Project description:Most knowledge about the structure, function, and evolution of early compound eyes is based on investigations in trilobites. However, these studies dealt mainly with the cuticular lenses and little was known about internal anatomy. Only recently some data on crystalline cones and retinula cells were reported for a Cambrian trilobite species. Here, we describe internal eye structures of two other trilobite genera. The Ordovician Asaphus sp. reveals preserved crystalline cones situated underneath the cuticular lenses. The same is true for the Devonian species Archegonus (Waribole) warsteinensis, which in addition shows the fine structure of the rhabdom in the retinula cells. These results suggest that an apposition eye with a crystalline cone is ancestral for Trilobita. The overall similarity of trilobite eyes to those of myriapods, crustaceans, and hexapods corroborates views of a phylogenetic position of trilobites in the stem lineage of Mandibulata.
Project description:Abstract Spinocerebellar ataxias (SCAs) are rare types of cerebellar ataxia with a dominant mode of inheritance. To date, 47 SCA subtypes have been identified, and the number of genes implicated in SCAs is continually increasing. Polyglutamine (polyQ) expansion diseases ( ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, CACNA1A/SCA6, ATXN7/SCA7, TBP/SCA17, and ATN1/DRPLA) are the most common group of SCAs. No preventive or curative treatments are currently available, but various therapeutic approaches, including RNA-targeting treatments, such as antisense oligonucleotides (ASOs), are being developed. Clinical trials of ASOs in SCA patients are already planned. There is, therefore, a need to identify valid outcome measures for such studies. In this review, we describe recent advances towards identifying appropriate biomarkers, which are essential for monitoring disease progression and treatment efficacy. Neuroimaging biomarkers are the most powerful markers identified to date, making it possible to reduce sample sizes for clinical trials. Changes on brain MRI are already evident at the premanifest stage in SCA1 and SCA2 carriers and are correlated with CAG repeat size. Other potential biomarkers have also been developed, based on neurological examination, oculomotor study, cognitive assessment, and blood and cerebrospinal fluid analysis. Longitudinal studies based on multimodal approaches are required to establish the relationships between parameters and to validate the biomarkers identified.
Project description:AimsTo explore the utility of first-person viewpoint cameras at home, for recording mother and infant behaviour, and for reducing problems associated with participant reactivity, which represent a fundamental bias in observational research.MethodsWe compared footage recording the same play interactions from a traditional third-person point of view (3rd PC) and using cameras worn on headbands (first-person cameras [1st PCs]) to record first-person points of view of mother and infant simultaneously. In addition, we left the dyads alone with the 1st PCs for a number of days to record natural mother-child behaviour at home. Fifteen mothers with infants (3-12 months of age) provided a total of 14h of footage at home alone with the 1st PCs.ResultsCodings of maternal behaviour from footage of the same scenario captured from 1st PCs and 3rd PCs showed high concordance (kappa >0.8). Footage captured by the 1st PCs also showed strong inter-rater reliability (kappa=0.9). Data from 1st PCs during sessions recorded alone at home captured more 'negative' maternal behaviours per min than observations using 1st PCs whilst a researcher was present (mean difference=0.90 (95% CI 0.5-1.2, p<0.001 representing 1.5 SDs).Conclusion1st PCs offer a number of practical advantages and can reliably record maternal and infant behaviour. This approach can also record a higher frequency of less socially desirable maternal behaviours. It is unclear whether this difference is due to lack of need of the presence of researcher or the increased duration of recordings. This finding is potentially important for research questions aiming to capture more ecologically valid behaviours and reduce demand characteristics.
Project description:Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome.
Project description:Due to the high prevalence and long incubation periods often without symptoms, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions of individuals globally, causing the coronavirus disease 2019 (COVID-19) pandemic. Even with the recent approval of the anti-viral drug, remdesivir, and Emergency Use Authorization of monoclonal antibodies against S protein, bamlanivimab and casirimab/imdevimab, efficient and safe COVID-19 vaccines are still desperately demanded not only to prevent its spread but also to restore social and economic activities via generating mass immunization. Recent Emergency Use Authorization of Pfizer and BioNTech's mRNA vaccine may provide a pathway forward, but monitoring of long-term immunity is still required, and diverse candidates are still under development. As the knowledge of SARS-CoV-2 pathogenesis and interactions with the immune system continues to evolve, a variety of drug candidates are under investigation and in clinical trials. Potential vaccines and therapeutics against COVID-19 include repurposed drugs, monoclonal antibodies, antiviral and antigenic proteins, peptides, and genetically engineered viruses. This paper reviews the virology and immunology of SARS-CoV-2, alternative therapies for COVID-19 to vaccination, principles and design considerations in COVID-19 vaccine development, and the promises and roles of vaccine carriers in addressing the unique immunopathological challenges presented by the disease.
