Diversity and evolution of the P450 family in arthropods

The P450 family (CYP genes) of arthropods encodes diverse enzymes involved in the metabolism of foreign compounds and in essential endocrine or ecophysiological functions. The P450 sequences (CYPome) from 40 arthropod species were manually curated, including 31 complete CYPomes, and a maximum likelihood phylogeny of nearly 3000 sequences is presented. Arthropod CYPomes are assembled from members of six CYP clans of variable size, the CYP2, CYP3, CYP4 and mitochondrial clans, as well as the CYP20 and CYP16 clans that are not found in Neoptera. CYPome sizes vary from two dozen genes in some parasitic species to over 200 in species as diverse as collembolans or ticks. CYPomes are comprised of few CYP families with many genes and many CYP families with few genes, and this distribution is the result of dynamic birth and death processes. Lineage-specific expansions or blooms are found throughout the phylogeny and often result in genomic clusters that appear to form a reservoir of catalytic diversity maintained as heritable units. Among the many P450s with physiological functions, six CYP families are involved in ecdysteroid metabolism. However, five so-called Halloween genes are not universally represented and do not constitute the unique pathway of ecdysteroid biosynthesis. The diversity of arthropod CYPomes has only partially been uncovered to date and many P450s with physiological functions regulating the synthesis and degradation of endogenous signal molecules (including ecdysteroids) and semiochemicals (including pheromones and defense chemicals) remain to be discovered. Sequence diversity of arthropod P450s is extreme, and P450 sequences lacking the universally conserved Cys ligand to the heme have evolved several times. A better understanding of P450 evolution is needed to discern the relative contributions of stochastic processes and adaptive processes in shaping the size and diversity of CYPomes

7-Nitro indazole, an inhibitor of neuronal nitric oxide synthase, attenuates pilocarpine-induced seizures

7-Nitro indazole (25–100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO) synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced seizures in mice. This indicates that the decreased neuroexcitability of the central nervous system (CNS) following administration of 7-nitro indazole may be due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory and proconvulsant factor in the CNS

Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung

The lungs are frequently challenged by viruses, and resident CD8+ T cells likely contribute to the surveillance of these pathogens. To obtain insight into local T cell immunity to respiratory viruses in humans, we determined the specificity, phenotype, and function of lung-residing CD8+ T cells and peripheral blood CD8+ T cells in a paired analysis. The lung contained markedly higher frequencies of influenza (FLU)-specific and respiratory syncytial virus (RSV)-specific CD8+ T cells when compared with the circulation. This contrasted with an equal distribution of cytomegalovirus- and Epstein-Bar virus–specific CD8+ T cells. Noticeably, a substantial fraction of the lung-residing FLU- and RSV-specific CD8+ T cells had progressed to a relatively late differentiation phenotype, reflected by low expression of CD28 and CD27. Lung-derived FLU-specific CD8+ T cells had low activation requirements, as expansion of these cells could be initiated by cognate peptide in the absence of helper cell–derived signals. Thus, the human lung contains high numbers of differentiated FLU- and RSV-specific memory CD8+ T cells that can readily expand upon reexposure to virus. Resident lung T cells may provide immediate immunological protection against pulmonary virus infections

High-resolution QTL mapping in Tetranychus urticae reveals acaricide-specific responses and common target-site resistance after selection by different METI-I acaricides

Arthropod herbivores cause dramatic crop losses, and frequent pesticide use has led to widespread resistance in numerous species. One such species, the two-spotted spider mite, Tetranychus urticae, is an extreme generalist herbivore and a major worldwide crop pest with a history of rapidly developing resistance to acaricides. Mitochondrial Electron Transport Inhibitors of complex I (METI-Is) have been used extensively in the last 25 years to control T. urticae around the globe, and widespread resistance to each has been documented. METI-I resistance mechanisms in T. urticae are likely complex, as increased metabolism by cytochrome P450 monooxygenases as well as a target-site mutation have been linked with resistance. To identify loci underlying resistance to the METI-I acaricides fenpyroximate, pyridaben and tebufenpyrad without prior hypotheses, we crossed a highly METI-I-resistant strain of T. urticae to a susceptible one, propagated many replicated populations over multiple generations with and without selection by each compound, and performed bulked segregant analysis genetic mapping. Our results showed that while the known H92R target-site mutation was associated with resistance to each compound, a genomic region that included cytochrome P450-reductase (CPR) was associated with resistance to pyridaben and tebufenpyrad. Within CPR, a single nonsynonymous variant distinguished the resistant strain from the sensitive one. Furthermore, a genomic region linked with tebufenpyrad resistance harbored a non-canonical member of the nuclear hormone receptor 96 (NHR96) gene family. This NHR96 gene does not encode a DNA-binding domain (DBD), an uncommon feature in arthropods, and belongs to an expanded family of 47 NHR96 proteins lacking DBDs in T. urticae. Our findings suggest that although cross-resistance to METI-Is involves known detoxification pathways, structural differences in METI-I acaricides have also resulted in resistance mechanisms that are compound-specific

Spiritual care by nurses in curative oncology:a national, multicenter, mixed method study

