Recent reports suggest that the COVID-19 lockdown resulted in changes in mental health, however, potential age-related changes and risk factors remain unknown. We measured COVID-19 lockdown-induced stress levels and the severity of depressive symptoms prior to and during the COVID-19 lockdown in different age groups and then searched for potential risk factors in a well-characterized general population-based sample. A total of 715 participants were tested for mental distress and related risk factors at two time-points, baseline testing prior to COVID-19 and follow-up testing during COVID-19, using a battery of validated psychological tests including the Perceived Stress Scale and the Patient Health Questionnaire. Longitudinal measurements revealed that the prevalence of moderate to high stress and the severity of depressive symptoms increased 1.4- and 5.5-fold, respectively, during the COVID-19 lockdown. This surge in mental distress was more severe in women, but was present in all age groups with the older age group exhibiting, cross-sectionally, the lowest levels of mental distress prior to and during the lockdown. Illness perception, personality characteristics such as a feeling of loneliness, and several lifestyle components were found to be associated with a significant increase in mental distress. The observed changes in mental health and the identified potential risk factors underlying these changes provide critical data justifying timely and public emergency-tailored preventive, diagnostic, and therapeutic mental health interventions, which should be integrated into future public health policies globally.

In most vertebrates, pharyngeal arches form in a stereotypic anterior-to-posterior progression. To gain insight into the mechanisms underlying evolutionary changes in pharyngeal arch development, here we investigate embryos and larvae of bichirs. Bichirs represent the earliest diverged living group of ray-finned fishes, and possess intriguing traits otherwise typical for lobe-finned fishes such as ventral paired lungs and larval external gills. In bichir embryos, we find that the anteroposterior way of formation of cranial segments is modified by the unique acceleration of the entire hyoid arch segment, with earlier and orchestrated development of the endodermal, mesodermal, and neural crest tissues. This major heterochronic shift in the anteroposterior developmental sequence enables early appearance of the external gills that represent key breathing organs of bichir free-living embryos and early larvae. Bichirs thus stay as unique models for understanding developmental mechanisms facilitating increased breathing capacity.

In the last decade, the CRISPR/Cas9 bacterial virus defense system has been adapted as a user-friendly, efficient, and precise method for targeted mutagenesis in eukaryotes. Though CRISPR/Cas9 has proven effective in a diverse range of organisms, it is still most often used to create mutant lines in lab-reared genetic model systems. However, one major advantage of CRISPR/Cas9 mutagenesis over previous gene targeting approaches is that its high efficiency allows the immediate generation of near-null mosaic mutants. This feature could potentially allow genotype to be linked to phenotype in organisms with life histories that preclude the establishment of purebred genetic lines; a group that includes the vast majority of vertebrate species. Of particular interest to scholars of early vertebrate evolution are several long-lived and slow-maturing fishes that diverged from two dominant modern lineages, teleosts and tetrapods, in the Ordovician, or before. These early-diverging or “basal” vertebrates include the jawless cyclostomes, cartilaginous fishes, and various non-teleost ray-finned fishes. In addition to occupying critical phylogenetic positions, these groups possess combinations of derived and ancestral features not seen in conventional model vertebrates, and thus provide an opportunity for understanding the genetic bases of such traits. Here we report successful use of CRISPR/Cas9 mutagenesis in one such non-teleost fish, sterlet Acipenser ruthenus, a small species of sturgeon. We introduced mutations into the genes Tyrosinase, which is needed for melanin production, and Sonic hedgehog, a pleiotropic developmental regulator with diverse roles in early embryonic patterning and organogenesis. We observed disruption of both loci and the production of consistent phenotypes, including both near-null mutants’ various hypomorphs. Based on these results, and previous work in lamprey and amphibians, we discuss how CRISPR/Cas9 F0 mutagenesis may be successfully adapted to other long-lived, slow-maturing aquatic vertebrates and identify the ease of obtaining and injecting eggs and/or zygotes as the main challenges.

