A Review of Control Options and Externalities for Verticillium Wilts.

Plant pathogens migrate to new regions through human activities such as trade, where they may establish themselves and cause disease on agriculturally important crops. Verticillium wilt of lettuce, caused by Verticillium dahliae, is a soilborne fungus that was introduced to coastal California via infested spinach seeds. It has caused significant losses for lettuce growers. Once introduced, Verticillium wilt could be managed by fumigating with methyl bromide and chloropicrin, but this option is no longer available. Growers can also manage the disease by planting broccoli or not planting spinach. These control options require long-term investments for future gain. Verticillium wilt can also be prevented or controlled by testing and providing spinach seeds with little or no V. dahliae infestation. However, seed companies have been reluctant to test or clean spinach seeds, as spinach crops are not affected by Verticillium wilt. Thus, available control options are affected by externalities. Renters and other producers with short time horizons will not undertake long-term investments and seed companies do not take into account the effect of their decision not to test on lettuce producers. We review the literature on the economics of managing crop disease; discuss the economics of managing Verticillium wilt; and review the recent research on the externalities that arise with short-term growers, and between seed companies and growers due to Verticillium wilt. An externality arises whenever the actions of one individual or firm affects the payoffs to another individual or firm not involved in a specific transaction. These externalities have important implications for the management of Verticillium wilt and, more broadly, for the management of migratory pathogens and the diseases they cause in agriculture in general. This review is of interest to policy-makers, the producers, marketers, seed companies, and researchers.

Identification of a unique hybrid macrophage-polarization state following recovery from lipopolysaccharide tolerance.

LPS tolerance is an essential immune-homeostatic response to repeated exposure to LPS that prevents excessive inflammatory responses. LPS tolerance induces a state of altered responsiveness in macrophages, resulting in repression of proinflammatory gene expression and increased expression of factors that mediate the resolution of inflammation. In this study, we analyzed the transcriptional plasticity of macrophages following LPS tolerance using genome-wide transcriptional profiling. We demonstrate that LPS tolerance is a transient state and that the expression of proinflammatory genes is restored to levels comparable to the acute response to LPS. However, following recovery from LPS tolerance a number of genes remained locked in a tolerizable state, including IL-33, CD86, IL-10, and NFIL3. Furthermore, we identified of a number of genes uniquely induced following recovery from LPS tolerance. Thus, macrophages adopt a unique transcriptional profile following recovery from LPS tolerance and have a distinct expression pattern of regulators of Ag presentation, antiviral responses, and transcription factors. Our data suggest that recovery from LPS tolerance leads to a hybrid macrophage activation state that is proinflammatory and microbicidal in nature but that possesses a regulatory anti-inflammatory profile distinct from that of LPS-tolerant and LPS-activated macrophages.

Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription.

NF-κB is the master regulator of the immune response and is responsible for the transcription of hundreds of genes controlling inflammation and immunity. Activation of NF-κB occurs in the cytoplasm through the kinase activity of the IκB kinase complex, which leads to translocation of NF-κB to the nucleus. Once in the nucleus, NF-κB transcriptional activity is regulated by DNA binding-dependent ubiquitin-mediated proteasomal degradation. We have identified the deubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-κB transcriptional activity. USP7 deubiquitination of NF-κB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-κB, leading to reduced promoter occupancy and reduced expression of target genes in response to Toll-like- and TNF-receptor activation. These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the deubiquitination of NF-κB by USP7 is critical for target gene transcription.

Supporting parents following pregnancy loss: a cross-sectional study of telephone peer supporters.

BACKGROUND: The death of a baby before or soon after birth can place an enormous psychological toll on parents. Parent support groups have grown in response to bereaved parents' unmet needs for support. Peer support is the hallmark of these organisations but little is known about the experiences of volunteers who provide support. This study examines the perceptions and experiences of parent support group volunteers who deliver a 24-h telephone support service for the Australian Stillbirth and Newborn Death Support (Sands) organisation in order to inform the ongoing development and sustainability of effective peer support. This parent-led organisation has delivered support to those affected by miscarriage, stillbirth and newborn death for more than 30 years. METHODS: Twenty-four Parent Supporters completed an online questionnaire. A mix of open- and closed questions asked about aspects of the Parent Supporter role. Quantitative data was summarised using descriptive statistics. Free-text responses to open-ended items were categorised and used to extend and illustrate the quantitative findings. RESULTS: Our findings reveal a group of highly dedicated and experienced volunteers who had taken 473 calls in the preceding 12 months. Calls were diverse but most were from bereaved mothers seeking 'to talk with someone who understands' in the early weeks and months after stillbirth or miscarriage. Most Parent Supporters indicated they felt well-prepared, confident, and satisfied in their role. Challenges include balancing the demands of the role and ongoing training and support. CONCLUSIONS: Peer volunteers contribute to addressing a significant need for support following pregnancy loss. Delivering and sustaining high quality parent-led support depends on volunteer recruitment and retention and this, in turn, requires organisational responses.

mRNA initiation and termination are spatially coordinated.

