Metabolic Stress Responses in Drosophila Are Modulated by Brain Neurosecretory Cells That Produce Multiple Neuropeptides

In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a): Drosophila tachykinin (DTK), short neuropeptide F (sNPF) and ion transport peptide (ITP). These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells

Problematic mobile phone use and smartphone addiction across generations: the roles of psychopathological symptoms and smartphone use

Contemporary technological advances have led to a significant increase in using mobile technologies. Recent research has pointed to potential problems as a consequence of mobile overuse, including addiction, financial problems, dangerous use (i.e. whilst driving) and prohibited use (i.e. use in forbidden areas). The aim of this study is to extend previous findings regarding the predictive power of psychopathological symptoms (depression, anxiety and stress), mobile phone use (i.e. calls, SMS, time spent on the phone, as well as the engagement in specific smartphone activities) across Generations X and Y on problematic mobile phone use in a sample of 273 adults. Findings revealed prohibited use and dependence were predicted by calls/day, time on the phone and using social media. Only for dependent mobile phone use (rather than prohibited), stress appeared as significant. Using social media and anxiety significantly predicted belonging to Generation Y, with calls per day predicted belonging to Generation X. This finding suggests Generation Y are more likely to use asynchronous social media-based communication, whereas Generation X engage more in synchronous communication. The findings have implications for prevention and awareness-raising efforts of possibly problematic mobile phone use for educators, parents and individuals, particularly including dependence and prohibited use

Viral-bacterial co-infection in Australian Indigenous children with acute otitis media

Background: Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation

Reducing the rate and duration of Re-ADMISsions among patients with unipolar disorder and bipolar disorder using smartphone-based monitoring and treatment -- the RADMIS trials: study protocol for two randomized controlled trials

Abstract Background Unipolar and bipolar disorder combined account for nearly half of all morbidity and mortality due to mental and substance use disorders, and burden society with the highest health care costs of all psychiatric and neurological disorders. Among these, costs due to psychiatric hospitalization are a major burden. Smartphones comprise an innovative and unique platform for the monitoring and treatment of depression and mania. No prior trial has investigated whether the use of a smartphone-based system can prevent re-admission among patients discharged from hospital. The present RADMIS trials aim to investigate whether using a smartphone-based monitoring and treatment system, including an integrated clinical feedback loop, reduces the rate and duration of re-admissions more than standard treatment in unipolar disorder and bipolar disorder. Methods The RADMIS trials use a randomized controlled, single-blind, parallel-group design. Patients with unipolar disorder and patients with bipolar disorder are invited to participate in each trial when discharged from psychiatric hospitals in The Capital Region of Denmark following an affective episode and randomized to either (1) a smartphone-based monitoring system including (a) an integrated feedback loop between patients and clinicians and (b) context-aware cognitive behavioral therapy (CBT) modules (intervention group) or (2) standard treatment (control group) for a 6-month trial period. The trial started in May 2017. The outcomes are (1) number and duration of re-admissions (primary), (2) severity of depressive and manic (only for patients with bipolar disorder) symptoms; psychosocial functioning; number of affective episodes (secondary), and (3) perceived stress, quality of life, self-rated depressive symptoms, self-rated manic symptoms (only for patients with bipolar disorder), recovery, empowerment, adherence to medication, wellbeing, ruminations, worrying, and satisfaction (tertiary). A total of 400 patients (200 patients with unipolar disorder and 200 patients with bipolar disorder) will be included in the RADMIS trials. Discussion If the smartphone-based monitoring system proves effective in reducing the rate and duration of re-admissions, there will be basis for using a system of this kind in the treatment of unipolar and bipolar disorder in general and on a larger scale. Trial registration ClinicalTrials.gov, ID: NCT03033420 . Registered 13 January 2017. Ethical approval has been obtained

Spatio-structural granularity of biological material entities

<p>Abstract</p> <p>Background</p> <p>With the continuously increasing demands on knowledge- and data-management that databases have to meet, ontologies and the theories of granularity they use become more and more important. Unfortunately, currently used theories and schemes of granularity unnecessarily limit the performance of ontologies due to two shortcomings: (i) they do not allow the integration of multiple granularity perspectives into one granularity framework; (ii) they are not applicable to cumulative-constitutively organized material entities, which cover most of the biomedical material entities.</p> <p>Results</p> <p>The above mentioned shortcomings are responsible for the major inconsistencies in currently used spatio-structural granularity schemes. By using the Basic Formal Ontology (BFO) as a top-level ontology and Keet's general theory of granularity, a granularity framework is presented that is applicable to cumulative-constitutively organized material entities. It provides a scheme for granulating complex material entities into their constitutive and regional parts by integrating various compositional and spatial granularity perspectives. Within a scale dependent resolution perspective, it even allows distinguishing different types of representations of the same material entity. Within other scale dependent perspectives, which are based on specific types of measurements (e.g. weight, volume, etc.), the possibility of organizing instances of material entities independent of their parthood relations and only according to increasing measures is provided as well. All granularity perspectives are connected to one another through overcrossing granularity levels, together forming an integrated whole that uses the <it>compositional object perspective </it>as an integrating backbone. This granularity framework allows to consistently assign structural granularity values to all different types of material entities.</p> <p>Conclusions</p> <p>The here presented framework provides a spatio-structural granularity framework for all domain reference ontologies that model cumulative-constitutively organized material entities. With its multi-perspectives approach it allows querying an ontology stored in a database at one's own desired different levels of detail: The contents of a database can be organized according to diverse granularity perspectives, which in their turn provide different <it>views </it>on its content (i.e. data, knowledge), each organized into different levels of detail.</p

