Toll-like receptor-MyD88 and Fc receptor pathways of mast cells mediate the thyroid dysfunctions observed during nonthyroidal illness

Bacterial infections and other pathologic conditions induce complex dysfunctions of the hypothalamic–pituitary–thyroid axis, collectively known as nonthyroidal illness (NTI). To explore the pathogenesis of bacterial NTI, we injected Mycobacterium tuberculosis extracts or Escherichia coli LPS in mice lacking key components of the Toll-like receptor or crystallizable fragment (Fc) receptor pathways. In wild-type mice, the bacterial components induced a hypothyroidism characterized by elements of both hypothalamic and thyroidal dysfunction. This NTI hypothyroidism did not develop in mice lacking the MyD88 adaptor or in those with a reduced number of mast cells. The hypothyroid responsiveness to LPS, however, was restored upon reconstitution with mast cells derived from the bone marrow of wild-type donors. In addition to bacterial components, whole immunoglobulins induced NTI hypothyroidism in wild-type mice, but not in those lacking activating Fc receptors or mast cells. The study demonstrates a link between Toll-like and Fc receptor signaling and thyroid gland function, uncovering a role of mast cells in murine NTI

Mass spectrometry-driven discovery of neuropeptides mediating nictation behavior of nematodes

Neuropeptides regulate animal physiology and behavior, making them widely studied targets of functional genetics research. While the field often relies on differential -omics approaches to build hypotheses, no such method exists for neuropeptidomics. It would nonetheless be valuable for studying behaviors suspected to be regulated by neuropeptides, especially when little information is otherwise available. This includes nictation, a phoretic strategy of Caenorhabditis elegans dauers that parallels host-finding strategies of infective juveniles of many pathogenic nematodes. We here developed a targeted peptidomics method for the model organism C. elegans and show that 161 quantified neuropeptides are more abundant in its dauer stage compared with L3 juveniles. Many of these have orthologs in the commercially relevant pathogenic nematode Steinernema carpocapsae, in whose infective juveniles, we identified 126 neuropeptides in total. Through further behavioral genetics experiments, we identify flp-7 and flp-11 as novel regulators of nictation. Our work advances knowledge on the genetics of nictation behavior and adds comparative neuropeptidomics as a tool to functional genetics workflows

Evaluation of 11 years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature: Strategies for optimization.

Contains fulltext : 225118.pdf (publisher's version ) (Open Access)Maple syrup urine disease (MSUD) leads to severe neurological deterioration unless diagnosed early and treated immediately. We have evaluated the effectiveness of 11 years of MSUD newborn screening (NBS) in the Netherlands (screening >72 hours, referral if both total leucine (Xle) and valine ≥400 μmol/L blood) and have explored possibilities for improvement by combining our data with a systematic literature review and data from Collaborative Laboratory Integrated Reports (CLIR). Dutch MSUD NBS characteristics and accuracy were determined. The hypothetical referral numbers in the Dutch population of additional screening markers suggested by CLIR were calculated. In a systematic review, articles reporting NBS leucine concentrations of confirmed patients were included. Our data showed that NBS of 1 963 465 newborns identified 4 MSUD patients and led to 118 false-positive referrals (PPV 3.28%; incidence 1:491 000 newborns). In literature, leucine is the preferred NBS parameter. Total leucine (Xle) concentrations (mass-spectrometry) of 53 detected and 8 false-negative patients (sampling age within 25 hours in 3 patients) reported in literature ranged from 288 to 3376 (median 900) and 42 to 325 (median 209) μmol/L blood respectively. CLIR showed increasing Xle concentrations with sampling age and early NBS sampling and milder variant MSUD phenotypes with (nearly) normal biochemical profiles are causes of false-negative NBS results. We evaluated the effect of additional screening markers and established the Xle/phenylalanine ratio as a promising additional marker ratio for increasing the PPV, while maintaining high sensitivity in the Dutch MSUD NBS

The use of a neonatal mouse model to study respiratory syncytial virus infections

Respiratory syncytial virus (RSV) infection is the most significant cause of viral death in infants worldwide. The significant morbidity and mortality associated with this disease underscores the urgent need for the development of an RSV vaccine. The development of an RSV vaccine has been hampered by our limited understanding of the human host immune system, which plays a significant role in RSV pathogenesis, susceptibility and vaccine efficacy. As a result, animal models have been developed to better understand the mechanisms by which RSV causes disease. Within the past few years, a revolutionary variation on these animal models has emerged – age at time of initial infection – and early studies in neonatal mice (aged <7 days at time of initial infection) indicate the validity of this model to understand RSV infection in infants. This article reviews available information on current murine and emerging neonatal mouse RSV models

Peritraumatic distress: A review and synthesis of 15 years of research

ContextAlthough the subjective trauma exposure criterion was removed from the DSM‐5 criteria set for posttraumatic stress disorder (PTSD), emerging literature suggests that peritraumatic distress may be useful in predicting outcomes after exposure to a stressful event.MethodWe conducted a comprehensive review of the literature examining the association between peritraumatic distress and PTSD and other psychiatric outcomes. The 57 studies herein varied in both experimental design and target populations.ResultsForty‐eight studies found associations between peritraumatic distress and PTSD outcome measures, 23 found associations between peritraumatic distress and other psychiatric outcomes, and three found associations between peritraumatic distress and PTSD‐related symptoms or other psychiatric outcomes after non‐Criterion A stressful events by DSM‐5 criteria.ConclusionPeritraumatic distress is associated with PTSD symptom severity, other psychiatric symptoms, and severity of PTSD‐related symptoms after exposure to non‐Criterion A events, suggesting that peritraumatic distress is a risk factor for various psychiatric outcomes and furthering our understanding of the impact of subjective experience on trauma psychopathology.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146284/1/jclp22612.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146284/2/jclp22612_am.pd