Future Tail Tales: A Forward-Looking, Integrative Perspective on Tail Research.

Synopsis Tails are a defining characteristic of chordates and show enormous diversity in function and shape. Although chordate tails share a common evolutionary and genetic-developmental origin, tails are extremely versatile in morphology and function. For example, tails can be short or long, thin or thick, and feathered or spiked, and they can be used for propulsion, communication, or balancing, and they mediate in predator-prey outcomes. Depending on the species of animal the tail is attached to, it can have extraordinarily multi-functional purposes. Despite its morphological diversity and broad functional roles, tails have not received similar scientific attention as, for example, the paired appendages such as legs or fins. This forward-looking review article is a first step toward interdisciplinary scientific synthesis in tail research. We discuss the importance of tail research in relation to five topics: (1) evolution and development, (2) regeneration, (3) functional morphology, (4) sensorimotor control, and (5) computational and physical models. Within each of these areas, we highlight areas of research and combinations of long-standing and new experimental approaches to move the field of tail research forward. To best advance a holistic understanding of tail evolution and function, it is imperative to embrace an interdisciplinary approach, re-integrating traditionally siloed fields around discussions on tail-related research.

Serum evaluation of leptin, IL-6, IGF-1 and estrogen in obese bitches with early stages of mammary carcinoma / Avaliação sérica de leptina, IL-6, IGF-1 e estrógeno em cadelas com excesso de peso e portadoras de carcinomas mamários em estágio inicial

The aim of this study was to relate the serum concentration IL-6, IGF-1, leptin and estrogen in non-castrated bitches with or without overweight and early stage mammary carcinomas. Forty-three bitches were divided into four groups, two groups without mammary carcinomas with and without overweight, and two groups with mammary carcinomas with and without overweight. Overweight bitches, with or without mammary carcinomas, were statistically different from bitches by ideal weight, in relation to ECC, IMCC and body fat percentages (P< 0.0001). There was a positive correlation between ECC and IMCC (P< 0.0001), ECC and % GC (P< 0.0001), and IMCC and % GC (P< 0.0001). A positive correlation was found between serum leptin and IL-6 (P= 0.0451) and leptin and IGF-1 (P= 0.05). A positive correlation (P= 0.0053) between ECC and leptin was found in the analysis of body evaluation methods and serum concentrations, and a negative correlation between ECC and IL-6 (P= 0.0435). Among the fat percentage and the leptin concentration, there was a positive correlation (P= 0.0016), as found between the IMCC and leptin (P= 0, 0209). In this study, no association was observed between excessive weight and the presence of early stage mammary carcinomas.(AU)

Este estudo teve por objetivo relacionar a concentração sérica de IL-6, IGF-1, leptina e estrógeno, em cadelas não castradas com ou sem excesso de peso, e carcinomas mamários em estágio inicial. Quarenta e três cadelas foram divididas em quatro grupos, sendo dois de cadelas sem carcinomas mamários, com e sem excesso de peso, e dois de cadelas com carcinomas mamários, com e sem excesso de peso. Cadelas com excesso de peso, com ou sem carcinomas mamários, foram estatisticamente diferentes de cadelas em peso ideal, em relação às avaliações corporais de ECC, IMCC e percentual de gordura corpórea (P<0,0001). Foi observada uma correlação positiva entre ECC e IMCC (P<0,0001), ECC e %GC (P<0,0001), e IMCC e %GC (P<0,0001). As análises de estrógeno, leptina, IL-6 e IGF-1 não apresentaram diferenças estatísticas entre os grupos. Demonstrou-se correlação positiva entre as concentrações séricas de leptina e IL-6 (P=0,0451) e leptina e IGF-1 (P=0,05). Encontrou-se correlação positiva entre ECC e leptina (P=0,0053) e negativa entre ECC e IL-6 (P=0,0435). Entre o percentual de gordura e leptina encontrou-se correlação positiva (P=0,0016), assim como entre IMCC e leptina (P=0,0209). Neste estudo, não se observou associação entre excesso de peso e a presença de carcinomas mamários em estadio inicial.(AU)

