Expansion of the Knockdown Resistance Frequency Map for Human Head Lice (Phthiraptera: Pediculidae) in the United States Using Quantitative Sequencing

Pediculosis is a prevalent parasitic infestation of humans, which is increasing due, in part, to the selection of lice resistant to either the pyrethrins or pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine the extent and magnitude of thekdr-type mutations responsible for this resistance, lice were collected from 138 collection sites in 48 U.S. states from 22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously published data were used for comparisons of the changes in the frequency of thekdr-type mutations over time. Mean percent resistance allele frequency (mean % RAF) values across the three mutation loci were determined from each collection site. The overall mean % RAF (+/-SD) for all analyzed lice was 98.3 +/- 10%. 132/138 sites (95.6%) had a mean % RAF of 100%, five sites (3.7%) had intermediate values, and only a single site had no mutations (0.0%). Forty-two states (88%) had a mean % RAF of 100%. The frequencies ofkdr-type mutations did not differ regardless of the human population size that the lice were collected from, indicating a uniformly high level of resistant alleles. The loss of efficacy of the Nix formulation (Prestige Brand, Tarrytown, NY) from 1998 to 2013 was correlated to the increase inkdr-type mutations. These data provide a plausible reason for the decrease in the effectiveness of permethrin in the Nix formulation, which is the parallel increase ofkdr-type mutations in lice over time

Quantitative Sequencing for the Determination of Kdr-type Resistance Allele (V419L,L925I, I936F) Frequencies in Common Bed Bug, Cimex lectularius L., (Hemiptera: Cimicidae) Populations Collected from Israel

Human bed bug infestations have dramatically increased worldwide since the mid-1990s. A similar phenomenon was also observed in Israel since 2005, when infestations were reported from all over the country. Two single nucleotide polymorphisms (V419L and L925I) in the bed bug voltage sensitive sodium channel confer kdr-type resistance to pyrethroids. Using quantitative sequencing (QS), the resistance allele frequencies of Israeli bed bug populations from across the country were determined. Genomic DNA was extracted from samples of 12 populations of bed bugs collected from Israel and DNA fragments containing the V419L or L925I and I936F mutations sites were PCR amplified. The PCR products were analyzed by QS and the nucleotide signal ratios calculated and used to predict the resistance allele frequencies of the unknown populations. Results of the genetic analysis show that resistant nucleotide signals are highly correlated to resistance allele frequencies for both mutations. Ten of the 12 tested populations had 100% of the L925I mutation and 0% of the V419L mutation. One population was heterogeneous for the L925I mutation and had 0% of the V419L mutation and another population was heterozygous for the V419L mutation and had 100% of the L925I mutation. I936F occurred only at low levels. These results indicate that bed bugs in Israel are genetically resistant to pyrethroids. Thus, pyrethroids should only be used for bed bug management with caution using effective application and careful monitoring procedures. Additionally, new and novel-acting insecticides and non-chemical means of controlling bed bugs should be explored

A Systems Approach Uncovers Restrictions for Signal Interactions Regulating Genome-wide Responses to Nutritional Cues in Arabidopsis

As sessile organisms, plants must cope with multiple and combined variations of signals in their environment. However, very few reports have studied the genome-wide effects of systematic signal combinations on gene expression. Here, we evaluate a high level of signal integration, by modeling genome-wide expression patterns under a factorial combination of carbon (C), light (L), and nitrogen (N) as binary factors in two organs (O), roots and leaves. Signal management is different between C, N, and L and in shoots and roots. For example, L is the major factor controlling gene expression in leaves. However, in roots there is no obvious prominent signal, and signal interaction is stronger. The major signal interaction events detected genome wide in Arabidopsis roots are deciphered and summarized in a comprehensive conceptual model. Surprisingly, global analysis of gene expression in response to C, N, L, and O revealed that the number of genes controlled by a signal is proportional to the magnitude of the gene expression changes elicited by the signal. These results uncovered a strong constraining structure in plant cell signaling pathways, which prompted us to propose the existence of a “code” of signal integration

