Caspar specifies primordial germ cell count and identity in .

Repurposing of pleiotropic factors during execution of diverse cellular processes has emerged as a regulatory paradigm. Embryonic development in metazoans is controlled by maternal factors deposited in the egg during oogenesis. Here, we explore maternal role(s) of Caspar (Casp), the orthologue of human Fas-associated factor-1 (FAF1) originally implicated in host-defense as a negative regulator of NF-κB signaling.

Exploring the versatility of zygotic genome regulators: A comparative and functional analysis.

The activation of the zygotic genome constitutes an essential process during early embryogenesis that determines the overall progression of embryonic development. Zygotic genome activation (ZGA) is tightly regulated, involving a delicate interplay of activators and repressors, to precisely control the timing and spatial pattern of gene expression. While regulators of ZGA vary across species, they accomplish comparable outcomes.

High-affinity biomolecular interactions are modulated by low-affinity binders.

The strength of molecular interactions is characterized by their dissociation constants (K). Only high-affinity interactions (K ≤ 10 M) are extensively investigated and support binary on/off switches. However, such analyses have discounted the presence of low-affinity binders (K > 10 M) in the cellular environment.

Hedgehog signaling guides migration of primordial germ cells to the Drosophila somatic gonad.

In addition to inducing nonautonomous specification of cell fate in both Drosophila and vertebrates, the Hedgehog pathway guides cell migration in a variety of different tissues. Although its role in axon guidance in the vertebrate nervous system is widely recognized, its role in guiding the migratory path of primordial germ cells (PGCs) from the outside surface of the Drosophila embryo through the midgut and mesoderm to the SGPs (somatic gonadal precursors) has been controversial. Here we present new experiments demonstrating (1) that Hh produced by mesodermal cells guides PGC migration, (2) that HMG CoenzymeA reductase (Hmgcr) potentiates guidance signals emanating from the SGPs, functioning upstream of hh and of 2 Hh pathway genes important for Hh-containing cytonemes, and (3) that factors required in Hh receiving cells in other contexts function in PGCs to help direct migration toward the SGPs.

Valbenazine isomers and enantiomer determination by chiral normal phase liquid chromatography.

A novel, simple, specific, rapid, enantioselective normal phase chiral high-performance liquid chromatographic method with amylose-based Chiral Pak IG-3(250 × 4.6 mM) 3.0 μM column was developed and validated for separation and quantification of isomers and enantiomer of Valbenazine.

Estimation of purity of antimicrobial lead compound sulfonamide-anthranilate derivative methyl-ester-toluene-sulfonamide using LC to develop a new drug application.

The newly synthesized lead molecule methyl-ester-toluene-sulfonamide is the combined derivative of sulfonamide-anthranilate. It was estimated by gradient elution using 0.1% triethylamine in water with pH 2.

Germline/soma distinction in embryos requires regulators of zygotic genome activation.

In embryos, somatic versus germline identity is the first cell fate decision. Zygotic genome activation (ZGA) orchestrates regionalized gene expression, imparting specific identity on somatic cells. ZGA begins with a minor wave that commences at nuclear cycle (NC)8 under the guidance of chromatin accessibility factors (Zelda, CLAMP, GAF), followed by the major wave during NC14.

Extracranial-intracranial bypass in a neonate with multiple ruptured middle cerebral artery aneurysms: illustrative case.

Background: Reports of ruptured neonatal aneurysms are rare in neurosurgical literature. Pediatric aneurysms differ from adult aneurysms, notably in morphology, size, number, and risk of rerupture. Many authors report experience with clipping, citing durability and decreased use of radiation as benefits over endovascular intervention.

Response of focal refractory status epilepticus to lacosamide in an infant.

Status epilepticus (SE) is a life-threatening medical emergency which is frequently encountered in the critical care setting and can be refractory to treatment. Refractory status epilepticus (RSE) is defined as SE that has failed to respond to adequately used first-line and second-line antiepileptic medications. Super refractory status epilepticus is defined as SE that persists for 24 hours or more after the use of an anaesthetic agent or recurs after its withdrawal.

Basilar artery stroke in Crohn's disease treated with endovascular thromboembolectomy.

We describe a girl in middle childhood with newly diagnosed Crohn's disease, who presented with seizures and altered mental status. MRI showed an abnormal vascular signal at the basilar artery, but no evidence of acute ischaemia. Her weakness worsened over the next 8 hours to dense quadriplegia.

PASS-A course in Pediatric Acute Surgical Support to build pediatric surgical emergencies capacity in developing countries.

Objectives: The burden of pediatric trauma and emergency, including pediatric surgical emergencies in low middle income countries (LMIC) is high. The goal of Pediatric Acute Surgical Support (PASS) course is to prepare caregivers in LMIC for the acute management of life-threatening pediatric surgical emergencies. We aim to show the feasibility of its initial deployment.

Nucleoporin107 mediates female sexual differentiation via Dsx.