Introduction: Spiritual care by nurses is often linked to palliative and terminal care. It is hardly known whether SC is also considered vital among nurses who care for patients who are treated with curative intent. Therefore, we have explored the level of and the experiences with spiritual care by nurses in curative cancer care.Methods: In this mixed-method study, nurses were recruited in eight hospitals in the Netherlands. A spirituality scale, a spiritual care competence scale and five questions on spiritual care were completed by 57 participants. Afterwards, the scores were quantitatively analyzed. Because of data saturation, qualitative analysis was limited to 31 semi-structured interviews, using content analysis.Results: The great majority of nurses indicated on the questionnaire that they frequently provide spiritual care. However, in interviews, the nurses described few examples of spiritual care. Nurses also indicated that they had not learned so much in providing spiritual care in their educational program; rather, they had learned it in clinical practice.Conclusions: As the questionnaire could be liable to socially desirable responding, we based our conclusions on the qualitative data, and concluded that spiritual care was rather modest among the nurses providing curative care in this stud

Defining the mission - from policy statement to learning outcomes. A triple case study of faith-based nursing education Institutions in Northern Europe

This article focuses on faith-based nursing education in a pluralistic society. It discusses how faith-based colleges describe their mission and purpose in their policy documents, and how these statements are interpreted in the learning outcomes of nursing education. Three institutions of higher education participated in the study: Diaconia University of Applied Sciences (Diak) (Finland), Diakonhjemmet University College (DUC) (Norway) and Viaa Christian University of Applied Sciences (The Netherlands). Two of the colleges, Diak and DUC, belong to the so-called diaconalmovement within the Lutheran churches in Northern Europe. Viaa was founded within the Reformed church tradition as an alternative to secular professional education. This study explores how the three different colleges present themselves and describe themselves as faith-based educational institutions with a Christian affiliation and their particular purpose within the general landscape of higher education. The study shows how the institutions presents faith in their institutional self-presentation and the integration of faith base in learning outcomes of nursing program. This study took place as a case study.As study material we used the strategic documents provided by each college. The study reported in this article is part of a broader investigation of the three institutions, including various qualitative methods such as individual interviews and focus-group interviews. Translating mission goals and values to the curriculum is most visible in the description of learning outcomes, because those are the more practical and concrete goals of vocational education. Upon analysing the learning outcomes of nursing education within the three universities, it became obvious that the most explicit voice is given to its purpose, which in all three cases focuses on ethics. The study led to the question how best to discuss values and beliefs in institutes of higher education, and who would facilitate, maintain and participate in those discussions.publishedVersio

COVID-19 outbreaks among crew on commercial ships at the Port of Rotterdam, the Netherlands, 2020 to 2021

BackgroundDuring the COVID-19 pandemic, international shipping activity was disrupted as movement of people and goods was restricted. The Port of Rotterdam, the largest port in Europe, remained operational throughout.AimWe describe the burden of COVID-19 among crew on sea-going vessels at the port and recommend improvements in future infectious disease event notification and response at commercial ports.MethodsSuspected COVID-19 cases on sea-going vessels were notified to port authorities and public health (PH) authorities pre-arrival via the Maritime Declaration of Health. We linked data from port and PH information systems between 1 January 2020 and 31 July 2021, derived a notification rate (NR) of COVID-19 events per arrival, and an attack rate (AR) per vessel (confirmed cases). We compared AR by vessel type (workship/tanker/cargo/passenger), during wildtype-, alpha- and delta-dominant calendar periods.ResultsEighty-four COVID-19 events were notified on ships, involving 622 cases. The NR among 45,030 new arrivals was 173 per 100,000 impacting 1% of vessels. Events per week peaked in April 2021 and again in July 2021, when the AR was also highest. Half of all cases were notified on workships, events occurring earlier and more frequently than on other vessels.ConclusionNotification of COVID-19 events on ships occurred infrequently, although case under-ascertainment was likely. Pre-agreed protocols for data-sharing between stakeholders locally and across Europe would facilitate more efficient pandemic response. Public health access to specimens for sequencing and environmental sampling would give greater insight into viral spread on ships.</p

Disrupted upregulation of salience network connectivity during acute stress in siblings of schizophrenia patients

BACKGROUND: An adaptive neural stress response is essential to adequately cope with a changing environment. It was previously argued that sympathetic/noradrenergic activity during acute stress increases salience network (SN) connectivity and reduces executive control network (ECN) connectivity in healthy controls, with opposing effects in the late aftermath of stress. Altered temporal dynamics of these networks in response to stress are thought to play a role in the development of psychopathology in vulnerable individuals. METHODS: We exposed male healthy controls (n = 40, mean age = 33.9) and unaffected siblings of schizophrenia patients (n = 39, mean age = 33.2) to the stress or control condition of the trier social stress test and subsequently investigated resting state functional connectivity of the SN and ECN directly after and 1.5 h after stress. RESULTS: Acute stress resulted in increased functional connectivity within the SN in healthy controls, but not in siblings (group × stress interaction pfwe < 0.05). In the late aftermath of stress, stress reduced functional connectivity within the SN in both groups. Moreover, we found increased functional connectivity between the ECN and the cerebellum in the aftermath of stress in both healthy controls and siblings of schizophrenia patients. CONCLUSIONS: The results show profound differences between siblings of schizophrenia patients and controls during acute stress. Siblings lacked the upregulation of neural resources necessary to quickly and adequately cope with a stressor. This points to a reduced dynamic range in the sympathetic response, and may constitute a vulnerability factor for the development of psychopathology in this at-risk group

Lifelong challenge of calcium homeostasis in male mice lacking TRPV5 leads to changes in bone and calcium metabolism

Trpv5 plays an important role in calcium (Ca2+) homeostasis, among others by mediating renal calcium reabsorption. Accordingly, Trpv5 deficiency strongly stresses Ca2+ homeostasis in order to maintain stable serum Ca2+. We addressed the impact of lifelong challenge of calcium homeostasis on the bone phenotype of these mice. Aging signifi