology that will enable progress in the understanding of human infertility, as well as for applications in the conservation of endangered species and for accelerating genetic selection of livestock. The realisation of this potential depends on overcoming key technical challenges and of gaining more detailed knowledge of the ontogeny and developmental programme in different species. Important differences in the molecular mechanisms of germ cell determination and epigenetic reprogramming between mice and other animals have been elucidated in recent years.

NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl.

Pluripotency defines the unlimited potential of individual cells of vertebrate embryos, from which all adult somatic cells and germ cells are derived. Understanding how the programming of pluripotency evolved has been obscured in part by a lack of data from lower vertebrates; in model systems such as frogs and zebrafish, the function of the pluripotency genes NANOG and POU5F1 have diverged. Here, we investigated how the axolotl ortholog of NANOG programs pluripotency during development.

Efficacy and Safety of Paliperidone Palmitate 6-Month versus Paliperidone Palmitate 3-Month Long-Acting Injectable in European Patients with Schizophrenia: A Post Hoc Analysis of a Global Phase-3 Double-Blind Randomized Non-Inferiority Study.

Purpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M).

Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq.

The Reamer-Irrigator-Aspirator (RIA) System for the treatment of aseptic femoral nonunions: Report of two cases and literature review.

Femoral shaft nonunions are disabling complications of fractures, with relevant socioeconomic and psychological impact. The incidence of femoral shaft nonunions is not negligible, ranging between 1% and 10% after intramedullary nailing, but can exceed 20% in case of subtrochanteric fractures. Treatment options are influenced by pathomechanical, anatomical, and clinical factors.

In vitro culture of ovine embryos up to early gastrulating stages.

Developmental failures occurring shortly after blastocyst hatching from the zona pellucida constitute a major cause of pregnancy losses in both humans and farm ungulates. The developmental events occurring following hatching in ungulates include the proliferation and maturation of extra-embryonic membranes - trophoblast and hypoblast - and the formation of a flat embryonic disc, similar to that found in humans, which initiates gastrulation prior to implantation. Unfortunately, our understanding of these key processes for embryo survival is limited because current culture systems cannot sustain ungulate embryo development beyond hatching.

Pluripotent stem cells related to embryonic disc exhibit common self-renewal requirements in diverse livestock species.

Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment.

Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?

In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine.

Total Hip Arthroplasty (THA) for Femoral Neck Fractures: Comparison between Standard and Dual Mobility Implants.

The purpose of this retrospective study is to compare the short-term clinical and radiological results between standard and dual mobility THA for femoral neck fractures (FNF) in older patients. The hypothesis is that the dual mobility cup (DMC) has the same outcomes but a lower dislocation rate than the standard THA. The study population included 56 patients (mean age 77.

Short-Term Outcomes of the Grammont Reverse Shoulder Arthroplasty: Comparison between First and Second Generation Delta Prosthesis.

 This article compares short-term outcomes of two series of patients, who underwent reverse total shoulder arthroplasty (RTSA) with two different implants, both based on Grammont's principles: the Delta III (D-3) and the Delta Xtend (D-XT) prostheses.  The D-3 group included a consecutive series of 26 patients (mean age 75 years), that were treated between 2000 and 2006; the D-XT group included a consecutive series of 31 patients (mean age 72.5 years), for a total of 33 implants performed between 2011 and 2015.

25th ANNIVERSARY OF CLONING BY SOMATIC-CELL NUCLEAR TRANSFER: Nuclear transfer and the development of genetically modified/gene edited livestock.

The birth and adult development of 'Dolly' the sheep, the first mammal produced by the transfer of a terminally differentiated cell nucleus into an egg, provided unequivocal evidence of nuclear equivalence among somatic cells. This ground-breaking experiment challenged a long-standing dogma of irreversible cellular differentiation that prevailed for over a century and enabled the development of methodologies for reversal of differentiation of somatic cells, also known as nuclear reprogramming. Thanks to this new paradigm, novel alternatives for regenerative medicine in humans, improved animal breeding in domestic animals and approaches to species conservation through reproductive methodologies have emerged.

Conserved features of non-primate bilaminar disc embryos and the germline.