The expression of a precise mRNA transcriptome is crucial for establishing cell identity and function, with dozens of alternative isoforms produced for a single gene sequence. The regulation of mRNA isoform usage occurs by the coordination of co-transcriptional mRNA processing mechanisms across a gene. Decisions involved in mRNA initiation and termination underlie the largest extent of mRNA isoform diversity, but little is known about any relationships between decisions at both ends of mRNA molecules. Here, we systematically profile the joint usage of mRNA transcription start sites (TSSs) and polyadenylation sites (PASs) across tissues and species. Using both short and long read RNA-seq data, we observe that mRNAs preferentially using upstream TSSs also tend to use upstream PASs, and congruently, the usage of downstream sites is similarly paired. This observation suggests that mRNA 5' end choice may directly influence mRNA 3' ends. Our results suggest a novel "Positional Initiation-Termination Axis" (PITA), in which the usage of alternative terminal sites are coupled based on the order in which they appear in the genome. PITA isoforms are more likely to encode alternative protein domains and use conserved sites. PITA is strongly associated with the length of genomic features, such that PITA is enriched in longer genes with more area devoted to regions that regulate alternative 5' or 3' ends. Strikingly, we found that PITA genes are more likely than non-PITA genes to have multiple, overlapping chromatin structural domains related to pairing of ordinally coupled start and end sites. In turn, PITA coupling is also associated with fast RNA Polymerase II (RNAPII) trafficking across these long gene regions. Our findings indicate that a combination of spatial and kinetic mechanisms couple transcription initiation and mRNA 3' end decisions based on ordinal position to define the expression mRNA isoforms.

Evidence that marine-derived, multi-mineral, Aquamin inhibits the NF-κB signaling pathway in vitro.

It is well established that nuclear factor kappa B (NF-κB) is a central regulator of the immune response and that dysregulation of NF-κB contributes to the pathogenesis of many autoimmune and inflammatory diseases. The food supplement Aquamin is a natural multi-mineral derived from the red algae Lithothamnion corallioides, rich in calcium, magnesium and 72 other trace minerals. This study describes an anti-inflammatory role for Aquamin in inhibiting NF-κB activation through reducing the phosphorylation and degradation of its upstream inhibitor IκBα. Aquamin inhibition of NF-κB activation results in significantly reduced cyclo-oxygenase-2 gene expression following treatment of macrophage cells with lipopolysaccharide. These data suggest that nutritional supplements such as Aquamin may play an important role in regulating the inflammatory response by modulating the nuclear factor kappa B signalling pathway.

Acute on chronic back pain as the presentation of an occult foreign body bowel perforation with resultant epidural abscess, osteomyelitis and sepsis.

A 29-year-old male paratrooper presented to multiple emergency departments (EDs) and his primary provider multiple times over sequential days. Each time, the patient received the same diagnosis of acute on chronic back pain. The patient was treated conservatively and routine MRI of the lumbar spine was performed 5 days after the last visit. It revealed a lesion occupying nearly all the visualised portion of the spinal canal. The patient was immediately called back for further imaging. The patient was then diagnosed with a foreign body perforating the rectosigmoid colon, an epidural abscess and pelvic osteomyelitis. The patient was immediately taken to the ED where he was found to be septic. The foreign body was surgically removed and determined to be a swallowed toothpick. Urgent surgical decompression of epidural space was also performed. The patient then underwent a prolonged but near complete recovery.

Timing dysfunctions in schizophrenia span from millisecond to several-second durations.

