Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats.

Untreated insulin-deficient diabetes causes hyperphagia and neuroendocrine disturbances that may be partly mediated by increased hypothalamic activity of neuropeptide Y (NPY), a potent central appetite stimulant. The metabolic signal that stimulates hypothalamic NPY is unknown. This study aimed to determine whether insulin deficiency or hyperglycemia was responsible. Regional hypothalamic NPY concentrations were compared in streptozocin-diabetic (STZ-D) rats rendered nearly normoglycemic by either insulin replacement or food restriction. Untreated STZ-D rats were hyperphagic and showed significantly increased (p less than 0.01) hypothalamic NPY concentrations in the arcuate nucleus and lateral hypothalamic area. Once-daily ultralente insulin injections corrected hypoinsulinemia and hyperglycemia, abolished hyperphagia, and normalized NPY concentrations in all hypothalamic regions. By contrast, food restriction effectively lowered glycemia without raising insulin levels. In these underfed diabetic rats, NPY concentrations rose further and were significantly higher than nondiabetic and untreated diabetic levels in most hypothalamic regions. We conclude that insulin deficiency is a major stimulus to hypothalamic NPY in STZ-D, whereas hyperglycemia may exert an inhibitory influence. These findings support the hypothesis that hypothalamic NPY responds to specific metabolic cues and is involved in regulating energy balance and conserving body weight.     

A role for artificial night-time lighting in long-term changes in populations of 100 widespread macro-moths in UK and Ireland: a citizen-science study

The abundance of 100 of the most widespread species of macro-moth in the UK and Ireland was estimated from light-trap records reported to the UK and Ireland Garden Moth Scheme between 2005 and 2015. Recording sites were classified into low, medium and high night-time illumination categories by satellite imagery, into land-use types from the dominant use in the 1–2 km surrounding area, and by latitude. Most urban sites were in the group classified as having high night-time illumination. Comparison between medium and low night-time illuminated sites allowed differences between levels of illumination free from the effect of urbanization on moth abundance to be assessed. The medium and low night-time illuminated sites differed significantly in the frequency of grassland and arable land-use types and in geographic location with more grassland and north-western sites in the low-light category. After adjustment for these differences and for variations between taxonomic family groups, the medium to low night-time lighting abundance ratios explained a significant (P?<?0.001) 20% of the variance in long-term changes in moth abundance reported by the Rothamsted Insect Survey for the years 1968–2002. This is the first demonstration that artificial night-time lighting has had, in combination with other factors, a significant influence on levels of abundance of moth populations.     

Alleviating praxis shock: Induction policy and programming for urban music educators

An integral part of a teacher learning continuum ranging from preservice education to professional development for experienced educators, new teacher induction holds particular potential to effect change in urban education. Accordingly, this article offers recommendations for induction-related policy and programming capable of supporting beginning music educators' professional growth in urban settings. Four programmatic components well-suited to addressing urban music teachers' distinctive learning needs are discussed: professional development tailored to urban settings, collaborative communities of practice, mentoring, and school-university partnerships.     

Integrated genetic and morphological data support eco‐evolutionary divergence of Angolan and South African populations of Diplodus hottentotus

The genus Diplodus presents multiple cases of taxonomic conjecture. Among these the D. cervinus complex was previously described as comprising three subspecies that are now regarded as separate species: Diplodus cervinus, Diplodus hottentotus and Diplodus omanensis. Diplodus hottentotus exhibits a clear break in its distribution around the Benguela Current system, prompting speculation that Angolan and South African populations flanking this area may be isolated and warrant formal taxonomic distinction. This study reports the first integrated genetic [mitochondrial (mt)DNA and nuclear microsatellite] and morphological (morphometric, meristic and colouration) study to assess patterns of divergence between populations in the two regions. High levels of cytonuclear divergence between the populations support a prolonged period of genetic isolation, with the sharing of only one mtDNA haplotype (12 haplotypes were fully sorted between regions) attributed to retention of ancestral polymorphism. Fish from the two regions were significantly differentiated at a number of morphometric (69·5%) and meristic (46%) characters. In addition, Angolan and South African fish exhibited reciprocally diagnostic colouration patterns that were more similar to Mediterranean and Indian Ocean congeners, respectively. Based on the congruent genetic and phenotypic diversity we suggest that the use of hottentotus, whether for full species or subspecies status, should be restricted to South African D. cervinus to reflect their status as a distinct species‐like unit, while the relationship between Angolan and Atlantic–Mediterranean D. cervinus will require further demo‐genetic analysis. This study highlights the utility of integrated genetic and morphological approaches to assess taxonomic diversity within the biogeographically dynamic Benguela Current region.     