Project description:Flax (Linum usitatissimum L.) is an important oil seed crop that is mostly cultivated in temperate climates. In addition to many commercial applications, flax is also used as a fibrous species or for livestock feed (animal fodder). For the last 40 years, flax has been used as a phytoremediation tool for the remediation of different heavy metals, particularly for phytoextraction when cultivated on metal contaminated soils. Among different fibrous crops (hemp, jute, ramie, and kenaf), flax represents the most economically important species and the majority of studies on metal contaminated soil for the phytoextraction of heavy metals have been conducted using flax. Therefore, a comprehensive review is needed for a better understanding of the phytoremediation potential of flax when grown in metal contaminated soil. This review describes the existing studies related to the phytoremediation potential of flax in different mediums such as soil and water. After phytoremediation, flax has the potential to be used for additional purposes such as linseed oil, fiber, and important livestock feed. This review also describes the phytoremediation potential of flax when grown in metal contaminated soil. Furthermore, techniques and methods to increase plant growth and biomass are also discussed in this work. However, future research is needed for a better understanding of the physiology, biochemistry, anatomy, and molecular biology of flax for increasing its pollutant removal efficiency.
Project description:The tendency for crystallization during storage and administration is the most considerable hurdle for poorly water-soluble drugs formulated in the amorphous form. There is a need to better detect often subtle and complex surface crystallization phenomena and understand their influence on the critical quality attribute of dissolution. In this study, the interplay between surface crystallization of the amorphous form during storage and dissolution testing, and its influence on dissolution behavior, is analyzed for the first time with multimodal nonlinear optical imaging (coherent anti-Stokes Raman scattering (CARS) and sum frequency generation (SFG)). Complementary analyses are provided with scanning electron microscopy, X-ray diffraction and infrared and Raman spectroscopies. Amorphous indomethacin tablets were prepared and subjected to two different storage conditions (30 °C/23% RH and 30 °C/75% RH) for various durations and then dissolution testing using a channel flow-through device. Trace levels of surface crystallinity previously imaged with nonlinear optics after 1 or 2 days of storage did not significantly decrease dissolution and supersaturation compared to the freshly prepared amorphous tablets while more extensive crystallization after longer storage times did. Multimodal nonlinear optical imaging of the tablet surfaces after 15 min of dissolution revealed complex crystallization behavior that was affected by both storage condition and time, with up to four crystalline polymorphs simultaneously observed. In addition to the well-known ?- and ?-forms, the less reported metastable ?- and ?-forms were also observed, with the ?-form being widely observed in samples that had retained significant surface amorphousness during storage. This form was also prepared in the pure form and further characterized. Overall, this study demonstrates the potential value of nonlinear optical imaging, together with more established solid-state analysis methods, to understand complex surface crystallization behavior and its influence on drug dissolution during the development of amorphous drugs and dosage forms.
Project description:The current review paper was written in collaboration with breast cancer surgeons from the European Breast Cancer Research Association of Surgical Trialists (EUBREAST), a breast pathologist from the Danish Breast Cancer Group (DBCG), and representatives from the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer course. Herein we summarize the different mastectomies and reconstruction procedures and define high-risk anatomical areas for breast cancer recurrences, to further specify the challenges in the surgical procedure, histopathological evaluation, and target volumes in case of postmastectomy irradiation, as recommended by the ESTRO guidelines according to the surgical procedure. The paper has original figures and illustrations for all disciplines for in-depth understanding of the differences between the procedures.
Project description:Photoreceptor cells in the eyes of Bilateria are often classified into microvillar cells with rhabdomeric opsin and ciliary cells with ciliary opsin, each type having specialized molecular components and physiology. First data on the recently discovered xenopsin point towards a more complex situation in protostomes. In this study, we provide clear evidence that xenopsin enters cilia in the eye of the larval bryozoan Tricellaria inopinata and triggers phototaxis. As reported from a mollusc, we find xenopsin coexpressed with rhabdomeric-opsin in eye photoreceptor cells bearing both microvilli and cilia in larva of the annelid Malacoceros fuliginosus. This is the first organism known to have both xenopsin and ciliary opsin, showing that these opsins are not necessarily mutually exclusive. Compiling existing data, we propose that xenopsin may play an important role in many protostome eyes and provides new insights into the function, evolution, and possible plasticity of animal eye photoreceptor cells.