The Short Non-Coding Transcriptome of the Protozoan Parasite Trypanosoma cruzi

The pathway for RNA interference is widespread in metazoans and participates in numerous cellular tasks, from gene silencing to chromatin remodeling and protection against retrotransposition. The unicellular eukaryote Trypanosoma cruzi is missing the canonical RNAi pathway and is unable to induce RNAi-related processes. To further understand alternative RNA pathways operating in this organism, we have performed deep sequencing and genome-wide analyses of a size-fractioned cDNA library (16–61 nt) from the epimastigote life stage. Deep sequencing generated 582,243 short sequences of which 91% could be aligned with the genome sequence. About 95–98% of the aligned data (depending on the haplotype) corresponded to small RNAs derived from tRNAs, rRNAs, snRNAs and snoRNAs. The largest class consisted of tRNA-derived small RNAs which primarily originated from the 3′ end of tRNAs, followed by small RNAs derived from rRNA. The remaining sequences revealed the presence of 92 novel transcribed loci, of which 79 did not show homology to known RNA classes

Increasing IT Value for Customers: A Challenge for Higher Education

This research bulletin strives to answer the question, What must a central IT organization in an academic environment do to increase its value to its clients and its institution? It is not a cookbook for how to create a successful IT organization, but rather a discussion of considerations for increasing value. Treacy and Wiersema suggest that successful IT organizations choose to focus almost exclusively on one value proposition from among these three: product leadership, operational excellence, and customer intimacy. While these three areas offered us a good starting point, our research suggested that a single focus was less applicable for a central IT organization in higher education. Rather, we discovered that a combination of slightly modified propositions is more suited to the academic environment: operational excellence, organizational management, and client partnership. We concluded that an organization that excels in these three areas will be highly valued by the people who use its services. In this way, IT can make a dramatic shift from being regarded on campus as an expense that needs to be controlled to being viewed as a strategic partner in addressing and solving academic and business problems

Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention

Alzheimer’s disease (AD) is a neurodegenerative dementia that affects nearly 50 million people worldwide and is a major source of morbidity, mortality, and healthcare expenditure. While there have been many attempts to develop disease-modifying therapies for late-onset AD, none have so far shown efficacy in humans. However, the long latency between the initial neuronal changes and onset of symptoms, the ability to identify patients at risk based on family history and genetic markers, and the emergence of AD biomarkers for preclinical disease suggests that early risk-reducing interventions may be able to decrease the incidence of, delay or prevent AD. In this review, we discuss six mechanisms—dysregulation of glucose metabolism, inflammation, oxidative stress, trophic factor release, amyloid burden, and calcium toxicity—involved in AD pathogenesis that offer promising targets for risk-reducing interventions. In addition, we offer a blueprint for a multi-modality AD risk reduction program that can be clinically implemented with the current state of knowledge. Focused risk reduction aimed at particular pathological factors may transform AD to a preventable disorder in select cases

The putative high-affinity nitrate transporter NRT2.1 represses lateral root initiation in response to nutritional cues

Lateral root initiation is strongly repressed in Arabidopsis by the combination of high external sucrose and low external nitrate. A previously isolated mutant, lin1, can overcome this repression. Here, we show that lin1 carries a missense mutation in the NRT2.1 gene. Several allelic mutants, including one in which the NRT2.1 gene is completely deleted, show similar phenotypes to lin1 and fail to complement lin1. NRT2.1 encodes a putative high-affinity nitrate transporter that functions at low external nitrate concentrations. Direct measurement of nitrate uptake and nitrate content in the lin1 mutant seedlings established that both are indeed reduced. Because repression of lateral root initiation in WT plants can be relieved by increased concentrations of external nitrate, it is surprising to find that repression is also relieved by a defect in a component of the high-affinity nitrate uptake system. Furthermore, lateral root initiation is increased in lin1 relative to WT even when seedlings are grown on nitrate-free media, suggesting that the mutant phenotype is nitrate-independent. These results indicate that NRT2.1 is a repressor of lateral root initiation and that this role is independent of nitrate uptake. We propose that Arabidopsis NRT2.1 acts either as a nitrate sensor or signal transducer to coordinate the development of the root system with nutritional cues