Serum concentrations of legacy, alternative, and precursor per- and polyfluoroalkyl substances: a descriptive analysis of adult female participants in the MIREC-ENDO study.

BACKGROUND: Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk. METHODS: We collected serum samples from 289 adult female participants in a 2018-2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography-tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics. RESULTS: 17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among "White" participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than "White". Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status. CONCLUSIONS: We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS.

Resilience in adolescence during the COVID-19 crisis in Canada.

BACKGROUND: The COVID-19 pandemic constitutes a social crisis that will have long-term health consequences for much of the global population, especially for adolescents. Adolescents are triply affected as they: 1) are experiencing its immediate, direct effects, 2) will carry forward health habits they develop now into adulthood, and 3) as future parents, will shape the early life health of the next generation. It is therefore imperative to assess how the pandemic is influencing adolescent wellbeing, identify sources of resilience, and outline strategies for attenuating its negative impacts. METHODS: We report the results of longitudinal analyses of qualitative data from 28 focus group discussions (FGDs) with 39 Canadian adolescents and of cross-sectional analyses of survey data from 482 Canadian adolescents gathered between September 2020 and August 2021. FGD participants and survey respondents reported on their: socio-demographic characteristics; mental health and wellbeing before and during the pandemic; pre- and during-pandemic health behaviours; experiences living through a crisis; current perceptions of their school, work, social, media, and governmental environments; and ideas about pandemic coping and mutual aid. We plotted themes emerging from FGDs along a pandemic timeline, noting socio-demographic variations. Following assessment for internal reliability and dimension reduction, quantitative health/wellbeing indicators were analyzed as functions of composite socio-demographic, health-behavioural, and health-environmental indicators. RESULTS: Our mixed methods analyses indicate that adolescents faced considerable mental and physical health challenges due to the pandemic, and were generally in poorer health than expected in non-crisis times. Nevertheless, some participants showed significantly better outcomes than others, specifically those who: got more exercise; slept better; were food secure; had clearer routines; spent more time in nature, deep in-person social relationships, and leisure; and spent less time on social media. CONCLUSIONS: Support for youth during times of crisis is essential to future population health because adolescence is a period in the life course which shapes the health behaviours, socio-economic capacities, and neurophysiology of these future parents/carers and leaders. Efforts to promote resilience in adolescents should leverage the factors identified above: helping them find structure and senses of purpose through strong social connections, well-supported work and leisure environments, and opportunities to engage with nature.

Endocrine disruptors: Challenges and future directions in epidemiologic research.

Public concern about the impact of endocrine disrupting chemicals (EDCs) on both humans and the environment is growing steadily. Epidemiologic research provides key information towards our understanding of the relationship between environmental exposures like EDCs and human health outcomes. Intended for researchers in disciplines complementary to epidemiology, this paper highlights the importance and challenges of epidemiologic research in order to present the key elements pertaining to the design and interpretation of an epidemiologic study on EDCs. The conduct of observational studies on EDCs derives from a thoughtful research question, which will help determine the subsequent methodological choices surrounding the careful selection of the study population (including the comparison group), the adequate ascertainment of exposure(s) and outcome(s) of interest, and the application of methodological and statistical concepts more specific to epidemiology. The interpretation of epidemiologic results may be arduous due to the latency occurring between EDC exposure and certain outcome(s), the complexity in capturing EDC exposure(s), and traditional methodological and statistical issues that also deserve consideration (e.g., confounding, effect modification, non-monotonic responses). Moving forward, we strongly advocate for an integrative approach of expertise in the fields of epidemiology, exposure science, risk assessment and toxicology to adequately study the health risks associated with EDCs while tackling their challenges.

Immunological features in pediatric patients with recurrent and severe infection: Identification of Primary Immunodeficiency Diseases in Merida, Venezuela.

INTRODUCTION AND OBJECTIVES: Primary immunodeficiency diseases (PIDs) are disorders associated mainly with recurrent and severe infection and an increase in susceptibility to autoimmune conditions and cancer. In Venezuela, PIDs are underdiagnosed and there is usually a delay in their diagnosis. Hence there are no data concerning the frequency and type of PIDs that occur. The aim of this study was to identify and quantify the types of PIDs that occur in Merida, a population within Venezuela. PATIENTS OR MATERIALS AND METHODS: Following an informative program designed to alert local health professionals to the warning signs for PIDs, patients with a history of recurrent infections were referred to the Instituto de Inmunologia Clinica, Universidad de Los Andes. RESULTS AND CONCLUSIONS: During the three-year period January 2014 to January 2017, thirty-two cases of PIDs were identified in pediatric patients, and 17 different types of PIDs, were identified. Predominantly antibody deficiencies were most frequent (40.6%), followed by immunodeficiencies affecting cellular and humoral immunity (21.8%), congenital defects of phagocyte (18.7%), CID with associated or syndromic features (9.3%), defects in intrinsic and innate immunity (6.4%) and diseases of immune dysregulation (3.2%). These results have important implications not only to the future approach for management of patients in our regions, but add important knowledge concerning PIDs in Latin America and worldwide.