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. However, the majority of studies that have examined timing behavior in schizophrenia have employed temporal durations in the range of several seconds, which requires higher cognitive processes beyond initial sensory registration for temporal encoding. Accordingly, the present study assessed both millisecond and several-second duration estimates in schizophrenia using a well-established task of time perception. Twenty-eight individuals with schizophrenia and 31 non-psychiatric control participants completed two temporal bisection tasks, which required participants to make temporal judgments about auditory durations ranging from either 300 to 600 ms or 3000 to 6000 ms. Participants with schizophrenia displayed significantly greater timing variability under both millisecond and several-second timing conditions than the non-psychiatric group. These findings were consistent with parameter estimates obtained from a quantitative model of time estimation, and provide evidence for a fundamental timing deficit in schizophrenia that may be independent of the length of the to-be-timed duration.

Timing dysfunctions in schizophrenia as measured by a repetitive finger tapping task.

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. Although a variety of behavioral studies have provided strong evidence for perceptual timing deficits in schizophrenia, no study to date has directly examined overt temporal performance in schizophrenia using a task that differentially engages perceptual and motor-based timing processes. The present study aimed to isolate perceptual and motor-based temporal performance in individuals diagnosed with schizophrenia using a repetitive finger-tapping task that has previously been shown to differentially engage brain regions associated with perceptual and motor-related timing behavior. Thirty-two individuals with schizophrenia and 31 non-psychiatric control participants completed the repetitive finger-tapping task, which required participants to first tap in time with computer-generated tones separated by a fixed intertone interval (tone-paced tapping), after which the tones were discontinued and participants were required to continue tapping at the established pace (self-paced tapping). Participants with schizophrenia displayed significantly faster tapping rates for both tone- and self-paced portions of the task compared to the non-psychiatric group. Individuals diagnosed with schizophrenia also displayed greater tapping variability during both tone- and self-paced portions of the task. The application of a mathematical timing model further indicated that group differences were primarily attributable to increased timing--as opposed to task implementation--difficulties in the schizophrenia group, which is noteworthy given the broad range of impairments typically associated with the disorder. These findings support the contention that schizophrenia is associated with a broad range of timing difficulties, including those associated with time perception as well as time production.

Contributions of spectral frequency analyses to the study of P50 ERP amplitude and suppression in bipolar disorder with or without a history of psychosis.

OBJECTIVE: The present study investigated event-related brain potential (ERP) indices of auditory processing and sensory gating in bipolar disorder and subgroups of bipolar patients with or without a history of psychosis using the P50 dual-click procedure. Auditory-evoked activity in two discrete frequency bands also was explored to distinguish between sensory registration and selective attention deficits. METHODS: Thirty-one individuals with bipolar disorder and 28 non-psychiatric controls were compared on ERP indices of auditory processing using a dual-click procedure. In addition to conventional P50 ERP peak-picking techniques, quantitative frequency analyses were applied to the ERP data to isolate stages of information processing associated with sensory registration (20-50 Hz; gamma band) and selective attention (0-20 Hz; low-frequency band). RESULTS: Compared to the non-psychiatric control group, patients with bipolar disorder exhibited reduced S1 response magnitudes for the conventional P50 peak-picking and low-frequency response analyses. A bipolar subgroup effect suggested that the attenuated S1 magnitudes from the P50 peak-picking and low-frequency analyses were largely attributable to patients without a history of psychosis. CONCLUSIONS: The analysis of distinct frequency bands of the auditory-evoked response elicited during the dual-click procedure allowed further specification of the nature of auditory sensory processing and gating deficits in bipolar disorder with or without a history of psychosis. The observed S1 effects in the low-frequency band suggest selective attention deficits in bipolar patients, especially those patients without a history of psychosis, which may reflect a diminished capacity to selectively attend to salient stimuli as opposed to impairments of inhibitory sensory processes.

Temporal processing dysfunction in schizophrenia.

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. Despite the growing interest and centrality of time-dependent conceptualizations of the pathophysiology of schizophrenia, there remains a paucity of research directly examining overt timing performance in the disorder. Accordingly, the present study investigated timing in schizophrenia using a well-established task of time perception. Twenty-three individuals with schizophrenia and 22 non-psychiatric control participants completed a temporal bisection task, which required participants to make temporal judgments about auditory and visually presented durations ranging from 300 to 600 ms. Both schizophrenia and control groups displayed greater visual compared to auditory timing variability, with no difference between groups in the visual modality. However, individuals with schizophrenia exhibited less temporal precision than controls in the perception of auditory durations. These findings correlated with parameter estimates obtained from a quantitative model of time estimation, and provide evidence of a fundamental deficit in temporal auditory precision in schizophrenia.

An Unusual Presentation of Murine Typhus and Mononucleosis.

