Reproducibility is a current concern for everyone involved in the conduct and publication of biomedical research. Recent attempts testing reproducibility, particularly the reproducibility project in cancer biology published in elife (https://elifesciences.org/collections/9b1e83d1/reproducibility-project-cancer-biology), have exposed major difficulties in repeating published preclinical experimental work. It is thought that some of these difficulties relate to uncertainty about the provenance of tools, lack of clarity in methodology and use of inappropriate approaches for analysis; the latter particularly related to untoward manipulation of images. In the past, some of these so-called untoward practices were considered the 'norm'; however, today, the landscape is different. The expectations, not only of the readers of the published scientific word but also of the publishers and funders of research, have changed. This collective group now expects that any published data should be reproducible; but for this to be possible, experimental detail, confirmation of selectivity and quality of reagents/ tools, analytical and statistical methods used need to be described adequately. Two powerful methodologies often used to support researchers' findings allow the detection of changes in protein expression, that is, immunoblotting (widely known as Western blotting) and immunohistochemistry. Undeniably, as a result of unintentional mistakes (often related to lack of antibody specificity; Baker, 2015), but, in some cases, deliberate alterations and questionable interpretations of results, the use of these two methods has led to many high profile retractions. Indeed, such images have driven the retractions that have occurred in BJP over the last two years.Today, immunoblotting and immunohistochemistry serve as primary methodologies for the detection and quantification of molecular signalling pathways and identification of therapeutic targets. This necessitates clear guidance for the application of these techniques, the need for controls (both positive and negative) and the most appropriate methods for quantification. Indeed, this need has spawned a number of initiatives to support researchers in assessing the validity of antibody resources including antibodypedia (Bjorling and Uhlen, 2008) and the resources available within 'The Human Protein Atlas' (Thul et al., 2017). The aim of this article is to outline the rationale for, and the expectations of, the BJP with respect to work published in the Journal that includes immunoblotting or immunohistochemical data. In creating these guidelines, our aim is to reduce potential misinterpretations and to maximise the communication and transparency of essential information, particularly with respect to the methodologies employed.We have generated the guidelines below for the benefit of authors, editors and reviewers. While we recognise other recently published guidelines (Uhlen et al., 2016) and indeed we have incorporated some of the advice provided in such reports, we focus, here, on th...
Results indicated that ocular and adnexal SCCs treated with adjuvant radiation therapy had a significantly lower recurrence rate, compared with SCCs treated without adjuvant radiation therapy, independent of anatomic location.
The association of myelographic spinal cord swelling with neurological outcome was examined in 46 dogs with intervertebral disc disease and absence of deep pain perception (DPP). Spinal cord swelling was measured by calculating a ratio of the length of the loss of the myelographic dye column to the length of the second lumbar vertebra (L2). A positive neurological outcome was defined as return of voluntary motor function. A cut-off value for swelling:L2 of 5.0 was established by the creation of a receiver operator characteristic curve. Using a swelling:L2 ratio of 5.0 as a cutoff for indication of neurological recovery yielded a sensitivity of 74% and a specificity of 61%. Overall neurological recovery rate was 43%. Dogs with spinal cord swelling:L2 ratios less than 5.0 had a recovery rate of 61%, whereas dogs with a ratio greater than or equal to 5.0 had a recovery rate of 26%. Evaluation of these data by chi square analysis confirmed that a ratio less than 5.0 was associated with a positive outcome, and a ratio greater than or equal to 5.0 was associated with a negative outcome, (P < .05). Although other factors, such as duration of neurological signs, affect neurological outcome in dogs with no DPP, evaluation of myelographic spinal cord swelling can assist in establishing a prognosis.
A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.
Data from 48 dogs with nasal carcinomas treated with palliative radiation therapy (PRT) were retrospectively reviewed. Factors potentially influencing resolution of clinical signs and survival after PRT were evaluated. Clinical signs completely resolved in 66% of dogs for a median of 120 days. The overall median survival time was 146 days. Duration of response to PRT was shorter in dogs that had clinical signs for <90 days before PRT. Survival times were shorter in dogs that had partial or no resolution of clinical signs after PRT than in dogs that had complete resolution of clinical signs.
