Molecular Detection of Invasive Species in Heterogeneous Mixtures Using a Microfluidic Carbon Nanotube Platform

Screening methods to prevent introductions of invasive species are critical for the protection of environmental and economic benefits provided by native species and uninvaded ecosystems. Coastal ecosystems worldwide remain vulnerable to damage from aquatic species introductions, particularly via ballast water discharge from ships. Because current ballast management practices are not completely effective, rapid and sensitive screening methods are needed for on-site testing of ships in transit. Here, we describe a detection technology based on a microfluidic chip containing DNA oligonucleotide functionalized carbon nanotubes. We demonstrate the efficacy of the chip using three ballast-transported species either established (Dreissena bugensis) or of potential threat (Eriocheir sinensis and Limnoperna fortuneii) to the Laurentian Great Lakes. With further refinement for on-board application, the technology could lead to real-time ballast water screening to improve ship-specific management and control decisions

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

The advantage of juvenile coloration in reef fishes

x, 59 leaves, bound : ill., maps ; 29 cm.Juvenile reef fishes often have a color pattern different from that of adults. It has been theorized that this reduces the aggression received by juveniles from adult conspecifics. This was tested using two species of Labroides cleaning wrasses in which certain-sized individuals can quickly shift back and forth between the adult and juvenile color patterns. Adult Labroides phthirophagus has the same single-male grouping social structure as previously described for L. dimidiatus. Small L. phthirophagus and L. dimidiatus in juvenile coloration shifted to adult coloration when isolated and then quickly shifted back to juvenile coloration when chased by an adult conspecific female. In L. phthirophagus the adult females attacked small cleaners more frequently when they displayed the adult color pattern, indicating that juvenile coloration gives some protection from conspecific aggression. Two other species oflabrids, Thalassoma duperrey and Coris gaimard, showed the ability to shift back to juvenile coloration when aggression was received from con specific adults, although the shift was not nearly as rapid as seen in Labroides species. Dascyllus albisella and Zebrasomajlavescens, common reef fishes, preferred to solicit cleaning (by posing) from the adult-colored L. phthirophagus, indicating that some hosts prefer the adult color pattern. Small L. phthirophagus shifted to adult coloration more quickly when starved than when provided with host fish on which to feed, indicating that the coloration shift is motivated by hunger. Even though juvenile coloration in some fishes may reduce the aggression received from adults, in cleaner wrasses it also reduces food availability, making it advantageous for them to shift to adult-coloration as soon as possible. Cleaner wrasses have developed a quick, reversible coloration shift that allows changing to adult coloration at a small size but allows reversing coloration if too much aggression is received

Posterior Reversible Encephalopathy Syndrome due to High Dose Corticosteroids for an MS Relapse

Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse

Dendritic Cells and Immunoregulation in the Pathogenesis and Prevention of Type 1 Diabetes

Dendritic cells govern the outcome of an immune response toward either tolerance or autoimmunity. Recent evidence has demonstrated that central tolerance is associated with relatively immature dendritic cells or quiescent mature dendritic cells that present self-antigens to autoreactive T cells, thereby silencing their autoreactive potential and/or activating regulatory T cells. Conversely, activated mature dendritic cells that have been instructed to become potent T cell stimulators by adjuvants or pathogens are capable of converting tolerance to immune activation. In combination with genetic and environmental influences, such mature dendritic cells are capable of orchestrating autoimmune responses. To explore the function of dendritic cells in type 1 diabetes, the authors evaluated peripheral dendritic cells from both patients with type 1 diabetes and the nonobese diabetic (NOD) mouse model that shares a pathologically analogous disease process. Dendritic cells in NOD mice are phenotypically comparable to dendritic cells from autoimmune-resistant controls with respect to expression of differentiation molecules. However, in response to maturation stimuli, such cells confer heightened activation of T cells and excessive production of pro-inflammatory cytokines. These findings highlight a putative contribution of unabated dendritic cell activation to the loss of self-tolerance and to chronic, self- directed responses that define type 1 diabetes. Moreover, effective manipulation of dendritic cell activation state pro- vides a promising avenue for regulating autoimmunity. Using a novel self-derived peptide that programs dendritic cell maturation and activation from monocytic precursors, the authors demonstrated suppression of autoreactivity in the NOD mouse model of type 1 diabetes. Collectively, these data are consistent with a model in which dendritic cells at different maturation and activation states regulate peripheral tolerance vs. autoimmunity