Chlorhexidine-releasing implant coating on intramedullary nail reduces infection in a rat model.

The use of internal intramedullary nails for long bone fracture fixation is a common practice among surgeons. Bacteria naturally attach to these devices, increasing the risk for wound infection, which can result in non- or malunion, additional surgical procedures and extended hospital stays. Intramedullary nail surface properties can be modified to reduce bacterial colonisation and potentially infectious complications. In the current study, a coating combining a non-fouling property with leaching chlorhexidine for orthopaedic implantation was tested. Coating stability and chlorhexidine release were evaluated in vitro. Using a rat model of intramedullary fixation and infection, the effect of the coating on microbial colonisation and fracture healing was evaluated in vivo by quantitative microbiology, micro-computed tomography, plain radiography, three-point bending and/or histology. Low dose systemic cefazolin was administered to increase the similarities to clinical practice, without overshadowing the effect of the anti-infective coating. When introduced into a contaminated wound, the non-fouling chlorhexidine-coated implant reduced the overall bacteria colonisation within the bone and on the implant, reduced the osteolysis and increased the radiographic union, confirming its potential for reducing complications in wounds at high risk of infection. However, when implanted into a sterile wound, non-union increased. Further studies are required to best optimise the anti-microbial effectiveness, while not sacrificing fracture union.

T-cell profiles elicited by Toxoplasma gondii in acutely/chronically infected humans.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that can infect almost all warm-blooded species and induce a chronic infection in human hosts. The aim of this work was to investigate Th1, Th2, Th17 and Treg polarization, induced by four important T. gondii antigens (SAG1, ROP1, GRA8 and MAG1) in acutely and chronically infected patients. For this purpose, SAG1, ROP1, GRA8 and MAG1 were expressed as recombinant proteins, purified, and used to evaluate the proinflammatory and regulatory immune response profiles in seropositive and seronegative individuals. Our results show that SAG1 and ROP1 elicited a proinflammatory profile (INF-γ, IL-12 and IL-17) in individuals in the acute phase, whereas MAG1 and GRA8 induced a regulatory pattern (Treg and TGF-ß) in chronically infected patients. These results reveal fundamental differences in T-cell polarization induced by T. gondii antigens, which could have important implications in the immunopathogenesis of the disease and in future proposals of therapeutic strategies.

Can Implementing New Services Organization Models to Better Meet the Needs of Young People Bring About Practice Changes? Analysis of an Experiment in Québec.

The research question addressed in this article is: Can implementing new services organization models to better meet the needs of young people bring about practice changes? More precisely, we examine the effects of a new model called Aire Ouverte (AO) which is implemented gradually across Quebec since 2019. This new model involves public sector and community organizations. To grasp practices' change, we use cultural historical activity theory (CHAT) and employ a qualitative approach. Beyond a precise description of work activities, we gained an inside view of how the actors involved represented their practice and context. Our results show that practice changes seen by actors are in line with the object of the intervention, that is, responding rapidly to the expressed needs of young people. The development of new tools, flexible functioning, strengthening of interprofessional and intersectoral collaboration, involvement of young people in decision-making, all should contribute to improving response to their needs. This being said, a critical look at practice changes reveals a challenge in aligning the design and objective of AO with the needs of some young people. We noted also a poor alignment of effective collaborative practices between levels of care and the practices sought from intersectoral collaboration.

A descriptive analysis of first trimester urinary concentrations of 14 bisphenol analogues in the MIREC Canadian pregnancy cohort.