Abstract. Photoperiodic control of testis growth in Passer domesticus (house sparrow) is mediated entirely by extraretinal photoreceptors in the brain. The eyes do not participate in photoperiodically significant photoreception. Removal of the pineal organ does not affect either the response to light or, to a first approximation, the process of recrudescence. The intensity of light reaching the retina and that reaching the extraretinal photoreceptor were varied independently. This technique will make it possible to study brain photoreception in species of birds that will not tolerate blinding. Extreme caution is necessary in the interpretation of brain lesion experiments in which reproductive function is modified, since photoreception by brain receptors of unknown anatomical location affects testicular state.In an earlier paper in this series1 we reported that seemingly normal testis growth occurred in Passer domesticus exposed to inductive daylengths even though the eyes had been surgically removed. We concluded that an extraretinal photoreceptor (ERR,-extraretinal receptor for photoperiodism) must be involved in the control of testicular recrudescence and speculated on the role of retinal light perception in the intact bird. Benoit has argued that both a retinal and a brain photoreceptor are involved in the testis response of ducks.2 We discussed his arguments and concluded that the question of whether the eyes were involved at all, remained open. We have since demonstrated3 that there are no significant differences in either rate or extent of testis growth in blinded, as opposed to unoperated, sparrows held on the same lighting regimen. This result was confirmed at several different photoperiods, light intensities, and times of year; and strongly suggests, although it does not prove, that retinal light perception is not involved in photoperiodically-mediated reproductive control in P. domesticus.We have shown that the synchronization (entrainment) of the circadian rhythm of activity in the sparrow is also mediated by an extraretinal light receptor (ERR,-extraretinal receptor for entrainment).4 Further, this receptor must be in the brain, as the behavioral response to light cycles can be manipulated by affecting the amount of light that penetrates the head.5The present paper applies techniques that have been shown to affect the amount of light reaching the ERR. to the study of photoperiodically-controlled 320
Obstructive lung diseases are common causes of disability and death worldwide. A hallmark feature is aberrant activation of G q protein-dependent signaling cascades. Currently, drugs targeting single G protein (heterotrimeric guanine nucleotide-binding protein AQ4 )-coupled receptors (GPCRs) are used to reduce airway tone. However, therapeutic efficacy is often limited, because various GPCRs contribute to bronchoconstriction, and chronic exposure to receptoractivating medications results in desensitization. We therefore hypothesized that pharmacological G q inhibition could serve as a central mechanism to achieve efficient therapeutic bronchorelaxation. We found that the compound FR900359 (FR), a membrane-permeable inhibitor of G q , was effective in silencing G q signaling in murine and human airway smooth muscle cells. Moreover, FR both prevented bronchoconstrictor responses and triggered sustained airway relaxation in mouse, pig, and human airway tissue ex vivo. Inhalation of FR in healthy wild-type mice resulted in high local concentrations of the compound in the lungs and prevented airway constriction without acute effects on blood pressure and heart rate. FR administration also protected against airway hyperreactivity in murine models of allergen sensitization using ovalbumin and house dust mite as allergens. Our findings establish FR as a selective G q inhibitor when applied locally to the airways of mice in vivo and suggest that pharmacological blockade of G q proteins may be a useful therapeutic strategy to achieve bronchorelaxation in asthmatic lung disease.
The medical records of eight dogs with histopathologically confirmed infiltrative thyroid carcinoma treated with external beam radiation were reviewed and a retrospective analysis of survival and local tumor control were performed. The dogs received a definitive radiotherapy protocol of 46.8-48 Gray. All dogs had a reduction in tumor size to a clinically undetectable level on follow up examinations. Kaplan-Meier analysis indicated a median survival time of 24.5 months. Pulmonary metastasis was detected in three dogs and one of these dogs had concurrent bone metastasis. One dog had bone metastasis alone. Two dogs were alive at the censor. This study suggests that fractionated, definitive radiation therapy using multiple, moderate doses of radiation is an effective treatment for local control of invasive thyroid carcinoma in dogs.
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