Middle-School Student Engagement in a Tick Testing Community Science Project.

Studies of tickborne illness have benefited from interactions between scientists and community members. Most participants in community science projects are well-educated adults, but there are anticipated benefits from engaging younger students in research. We evaluated whether an outreach experience for rural middle-school students promoted student interest in science and resulted in the generation of samples that could be used for tick testing to assess disease risk.

Induction of expression through JNK and cGAS-STING modulates DNA damage-induced cytokine production.

Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun amino-terminal kinase (JNK) and cGAS-STING and that expression was required for the subsequent production of the cytokines IL-1, IL-6, and IL-8. expression was stimulated by diverse cellular stresses, including inhibition of the DNA replication checkpoint kinase ATR (ataxia telangiectasia and Rad3-related protein), oncogene expression, replicative exhaustion, oxidative stress, and DNA double-strand breaks.

pH responsive poly amino-acid hydrogels formed via silk sericin templating.

Poly(amino acid) hydrogels have attracted a great deal of attention as biodegradable biomaterials that can limit products of synthetic polymer degradation. Here we report on a stimuli-responsive, porous, composite biomaterial based on the protein templating of the poly(amino acid) hydrogel from poly(aspartic acid) with the silk protein sericin. This low-cost, biocompatible and biodegradable hydrogel demonstrates a greatly increased porosity and improvement in volumetric swelling over networks formed from pure poly(aspartic acid).

RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells.

The ATR-CHK1 axis stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Here, we show that fork collapse in Atr-deleted cells is mediated through the combined effects the sumo targeted E3-ubiquitin ligase RNF4 and activation of the AURKA-PLK1 pathway. As indicated previously, Atr-deleted cells exhibited a decreased ability to restart DNA replication following fork stalling in comparison with control cells.

Ethanol-mediated perivascular renal sympathetic denervation: preclinical validation of safety and efficacy in a porcine model.

Aims: We report the use of a novel endovascular approach using chemical neurolysis, via periadventitial injection of dehydrated ethanol (EtOH) to perform renal artery denervation.

Methods And Results: A novel, three-needle delivery device was introduced into the renal arteries of adult swine using fluoroscopic guidance. EtOH was injected bilaterally with one injection per artery, via the three needles into the adventitial and periadventitial space, using EtOH doses 0.

Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR.

Oncogenic Ras and p53 loss-of-function mutations are common in many advanced sporadic malignancies and together predict a limited responsiveness to conventional chemotherapy. Notably, studies in cultured cells have indicated that each of these genetic alterations creates a selective sensitivity to ataxia telangiectasia and Rad3-related (ATR) pathway inhibition. Here, we describe a genetic system to conditionally reduce ATR expression to 10% of normal levels in adult mice to compare the impact of this suppression on normal tissues and cancers in vivo.

Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner.

Previous studies indicate that oncogenic stress activates the ATR-Chk1 pathway. Here, we show that ATR-Chk1 pathway engagement is essential for limiting genomic instability following oncogenic Ras transformation. ATR pathway inhibition in combination with oncogenic Ras expression synergistically increased genomic instability, as quantified by chromatid breaks, sister chromatid exchanges, and H2AX phosphorylation.

Differential roles for DNA polymerases eta, zeta, and REV1 in lesion bypass of intrastrand versus interstrand DNA cross-links.

Translesion DNA synthesis (TLS) is a process whereby specialized DNA polymerases are recruited to bypass DNA lesions that would otherwise stall high-fidelity polymerases. We provide evidence that TLS across cisplatin intrastrand cross-links is performed by multiple translesion DNA polymerases. First, we determined that PCNA monoubiquitination by RAD18 is necessary for efficient bypass of cisplatin adducts by the TLS polymerases eta (Poleta), REV1, and zeta (Polzeta) based on the observations that depletion of these proteins individually leads to decreased cell survival, cell cycle arrest in S phase, and activation of the DNA damage response.

Mice hypomorphic for Atr have increased DNA damage and abnormal checkpoint response.

The ATR checkpoint pathway responds to DNA damage during the S/G2 phases of the cell cycle and is activated early in tumorigenesis. Investigation of ATR's role in development and tumorigenesis is complicated by the lethality of homozygous knockout mice and the limited effects of heterozygous deficiency. To overcome this limitation, we sought to create mice with a hypomorphic Atr mutation based on the ATR mutation in the human disease Seckel syndrome-1 (SCKL1).

Replication stress induces genome-wide copy number changes in human cells that resemble polymorphic and pathogenic variants.

Copy number variants (CNVs) are an important component of genomic variation in humans and other mammals. Similar de novo deletions and duplications, or copy number changes (CNCs), are now known to be a major cause of genetic and developmental disorders and to arise somatically in many cancers. A major mechanism leading to both CNVs and disease-associated CNCs is meiotic unequal crossing over, or nonallelic homologous recombination (NAHR), mediated by flanking repeated sequences or segmental duplications.