Post-implantation embryo development commences with a bilaminar disc in most mammals, including humans. Whereas access to early human embryos is limited and subject to greater ethical scrutiny, studies on non-primate embryos developing as bilaminar discs offer exceptional opportunities for advances in gastrulation, the germline, and the basis for evolutionary divergence applicable to human development. Here, we discuss the advantages of investigations in the pig embryo as an exemplar of development of a bilaminar disc embryo with relevance to early human development.

Specification and epigenomic resetting of the pig germline exhibit conservation with the human lineage.

Investigations of the human germline and programming are challenging because of limited access to embryonic material. However, the pig as a model may provide insights into transcriptional network and epigenetic reprogramming applicable to both species. Here we show that, during the pre- and early migratory stages, pig primordial germ cells (PGCs) initiate large-scale epigenomic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and, potentially, base excision repair (BER).

Shoulder arthroplasty for proximal humerus fractures in the elderly: The path from Neer to Grammont.

Shoulder replacement is indicated for the surgical treatment of proximal humeral fractures in elderly patients, when severe comminution and osteoporosis jeopardize the chances of success of any fixation technique. Two different implants are available for this purpose: anatomical hemiarthroplasty (HA) and reverse total shoulder arthroplasty (RTSA). HA for fractures was popularized by Charles Neer in the '50s and for several decades remained the only reliable implant for these injuries.

Untangling early embryo development using single cell genomics.

The zygote undergoes five cell divisions prior to the first signs of lineage segregation. Blastocyst formation requires segregation of the trophectoderm, needed for implantation, and the inner cell mass, which differentiate towards the major lineages of the fetus. This process is broadly conserved in mammals, however, in recent years investigations using high throughput single cell transcriptomics have provided new insights on the gene regulatory networks and epigenetic mechanisms controlling these processes in different species, highlighting novel unique evolutionary adaptations.

Regulation of Cell Fate Decisions in Early Mammalian Embryos.

Early embryogenesis is characterized by the segregation of cell lineages that fulfill critical roles in the establishment of pregnancy and development of the fetus. The formation of the blastocyst marks the emergence of extraembryonic precursors, needed for implantation, and of pluripotent cells, which differentiate toward the major lineages of the adult organism. The coordinated emergence of these cell types shows that these processes are broadly conserved in mammals.

Direct anterior versus posterolateral approach for bipolar hip hemiarthroplasty in femoral neck fractures: a prospective randomised study.

Introduction: Femoral neck fractures are a major problem in orthopaedic practice, having a huge impact on society, and involving a large number of elderly patients for whom early recovery is paramount. Thus, the aim of this study was to compare 2 surgical approaches, direct anterior (DA group) versus posterolateral (PL group), used for bipolar hip hemiarthroplasty (BHA) with femoral neck fractures in order to assess pain recovery after surgery. Our hypothesis was that early pain recovery would be faster in the DA group.

A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos.

Background: The segregation of the hypoblast and the emergence of the pluripotent epiblast mark the final stages of blastocyst formation in mammalian embryos. In bovine embryos the formation of the hypoblast has been partially studied, and evidence shows that MEK signalling plays a limited role in the segregation of this lineage. Here we explored the role of different signalling pathways during lineage segregation in the bovine embryo using immunofluorescence analysis of NANOG and SOX17 as readouts of epiblast and hypoblast, respectively.

Methods of collection, extender type, and freezability of semen collected from creole bulls raised in the tropical highlands of Ecuador.

This study was conducted to determine the best combination between two collection method and two extenders in the cryopreservation of semen from creole bulls adapted to highlands of the Ecuadorian Andes. Sixty ejaculates from three adult Creole bulls were evaluated after collection by artificial vagina (AV) and electroejaculation (EE). Semen samples were split into two aliquots and diluted with a soy lecithin extender (Andromed®; A) or an egg yolk-containing extender (Triladyl®; T) and packed in straws of 0.

Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis.

High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are largely inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development.

Exogenous human OKSM factors maintain pluripotency gene expression of bovine and porcine iPS-like cells obtained with STEMCCA delivery system.

Objectives: The use of induced pluripotent stem (iPS) cells as an alternative to embryonic stem cells to produce transgenic animals requires the development of a biotechnological platform for their generation. In this study, different strategies for the generation of bovine and porcine iPS cells were evaluated. Lentiviral vectors were used to deliver human factors OCT4, SOX2, KLF4 and c-MYC (OKSM) into bovine and porcine embryonic fibroblasts and different culture conditions were evaluated.