Measurements of auto‐antibodies to α‐synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease

Biomarkers for α‐synuclein are needed for diagnosis and prognosis in Parkinson's disease (PD ). Endogenous auto‐antibodies to α‐synuclein could serve as biomarkers for underlying synucleinopathy, but previous assessments of auto‐antibodies have shown variability and inconsistent clinical correlations. We hypothesized that auto‐antibodies to α‐synuclein could be diagnostic for PD and explain its clinical heterogeneity. To test this hypothesis, we developed an enzyme‐linked immunosorbent assay for measuring α‐synuclein auto‐antibodies in human samples. We evaluated 69 serum samples (16 healthy controls (HC ) and 53 PD patients) and 145 CSF samples (52 HC and 93 PD patients) from our Institution. Both serum and CSF were available for 24 participants. Males had higher auto‐antibody levels than females in both fluids. CSF auto‐antibody levels were significantly higher in PD patients as compared with HC , whereas serum levels were not significantly different. CSF auto‐antibody levels did not associate with amyloid‐β_1–42, total tau, or phosphorylated tau. CSF auto‐antibody levels correlated with performance on the Montreal Cognitive Assessment, even when controlled for CSF amyloidβ_1–42. CSF hemoglobin levels, as a proxy for contamination of CSF by blood during lumbar puncture, did not influence these observations. Using recombinant α‐synuclein with N‐ and C‐terminal truncations, we found that CSF auto‐antibodies target amino acids 100 through 120 of α‐synuclein. We conclude that endogenous CSF auto‐antibodies are significantly higher in PD patients as compared with HC , suggesting that they could indicate the presence of underlying synucleinopathy. These auto‐antibodies associate with poor cognition, independently of CSF amyloidβ_1–42, and target a select C‐terminal region of α‐synuclein.

Read the Editorial Highlight for this article on page 433 .

     

Regulation of Shigella Effector Kinase OspG through Modulation of Its Dynamic Properties

Gram-negative pathogens secrete effector proteins into human cells to modulate normal cellular processes and establish a bacterial replication niche. Shigella and pathogenic Escherichia coli possess homologous effector kinases, OspG and NleH1/2, respectively. Upon translocation, OspG but not NleH binds to ubiquitin and a subset of E2 ~ Ub conjugates, which was shown to activate its kinase activity. Here we show that OspG, having a minimal kinase fold, acquired a novel mechanism of regulation of its activity. Binding of the E2 ~ Ub conjugate to OspG not only stimulates its kinase activity but also increases its optimal temperature for activity to match the human body temperature and stabilizes its labile C-terminal domain. The melting temperature (T_m) of OspG alone is only 31?°C, as compared to 41?°C to NleH1/2 homologs. In the presence of E2 ~ Ub, the T_m of OspG increases to ~ 42?°C, while Ub by itself increases the T_m to 39?°C. Moreover, OspG alone displays maximal activity at 26?°C, while in the presence of E2 ~ Ub, maximal activity occurs at ~ 42?°C. Using NMR and molecular dynamics calculations, we have identified the C-terminal lobe and, in particular, the C-terminal helix, as the key elements responsible for lower thermal stability of OspG as compared to homologous effector kinases.     

Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks

Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome‐wide binding of budding yeast Rif1 by chromatin immunoprecipitation, during G1 phase and in S phase with replication progressing normally or blocked by hydroxyurea. Rif1 associates strongly with telomeres through interaction with Rap1. By comparing genomic binding of wild‐type Rif1 and truncated Rif1 lacking the Rap1‐interaction domain, we identify hundreds of Rap1‐dependent and Rap1‐independent chromosome interaction sites. Rif1 binds to centromeres, highly transcribed genes and replication origins in a Rap1‐independent manner, associating with both early and late‐initiating origins. Interestingly, Rif1 also binds around activated origins when replication progression is blocked by hydroxyurea, suggesting association with blocked forks. Using nascent DNA labelling and DNA combing techniques, we find that in cells treated with hydroxyurea, yeast Rif1 stabilises recently synthesised DNA. Our results indicate that, in addition to controlling DNA replication initiation, budding yeast Rif1 plays an ongoing role after initiation and controls events at blocked replication forks.     

Detection and eradication of a non-native Collembola incursion in a hydroponics facility in East Antarctica

A non-native incursion of the collembolan, Xenylla sp. was found within the hydroponics facility at Davis Station, East Antarctica in May 2014. A rapid response was implemented to eradicate the incursion, including localised insecticide use, incineration of plants and growing media, sterilisation of the facility and three cycles of freezing/thawing of both internal rooms and external sub floor areas. Two consecutive years of summer monitoring programs have not detected any Collembola in station buildings or in the surrounding environment, suggesting the eradication was successful. This case highlights the importance of a multiple barrier approach to non-native species risks, and how activation of the last barrier—regular surveillance—resulted in early detection. The use of an online, real-time incident reporting system facilitated efficient communication between scientific experts, operational managers and expeditioners on site, resulting in a rapid and effective response following detection and potentially the first successful eradication of a non-native microarthropod in Antarctica. Monitoring will continue to confirm eradication.