A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants

Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious.To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12-35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group ("C"). None of these new strains could be cultured in traditional cell lines.By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group

Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors

Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. METHODS: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. RESULTS: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10- 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10- 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10- 6 and P = 3 × 10- 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10- 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. CONCLUSION: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts

A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions

<p>Abstract</p> <p>Background</p> <p>Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, <it>snpf</it>, encodes the precursor of short neuropeptide F (sNPF). To unravel possible functional diversity we have mapped the distribution of transcript of the <it>snpf </it>gene and its peptide products in the central nervous system (CNS) of <it>Drosophila </it>in relation to other neuronal markers.</p> <p>Results</p> <p>There are several hundreds of neurons in the larval CNS and several thousands in the adult <it>Drosophila </it>brain expressing <it>snpf </it>transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7).</p> <p>Conclusion</p> <p>It is likely that sNPF has multiple functions as neurohormone as well as local neuromodulator/co-transmitter in various CNS circuits, including olfactory circuits both at the level of the first synapse and at the mushroom body output level. Some of the sNPF immunoreactive axons terminate in close proximity to neurosecretory cells producing ILPs and adipokinetic hormone, indicating that sNPF also might regulate hormone production or release.</p

Keratan sulfate, a complex glycosaminoglycan with unique functional capability

From an evolutionary perspective keratan sulfate (KS) is the newest glycosaminoglycan (GAG) but the least understood. KS is a sophisticated molecule with a diverse structure, and unique functional roles continue to be uncovered for this GAG. The cornea is the richest tissue source of KS in the human body but the central and peripheral nervous systems also contain significant levels of KS and a diverse range of KS-proteoglycans with essential functional roles. KS also displays important cell regulatory properties in epithelial and mesenchymal tissues and in bone and in tumor development of diagnostic and prognostic utility. Corneal KS-I displays variable degrees of sulfation along the KS chain ranging from non-sulfated polylactosamine, mono-sulfated and disulfated disaccharide regions. Skeletal KS-II is almost completely sulfated consisting of disulfated disaccharides interrupted by occasional mono-sulfated N-acetyllactosamine residues. KS-III also contains highly sulfated KS disaccharides but differs from KS-I and KS-II through 2-O-mannose linkage to serine or threonine core protein residues on proteoglycans such as phosphacan and abakan in brain tissue. Historically, the major emphasis on the biology of KS has focused on its sulfated regions for good reason. The sulfation motifs on KS convey important molecular recognition information and direct cell behavior through a number of interactive proteins. Emerging evidence also suggest functional roles for the poly-N-acetyllactosamine regions of KS requiring further investigation. Thus further research is warranted to better understand the complexities of KS

Widespread movement of meltwater onto and across Antarctic ice shelves

Surface meltwater drains across ice sheets, forming melt ponds that can trigger ice-shelf collapse, acceleration of grounded ice flow and increased sea-level rise. Numerical models of the Antarctic Ice Sheet that incorporate meltwater’s impact on ice shelves, but ignore the movement of water across the ice surface, predict a metre of global sea-level rise this century5 in response to atmospheric warming. To understand the impact of water moving across the ice surface a broad quantification of surface meltwater and its drainage is needed. Yet, despite extensive research in Greenland and observations of individual drainage systems in Antarctica, we have little understanding of Antarctic-wide surface hydrology or how it will evolve. Here we show widespread drainage of meltwater across the surface of the ice sheet through surface streams and ponds (hereafter ‘surface drainage’) as far south as 85° S and as high as 1,300 metres above sea level. Our findings are based on satellite imagery from 1973 onwards and aerial photography from 1947 onwards. Surface drainage has persisted for decades, transporting water up to 120 kilometres from grounded ice onto and across ice shelves, feeding vast melt ponds up to 80 kilometres long. Large-scale surface drainage could deliver water to areas of ice shelves vulnerable to collapse, as melt rates increase this century. While Antarctic surface melt ponds are relatively well documented on some ice shelves, we have discovered that ponds often form part of widespread, large-scale surface drainage systems. In a warming climate, enhanced surface drainage could accelerate future ice-mass loss from Antarctic, potentially via positive feedbacks between the extent of exposed rock, melting and thinning of the ice sheet