Epidemiological, clinical and pathological evaluation of overall survival in canines with mammary neoplasms / Estudo epidemiológico, clínico-patológico e avaliação de sobrevida global em cadelas com neoplasias mamárias

Canine mammary neoplasms (CMNs) are the most frequent lesions and in female dogs. However, studies correlating pathological criteria with clinical evolution in female dogs with mammary neoplasms are scarce. The present study aims to present epidemiological, clinical-pathological and overall survival data to help establish the prognosis and understand the biological behavior of CMNs. A total of 1539 cases were included (85% malignant and 13% benign). Tumor size was an important prognostic factor and was associated with overall patient survival (P< 0.0001). Most dogs diagnosed with malignant neoplasms (83%) had initial clinical staging, although 17% had regional or distant metastases at the time of diagnosis and lower overall survival (P< 0.0001). Carcinoma in mixed tumor was the most frequent histological type and had a better prognosis. Solid carcinomas, micropapillary carcinomas and carcinosarcomas were considered histological types with aggressive biological behavior and were associated with a worse prognosis and lower overall survival (P< 0.0001).(AU)

Neoplasias mamárias caninas (NMCs) são as lesões mais frequentes em cadelas. Estudos que correlacionam os critérios patológicos com a evolução clínica em cadelas com neoplasias mamárias são escassos. Este estudo objetiva apresentar dados epidemiológicos, clínico-patológicos e de sobrevida global fornecendo informações que auxiliam a estabelecer o prognóstico e a compreender o comportamento biológico de NMCs. Foram incluídos 1539 casos, 85% malignos e 13% benignos. O tamanho tumoral foi um importante fator prognóstico, sendo associado com a sobrevida global das pacientes (P<0,0001). A maioria das cadelas diagnosticadas com neoplasias malignas (83%) apresentavam estadiamentos clínicos iniciais, enquanto 17% apresentavam metástases regionais ou à distância no momento do diagnóstico, denotando menor sobrevida global (P<0,0001). O carcinoma em tumor misto foi o tipo histológico mais frequente e de melhor prognóstico. Os carcinomas sólidos, carcinomas micropapilares e carcinossarcomas foram considerados tipos histológicos de comportamento biológico agressivo, sendo associados a pior prognóstico e menor sobrevida global (P<0,0001).(AU)

Evaluation of adjuvant chemotherapy in feline injection site-associated sarcoma / Avaliação da quimioterapia no tratamento do sarcoma de aplicação felino

Feline Injection Site-Associated Sarcoma (FISS) is a neoplasm that implies in reduction of quality of life and overall survival in feline patients. A retrospective study of 13 cases of FISS was conducted to evaluate the efficacy of surgical treatment associated to chemotherapy with doxorubicin or carboplatin. Local recurrence occurred in all patients. Patients treated with surgery and chemotherapy presented a longer overall survival and disease-free interval when compared to those that solely received surgical treatment, although no statistical significance was observed (p= 0.3360 and 0.7506, respectively). Surgery remains as the main option for FISS treatment. Further prospective studies with larger samples are warranted to investigate the benefit of chemotherapy for this neoplasm.(AU)

O Sarcoma de Aplicação Felino (SAF) é uma neoplasia associada a redução na qualidade de vida e sobrevida global. O objetivo deste estudo foi avaliar a eficácia da quimioterapia associada à cirurgia no manejo do SAF. Estudo retrospectivo de 13 pacientes com SAF submetidos à cirurgia isolada ou associada a quimioterapia com carboplatina ou doxorrubicina. Recorrência local ocorreu em todos os pacientes. Pacientes tratados com cirurgia e quimioterapia apresentaram maior sobrevida global e intervalo livre de doença quando comparados àqueles que receberam apenas tratamento cirúrgico, mas não foi observada diferença estatística (p=0,3360 e 0,7506, respectivamente). A cirurgia continua sendo a principal opção para o tratamento do SAF. Estudos prospectivos são necessários para investigação do real benefício da quimioterapia para esta neoplasia.(AU)

Glycogen-rich clear cell carcinoma of the feline mammary gland: case report / Carcinoma de células claras rico em glicogênio da glândula mamária felina: relato de caso

The aim of this report is to describe the first histopathological, immunohistochemical, and clinical characteristics of a feline glycogen-rich clear cell carcinoma (GRCCC). A Persian queen was admitted with mammary gland tumors and underwent radical unilateral mastectomy. Overall survival was considered 33 days and death was due to clinical evolution of the disease. Microscopic evaluation demonstrated epithelial cells arranged in a predominantly solid pattern, tumor cells presented an ample, granular, and foamy clear cytoplasm, and moderate cellular pleomorfism. The presence of cytoplasmatic glycogen was confirmed through diastase digestion followed by PAS staining. Histopathological and histochemical findings lead to the diagnosis of GRCCC with regional metastases.(AU)

O objetivo deste relato de caso é descrever as características clínicas, histopatológicas e imuno-histoquímicas do primeiro carcinoma mamário de células claras rico em glicogênio em felino. Uma gata persa foi atendida com tumores na glândula mamária e foi submetida à mastectomia radical unilateral. A sobrevida livre de doença foi considerada 33 dias, e o óbito foi devido à evolução da doença. A avaliação microscópica demonstrou células epiteliais arranjadas em um padrão predominantemente sólido, as células tumorais apresentaram um citoplasma claro, amplo, granular e espumoso e pleomorfismo celular moderado. A presença do glicogênio citoplasmático foi confirmada pela digestão pela diástase, seguida da coloração de PAS. Achados histopatológicos e histoquímicos levaram ao diagnóstico de carcinoma de células claras rico em glicogênio felino com metástase regional.(AU)

Absence of significant adverse events following thalidomide administration in bitches diagnosed with mammary gland carcinomas.

The aim of the study was to evaluate the incidence of adverse events (AEs) in female dogs diagnosed with advanced clinical stage mammary gland neoplasms following treatment with thalidomide. A prospective analysis of 29 female dogs treated with a high dose (HD) of 20 mg/kg/day of thalidomide for three months followed by a low dose (LD) of 10 mg/kg/day of thalidomide for three months was performed. All patients underwent physical examination, complete blood count, serum biochemistry profile, thoracic radiographs, and abdominal ultrasound analysis before the treatment and after the HD and LD. Clinical AEs were absent in 16/29 (55.17 per cent) patients following HD. An initial 3-5 day period of somnolence was described in 4/29 (13.79 per cent), prolonged somnolence in 5/29 (17.24 per cent), a short period of somnolence lasting only a few hours in 3/29 (10.34 per cent), and difficulty to rouse was described in 5/29 (17.24 per cent) cases. Two patients (6.89 per cent) presented with prolonged somnolence that interfered with activities of daily living, resulting in anticipation of the dose reduction to the proposed LD after 15 days of the HD treatment. Following dose reduction, AE improvement was observed in all patients. Albeit remaining within the reference ranges, erythrocytes, haematocrit, total leucocyte count, neutrophils, lymphocytes, monocytes and γ-glutamyltranspeptidase showed significant alteration associated to thalidomide treatment.

Reduced circulating miR-196b levels is associated with preeclampsia.

MicroRNAs (miRs) are small noncoding RNAs, highly stable in plasma, that regulate gene expression by base-pairing to the 3'-untranslated region of target mRNAs. We compared the expression of 3 circulating miRs (miR-125b, miR-146a, and miR-196b), which is related to the control of cell proliferation, differentiation, and apoptosis in preeclamptic (n=19) and healthy pregnant women (n=14). We found that women with preeclampsia (PE) presented lower expression of miR-196b (-2.9-fold change). The other miRs were at similar levels. This study is the first to demonstrate this difference, and highlights new opportunities for investigation into the role of miRs in PE.

Cistoadenocarcinoma simulando hemangiossarcoma de glândula salivar em cão: relato de caso / Cystadenocarcinoma simulating hemangiosarcoma of the salivary gland in dog: case report

Cystadenocarcinoma is regarded as a rare adenocarcinoma variant in animals. This work reports the case of an 8-year-old female Poodle dog with salivary gland cystadenocarcinoma with morphological characteristics similar to a hemangiosarcoma. Histopathological analysis showed a tumor mass with cystic formations containing a large amount of red blood cells. In order to distinguish these two entities, periodic acid Schiff (PAS) staining and immunohistochemical analysis were carried out with the use of cytokeratin AE1/AE3 (CK) and CD31-specific antibodies. Neoplastic cells were PAS-negative, CK-positive and CD31-negative confirming their epithelial origin. Based on the findings, the diagnosis of high grade cystadenocarcinoma was established.

O cistoadenocarcinoma é considerado uma variante do adenocarcinoma de rara ocorrência em animais. Este trabalho relata um caso de cadela Poodle de oito anos, portadora de cistoadenocarcinoma de glândula salivar com características morfológicas semelhantes a de hemangiossarcoma. Na análise histopatológica observou-se uma massa tumoral com formações císticas contendo grande quantidade de hemácias. Para a diferenciação entre as duas entidades realizou-se coloração pelo ácido periódico de Schiff (PAS) e análise imuno-histoquímica com a utilização de anticorpos para citoqueratina AE1/AE3 (CK) e CD31. As células neoplásicas apresentaram-se PAS negativas, CK positivas e CD31 negativas demonstrando a origem epitelial. Com base nos achados firmou-se o diagnóstico de cistoadenocarcinoma de alto grau.

Low level laser therapy (LLLT) decreases pulmonary microvascular leakage, neutrophil influx and IL-1beta levels in airway and lung from rat subjected to LPS-induced inflammation.

BACKGROUND AND OBJECTIVE: Low level laser therapy (LLLT) is a known anti-inflammatory therapy. Herein we studied the effect of LLLT on lung permeability and the IL-1beta level in LPS-induced pulmonary inflammation. STUDY DESIGN/METHODOLOGY: Rats were divided into 12 groups (n = 7 for each group). Lung permeability was measured by quantifying extravasated albumin concentration in lung homogenate, inflammatory cells influx was determined by myeloperoxidase activity, IL-1beta in BAL was determined by ELISA and IL-1beta mRNA expression in trachea was evaluated by RT-PCR. The rats were irradiated on the skin over the upper bronchus at the site of tracheotomy after LPS. RESULTS: LLLT attenuated lung permeability. In addition, there was reduced neutrophil influx, myeloperoxidase activity and both IL-1beta in BAL and IL-1beta mRNA expression in trachea obtained from animals subjected to LPS-induced inflammation. CONCLUSION: LLLT reduced the lung permeability by a mechanism in which the IL-1beta seems to have an important role.

Activation of p38 mitogen-activated protein kinase during normal mitosis in the developing retina.

The p38 member of the mitogen-activated protein kinase superfamily is engaged by phosphorylation in response to environmental stress signals, and may have either permissive or inhibitor roles upon cell proliferation. The cell cycle in the proliferative zone of the retina is tightly controlled and proceeds in synchrony with interkinetic migration of the neuroblast nuclei. We examined the association of p38 kinase activity with the cell cycle in the normal, non-stressed retina of the developing rat, maintained either in vivo or in vitro. Using immunohistochemistry, we show that mitotic profiles in the developing retina are highly enriched for phosphorylated p38. Blockade of p38 activity with the chemical inhibitor SB203580 for 4 h transiently arrested cells at the metaphase-anaphase transition and induced cell death after 20 h. p38 inhibition induced an aberrant mitotic profile, with chromosomes arranged in one side of the cell. The data show that p38 is active during normal mitosis and we suggest that p38 is required for the proper cell cycle progression during metaphase-anaphase transition in retinal neuroblasts.

Leishmania braziliensis, molecular characterization of an elongation factor 1alpha gene.

The elongation factor EF-1alpha is one of the most studied components of the translation machinery owing to its abundance and possible role in other cellular functions. EF-1alpha mediates the correct coupling of the aminoacyl-tRNA on the A site of the ribosome in a GTP-dependent reaction. We have previously described an EF-1alpha DNA sequence in Leishmania amazonensis, pLEF11 (accession No. M92653), using PCR. In this paper we describe the DNA sequence and genomic organization of L. braziliensis EF-1alpha gene. Southern blot analysis revealed that EF-1alpha is organized as a 2 kb tandem repeat. The pLEF11 probe recognized a 1.8 kb mRNA from promastigotes in Northern blots. A clone containing the first copy and a half of the EF-1alpha tandem repeat was isolated by screening a L. braziliensis genomic library. Southern blot analysis showed that the isolated clone (lambda2.2) presented the same hybridization profile as that of a genomic blot. The partial sequencing of clone lambda2.2 spans 2959 nucleotides in length, which has two open reading frames separated by a putative non-coding region. The nucleotide and the predicted peptide sequence of the first coding region presented approximately 80% identity with other eukaryotic EF-1alpha genes. The sequence also displayed the four consensus motifs corresponding to the GTP-binding site (G1, G2, G3 and G4). Computer analysis of the sequence of both coding regions revealed three divergent nucleotides, which generated two changes at the amino acid level. One was found to be located in the G2 domain. The non-coding region of the EF-1alpha gene sequence showed potential regulatory elements such as polypyrimidine tracks, chi-homologous sequences and stem-loop forming sequences.

Protein kinases selectively modulate apoptosis in the developing retina in vitro.

In the retina of newborn rats there is evidence for two mechanisms of programmed cell death. Apoptosis of ganglion cells (RGCs) following axotomy depends on protein synthesis. In contrast, inhibition of protein synthesis leads to apoptosis in the neuroblastic layer (NBL). The induction of apoptosis following translational arrest suggests that post-translational modifications of apoptosis-associated proteins may be crucial to the cell death programs in the developing retina. We investigated the possible role of protein kinases upon apoptosis in retinal explants in vitro. An increase in the intracellular concentration of cAMP produced either by the adenylyl-cyclase activator forskolin (10 microM) or by 8-Br-cAMP (1 mM), prevented apoptosis induced in the NBL by inhibition of protein synthesis, but had no statistically significant effect upon RGC death. In contrast, neither 8-Br-cGMP (1 mM) nor the specific cGMP-phosphodiesterase inhibitor zaprinast (10-100 microM) had significant effects on apoptosis in the retina. The cAMP-phosphodiesterase inhibitors isobutylmethylxantine (IBMX, 0.1-1 mM) and Ro-201724 (50-200 microM) also prevented apoptosis in the NBL. The isoquinolinesulfonamide H89 (20 microM), a specific cAMP-dependent protein kinase inhibitor, partially reverted the protective effect of either forskolin or IBMX within the NBL. Neither 12-O-tetradecanoyl phorbol-13-acetate (TPA, 10 nM) nor bisindolylmaleimide (0.2-0.5 microM), respectively an activator and an inhibitor of protein kinase C had significant effects upon the retinal explants. The protein kinase inhibitor 2-aminopurine (2-AP, 10 mM) prevented apoptosis of axotomized ganglion cells and induced apoptosis in the NBL. Forskolin prevented the apoptosis induced by 2-AP in the NBL, whereas TPA had no effect. The effects of 2-AP were, however, not dependent on inhibition of protein synthesis. The data indicate that modulation of the activity of both cAMP-dependent protein kinase and several protein kinases sensitive to 2-aminopurine selectively affect apoptosis in distinct cell layers of the developing retina.

Death in a dish: controls of apoptosis within the developing retinal tissue.

Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retinal tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.

Death in dish: controls of apoptosis within the developing retinal tissue

Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retianl tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.

Identification of GTPase genes in the protozoa parasites Trypanosoma cruzi and Leishmania amazonensis.

A PCR based assay was designed in order to amplify putative ras gene sequences of the GTPase superfamily eventually present in Leishmania amazonensis and Trypanosoma cruzi. A set of primers corresponding to the conserved motifs G1 and G3 of the GTP binding proteins was synthesized. Sequencing of six PCR products (three from Leishmania and three from Trypanosoma) identified, however, two other different GTPases. The 270 bp L. amazonensis clone, pLef-11, shared an amino acid identity of around 80% with an eukaryotic elongation factor 1a of protein synthesis. On the other hand, the 168 bp T. cruzi clone, pTCr1, demonstrated over 60% amino acid identity to ras-related proteins of the rab-YPT-SEC4 family involved in control of vesicular traffic. To our knowledge, this is the first report of GTP binding protein genes in trypanosomatids.