Escherichia coli phage-inducible chromosomal island aids helper phage replication and represses the LEE pathogenicity island.

In this study, we identify and characterize a novel phage-inducible chromosomal island found in commensal Escherichia coli MP1. This novel element, EcCIMP1, is induced and mobilized by the temperate helper phage vB_EcoP_Kapi1. EcCIMP1 contributes to superinfection immunity against its helper phage, impacting bacterial competition outcomes.

Perspectives of preimplantation genetic testing patients in Belgium on the ethics of polygenic embryo screening.

Research Question: What are the perspectives of preimplantation genetic testing (PGT) patients in Belgium on the ethics of PGT for polygenic risk scoring (PGT-P)?

Design: In-depth interviews (18 in total, 10 couples, 8 women, n = 28) were performed with patients who had undergone treatment with PGT for monogenic/single-gene defects (PGT-M) or chromosomal structural rearrangements (PGT-SR) between 2017 and 2019 in Belgium. Participants were asked about their own experiences with PGT-M/SR and about their viewpoints on PGT-P, including their own interest and their ideas on its desirability, scope and consequences. Inductive content analysis was used to analyse the interviews.

Polygenic embryo screening: quo vadis?

Recently, the use of polygenic risk scores in embryo screening (PGT-P) has been introduced on the premise of reducing polygenic disease risk through embryo selection. However, it has been met with extensive critique: considered "technology-driven" rather than "evidence-based", concerns exist about its validity, utility, ethics, and societal effects. Its scientific foundations and criticisms thus need to be carefully considered.

A splice site variant in MADD affects hormone expression in pancreatic β cells and pituitary gonadotropes.

MAPK activating death domain (MADD) is a multifunctional protein regulating small GTPases RAB3 and RAB27, MAPK signaling, and cell survival. Polymorphisms in the MADD locus are associated with glycemic traits, but patients with biallelic variants in MADD manifest a complex syndrome affecting nervous, endocrine, exocrine, and hematological systems. We identified a homozygous splice site variant in MADD in 2 siblings with developmental delay, diabetes, congenital hypogonadotropic hypogonadism, and growth hormone deficiency.

Prenatal, newborn and childhood factors and the timing of puberty in boys and girls.

Background: Our aim was to determine if prenatal factors, gestational age, birth weight and length, and childhood body mass index (BMI) are associated with the timing of puberty.

Methods: Our population-based study comprised 4826 girls and 5112 boys born between 1997 and 2002. Multiple linear regression modeled the relationships between the maternal and child predictors and the age at peak height velocity (PHV).

The sensor of the bacterial histidine kinase CpxA is a novel dimer of extracytoplasmic Per-ARNT-Sim domains.

Histidine kinases are key bacterial sensors that recognize diverse environmental stimuli. While mechanisms of phosphorylation and phosphotransfer by cytoplasmic kinase domains are relatively well-characterized, the ways in which extracytoplasmic sensor domains regulate activation remain mysterious. The Cpx envelope stress response is a conserved Gram-negative two-component system which is controlled by the sensor kinase CpxA.

Central precocious puberty in boys: secular trend and clinical features.

Objective: Recent studies suggest that boys enter puberty at a younger age, and the incidence of male central precocious puberty (CPP) is increasing. In this study, we explore the incidence of male CPP and identify key clinical and auxological indicators for organic CPP (OCPP).

Design: A retrospective registry-based study.

Complete genome sequence of MP1.

Here, we report the complete genome sequence of strain MP1, consisting of one circular chromosome and one circular plasmid. Long-read assembly was performed using a consensus approach, followed by long- and short-read polishing, and gene annotation.

HiHo-AID2: boosting homozygous knock-in efficiency enables robust generation of human auxin-inducible degron cells.

Recent developments in auxin-inducible degron (AID) technology have increased its popularity for chemogenetic control of proteolysis. However, generation of human AID cell lines is challenging, especially in human embryonic stem cells (hESCs). Here, we develop HiHo-AID2, a streamlined procedure for rapid, one-step generation of human cancer and hESC lines with high homozygous degron-tagging efficiency based on an optimized AID2 system and homology-directed repair enhancers.

"Are we not going too far?": Socio-ethical considerations of preimplantation genetic testing using polygenic risk scores according to healthcare professionals.

The recent introduction of polygenic risk scores within preimplantation genetic testing (PGT-P) has been met with many concerns. To get more insights into the perspectives of relevant stakeholders on the socio-ethical aspects of PGT-P, an interview study with 31 healthcare professionals involved in reproductive medicine and genetics in Europe and North-America was performed. Healthcare professionals in our study were concerned that PGT-P was going too far in terms of selection, with regards to both medical conditions and non-medical traits.