Development of Autoantibodies in the TrialNet Natural History Study

OBJECTIVE: Understanding the relationship between age and islet autoantibody (Ab) seroconversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive (GAD65(+)), insulin positive (mIAA(+)), and insulinoma-associated protein 2 positive (ICA512(+)) in a large cohort of relatives of type 1 diabetes probands undergoing Ab rescreening in the TrialNet Natural History Study. RESEARCH DESIGN AND METHODS: Of 32,845 children aged <18 years screened for Abs, 1,287 (3.9%) were GAD65(+), 778 (2.4%) were mIAA(+), 677 (2.1%) were ICA512(+), and 31,038 were Ab-negative. Ab-negative children were offered annual rescreening up to 18 years of age. Cox regression was used to estimate the risk for GAD65, mIAA, and ICA512 seroconversion. RESULTS: There were 205 children who seroconverted to GAD65(+), 155 who seroconverted to mIAA(+), and 53 who seroconverted to ICA512(+) over 5.8 years of follow-up. The risk of mIAA (hazard ratio 0.89 [95% CI 0.85–0.92]) and GAD65 (0.96 [0.93–0.99]) seroconversion significantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of seroconversion decreased by 11% [P < 0.0001] for mIAA and 4% [P = 0.04] for GAD65) across all ages. The cumulative Ab seroconversion was 2% for those <10 years of age versus 0.7% for those ≥10 years of age. CONCLUSIONS: The risk of development of islet Abs declines with increasing age in type 1 diabetes relatives. These data support annual screening for children <10 years of age and one additional screening in adolescence

Development of Autoantibodies in the TrialNet Natural History Study

OBJECTIVE: Understanding the relationship between age and islet autoantibody (Ab) seroconversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive (GAD65(+)), insulin positive (mIAA(+)), and insulinoma-associated protein 2 positive (ICA512(+)) in a large cohort of relatives of type 1 diabetes probands undergoing Ab rescreening in the TrialNet Natural History Study. RESEARCH DESIGN AND METHODS: Of 32,845 children aged <18 years screened for Abs, 1,287 (3.9%) were GAD65(+), 778 (2.4%) were mIAA(+), 677 (2.1%) were ICA512(+), and 31,038 were Ab-negative. Ab-negative children were offered annual rescreening up to 18 years of age. Cox regression was used to estimate the risk for GAD65, mIAA, and ICA512 seroconversion. RESULTS: There were 205 children who seroconverted to GAD65(+), 155 who seroconverted to mIAA(+), and 53 who seroconverted to ICA512(+) over 5.8 years of follow-up. The risk of mIAA (hazard ratio 0.89 [95% CI 0.85–0.92]) and GAD65 (0.96 [0.93–0.99]) seroconversion significantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of seroconversion decreased by 11% [P < 0.0001] for mIAA and 4% [P = 0.04] for GAD65) across all ages. The cumulative Ab seroconversion was 2% for those <10 years of age versus 0.7% for those ≥10 years of age. CONCLUSIONS: The risk of development of islet Abs declines with increasing age in type 1 diabetes relatives. These data support annual screening for children <10 years of age and one additional screening in adolescence

Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies

Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR. One hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above-threshold, uncertain) by the IEMA was derived and validated against FPIR by the RIA. The insulin IEMA-based rule accurately classified below- and above-threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161 (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was more likely among below-threshold vs above-threshold FPIRs by the RIA (64% [30/47] vs. 18% [21/114], respectively; p<0.05). An insulin IEMA for FPIR in subjects at risk for type 1 diabetes accurately determined below- and above-threshold FPIRs in 2/3 of tests relative to the current standard of the insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is limiting the insulin RIA for FPIR to the latter given the practical advantages of the more specific IEMA. ► Low first-phase insulin release (FPIR) is important to type 1 diabetes prediction and prevention studies. ► The reference standard for FPIR uses an insulin radioimmunoassay (RIA). ► We compared FPIRs by the insulin RIA to a more specific, faster insulin immunoenzymometric assay (IEMA). ► The insulin IEMA accurately classified FPIRs compared to RIA-based FPIRs in 68% of subjects. ► FPIR by the less practical insulin RIA can be limited to subjects at risk for type 1 diabetes with an uncertain FPIR by an insulin IEMA