A 20-year-old female presented to the emergency department complaining of fever, cough, and dyspnea after a recent camping trip. The patient remained ill appearing, persistently tachycardic and dyspneic despite nebulizer treatments, and fluids in the emergency department. She was admitted for observation and gradually improved over the next 4 d. Inpatient laboratory studies indicated acute Epstein-Barr virus infection and she was discharged with a presumptive diagnosis of infectious mononucleosis. However, further testing showed a simultaneous rickettsial infection producing murine typhus. The patient ultimately recovered uneventfully once proper treatment was initiated. This patient's presentation represents a unique description of simultaneous infectious mononucleosis and murine typhus which underscores the importance of maintaining a broad differential diagnosis in the approach to febrile illnesses.

Toll-Like Receptors Drive Specific Patterns of Tolerance and Training on Restimulation of Macrophages.

Tolerance is a long-recognized property of macrophages that leads to an altered response to repeated or chronic exposure to endotoxin. The physiological role of tolerance is to limit the potential damage to host tissue that may otherwise result from prolonged production of pro-inflammatory cytokines. Tolerance is induced by all toll-like receptor (TLR) ligands tested to date, however, tolerance induced by the TLR4 ligand lipopolysaccharide (LPS) is by far the best studied. LPS tolerance involves a global transcriptional shift from a pro-inflammatory response toward one characterized by the expression of anti-inflammatory and pro-resolution factors. Although largely reversible, LPS-tolerance leads to a hybrid macrophage activation state that is pro-inflammatory in nature, but possesses distinct regulatory anti-inflammatory features. Remarkably, a comparative transcriptomic analysis of tolerance induced by different TLR ligands has not previously been reported. Here, we describe the transcriptomic profiles of mouse macrophages tolerized with ligands for TLR2, TLR3, TLR4 and TLR 9. While we identified TLR-specific transcriptional profiles in macrophages tolerized with each ligand, tolerance induced by TLR4 represented an archetype pattern, such that each gene tolerized by any of the TLRs tested was also found to be tolerized by TLR4. Pro-inflammatory cytokines are not universally suppressed in all tolerant cells, but distinct patterns of cytokine expression distinguished TLR-specific tolerance. Analysis of gene regulatory regions revealed specific DNA sequence motifs associated with distinct states of TLR tolerance, implicating previously identified as well as novel transcriptional regulators of tolerance in macrophages. These data provide a basis for the future exploitation of TLR-specific tolerant states to achieve therapeutic re-programming of the innate immune response.

Nonspecific Headache Diagnosed as a Brain Colloid Cyst with Hydrocephalus.

A 29-year-old male presented to our emergency department with complaints of a left frontal headache, similar to his prior headaches. He also reported about 30 minutes of facial and tongue numbness, left arm weakness, slurred speech and changes in hearing that had resolved prior to his arrival. Despite the short duration of the other neurologic symptoms, he also endorsed persistent "dizziness." Despite his history of recurrent headaches, he had never had any neuroimaging. This, as well as his reports of new neurological symptoms, prompted his care team to obtain a non-contrast brain computed tomography. The findings were consistent with a mass with mild hydrocephalus. Patient underwent neurosurgical resection of the mass at a tertiary center. He did well after surgery and was discharged on postop day 6 with a diagnosis of colloid cyst.

Winging of the scapula diagnosed as Parsonage-Turner syndrome: a case report.

A 24-year-old active duty female Soldier complained of right shoulder burning, stinging, electrical shock-like pain with radiation to the right hand after completing a ruck march. She also complained of swelling and feelings of her cold right hand. Examination showed a deficit in the deltoid, upper trapezius, supraspinatus, and also right winging of the scapula. She also exhibited weakness to right arm, weak right hand grip, and decreased sensation over the dorsal right hand. The right hand was also noticed to be colder to touch than the left one. She had tenderness to palpation over right paracervical muscles from C3 to C7. A previous magnetic resonance arthrogram of the right shoulder revealed no findings. The cervical magnetic resonance imagery showed mild disc protrusion at C5-C6 without spinal cord impingement. Based on the history and the physical findings, the patient was diagnosed with Parsonage-Turner syndrome.

Various mutations compensate for a deleterious lacZα insert in the replication enhancer of M13 bacteriophage.

