RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1.

Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene.

The Promotion of Genomic Instability in Human Fibroblasts by Adenovirus 12 Early Region 1B 55K Protein in the Absence of Viral Infection.

The adenovirus 12 early region 1B55K (Ad12E1B55K) protein has long been known to cause non-random damage to chromosomes 1 and 17 in human cells. These sites, referred to as Ad12 modification sites, have marked similarities to classic fragile sites. In the present report we have investigated the effects of Ad12E1B55K on the cellular DNA damage response and on DNA replication, considering our increased understanding of the pathways involved.

Metabolic mechanisms of indoxacarb resistance in field populations of Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae).

Synergism and metabolic studies were conducted to identify the resistance mechanism against indoxacarb in two Choristoneura rosaceana (Harris) field populations compared to a susceptible population. The synergism study was carried out using diet incorporation bioassay for indoxacarb and the three synergists PBO, DEM, and DEF. The metabolic study consists of indoxacarb in vitro reaction with fifth instar larvae 12,000 g midgut supernatant or with pre-inhibited (in vivo by the esterases inhibitor DEF) fifth instar larvae 12,000 g midgut supernatant at different incubation times.

Productive herpesvirus lytic replication in primary effusion lymphoma cells requires S-phase entry.

Gammaherpesviruses establish lifelong latent infection in B lymphocytes and are the causative agent of several B-cell malignancies and lymphoproliferative disorders. While a quiescent latent infection allows these pathogens to evade immune detection, initiation of an alternative lifecycle stage, known as lytic replication, is an essential step in the production and dissemination of infectious progeny. Although cessation of cellular proliferation is an eventual consequence of lytic induction, exactly how gammaherpesviruses manipulate the cell cycle prior to amplification of viral DNA remains under debate.

Degradation of a Novel DNA Damage Response Protein, Tankyrase 1 Binding Protein 1, following Adenovirus Infection.

Infection by most DNA viruses activates a cellular DNA damage response (DDR), which may be to the detriment or advantage of the virus. In the case of adenoviruses, they neutralize antiviral effects of DDR activation by targeting a number of proteins for rapid proteasome-mediated degradation. We have now identified a novel DDR protein, tankyrase 1 binding protein 1 (TNKS1BP1) (also known as Tab182), which is degraded during infection by adenovirus serotype 5 and adenovirus serotype 12.

Localization of Double-Strand Break Repair Proteins to Viral Replication Compartments following Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus.

Double-strand breaks (DSBs) in DNA are recognized by the Ku70/80 heterodimer and the MRE11-RAD50-NBS1 (MRN) complex and result in activation of the DNA-PK and ATM kinases, which play key roles in regulating the cellular DNA damage response (DDR). DNA tumor viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) are known to interact extensively with the DDR during the course of their replicative cycles. Here we show that during lytic amplification of KSHV DNA, the Ku70/80 heterodimer and the MRN complex consistently colocalize with viral genomes in replication compartments (RCs), whereas other DSB repair proteins form foci outside RCs.

BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis.

A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date, however, the expression of iron regulatory protein-2 (IRP2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by quantitative RT-PCR and immunohistochemistry in human colorectal cancer tissue.

Activation of the DNA Damage Response by RNA Viruses.

RNA viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. Numerous viruses introduce DNA damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the DNA damage response (DDR), a complex and sophisticated series of cellular pathways that have evolved to detect and repair DNA lesions. Activation and manipulation of the DDR by DNA viruses has been extensively studied.

Activation of DNA Damage Response Pathways during Lytic Replication of KSHV.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of several human malignancies. Human tumour viruses such as KSHV are known to interact with the DNA damage response (DDR), the molecular pathways that recognise and repair lesions in cellular DNA. Here it is demonstrated that lytic reactivation of KSHV leads to activation of the ATM and DNA-PK DDR kinases resulting in phosphorylation of multiple downstream substrates.

Modulation of DNA damage and repair pathways by human tumour viruses.