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A specific form of endometrial cancer (EC) can develop in breast cancer patients previously treated with tamoxifen (ET), an antagonist of estrogen receptor (ER) that inhibits proliferation of ER positive breast cancer. ET tumors have a different phenotype than endometrial tumors, which typically develop de novo without previous exposure to tamoxifen (EN). Here we aimed to identify specific protein markers that could serve as specific molecular targets in either phenotype. A set of total 45 formalin-fixed paraffin-embedded (FFPE) endometrial tumor tissues and adjacent myometrium tissue samples were analyzed using LC−MS/MS in SWATH-MS mode. We found that calcyphosin (CAPS) levels were elevated in EN tumors compared to ET tumors. The higher CAPS level in EC tissue invading to myometrium supports its relationship to EC aggressiveness. Further, stathmin (STMN1) levels were found significantly elevated in ET versus EN tumors and significantly associated with patient survival. This finding connects elevated levels of this cell cycle regulating, proliferation-associated protein with tamoxifen exposure. In summary, using SWATH-MS we show that CAPS and STMN1 should be recognized as clinicopathologically different EC markers of which STMN1 is specifically connected with a previous tamoxifen exposition.

Vertebrate dentitions arise at various places within the oropharyngeal cavity including the jaws, the palate, or the pharynx. These dentitions develop in a highly organized way, where new tooth germs are progressively added adjacent to the initiator center, the first tooth. At the same time, the places where dentitions develop house the contact zones between the outer ectoderm and the inner endoderm, and this colocalization has instigated various suggestions on the roles of germ layers for tooth initiation and development. Here, we study development of the axolotl dentition, which is a complex of five pairs of tooth fields arranged into the typically tetrapod outer and inner dental arcades. By tracking the expression patterns of odontogenic genes, we reason that teeth of both dental arcades originate from common tooth-competent zones, one present on the mouth roof and one on the mouth floor. Progressive compartmentalization of these zones and a simultaneous addition of new tooth germs distinct for each prospective tooth field subsequently control the final shape and composition of the axolotl dentition. Interestingly, by following the fate of the GFP-labeled oral ectoderm, we further show that, in three out of five tooth field pairs, the first tooth develops right at the ecto-endodermal boundary. Our results thus indicate that a single tooth-competent zone gives rise to both dental arcades of a complex tetrapod dentition. Further, we propose that the ecto-endodermal boundary running through this zone should be accounted for as a potential source of instruction factors instigating the onset of the odontogenic program.

The northern pike, Esox lucius, is one of the largest temperate freshwater apex predators with a characteristic morphology: an elongated body with pelvic, dorsal, and anal fins located at the rear as a functional feature to sprint predation. However, the typical pike character is its head, which is characterized by a long, flattened snout, a well‐armed mouth with numerous teeth, and large eyes characteristic of shallow water visual predators. Although the northern pike is becoming increasingly popular as a model system for ecology and evolutionary research, a detailed staging table has not yet been reported. In this study, we report the first comprehensive staging table for the northern pike, spanning from the one‐cell stage to the freely‐swimming juvenile stage. In addition to classical embryological descriptions, we use a DAPI staining to distinguish individual cells and embryonic structures during the early development. This dataset, in combination with the genomic and transcriptomic resources already available, serves as a foundation for in‐depth mechanistic studies dealing with development using this species.

The association between lateral‐line canals and skull bones in fishes has been the subject of several studies and raised a series of controversies, particularly with regard to the hypothesized role of lateral‐line organs (i.e. neuromasts) in osteogenesis and the consequences for hypotheses of homology of the bones associated with lateral‐line canals. Polypteridae, a group of freshwater fishes that occupies a key phylogenetic position as the most basal extant lineage of ray‐finned fishes (Actinopterygii), provides an interesting model for the study of the relationships between lateral‐line canals and skull bones. We describe the development of bones associated with lateral‐line canals in the Senegal Bichir, Polypterus senegalus, and use these data to re‐address previous hypotheses of homology of skull bones of polypterids. We demonstrate that the lateral‐line canals constitute a separate component of the dermatocranium that may interact with a membranodermal component, thereby forming compound bones in the adult. Differences in the interactions between these components determine the characteristics of the development of each independent bone in the skull of adult P. senegalus. Our results shed light on long‐standing controversies about the identity of skull bones such as the rostral, preopercle, and sphenotic in Polypteridae, and suggest the presence of an ancestral two‐component pattern of formation of bones associated with lateral‐line canals in bony fishes. These findings reveal the need to re‐address previous hypotheses of homology of bones associated with lateral‐line canals in different groups of bony fishes, especially fossil taxa.