Marginal resection and adjuvant strontium plesiotherapy in the management of feline eyelid malignant peripheral nerve sheath tumours: two cases

Case series summary Two cats with a marginally resected eyelid malignant peripheral nerve sheath tumour were treated with adjuvant strontium plesiotherapy a few weeks after surgery. The dose applied in both cases was 200 Gy to the surface, in five fractions, on a Monday–Wednesday–Friday basis. The treatment aimed to achieve a clinical margin of approximately 1 cm around the surgical scar and multiple application fields were required to cover such an area. Local recurrence was not seen in either case after 1330 and 645 days, respectively. Relevance and novel information The majority of periocular malignant peripheral nerve sheath tumours reported in the literature recur after surgery. In the two cases described in this report the combination of surgery and adjuvant plesiotherapy has been able to provide good local control with minimal toxicity. This multimodal approach could be considered as an alternative to aggressive surgery such as enucleation or exenteration

Efficient clofilium tosylate-mediated rescue of POLG-related disease phenotypes in zebrafish

The DNA polymerase gamma (Polg) is a nuclear-encoded enzyme involved in DNA replication in animal mitochondria. In humans, mutations in the POLG gene underlie a set of mitochondrial diseases characterized by mitochondrial DNA (mtDNA) depletion or deletion and multiorgan defects, named POLG disorders, for which an effective therapy is still needed. By applying antisense strategies, ENU- and CRISPR/Cas9-based mutagenesis, we have generated embryonic, larval-lethal and adult-viable zebrafish Polg models. Morphological and functional characterizations detected a set of phenotypes remarkably associated to POLG disorders, including cardiac, skeletal muscle, hepatic and gonadal defects, as well as mitochondrial dysfunctions and, notably, a perturbed mitochondria-to-nucleus retrograde signaling (CREB and Hypoxia pathways). Next, taking advantage of preliminary evidence on the candidate molecule Clofilium tosylate (CLO), we tested CLO toxicity and then its efficacy in our zebrafish lines. Interestingly, at well tolerated doses, the CLO drug could successfully rescue mtDNA and Complex I respiratory activity to normal levels, even in mutant phenotypes worsened by treatment with Ethidium Bromide. In addition, the CLO drug could efficiently restore cardio-skeletal parameters and mitochondrial mass back to normal values. Altogether, these evidences point to zebrafish as a valuable vertebrate organism to faithfully phenocopy multiple defects detected in POLG patients. Moreover, this model represents an excellent platform to screen, at the whole-animal level, candidate molecules with therapeutic effects in POLG disorders

ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC.POCI/CVT/62940/2004 and by the PhD grants (SFRH/BD/23406/2005 and SFRH/BD/31754/2006, of the Science and Technology Foundation (FCT) from Portugal

Multi-step optimization strategy for fuel-optimal orbital transfer of low-thrust spacecraft

An effective method for the design of fuel-optimal transfers in two- and three-body dynamics is presented. The optimal control problem is formulated using calculus of variation and primer vector theory. This leads to a multi-point boundary value problem (MPBVP), characterized by complex inner constraints and a discontinuous thrust profile. The first issue is addressed by embedding the MPBVP in a parametric optimization problem, thus allowing a simplification of the set of transversality constraints. The second problem is solved by representing the discontinuous control function by a smooth function depending on a continuation parameter. The resulting trajectory optimization method can deal with different intermediate conditions, and no a priori knowledge of the control structure is required. Test cases in both the two- and three-body dynamics show the capability of the method in solving complex trajectory design problem

Morphological organization and variability of the reproductive apparatus in gobies.

"Among all vertebrates, gobies are second in diversity only to the teleost family Cyprinidae. The Gobiidae consists of more than 200 genera and nearly 2,000 species and make up the largest family of marine fishes. Gobies account for as much as 50% of the energy flow in coral reef communities. Their small size, ability to adapt to numerous ecological niches and to be bred in aquaria has led to numerous studies both in the field and laboratory. Gobies are found from above the high tide line to depths of over 1,100 m. Some species are found only within caves, others deep inside sponges, and some others climb waterfalls to return to their native streams. They vary reproductively from gonochoric to hermaphrodite, monogamy to polygyny and promiscuity, some have short life spans and reproduce only once while others have longer life spans reproducing one or more times per year. The Biology of Gobies written by over 30 experts from 15 countries summarizes what is known about the systematics, ecology, zoogeography, and general biology of the Gobiiformes. This foundation will provide the basic information necessary for future studies"--Provided by publisher