BACKGROUND: Concern over the health effects of BPA, particularly for the developing fetus, has led to an increasing use of bisphenol analogues in industrial and consumer products, which may be as hormonally active as BPA. Biomonitoring data for many bisphenol analogues, especially in pregnant populations, are limited. METHODS: We measured concentrations of 14 bisphenol analogues in 1st trimester urine samples (n = 1851) from the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort (2008-2011). We examined patterns of exposure according to sociodemographic and sampling characteristics as well as occupation and frequency of consumption of canned fish within the previous 3 months. RESULTS: BPA was detected in 89% of participants with a specific gravity standardized geometric mean concentration of 0.990 µg/L. Biphenol 4,4' (BP 4,4'), 4,4'-dihydroxydiphenyl ether (DHDPE), and bisphenol E (BPE) were detected in >97% of participants. Bisphenol F (BPF) and bisphenol S (BPS) were detected in >60% of participants. Specific gravity standardized geometric mean concentrations of these 5 compounds ranged from 0.024 to 0.564 µg/L. Nine bisphenol analogues were detected in <9% of participants. Concentrations of BP 4,4', DHDPE, and BPE were higher in younger women and those with higher pre-pregnancy BMI, lower household income, lower education, and among smokers. We found a similar pattern of differences in BPF for age, education, and smoking status while BPS similarly differed across categories of pre-pregnancy BMI. Participants who were unemployed or working in the service industry had higher molar sum of 7 bisphenol analogues than those working in healthcare, education, or an office setting. Canned fish consumption was not related to bisphenol analogue concentrations. CONCLUSION: BP 4,4', DHDPE, BPE, BPF, and BPS were highly detected in 1st trimester urine samples in this large pan-Canadian pregnancy cohort. This suggests widespread exposure to these analogues around 2008-2011 and warrants further investigation into associations with health outcomes.

The novel Mechanical Ventilator Milano for the COVID-19 pandemic.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.

Consensus statement: summary of the Quebec Lung Cancer Network recommendations for prioritizing patients with thoracic cancers in the context of the COVID-19 pandemic.

Background: The emergence of covid-19 has the potential to change the way in which the health care system can accommodate various patient populations and might affect patients with non-covid-19 problems. The Quebec Lung Cancer Network, which oversees thoracic oncology services in the province of Quebec under the direction of the Ministère de la Santé et des Services sociaux, convened to develop recommendations to deal with the potential disruption of services in thoracic oncology in the province of Quebec. The summary provided here has been adapted from the original document posted on the Programme québécois du cancer Web site at: https://www.msss.gouv.qc.ca/professionnels/documents/coronavirus-2019-ncov/PJ1_Recommandations_oncologie-thoracique-200415.pdf. Methods: Plans to optimize the health care system and potentially to prioritize services were discussed with respect to various levels of activity. For each level-of-activity scenario, suggestions were made for the services and treatments to prioritize and for those that might have to be postponed, as well as for potential alternatives to care. Results: The principal recommendation is that the cancer centre executive committee and the multidisciplinary tumour board always try to find a solution to maintain standard-of-care therapy for all patients with thoracic tumours, using novel approaches to treatment and the adoption of a network approach to care, as needed. Conclusions: The effect of the covid-19 pandemic on the health care system remains unpredictable and requires that cancer teams unite and offer the most efficient and innovative therapies to all patients under the various conditions that might be forced upon them.

Seven ways to get a grip on implementing Competency-Based Medical Education at the program level.

Competency-based medical education (CBME) curricula are becoming increasingly common in graduate medical education. Put simply, CBME is focused on educational outcomes, is independent of methods and time, and is composed of achievable competencies.1 In spite of widespread uptake, there remains much to learn about implementing CBME at the program level. Leveraging the collective experience of program leaders at Queen's University, where CBME simultaneously launched across 29 specialty programs in 2017, this paper leverages change management theory to provide a short summary of how program leaders can navigate the successful preparation, launch, and initial implementation of CBME within their residency programs.

Les programmes de formation médicale fondée sur les compétences (FMFC) sont de plus en plus répandus dans les études supérieures en médecine. En termes simples, la FMFC est centrée sur les résultats scolaires, elle est indépendante des méthodes et du temps, et est constituée de compétences réalisables.1 Malgré cette adoption généralisée, il reste encore beaucoup à apprendre sur la mise en œuvre de la FMFC au niveau des programmes. Tirant profit de l'expérience collective des responsables de programmes à l'Université Queen, où la FMFC a été lancée simultanément dans 29 programmes de spécialité en 2017,le présent article s'appuie sur la théorie de la gestion du changement pour produire un court résumé de la manière dont les responsables de programmes peuvent gérer avec succès la préparation, le lancement et la mise en œuvre initiale de la FMFC au sein de leurs programmes de résidence.

Plumbing in the embryo: developmental defects of the urinary tracts.