With between 10% and 15% of human cancers attributable to viral infection, there is great interest, from both a scientific and clinical viewpoint, as to how these pathogens modulate host cell functions. Seven human tumour viruses have been identified as being involved in the development of specific malignancies. It has long been known that the introduction of chromosomal aberrations is a common feature of viral infections.

Defining terms for proactive management of resistance to Bt crops and pesticides.

Evolution of pest resistance to pesticides is an urgent global problem with resistance recorded in at least 954 species of pests, including 546 arthropods, 218 weeds, and 190 plant pathogens. To facilitate understanding and management of resistance, we provide definitions of 50 key terms related to resistance. We confirm the broad, long-standing definition of resistance, which is a genetically based decrease in susceptibility to a pesticide, and the definition of "field-evolved resistance," which is a genetically based decrease in susceptibility to a pesticide in a population caused by exposure to the pesticide in the field.

Resistance of codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), larvae in Michigan to insecticides with different modes of action and the impact on field residual activity.

Background: The codling moth is one of the principal pests of apple in the world. Resistance monitoring is crucial to the effective management of resistance in codling moth. Three populations of codling moth in neonate larvae were evaluated for resistance to seven insecticides via diet bioassays, and compared with a susceptible population.

Neural actions of imidacloprid and their involvement in resistance in the Colorado potato beetle, Leptinotarsa decemlineata (Say).

Background: The development of resistance to imidacloprid in eastern US populations of the Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), threatens this critical use for neonicotinoid insecticides. Previous pharmacokinetic studies with resistant adult CPBs provided no explanation for the high resistance level (over 200-fold) to topically applied imidacloprid. The authors assessed the neural activity of imidacloprid by recording spontaneous activity from a motor nerve leaving the isolated central nervous system to compare the sensitivity of the latter to imidacloprid between susceptible and resistant CPBs.

Agonist actions of neonicotinoids on nicotinic acetylcholine receptors expressed by cockroach neurons.

The agonist actions of seven commercial neonicotinoid insecticides and nicotine were studied on nicotinic acetylcholine receptors (nAChRs) expressed by neurons isolated from the three thoracic ganglia of the American cockroach, Periplaneta americana. Single electrode voltage clamp recording was used to measure agonist-induced inward currents. Acetylcholine, nicotine and all neonicotinoids tested, except thiamethoxam, caused inward currents which were blocked reversibly by methyllycaconitine, a nAChR antagonist.

Resistance and cross-resistance to neonicotinoid insecticides and spinosad in the Colorado potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae).

The Colorado potato beetle, Leptinotarsa decemlineata (Say), has developed resistance to many insecticides used for its control, recently including imidacloprid, a neonicotinoid compound. Other neonicotinoids are now being deployed to control this pest. A key point in the strategies of resistance management is the monitoring of resistance and cross-resistance.

Synergism of insecticides provides evidence of metabolic mechanisms of resistance in the obliquebanded leafroller Choristoneura rosaceana (Lepidoptera: Tortricidae).

The interactions between six insecticides (indoxacarb, cypermethrin, chlorpyrifos, azinphosmethyl, tebufenozide and chlorfenapyr) and three potential synergists, (piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF) and diethyl maleate (DEM)) were studied by dietary exposure in a multi-resistant and a susceptible strain of the obliquebanded leafroller, Choristoneura rosaceana (Harris). The synergists did not produce appreciable synergism with most of the insecticides in the susceptible strain. Except for tebufenozide, PBO synergized all the insecticides to varying degrees in the resistant strain.

Broad-spectrum insecticide resistance in obliquebanded leafroller Choristoneura rosaceana (Lepidoptera: Tortricidae) from Michigan.

Nineteen insecticides, belonging to nine chemical classes, were bioassayed by dietary exposure against two strains of obliquebanded leafroller, Choristoneura rosaceana, collected from Michigan apple orchards. Berrien is a putatively organophosphate-resistant strain from a commercial orchard with a history of insecticide use, and Kalamazoo a susceptible strain from an isolated and unsprayed orchard. The Berrien strain was moderately resistant (about 25-fold) to organophosphates such as azinphos-methyl and chlorpyrifos.