We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modeling of the human mutation in or specific knockdown of Nup107 in the gonadal soma resulted in ovarian-dysgenesis-like phenotypes. Transcriptomic analysis identified the somatic sex-determination gene ) as a target of Nup107.

Preformation and epigenesis converge to specify primordial germ cell fate in the early Drosophila embryo.

A critical step in animal development is the specification of primordial germ cells (PGCs), the precursors of the germline. Two seemingly mutually exclusive mechanisms are implemented across the animal kingdom: epigenesis and preformation. In epigenesis, PGC specification is non-autonomous and depends on extrinsic signaling pathways.

Calcium Responsive Pediatric Septic Shock Refractory to Isotonic Crystalloids and Inotropic Agents.

Pediatric septic shock is a life-threatening condition with significant rates of morbidity and mortality. Standard management includes fluid resuscitation, timely antimicrobial administration, and epinephrine or norepinephrine if unresolved with initial management. Additional therapies are not well defined and include vasopressin, hydrocortisone, phenylephrine, levosimendan, dopamine, and others.

CLAMP regulates zygotic genome activation in Drosophila embryos.

Embryonic patterning is critically dependent on zygotic genome activation (ZGA). In Drosophila melanogaster embryos, the pioneer factor Zelda directs ZGA, possibly in conjunction with other factors. Here, we have explored the novel involvement of Chromatin-Linked Adapter for MSL Proteins (CLAMP) during ZGA.

Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis.

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear.

Germline soma communication mediated by gap junction proteins regulates epithelial morphogenesis.

Gap junction (GJ) proteins, the primary constituents of GJ channels, are conserved determinants of patterning. Canonically, a GJ channel, made up of two hemi-channels contributed by the neighboring cells, facilitates transport of metabolites/ions. Here we demonstrate the involvement of GJ proteins during cuboidal to squamous epithelial transition displayed by the anterior follicle cells (AFCs) from Drosophila ovaries.

CLAMP and Zelda function together to promote zygotic genome activation.

During the essential and conserved process of zygotic genome activation (ZGA), chromatin accessibility must increase to promote transcription. is a well-established model for defining mechanisms that drive ZGA. Zelda (ZLD) is a key pioneer transcription factor (TF) that promotes ZGA in the embryo.

Association of transcutaneous CO with respiratory support: a prospective double blind observational study in children with bronchiolitis and reactive airway disease.

The use of clinical scoring to assess for severity of respiratory distress and respiratory failure is challenging due to subjectivity and interrater variability. Transcutaneous Capnography (TcpCO) can be used as an objective tool to assess a patient's ventilatory status. This study was designed to assess for any correlation of continuous monitoring of TcpCO with the respiratory clinical scores and deterioration in children admitted for acute respiratory distress.

Evaluation of the Development of Tolerance Following Frequent Administration of Propofol in Children Requiring Successive Sedation for Separate Procedures.

Objective: Propofol is frequently used for outpatient sedation for pediatric patients, some of whom require multiple rounds of sedation for separate procedures within a short period. Anecdotal experience suggests that frequent use of propofol results in escalating doses; however, clinical evidence is unconvincing. This study was designed to evaluate if tolerance develops with frequent administration of propofol for children requiring multiple successive sedations.

Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes.

Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive.

Antagonism between and Torso receptor regulates transcriptional quiescence underlying germline/soma distinction.

Transcriptional quiescence, an evolutionarily conserved trait, distinguishes the embryonic primordial germ cells (PGCs) from their somatic neighbors. In , PGCs from embryos maternally compromised for () misexpress somatic genes, possibly resulting in PGC loss. Recent studies documented a requirement for Gcl during proteolytic degradation of the terminal patterning determinant, Torso receptor.

The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial.

Background: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity.

Methods: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units.

Reactive oxygen species signaling in primordial germ cell development in Drosophila embryos.

REDOX mechanisms that induce biosynthesis of the reactive oxygen species (ROS) have attracted considerable attention due to both the deleterious and beneficial responses elicited by the reactive radical. In several organisms including Drosophila melanogaster, modulation of ROS activity is thought to be crucial for the maintenance of cell fates in developmental contexts. Interestingly, REDOX mechanisms have been shown to be involved in maintaining progenitor fate of stem cells as well as their proliferation and differentiation.

Illustration of the current practice and outcome comparison of early versus late tracheostomy after pediatric ECMO.

Objective: Pediatric extracorporeal membrane oxygenation typically necessitates protracted ventilator support, yet not much is known about the use of tracheostomy in the pediatric subpopulation. The study was designed with an objective to quantify the prevalence of tracheostomy in children with respiratory/cardiac failure requiring extracorporeal membrane oxygenation and to compare outcomes for patients undergoing early, late, and no tracheostomy.

Methods: Data of patients <18 years of age who underwent extracorporeal membrane oxygenation for respiratory/cardiac failure between 2009 and 2015 were obtained from the Virtual Pediatric Systems (VPS, LLC) Database.