In situ recordings of large gelatinous spheres from NE Atlantic, and the first genetic confirmation of egg mass of Illex coindetii (Vérany, 1839) (Cephalopoda, Mollusca)

In total, 90 gelatinous spheres, averaging one meter in diameter, have been recorded from ~ 1985 to 2019 from the NE Atlantic Ocean, including the Mediterranean Sea, using citizen science. More than 50% had a dark streak through center. They were recorded from the surface to ~ 60–70 m depth, mainly neutrally buoyant, in temperatures between 8 and 24°C. Lack of tissue samples has until now, prohibited confirmation of species. However, in 2019 scuba divers secured four tissue samples from the Norwegian coast. In the present study, DNA analysis using COI confirms species identity as the ommastrephid broadtail shortfin squid Illex coindetii (Vérany, 1839); these are the first confirmed records from the wild. Squid embryos at different stages were found in different egg masses: (1) recently fertilized eggs (stage ~ 3), (2) organogenesis (stages ~ 17–19 and ~ 23), and (3) developed embryo (stage ~ 30). Without tissue samples from each and every record for DNA corroboration we cannot be certain that all spherical egg masses are conspecific, or that the remaining 86 observed spheres belong to Illex coindetii. However, due to similar morphology and size of these spheres, relative to the four spheres with DNA analysis, we suspect that many of them were made by I. coindetii

β-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner

Amyloid precursor protein (APP) is a transmembrane glycoprotein that has been the subject of intense research because of its implication in Alzheimer's disease. However, the physiological function of APP in the development and maintenance of the central nervous system remains largely unknown. We have previously shown that the APP homologue in zebrafish (Danio rerio), Appb, is required for motor neuron patterning and formation. Here we study the function of Appb during neurogenesis in the zebrafish hindbrain. Partial knockdown of Appb using antisense morpholino oligonucleotides blocked the formation of the Mauthner neurons, uni- or bilaterally, with an aberrant behavior as a consequence of this cellular change. The Appb morphants had decreased neurogenesis, increased notch signaling and notch1a expression at the expense of deltaA/D expression. The Mauthner cell development could be restored either by a general decrease in Notch signaling through γ-secretase inhibition or by a partial knock down of Notch1a. Together, this demonstrates the importance of Appb in neurogenesis and for the first time shows the essential requirement of Appb in the formation of a specific cell type, the Mauthner cell, in the hindbrain during development. Our results suggest that Appb-regulated neurogenesis is mediated through balancing the Notch1a signaling pathway and provide new insights into the development of the Mauthner cell

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

Association of plant-based diet and early onset of natural menopause.

OBJECTIVE To evaluate the association of plant-based diet index (PDI) with early onset of natural menopause in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). METHODS We conducted a prospective study with a mean follow-up time of 20 years among premenopausal women living across the US. Participants of the NHS (n = 121,701) and NHSII (n = 116,429) were included from 1984 (age mean [standard deviation]; 44.9 [4.3]) and 1991 (age mean [standard deviation]; 36.4 [4.6]), respectively. Early menopause was self-reported and defined as natural menopause before age 45 years. PDI was derived from semiquantitative food frequency questionnaires administered every 4 years. Cox proportional hazards models were used to assess the association between PDI in quintiles and early menopause in NHS and NHSII separately, and fixed-effect models to pool the results from both cohorts. RESULTS During follow-up, 715 and 2,185 women experienced early natural menopause in NHS and NHSII, respectively. After adjustment for potential confounders, no association was observed between PDI and incidence of early natural menopause in either cohort, or when pooling the results from both cohorts, with an exception for unhealthy plant-based diet index which was associated with higher risk of early menopause with increasing levels of consumption (P trend = 0.04). CONCLUSION Adherence to PDI was not associated with timing of menopause while unhealthy plant-based diet might be associated with higher risk of experiencing early menopause

Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells

Several naturally occurring cationic antimicrobial peptides (CAPs), including bovine lactoferricin (LfcinB), display promising anticancer activities. These peptides are unaffected by multidrug resistance mechanisms and have been shown to induce a protective immune response against solid tumors, thus making them interesting candidates for developing novel lead structures for anticancer treatment. Recently, we showed that the anticancer activity by LfcinB was inhibited by the presence of heparan sulfate (HS) on the surface of tumor cells. Based on extensive structure-activity relationship studies performed on LfcinB, shorter and more potent peptides have been constructed. In the present study, we have investigated the anticancer activity of three chemically modified 9-mer peptides and the influence of HS and chondroitin sulfate (CS) on their cytotoxic activity. Various cell lines and red blood cells were used to investigate the anticancer activity and selectivity of the peptides. The cytotoxic effect of the peptides against the different cell lines was measured by use of a colorimetric MTT viability assay. The influence of HS and CS on their cytotoxic activity was evaluated by using HS/CS expressing and HS/CS deficient cell lines. The ability of soluble HS and CS to inhibit the cytotoxic activity of the peptides and the peptides’ affinity for HS and CS were also investigated. The 9-mer peptides displayed selective anticancer activity. Cells expressing HS/CS were equally or more susceptible to the peptides than cells not expressing HS/CS. The peptides displayed a higher affinity for HS compared to CS, and exogenously added HS inhibited the cytotoxic effect of the peptides. In contrast to the previously reported inhibitory effect of HS on LfcinB, the present study shows that the cytotoxic activity of small lytic peptides was increased or not affected by cell surface HS

The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells

<p>Abstract</p> <p>Background</p> <p>Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs.</p> <p>Methods</p> <p>Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB) and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated.</p> <p>Results</p> <p>We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity.</p> <p>Conclusion</p> <p>Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis.</p

Stability and reproducibility of proteomic profiles measured with an aptamer-based platform

The feasibility of SOMAscan, a multiplex, high sensitivity proteomics platform, for use in studies using archived plasma samples has not yet been assessed. We quantified 1,305 proteins from plasma samples donated by 16 Nurses’ Health Study (NHS) participants, 40 NHSII participants, and 12 local volunteers. We assessed assay reproducibility using coefficients of variation (CV) from duplicate samples and intra-class correlation coefficients (ICC) and Spearman correlation coefficients (r) of samples processed (i.e., centrifuged and aliquoted into separate components) immediately, 24, and 48 hours after collection, as well as those of samples collected from the same individuals 1 year apart. CVs were <20% for 99% of proteins overall and <10% for 92% of proteins in heparin samples compared to 66% for EDTA samples. We observed ICC or Spearman r (comparing immediate vs. 24-hour delayed processing) ≥0.75 for 61% of proteins, with some variation by anticoagulant (56% for heparin and 70% for EDTA) and protein class (ranging from 49% among kinases to 83% among hormones). Within-person stability over 1 year was good (ICC or Spearman r ≥ 0.4) for 91% of proteins. These results demonstrate the feasibility of SOMAscan for analyses of archived plasma samples