Stably transfected common fragile site sequences exhibit instability at ectopic sites.

Common fragile sites (CFSs) are loci that are especially prone to forming gaps and breaks on metaphase chromosomes under conditions of replication stress. Although much has been learned about the cellular responses to gaps and breaks at CFSs, less is known about what makes these sites inherently unstable. CFS sequences are highly conserved in mammalian evolution and contain a number of sequence motifs that are hypothesized to contribute to their instability.

Replication stress induces tumor-like microdeletions in FHIT/FRA3B.

Common fragile sites (CFSs) are loci that preferentially exhibit metaphase chromosome gaps and breaks after partial inhibition of DNA synthesis. The fragile site FRA3B, which lies within the FHIT tumor-suppressor gene, is a site of frequent heterozygous and homozygous deletions in many cancer cells and precancerous lesions. The great majority of FHIT and other CFS-associated gene rearrangements in tumors are submicroscopic, intralocus deletions of hundreds of kilobases that often result in inactivation of associated genes.

Common fragile sites as targets for chromosome rearrangements.

Common fragile sites are large chromosomal regions that preferentially exhibit gaps or breaks after DNA synthesis is partially perturbed. Fragile site instability in cultured cells is well documented and includes gaps and breaks on metaphase chromosomes, translocation and deletions breakpoints, and sister chromosome exchanges. In recent years, much has been learned about the genomic structure at fragile sites and the cellular mechanisms that monitor their stability.

Closed treatment of nonrheumatoid extensor tendon dislocations at the metacarpophalangeal joint.

Purpose: Acute sagittal band injuries at the metacarpophalangeal (MCP) joint resulting in subluxation or dislocation of the extensor tendons may cause pain and swelling at the MCP joint and limit active extension of the MCP joint. These injuries often are treated with surgical repair or reconstruction. This article outlines a nonsurgical treatment protocol that uses a customized splint for acute, nonrheumatoid extensor tendon dislocations caused by injury to the sagittal bands.

Forearm compartment syndrome in the newborn: report of 24 cases.

Purpose: Isolated cases of ischemia, compartment syndrome, or Volkmann's ischemic contracture in the forearm of the newborn infant have been reported in the past. The purpose of this study is to review a large series of patients with neonatal forearm compartment syndrome and to report the important clinical features.

Methods: A search of medical records from 1980 to 2000 identified 24 children with evidence of ischemia of the forearm at the time of birth.

Relevance of carcass palpation in lambs to protecting public health.

We recently reviewed the Food Safety and Inspection Service's (FSIS's) inspection procedures for lambs. As a result, FSIS published a Federal Register notice informing the public of its intent to change from an inspection system that requires extensive carcass palpation to an inspection system that requires no carcass palpation for lambs. This decision was based on the following three points.

Teleradiology: experiences with magnetic resonance imaging using this new technology.

Teleradiology, a term encompassing electronic transmission of images for interpretation, is becoming an important part of telemedicine. Telemedicine is an exciting new electronic means of distributing specific medical knowledge by computer network. Teleradiology allows healthcare providers in locations that previously might not have had this service to access the use of radiology specialists and subspecialists.

Basimeningeal/spinal axis primitive neuroectodermal tumor without intraaxial lesion: radiological features.

Over a 12-year period, the authors encountered 2 patients with spinal axis/basimeningeal primitive neuroectodermal tumor (PNET) involving the spinal axis extramedullary, intradural compartment and the basimeninges. In neither patient was an intraaxial focus demonstrated. A 48-year-old woman had computed tomography (CT) findings of hydrocephalus and later abnormal basimeningeal enhancement.

Cerebral demyelination syndrome in a patient treated with 5-fluorouracil and levamisole. The use of thallium SPECT imaging to assist in noninvasive diagnosis--a case report.

Background: The use of 5-fluorouracil (5-FU) and levamisole in patients with Stage III adenocarcinoma of the colon has now become standard. There have been several reports of a multifocal cerebral demyelination syndrome following 5-FU and levamisole administration.

Methods: We describe a patient who developed focal neurologic symptoms while being treated with levamisole and 5-FU in whom the diagnosis of central nervous system (CNS) metastases was considered.

Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder.

We used a paradigm involving monozygotic (MZ) twin pairs discordant for schizophrenia (n = 20) and concordant for schizophrenia (n = 8), as well as normal MZ twin pairs (n = 7) in order to study cognitive measures of genetic risk in schizophrenia. A comparison between the unaffected twins from the discordant sample and the normal twins indicated subtle attenuations in some aspects of memory and executive functioning in the unaffected group and thus provided evidence for cognitive markers of a genetic component in schizophrenia. A comparison of the affected twins from the discordant pairs and the concordant twins yielded virtually no differences, suggesting that a distinction between familial and sporadic cases is not valid in this sample.