Kidney and urinary tract malformations are among the most frequent developmental defects identified in newborns. Ranging from asymptomatic to neonatal lethal, these malformations represent an important clinical challenge. Recent progress in understanding the developmental origin of urinary tract defects in the mouse and other animal models suggests a new framework for the interpretation of these defects in humans. Gene inactivation studies in mice provided invaluable information on the formation of the Wolffian duct, a central component of embryonic renal development, on ureter and kidney induction as well as on distal ureter maturation. All three developmental processes are crucial for normal urinary tract morphogenesis. A failure to complete these developmental steps is responsible for a spectrum of kidney and urinary tract malformations including renal agenesis, renal dysplasia, vesicoureteral reflux, hydroureter, hydronephrosis and ureterocele. Surprisingly, distal ureter maturation, the process by which the ureter is displaced from the Wolffian duct to its final position within the bladder wall, has only recently been characterized at the morphological level. Anomalies in this process are emerging as a major source of urinary tract developmental defects. This review is aimed at bridging the current knowledge on the morphological and molecular events identified in the mouse, together with clinical observations of urinary tract malformation in humans.

Calcium signaling by HBx protein in hepatitis B virus DNA replication.

Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase-2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein.

[Comparison of the urinary excretion of biomarkers of exposure to pyrethroids and pyrethrins between residents of urban and rural areas of the province of Quebec, Canada]. / Comparaison de l'excrétion urinaire de biomarqueurs d'exposition aux pyréthrinoïdes et aux pyréthrines chez les résidents de régions urbaine et rurale de la Province de Québec, Canada.

BACKGROUND: Residents of rural (agricultural) areas are often suspected of being exposed to higher levels of pesticides than residents of urban areas. However, only a limited number of studies have specifically evaluated the impact of the geographical area of residence on pyrethroid and pyrethrin exposure in the general population. This study aimed at comparing the levels of biomarkers of exposure between an urban and rural, adult and children, population of the Province of Quebec, Canada. METHODS: A total of 154 urban (Montreal) and 154 rural (Monteregie) participants provided a complete overnight timed-urine collection and filled a self-administered questionnaire. Urine samples were analyzed for pyrethroid and pyrethrin metabolites: cis- and trans-dichloro- and cis-dibromo- vinyldimethylcyclopropane carboxylic acids, phenoxy- and fluorophenoxy-benzoic acids and chrysanthemum dicarboxylic acid. Amounts of metabolites (pmol/12h par kilogram body weight) and their frequency of detection in the two populations were compared and interpreted with the help of the answers gathered by questionnaire. RESULTS: Adults and children from the rural area tended to excrete higher levels of the main urinary metabolites, the cis- and trans-dichlorovinyldimethylcyclopropane carboxylic acids and the phenoxybenzoic acid, than those living in the urban area. When the adults and children were combined, this difference was statistically significant for the phenoxybenzoic acid (p=0.020), marginally significant for the trans-dichlorovinyldimethylcyclopropane carboxylic acid (p=0.053) and nonsignificant for the cis-dichlorovinyldimethylcyclopropane carboxylic acid (p=0.158). The chrysanthemum dicarboxylic acid, the fluorophenoxybenzoic acid and the dibromovinyldimethylcyclopropane carboxylic acid were detected in much lower proportion but, in the case of the fluorophenoxybenzoic acid, the relative frequency of detection was statistically significantly higher (p<0.001) in the rural population. CONCLUSION: The presence of a baseline level of biomarkers in the urban and rural population confirms the ubiquity of pyrethroids and pyrethrins in the environment. However, in the rural adult and infantile population under study, other factors possibly contributed to slightly increase exposure compared to the urban population, namely the use of mosquito repellents and household insecticides as reported by questionnaire.

Phosphorylation of GATA4 serine 105 but not serine 261 is required for testosterone production in the male mouse.