M13 and other members of the Ff class of filamentous bacteriophages have been extensively employed in myriad applications. The Ph.D. series of phage-displayed peptide libraries were constructed from the M13-based vector M13KE. As a direct descendent of M13mp19, M13KE contains the lacZα insert in the intergenic region between genes IV and II, where it interrupts the replication enhancer of the (+) strand origin. Phage carrying this 816-nucleotide insert are viable, but propagate in E. coli at a reduced rate compared to wild-type M13 phage, presumably due to a replication defect caused by the insert. We have previously reported thirteen compensatory mutations in the 5'-untranslated region of gene II, which encodes the replication initiator protein gIIp. Here we report several additional mutations in M13KE that restore a wild-type propagation rate. Several clones from constrained-loop variable peptide libraries were found to have ejected the majority of lacZα gene in order to reconstruct the replication enhancer, albeit with a small scar. In addition, new point mutations in the gene II 5'-untranslated region or the gene IV coding sequence have been spontaneously observed or synthetically engineered. Through phage propagation assays, we demonstrate that all these genetic modifications compensate for the replication defect in M13KE and restore the wild-type propagation rate. We discuss the mechanisms by which the insertion and ejection of the lacZα gene, as well as the mutations in the regulatory region of gene II, influence the efficiency of replication initiation at the (+) strand origin. We also examine the presence and relevance of fast-propagating mutants in phage-displayed peptide libraries.

Steady state visual evoked potential abnormalities in schizophrenia.

OBJECTIVE: The steady state visual evoked potential (SSVEP) can be used to test the frequency response function of neural circuits. Previous studies have shown reduced SSVEPs to alpha and lower frequencies of stimulation in schizophrenia. We investigated SSVEPs in schizophrenia at frequencies spanning the theta (4Hz) to gamma (40Hz) range. METHODS: The SSVEPs to seven different frequencies of stimulation (4, 8, 17, 20, 23, 30 and 40Hz) were obtained from 18 schizophrenia subjects and 33 healthy control subjects. Power at stimulating frequency (signal power) and power at frequencies above and below the stimulating frequency (noise power) were used to quantify the SSVEP responses. RESULTS: Both groups showed an inverse relationship between power and frequency of stimulation. Schizophrenia subjects showed reduced signal power compared to healthy control subjects at higher frequencies (above 17Hz), but not at 4 and 8Hz at occipital region. Noise power was higher in schizophrenia subjects at frequencies between 4 and 20Hz over occipital region and at 4, 17 and 20Hz over frontal region. CONCLUSIONS: SSVEP signal power at beta and gamma frequencies of stimulation were reduced in schizophrenia. Schizophrenia subjects showed higher levels of EEG noise during photic stimulation at beta and lower frequencies. SIGNIFICANCE: Inability to generate or maintain oscillations in neural networks may contribute to deficits in visual processing in schizophrenia.

Measurement of NF-κB transcriptional activity and identification of NF-κB cis-regulatory elements using luciferase assays.

The NF-κB family of transcription factors is activated in response to numerous environmental stimuli and coordinates the transcriptional response to immunoreceptors such as the Toll-like receptors, cytokine receptors, and antigen receptors, growth factors, survival factors, and stress signals such as ultraviolet irradiation and oxidative stress. The transcriptional targets of these various pathways include approximately 500 experimentally indentified genes, and it is highly likely that many others remain to be discovered. A genome-wide analysis of NF-κB-chromatin interactions has revealed a surprisingly large number of NF-κB binding sites across the entire genome, many of which are found in intergenic regions and many more do not appear to be associated with changes in transcription of nearby genes. Assessing the consequences of NF-κB binding at genomic sites is therefore essential to determine the functional role of NF-κB in regulating the expression of specific genes. Luciferase-based reporter assays provide a robust and flexible method to test the contribution of specific NF-κB sites to the regulation of gene transcription. The methods described in this chapter may be applied to any promoter sequence and used in a variety of cell lines and conditions to provide critical information on the regulation of gene expression by NF-κB.

Neural synchronization deficits to auditory stimulation in bipolar disorder.

Patients with bipolar disorder show cognitive deficits and disorganized behavior, which may reflect a disturbance in neural synchronization. We tested whether EEG measures of auditory neural synchronization were abnormal in bipolar disorder. Nineteen symptomatic patients with bipolar disorder and 32 non-psychiatric control subjects were evaluated. Click trains (500 ms duration) presented at 20, 30, 40 and 50 Hz were used to evoke EEG synchronization. Patients with bipolar disorder showed reduced power across the frequencies of stimulation. Phase-locking across trials was also disturbed in bipolar disorder, consistent with poor phase synchronization between the stimulus and EEG. Abnormal high frequency neural synchronization may contribute to cognitive deficits in bipolar disorder.