Congenital hypogonadotropic hypogonadism in a patient with a de novo POGZ mutation.

Objective: Congenital hypogonadotropic hypogonadism (CHH) is a rare, genetically heterogeneous reproductive disorder caused by gonadotropin-releasing hormone (GnRH) deficiency. Approximately half of CHH patients also have decreased or absent sense of smell, that is, Kallmann syndrome (KS). We describe a patient with White-Sutton syndrome (developmental delay and autism spectrum disorder) and KS due to a heterozygous de novo mutation in POGZ (c.

NlpE Is an OmpA-Associated Outer Membrane Sensor of the Cpx Envelope Stress Response.

Gram-negative bacteria utilize several envelope stress responses (ESRs) to sense and respond to diverse signals within a multilayered cell envelope. The CpxRA ESR responds to multiple stresses that perturb envelope protein homeostasis. Signaling in the Cpx response is regulated by auxiliary factors, such as the outer membrane (OM) lipoprotein NlpE, an activator of the response.

Limitations, concerns and potential: attitudes of healthcare professionals toward preimplantation genetic testing using polygenic risk scores.

Preimplantation genetic testing using polygenic risk scores (PGT-P) has recently been introduced. However, PGT-P has been met with many ethical concerns. It is therefore important to get insights into the perspectives of stakeholders regarding PGT-P.

Bacterial envelope stress responses: Essential adaptors and attractive targets.

Millions of deaths a year across the globe are linked to antimicrobial resistant infections. The need to develop new treatments and repurpose of existing antibiotics grows more pressing as the growing antimicrobial resistance pandemic advances. In this review article, we propose that envelope stress responses, the signaling pathways bacteria use to recognize and adapt to damage to the most vulnerable outer compartments of the microbial cell, are attractive targets.

Deciphering the Transcriptional Landscape of Human Pluripotent Stem Cell-Derived GnRH Neurons: The Role of Wnt Signaling in Patterning the Neural Fate.

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons lay the foundation for human development and reproduction; however, the critical cell populations and the entangled mechanisms underlying the development of human GnRH neurons remain poorly understood. Here, by using our established human pluripotent stem cell-derived GnRH neuron model, we decoded the cellular heterogeneity and differentiation trajectories at the single-cell level. We found that a glutamatergic neuron population, which generated together with GnRH neurons, showed similar transcriptomic properties with olfactory sensory neuron and provided the migratory path for GnRH neurons.

Timing of puberty and school performance: A population-based study.

Objective: To determine whether the timing of puberty associates with school performance.

Methods: Growth data on 13,183 children born between 1997 and 2002, were collected from child health clinics and school healthcare and school performance data from school records. Age at peak height velocity (PHV) marked pubertal timing.

Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency: A single center experience from over 30 years.

Background: Childhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease. We aimed to describe the clinical spectrum and genetic etiologies of CPHD in a single tertiary center and estimate the population-level incidence of congenital CPHD.

Methods: The retrospective clinical cohort comprised 124 CPHD patients (48 with congenital CPHD) treated at the Helsinki University Hospital (HUH) Children's Hospital between 1985 and 2018.

FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner.

Fibroblast growth factor 8 (FGF8), acting through the fibroblast growth factor receptor 1 (FGFR1), has an important role in the development of gonadotropin-releasing hormone-expressing neurons (GnRH neurons). We hypothesized that FGF8 regulates differentiation of human GnRH neurons in a time- and dose-dependent manner via FGFR1. To investigate this further, human pluripotent stem cells were differentiated during 10 days of dual-SMAD inhibition into neural progenitor cells, followed either by treatment with FGF8 at different concentrations (25 ng/ml, 50 ng/ml or 100 ng/ml) for 10 days or by treatment with 100 ng/ml FGF8 for different durations (2, 4, 6 or 10 days); cells were then matured through DAPT-induced inhibition of Notch signaling for 5 days into GnRH neurons.

The Wsp system of links surface sensing and cell envelope stress.

Surface sensing is a critical process that promotes the transition to a biofilm lifestyle. Several surface-sensing mechanisms have been described for a range of species, most involving surface appendages, such as flagella and pili. Pseudomonas aeruginosa uses the Wsp chemosensory-like signal transduction pathway to sense surfaces and promote biofilm formation.

Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors: modeling the function of an inactivating receptor mutation.

Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells.

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.

An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency.