Unraveling the transcriptomic landscape of eye migration and visual adaptations during flatfish metamorphosis.

Flatfish undergo a remarkable metamorphosis from symmetrical pelagic larvae to fully asymmetrical benthic juveniles. The most distinctive features of this transformation is the migration of one eye. The molecular role of thyroid hormone in the metamorphosis process in flatfishes is well established. However, the regulatory network that facilitates eye movement remains enigmatic. This paper presents a morphological investigation of the metamorphic process in turbot eyes, using advanced imaging techniques and a global view of gene expression. The study covers migrant and non-migrant eyes and aims to identify the genes that are active during ocular migration. Our transcriptomic analysis shows a significant up-regulation of immune-related genes. The analysis of eye-specific genes reveals distinct patterns during the metamorphic process. Myosin is highlighted in the non-migrant eye, while ependymin is highlighted in the migrant eye, possibly involved in optic nerve regeneration. Furthermore, a potential association between the alx3 gene and cranial restructuring has been identified. Additionally, it confirmed simultaneous adaptation to low light in both eyes, as described by changes in opsins expression during the metamorphic process. The study also revealed that ocular migration activates systems asynchronously in both eyes, providing insight into multifaceted reorganization processes during metamorphosis of flatfish.

Genome-wide chromatin accessibility and gene expression profiling during flatfish metamorphosis.

Metamorphosis is a widely studied post-embryonic process in which many tissues undergo dramatic modifications to adapt to the new adult lifestyle. Flatfishes represent a good example of metamorphosis in teleost fishes. During metamorphosis of flatfish, organ regression and neoformation occur, with one of the most notable changes being the migration of one of the eyes to the other side of the body. In order to create a useful and reliable tool to advance the molecular study of metamorphosis in flatfish, we generated a chromatin accessible atlas as well as gene expression profile during four developmental stages ranging from a phylotypic to a post-metamorphic stage. We identified 29,019 differentially accessible chromatin regions and 3,253 differentially expressed genes. We found stage-specific regulatory regions and gene expression profiles, supporting the quality of the results. Our work provides strongly reproducible data for further studies to elucidate the regulatory elements that ensure successful metamorphosis in flatfish species.

De novo transcriptome reconstruction in aquacultured early life stages of the cephalopod Octopus vulgaris.

Cephalopods have been considered enigmatic animals that have attracted the attention of scientists from different areas of expertise. However, there are still many questions to elucidate the way of life of these invertebrates. The aim of this study is to construct a reference transcriptome in Octopus vulgaris early life stages to enrich existing databases and provide a new dataset that can be reused by other researchers in the field. For that, samples from different developmental stages were combined including embryos, newly-hatched paralarvae, and paralarvae of 10, 20 and 40 days post-hatching. Additionally, different dietary and rearing conditions and pathogenic infections were tested. At least three biological replicates were analysed per condition and submitted to RNA-seq analysis. All sequencing reads from experimental conditions were combined in a single dataset to generate a reference transcriptome assembly that was functionally annotated. The number of reads aligned to this reference was counted to estimate the transcript abundance in each sample. This dataset compiled a complete reference for future transcriptomic studies in O. vulgaris.

Brains in Metamorphosis: Temporal Transcriptome Dynamics in Hatchery-Reared Flatfishes.

Metamorphosis is a captivating process of change during which the morphology of the larva is completely reshaped to face the new challenges of adult life. In the case of fish, this process initiated in the brain has traditionally been considered to be a critical rearing point and despite the pioneering molecular work carried out in other flatfishes, the underlying molecular basis is still relatively poorly characterized. Turbot brain transcriptome of three developmental stages (pre-metamorphic, climax of metamorphosis and post-metamorphic) were analyzed to study the gene expression dynamics throughout the metamorphic process. A total of 1570 genes were differentially expressed in the three developmental stages and we found a specific pattern of gene expression at each stage. Unexpectedly, at the climax stage of metamorphosis, we found highly expressed genes related to the immune response, while the biological pathway enrichment analysis in pre-metamorphic and post-metamorphic were related to cell differentiation and oxygen carrier activity, respectively. In addition, our results confirm the importance of thyroid stimulating hormone, increasing its expression during metamorphosis. Based on our findings, we assume that immune system activation during the climax of metamorphosis stage could be related to processes of larval tissue inflammation, resorption and replacement, as occurs in other vertebrates.

Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group.

PURPOSE: To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain. PATIENTS AND METHODS: One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opioid analgesics. RESULTS: Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%). CONCLUSION: Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.

Glioblastoma: changing expectations?

Glioblastoma (GB) represents the most aggressive glioma in the adult population. Despite recent research efforts, the prognosis of patients with GB has remained dismal. Lately, the knowledge of genetic information about gliomagenesis has increased; we even have a classification of the genetic expression of the tumour. The main problem is that at the moment we do not have any therapeutical resources to help us better treat these tumours, as we can do, with others tumours like breast, lung and colorectal cancer. We have also improved on diagnostic imaging, especially with the new MRI sequences; we can now better define the characteristics of the tumour area and the surrounding brain structures, allowing us to adjust resections. Thanks to the most advanced surgery techniques, such as neuronavigation, intraoperative control of the nervous function and the tumour volume, the neurosurgeon is able to complete tumour exeresis with less morbidity. These imaging techniques allow the radiation oncologist to better contour the irradiation target volume, the structures and the organs at risk, to diminish the irradiation of apparently healthy tissue. Nowadays, knowledge of brain stem cells provides new expectations for future treatments. Novel targeted agents such as bevacizumab, imatinib, erlotinib, temsirolimus, immunotherapy, cilengitide, talampanel, etc. are helping classical chemotherapeutic agents, like temozolomide, to achieve an increase in overall survival. The main objective is to improve median overall survival, which is currently between 9 and 12 months, with a good quality of life, measured by the ability to carry out daily life activities.

Phase II study of temozolomide and cisplatin as primary treatment prior to radiotherapy in newly diagnosed glioblastoma multiforme patients with measurable disease. A study of the Spanish Medical Neuro-Oncology Group (GENOM).

UNLABELLED: This phase II study evaluates the activity of temozolomide and cisplatin administered before radiation therapy in newly diagnosed glioblastoma multiforme patients, in terms of response, time to progression and survival. PATIENTS AND METHODS: Forty patients with measurable disease after surgery, a Karnofsky status > 60, and Barthel Index > 10 were included. They were treated with three cycles of temozolomide 200 mg/m2/day for 5 days and cisplatin 100 mg/m2 on day 1. Conventional focal radiation therapy to 60 Gy was administered after response evaluation. RESULTS: Three patients were not evaluable for central reviewed response but all 40 were evaluable for toxicity, time to progression and survival. Objective responses by Macdonald criteria on an intent to treat basis were 45% including complete response in three patients (7.5%), and partial response in 15 patients (37.5%). Responses were seen in biopsy-only patients (33.4%) as well as in partial surgery patients (52%). Median survival for all patients was 12.5 months. Biopsy-only patients had a median survival of 12.8 months. Grade 3 to 4 neutropenia was the most important toxicity, and occurred in 37.5% of patients. A delay in 18.2% and a dose reduction in 9.6% of cycles were necessary due to myelosuppression on day 28. Two patients had neutropenic fever resulting in one treatment-related death. Eighty-two percent of patients received radiotherapy. CONCLUSION: This regimen has significant activity, as it induces objective responses even in biopsy-only patients, appearing to improve their median survival. A better combination schedule is needed to improve the toxicity profile.