BACKGROUND: GATA4 is a transcription factor essential for male sex determination, testicular differentiation during fetal development, and male fertility in the adult. GATA4 exerts part of its function by regulating multiple genes in the steroidogenic enzyme pathway. In spite of these crucial roles, how the activity of this factor is regulated remains unclear. OBJECTIVES: Studies in gonadal cell lines have shown that GATA4 is phosphorylated on at least two serine residues-serine 105 (S105) and serine 261 (S261)-and that this phosphorylation is important for GATA4 activity. The objective of the present study is to characterize the endogenous role of GATA4 S105 and S261 phosphorylation in the mouse testis. MATERIALS AND METHODS: We examined both previously described GATA4 S105A mice and a novel GATA4 S261A knock-in mouse that we generated by CRISPR/Cas9 gene editing. The male phenotype of the mutants was characterized by assessing androgen-dependent organ weights, hormonal profiles, and expression of multiple testicular target genes using standard biochemical and molecular biology techniques. RESULTS: The fecundity of crosses between GATA4 S105A mice was reduced but without a change in sex ratio. The weight of androgen-dependent organs was smaller when compared to wild-type controls. Plasma testosterone levels showed a 70% decrease in adult GATA4 S105A males. This decrease was associated with a reduction in Cyp11a1, Cyp17a1, and Hsd17b3 expression. GATA4 S261A mice were viable and testis morphology appeared normal. Testosterone production and steroidogenic enzyme expression were not altered in GATA4 S261A males. DISCUSSION AND CONCLUSION: Our analysis showed that blocking GATA4 S105 phosphorylation is associated with decreased androgen production in males. In contrast, S261 phosphorylation by itself is dispensable for GATA4 function. These results confirm that endogenous GATA4 action is essential for normal steroid production in males and that this activity requires phosphorylation on at least one serine residue.

Adaptation changes the spatial frequency tuning of adult cat visual cortex neurons.

The modular layout of striate cortex is arguably a hallmark of all cortical organization. Neurons of a given module or domain respond optimally to very few specific properties, such as orientation or direction. However, it is possible, under appropriate conditions, to compel a neuron to respond preferentially to a different optimal property. In anesthetized cats, prepared for electrophysiological recordings in the visual cortex, we applied a spatial frequency (SF) that differs (by 0.25-3.0 octaves) from the optimal one for 7-13 min without interruption. This application shifted the tuning curve of the cell mainly in the direction of the imposed SF. Indeed, results indicate an attractive push occurring more frequently (50%) than a repulsive (30%) shift in cortical cells. The increase of responsivity is band-limited and is around the imposed SF, while flanked responses remained unmodified in all conditions. We hypothesize that the observed reversible plasticity is obtained by a modulation of the balance between the strengths of the respective synaptic inputs. These changes in preferred original optimal spatial frequencies may allow a dynamic reaction of cortex to a new environment and particularly to ''zoom'' cellular activity toward persistent stimuli in spite of the tuning inherited from genetic programming of response properties and environmental conditions during critical periods in new born animals.

Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8.

Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.

Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions.

Nectin-2 is a cell adhesion molecule encoded by a member of the poliovirus receptor gene family. This family consists of human, monkey, rat, and murine genes that are members of the immunoglobulin gene superfamily. Nectin-2 is a component of cell-cell adherens junctions and interacts with l-afadin, an F-actin-binding protein. Disruption of both alleles of the murine nectin-2 gene resulted in morphologically aberrant spermatozoa with defects in nuclear and cytoskeletal morphology and mitochondrial localization. Homozygous null males are sterile, while homozygous null females, as well as heterozygous males and females, are fertile. The production by nectin-2(-/-) mice of normal numbers of spermatozoa containing wild-type levels of DNA suggests that Nectin-2 functions at a late stage of germ cell development. Consistent with such a role, Nectin-2 is expressed in the testes only during the later stages of spermatogenesis. The structural defects observed in spermatozoa of nectin-2(-/-) mice suggest a role for this protein in organization and reorganization of the cytoskeleton during spermiogenesis.

Membrane fluidity response to odorants as seen by 2H-NMR and infrared spectroscopy.

Fourier transform infrared spectroscopy (FTIR) and deuterium nuclear magnetic resonance spectroscopy (2H-NMR) have been used to study the location of two odorants, beta-ionone and menthone, in a model membrane of dimyristoylphosphatidylcholine, as well as the effect of the odorants on the structure and dynamics of the phospholipids. The interaction has been investigated for two lipid-to-odorant molar ratios, 10:1 and 1:1. The two odorants were found to affect the fluidity of the membrane. More specifically, the 2H-NMR results indicate that at a lipid-to-odorant molar ratio of 10:1, both beta-ionone and menthone increase the order of the deuterons in the interfacial and headgroup regions of the lipid while the incorporation of the odorants at a lipid-to-odorant molar ratio of 1:1 decreases the order of both the lipid headgroup and acyl chains. On the other hand, the infrared results show that the incorporation of beta-ionone and menthone decreases the phase transition temperature and cooperativity of the lipid acyl chains. The results suggest that the site of incorporation of beta-ionone and menthone is very similar in DMPC membranes.